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• Volume 14, Issue 5
• How to manage alcohol-related liver disease: A case-based review
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• http://orcid.org/0000-0003-1530-5328 James B Maurice 1 ,
• http://orcid.org/0000-0001-5140-517X Samuel Tribich 2 ,
• Ava Zamani 3 ,
• Jennifer Ryan 4
• 1 Department of Gastroenterology and Hepatology, Southmead Hospital , North Bristol NHS Trust , Bristol , UK
• 2 Department of Hepatology, Royal London Hospital , Barts Health NHS Trust , London , UK
• 3 Hammersmith Hospital , Imperial College Healthcare NHS Trust , London , UK
• 4 Department of Hepatology and Liver Transplantation, Royal Free Hospital , Royal Free London NHS Foundation Trust , London , UK
• Correspondence to Dr James B Maurice, Department of Gastroenterology and Hepatology, Southmead Hospital, North Bristol NHS Trust, Bristol BS10 5NB, UK; james.maurice{at}nbt.nhs.uk

https://doi.org/10.1136/flgastro-2022-102270

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• alcoholic liver disease
• chronic liver disease

What is already known on this topic

Alcohol-related liver disease (ArLD) is a major cause of morbidity and mortality.

What this study adds

We present a typical case to illustrate current evidence-based investigation and management of a patient with ArLD.

This case-based review aims to concisely support the day-to-day decision making of clinicians looking after patients with ArLD, from risk stratification and fibrosis assessment in the community through to managing decompensated disease, escalation care to critical care and assessment for liver transplantation.

How this study might affect research, practice or policy

We summarise the evolving evidence for the benefit of liver transplantation in alcoholic hepatitis, and ongoing controversies shaping future research in this area.

ArLD is fundamentally a public health problem, and further efforts are required to implement effective policies to reduce consumption and prevent disease.

Introduction

Alcohol is the leading risk factor for premature death in young adults, of which alcohol-related liver disease (ArLD) is a major contributor. 1 The management of ArLD often requires complex decision-making, raising challenges for the clinician and wider multidisciplinary team. This case-based review follows the typical journey of a patient through the progressive stages of the disease process, from early diagnosis and risk stratification in the outpatient clinic through to alcoholic hepatitis and referral for liver transplantation. At each stage, we discuss a practical approach to clinical management and summarise the underlying evidence base.

Case part 1

A 47-year-old man is referred to the general hepatology clinic from his General Practitioner with abnormal liver function tests, ordered in the community following several episodes of non-specific abdominal pain which subsequently resolved. He is now asymptomatic. The referral states that he drinks one bottle of wine each weekday night and more at the weekends. He is on no regular medication, has no other significant medical history and works in construction. On clinical examination, there are a few …

Twitter @jamesbmaurice

Contributors JBM conceptualised the original article and the case. JBM, ST and AZ drafted the initial version of the manuscript. JBM and ST contributed further editing of various sections. JR provided senior critical review and edited the manuscript. All authors agreed upon the final version.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests None declared.

Provenance and peer review Not commissioned; externally peer reviewed.

Linked Articles

• Highlights from this issue UpFront R Mark Beattie Frontline Gastroenterology 2023; 14 357-358 Published Online First: 07 Aug 2023. doi: 10.1136/flgastro-2023-102519

Read the full text or download the PDF:

ANDREW SMITH, MD, KATRINA BAUMGARTNER, MD, AND CHRISTOPHER BOSITIS, MD

Am Fam Physician. 2019;100(12):759-770

Author disclosure: No relevant financial affiliations.

Cirrhosis is the 12th leading cause of death in the United States. Newer research has established that liver fibrosis is a dynamic process and that early cirrhosis may be reversible. Only one in three people with cirrhosis knows they have it. Most patients with cirrhosis remain asymptomatic until the onset of decompensation. When clinical signs, symptoms, or abnormal liver function tests are discovered, further evaluation should be pursued promptly. The most common causes of cirrhosis are viral hepatitis, alcoholic liver disease, and nonalcoholic steatohepatitis. Initial workup includes viral hepatitis serologies, ferritin, transferrin saturation, and abdominal ultrasonography as well as complete blood count, liver function tests, and prothrombin time/international normalized ratio, if not already ordered. Additional testing is based on demographics and risk factors. Common serum and ultrasound-based screening tests to assess fibrosis include the aspartate transaminase to platelet ratio index score, Fibrosis 4 score, FibroTest/FibroSure, nonalcoholic fatty liver fibrosis score, standard ultrasonography, and transient elastography. Generally, noninvasive tests are most useful in identifying patients with no to minimal fibrosis or advanced fibrosis. Chronic liver disease management includes directed counseling, laboratory testing, and ultrasound monitoring. Treatment goals are preventing cirrhosis, decompensation, and death. Varices are monitored with endoscopy and often require prophylaxis with nonselective beta blockers. Ascites treatment includes diuresis, salt restriction, and antibiotic prophylaxis for spontaneous bacterial peritonitis, when indicated. Hepatic encephalopathy is managed with lifestyle and nutritional modifications and, as needed, with lactulose and rifaximin. Hepatocellular carcinoma screening includes ultrasound screening every six months for patients with cirrhosis.

Cirrhosis is a diffuse process of liver damage considered irreversible in its advanced stages. In 2016, more than 40,000 Americans died because of complications related to cirrhosis, making it the 12th leading cause of death in the United States. 1 Recent projections suggest that this number is likely to grow. 2 An estimated 630,000 Americans have cirrhosis, yet less than one in three knows it. 3 Important racial and socioeconomic disparities exist, with prevalence highest among non-Hispanic blacks, Mexican Americans, and those living below the poverty level. 3 Cirrhosis and advanced liver disease cost the United States between $12 billion and $23 billion dollars in health care expenses annually. 4 , 5

WHAT'S NEW ON THIS TOPIC

Estimates suggest that nonalcoholic steatohepatitis will become the leading cause of cirrhosis in U.S. patients awaiting liver transplantation sometime between 2025 and 2035.

Liver biopsy remains the reference standard; however, transient elastography has become more widely available and is rapidly replacing biopsy as the preferred method for liver fibrosis staging.

Newer guidelines suggest targeted screening for esophageal varices in patients with clinically significant portal hypertension rather than screening all patients with cirrhosis.

The most common causes of cirrhosis in the United States are viral hepatitis (primarily hepatitis C virus [HCV] and hepatitis B virus [HBV]), alcoholic liver disease, and non-alcoholic steatohepatitis. HCV remains the leading cause of cirrhosis in patients awaiting liver transplant. With an increasing prevalence of nonalcoholic fatty liver disease (NAFLD) in the United States, estimates suggest that non-alcoholic steatohepatitis, a severe progression of NAFLD characterized by inflammatory steatohepatitis, will become the leading cause of cirrhosis in patients awaiting liver transplant sometime between 2025 and 2035. 6 , 7 Table 1 lists common etiologies of cirrhosis. 8

Pathophysiology and Natural History of Cirrhosis

Chronic liver injury causes inflammation and hepatic fibrosis. Regardless of the cause, this can lead to the formation of fibrous septae and nodules, collapse of liver structures, and distortion of hepatic parenchyma and vascular architecture. Progressive fibrosis and cirrhosis subsequently result in decreased metabolic and synthetic hepatic function, causing a rise in bilirubin and decreased production of clotting factors and thrombopoietin, as well as splenic platelet sequestration, increased portal pressure, and the development of ascites and esophageal varices.

Cirrhosis can result from chronic liver damage of any cause. In patients with the three most common causes of liver disease, 10% to 20% will develop cirrhosis within 10 to 20 years. 9 Factors associated with an increased risk of progression to cirrhosis include increased age, medical comorbidities (particularly patients coinfected with HIV and HCV), and male sex (except in alcoholic liver disease, where females progress more rapidly). 10 The point at which this process becomes irreversible, however, is not clear. Newer research has established that liver fibrosis is a dynamic process and that even early cirrhosis is reversible. 11 Studies have demonstrated biopsy-proven fibrosis improvement rates as high as 88% after antiviral treatment in patients with HBV and HCV and as high as 85% after bariatric surgery in patients with nonalcoholic steatohepatitis. 12 , 13

After cirrhosis is established, a patient may remain clinically stable, or compensated, for years. Patients with compensated cirrhosis caused by HBV, HCV, and alcoholic liver disease develop clinical signs of decompensation, which include ascites, hepatic encephalopathy, jaundice, or bleeding, at a rate of 4% to 10% per year. 14 Variability of disease progression is influenced by the underlying cause and the presence or absence of treatment and ongoing liver injury. The median survival for those with compensated cirrhosis is 12 years, compared with two years once decompensation occurs. 15

Clinical Presentation

Most patients with compensated cirrhosis remain asymptomatic. When symptoms occur, they include fatigue, weakness, loss of appetite, right upper quadrant discomfort, and unexplained weight loss. With the onset of decompensation, patients may report symptoms of impaired liver function such as jaundice, portal hypertension (including ascites and peripheral edema), and hepatic encephalopathy (such as confusion and disordered sleep).

PHYSICAL EXAMINATION

Physical examination findings that may be present in patients with advanced liver disease (cirrhosis) are summarized in Table 2 . 16 , 17 The Stanford Medicine 25 website is a good resource for photos and instructional videos that demonstrate findings associated with cirrhosis ( http://stanfordmedicine25.stanford.edu/the25/liverdisease.html ). 16 , 17

INITIAL LABORATORY FINDINGS

In early compensated disease, laboratory findings may be normal. Incidentally elevated liver enzymes or evidence of hepatic disease on imaging may prompt the initial suspicion of chronic liver injury. Findings suggestive of cirrhosis include low albumin (less than 3.5 g per dL [35 g per L]), thrombocytopenia (platelet count less than 160 × 10 3 per μL [160 × 10 9 per L]), aspartate transaminase (AST):alanine transaminase (ALT) ratio greater than 1, elevated bilirubin, and a prolonged prothrombin time (PT)/elevated international normalized ratio (INR). 18

Evaluation of Chronic Liver Disease

When chronic liver disease is suspected, a history should be conducted, reviewing any potentially hepatotoxic medications, alcohol consumption, and family history of liver disease. Basic laboratory tests, including complete blood count, ALT, AST, albumin, alkaline phosphatase, gamma-glutamyl transferase, total bilirubin, and PT/INR, should be ordered.

For those with clinical signs or symptoms of liver disease or abnormal liver function test results, regardless of duration, further evaluation to determine the potential etiology should be pursued promptly. 19 , 20 Viral hepatitis serologies, ferritin, transferrin saturation, and abdominal ultrasonography should be performed; complete blood count, liver function tests, and PT/INR should be completed, if not already ordered. If risk factors for NAFLD exist, testing of fasting lipid levels and A1C should be done. For patients with risk factors or demographics with concern for autoimmune hepatitis, antinuclear antibodies and smooth muscle antibodies should be tested. Table 3 lists additional suggested tests based on risk factors and clinical findings. 19 , 21 , 22

Staging Fibrosis and Diagnosing Cirrhosis

Liver fibrosis is scored on a scale from F0 to F4 ( Table 4 ) . 23 Differentiating between significant (F2 or greater) and advanced (F3 or greater) fibrosis and cirrhosis (F4) is difficult even with complete clinical, laboratory, and imaging data because findings are often nonspecific or insensitive. 24 Liver biopsy remains the reference standard for assessing liver fibrosis; however, use of noninvasive methods has become increasingly common in clinical practice. 18

Noninvasive testing includes serum-based and imaging modalities ( Table 5 25 – 37 ) . Generally, noninvasive tests are most useful in identifying patients with no to minimal fibrosis (F0) or advanced fibrosis (F3 to F4) and are less accurate at distinguishing early or intermediate stages of liver disease (F1 to F2). 24 , 38 They are most beneficial when combined with all available data, accounting for the pretest probability of fibrosis. 24 , 38

Most serum tests show indirect markers of liver damage, except hyaluronic acid (found in the liver's extracellular matrix), which is included in biomarker panels such as FibroMeter or Hepascore. 24 The AST to platelet ratio index (APRI; https://www.mdcalc.com/ast-platelet-ratio-index-apri ), Fibrosis 4 score ( http://gihep.com/calculators/hepatology/fibrosis-4-score/ ), and NAFLD fibrosis score ( http://nafldscore.com/ ) are accessible, serum-based, nonproprietary calculations. 18 , 39 FibroTest (FibroSure in the United States), FibroMeter, and Hepascore are patented calculations using several serum biomarkers, with FibroTest being the most validated. 24

Biomarkers are most validated in chronic HCV, 40 with the exception of the NAFLD fibrosis score for non-alcoholic steatohepatitis. 33 For other etiologies of liver disease, including alcoholic liver disease, few studies of noninvasive methods exist.

STANDARD ULTRASONOGRAPHY

Given its relatively low cost, accessibility, and lack of radiation, ultrasonography is useful for diagnosing cirrhosis, cirrhosis complications (e.g., splenomegaly, portal hypertension, ascites, hepatocellular carcinoma), and comorbid liver diseases (e.g., extrahepatic cholestasis). 24 Ultrasonography is good at detecting steatosis (94% sensitivity, 84% specificity), but it may frequently miss fibrosis or cirrhosis (for which it is 40% to 57% sensitive). 41 , 42 Characteristics of cirrhosis include hepatic nodularity, coarseness, and echogenicity, 24 with hepatic nodularity being the most specific. 36 Additionally, features consistent with portal hypertension, such as splenomegaly and portosystemic collaterals, are suggestive of cirrhosis. 37 Patients with cirrhosis and some with chronic HBV should undergo right upper quadrant ultrasonography every six months to screen for hepatocellular carcinoma. 43

TRANSIENT ELASTOGRAPHY

Transient elastography, which has become more widely available, is rapidly replacing biopsy as the preferred method for fibrosis staging. Transient elastography, an ultrasound technique performed with a specialized machine (Fibro-Scan), determines liver stiffness in kilopascals (kPa) by measuring the velocity of low-frequency elastic shear waves propagating through the liver. It is a five-minute procedure performed in an outpatient setting and provides point-of-care results. In a meta-analysis of more than 10,000 patients spanning multiple etiologies of liver disease, transient elastography was sensitive (81%) and specific (88%) for detecting liver fibrosis and cirrhosis 40 (see Table 5 25 – 37 for cutoff values). Transient elastography performs better than the biomarker-based tools in detecting cirrhosis and is accurate at excluding cirrhosis (negative predictive value greater than 90%). 38 Similar to serum tests, however, transient elastography is less accurate at distinguishing between intermediate stages of liver disease, and cutoff values vary depending on the etiology of liver disease and population studied. 24 , 38

LIMITATIONS

Abnormal serum results may be seen from non–liver-related causes, including bone marrow disease, hemolysis, and medications. Transient elastography is less reliable in patients with obesity (though an extra-large probe has been developed), ascites, excessive alcohol intake, and extrahepatic cholestasis. If performed during an episode of acute hepatic inflammation, these tests can also lead to falsely elevated results. 38

LIVER BIOPSY

Liver biopsy remains the reference standard in diagnosing cirrhosis; however, a 20% error rate still occurs in fibrosis staging. 44 Pathologic changes may be heterogeneous; therefore, sampling error is common, and interpretation should be made by an experienced pathologist using validated scoring systems. 38 Liver biopsy is recommended when concern for fibrosis remains after indeterminate or conflicting clinical, laboratory, and imaging results; in those for whom transient elastography is not suitable; or to clarify etiology of disease after inconclusive noninvasive evaluation. 9 Liver biopsy may be indicated to diagnose necroinflammation (in HBV) and steatohepatitis (nonalcoholic steatohepatitis) because they are not easily distinguished by noninvasive methods.

Staging Cirrhosis

After the diagnosis of cirrhosis is established, Child-Pugh ( https://www.mdcalc.com/child-pugh-score-cirrhosis-mortality ) and Model for End-Stage Liver Disease ( https://www.mdcalc.com/meld-score-model-end-stage-liver-disease-12-older ) scores should be used to identify the stage of cirrhosis and mortality risk, respectively. 9 , 45 A Child-Pugh grade B classification (seven to nine points) is consistent with early hepatic decompensation, 46 whereas a Model for End-Stage Liver Disease score of 12 or more is predictive of increased risk for cirrhosis complications. 9

Cirrhosis Management

The primary goals of liver disease management are to prevent cirrhosis complications, liver decompensation, and death. These goals are accomplished with rigorous prevention counseling, monitoring, and management by primary care physicians, in consultation with subspecialists as needed.

PREVENTION COUNSELING

For all patients with liver disease, counseling points should be discussed, including avoidance of alcohol; maintenance of a healthy weight; nutrition; medication and supplement review; prevention of infections (including receiving vaccinations); screening and treatment of causative factors; and avoidance of unnecessary surgical procedures. Table 6 provides more details on counseling for patients with chronic liver disease. 7 , 9 , 18 , 21 , 45 , 47 – 52

MONITORING OF PATIENTS WITH CIRRHOSIS

For patients with cirrhosis, a basic metabolic panel, liver function tests, complete blood count, and PT/INR should be completed every six months to recalculate Child-Pugh and Model for End-Stage Liver Disease scores. Patients with a Model for End-Stage Liver Disease score of 15 or higher should be referred for liver transplantation evaluation 37 , 45 ; patients with ascites, hepatic encephalopathy, or variceal hemorrhage should also be referred. 37 , 53

Screening and Management for Specific Complications

Patients with cirrhosis are at risk of multiple complications, including hepatic decompensation, hepatocellular carcinoma, and other more common conditions (e.g., malnutrition, leg cramps, umbilical hernias). Table 7 includes specific recommendations for the screening and management of select complications of cirrhosis. 7 , 9 , 43 , 45 , 46 , 49 , 53 – 55

COMMON COMPLICATIONS IN DECOMPENSATED CIRRHOSIS

Ascites, which develops in 5% to 10% of patients with cirrhosis per year, leads to decreased quality of life, frequent hospitalizations, and directly increases risk of further complications such as spontaneous bacterial peritonitis, umbilical hernias, and respiratory compromise. It also portends a poor prognosis, with a 30% five-year survival. 53 Hepatic encephalopathy, which occurs in 5% to 25% of patients within five years of a cirrhosis diagnosis, is likewise associated with increased medical cost and mortality, with a reported 15% inpatient mortality rate. 54

SCREENING FOR VARICES

Portal hypertension predisposes patients with cirrhosis to develop esophageal varices. Patients with varices have a one in three chance of developing a variceal bleed in the two years after diagnosis, with a 20% to 40% mortality rate per episode. 45 Endoscopy is the preferred screening method for esophageal varices. Many experts and guidelines recommend screening all patients with cirrhosis 9 ; however, newer recommendations suggest targeted screening of patients with clinically significant portal hypertension. 46 A liver stiffness greater than 20 kPa, alone or combined with a low platelet count (less than 150,000 per mm 3 ) and increased spleen size, and/or the presence of portosystemic collaterals on imaging may be sufficient to diagnose clinically significant portal hypertension and warrant endoscopic screening for varices. Repeat endoscopy should be performed every one to two years if small varices are found and every two to three years if no varices are found. 46

Consultation

Varices, hepatic encephalopathy, and ascites herald hepatic decompensation; these conditions warrant referral for subspecialist evaluation. The management of acute or refractory complications of cirrhosis (e.g., spontaneous bacterial peritonitis, acute gastrointestinal bleeding, hepatorenal syndrome, unresponsive portal hypertension, hepatic encephalopathy, ascites) is best addressed in the inpatient or referral setting.

This article updates previous articles on this topic by Starr and Raines , 56 Heidelbaugh and Bruderly , 57 and Riley and Bhatti . 58

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Understanding Liver Cirrhosis: Causes, Symptoms, and Treatment Options

Apr 11, 2023

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Liver cirrhosis is a chronic liver disease that results in scarring and damage to liver tissue, affecting liver function and overall health. Learn about the causes, symptoms, and treatment options available to manage this condition.<br><br>TO know more check here : https://www.livertransplantinternational.com/liver-cirrhosis/

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Understanding Liver Cirrhosis

Introduction • Definition of liver cirrhosis • Causes of liver cirrhosis • Symptoms of liver cirrhosis • Importance of early detection and treatment

What is Liver Cirrhosis? • A chronic liver disease that results in scarring and damage to liver tissue • Scar tissue replaces healthy liver tissue, making it difficult for the liver to function properly • Liver function is critical to overall health and well-being

Causes of Liver Cirrhosis • Alcohol abuse • Hepatitis B and C • Non-alcoholic fatty liver disease • Autoimmune disorders • Inherited diseases

Symptoms of Liver Cirrhosis • Fatigue and weakness • Loss of appetite • Nausea and vomiting • Weight loss • Jaundice (yellowing of the skin and eyes) • Abdominal pain and swelling • Itchy skin • Dark urine and pale stools

Diagnosis of Liver Cirrhosis • Blood tests to check liver function • Imaging tests, such as ultrasound or CT scan • Liver biopsy to confirm diagnosis and determine severity of liver damage

Treatment of Liver Cirrhosis • Treating the underlying cause, such as stopping alcohol abuse or treating viral hepatitis • Medications to manage symptoms and complications, such as diuretics to reduce fluid buildup • Liver transplant for severe cases

Complications of Liver Cirrhosis • Portal hypertension, which can lead to varices and bleeding • Ascites, which is fluid buildup in the abdomen • Hepatic encephalopathy, which is a brain disorder caused by liver failure • Liver cancer

Prevention of Liver Cirrhosis • Limit alcohol intake • Practice safe sex and get vaccinated for hepatitis B • Maintain a healthy weight and diet • Avoid exposure to harmful chemicals

Conclusion • Liver cirrhosis is a serious condition that can have severe complications • Early detection and treatment can help manage symptoms and prevent further damage • Prevention is key to reducing the risk of liver cirrhosis

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StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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Hepatic cirrhosis.

Bashar Sharma ; Savio John .

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• Continuing Education Activity

Cirrhosis is characterized by fibrosis and nodule formation of the liver secondary to chronic injury, leading to alteration of the normal lobular organization of the liver. Various insults can injure the liver, including viral infections, toxins, hereditary conditions, or autoimmune processes. With each injury, the liver initially forms scar tissue (fibrosis) without losing its function. After a chronic injury, most of the liver tissue becomes fibrotic, leading to loss of function and the development of cirrhosis. This activity reviews the causes, evaluation, and management of hepatic cirrhosis and highlights the interprofessional team's role in managing patients with this condition.

• Identify the pathophysiology of cirrhosis.
• Assess the etiology of cirrhosis.
• Evaluate the presentation of a patient with cirrhosis.
• Communicate the importance of improving care coordination amongst interprofessional team members to improve outcomes for cirrhotic patients.
• Introduction

Cirrhosis is characterized by fibrosis and nodule formation of the liver, secondary to a chronic injury, which leads to alteration of the normal lobular organization of the liver. Various insults can injure the liver, including viral infections, toxins, hereditary conditions, or autoimmune processes. The liver initially forms scar tissue (fibrosis) with each injury without losing its function. After a long-standing injury, most of the liver tissue gets fibrosed, leading to loss of function and the development of cirrhosis. See image. Cirrhosis, Liver.

Chronic liver diseases usually progress to cirrhosis. In the developed world, the most common causes of cirrhosis are hepatitis C virus (HCV), alcoholic liver disease, and nonalcoholic steatohepatitis (NASH). In contrast, hepatitis B virus (HBV) and HCV are the most common causes in the developing world. [1]  Other causes of cirrhosis include autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, hemochromatosis, Wilson disease, alpha-1 antitrypsin deficiency, Budd-Chiari syndrome, drug-induced liver cirrhosis, and chronic right-sided heart failure. Cryptogenic cirrhosis is defined as cirrhosis of unclear etiology.

• Epidemiology

The worldwide prevalence of cirrhosis is unknown; however, it has been estimated to be between 0.15% and 0.27% in the United States. [2] [3]

• Pathophysiology

Multiple cells play a role in liver cirrhosis, including hepatocytes and sinusoidal lining cells such as hepatic stellate cells (HSCs), sinusoidal endothelial cells (SECs), and Kupffer cells (KCs). HSCs form a part of the wall of the liver sinusoids, and their function is to store vitamin A. When these cells are exposed to inflammatory cytokines, they get activated, transform into myofibroblasts, and start depositing collagen, which results in fibrosis. SECs form the endothelial lining and are characterized by the fenestrations they make in the wall that allow the exchange of fluid and nutrients between the sinusoids and the hepatocytes. [4]  Defenestration of the sinusoidal wall can happen secondary to chronic alcohol use and promote perisinusoidal fibrosis. [5]  KCs are satellite macrophages that line the wall of the sinusoids as well. Studies from animal models have shown that they play a role in liver fibrosis by releasing harmful mediators when exposed to injurious agents and acting as antigen-presenting cells for viruses. [6]  Hepatocytes are also involved in cirrhosis's pathogenesis, as damaged hepatocytes release reactive oxygen species and inflammatory mediators that can promote activating HSCs and liver fibrosis. [7]

The major cause of morbidity and mortality in cirrhotic patients is the development of portal hypertension and hyperdynamic circulation. Portal hypertension develops secondary to fibrosis and vasoregulatory changes intrahepatically and systematically, leading to collateral circulation formation and hyperdynamic circulation. [8]  Intrahepatically, SECs synthesize nitric oxide (NO) and endothelin-1 (ET-1), which act on HSCs, causing relaxation or contraction of the sinusoids, respectively, and controlling sinusoidal blood flow. In patients with cirrhosis, there is an increase in ET-1 production and the sensitivity of its receptors with a decrease in NO production. This leads to increased intrahepatic vasoconstriction and resistance, initiating portal hypertension. Vascular remodeling mediated by the contractile effects of HSCs in the sinusoids augments the increase in vascular resistance. To compensate for this increase in intrahepatic pressure, collateral circulation is formed. [8]  In systemic and splanchnic circulation, the opposite effect happens, with an increase in NO production, leading to systemic and splanchnic vasodilation and decreased systemic vascular resistance. This activates the renin-angiotensin-aldosterone system, leading to sodium and water retention and hyperdynamic circulation. Thus, in cirrhosis with portal hypertension, there is a depletion of vasodilators (predominantly NO) intrahepatic-ally but a renin-excess of NO extrahepatically in the splanchnic and systemic circulation, leading to sinusoidal vasoconstriction and splanchnic (systemic) vasodilation. The collaterals also contribute to the hyperdynamic circulation by increasing the venous return to the heart. [8] [9]

• Histopathology

Cirrhosis is classified based on morphology or etiology. 

• Viral - hepatitis B, C, and D
• Toxins - alcohol, drugs 
• Autoimmune - autoimmune hepatitis
• Cholestatic - primary biliary cholangitis, primary sclerosing cholangitis 
• Vascular - Budd-Chiari syndrome, sinusoidal obstruction syndrome, cardiac cirrhosis
• History and Physical

Patients with cirrhosis can be asymptomatic or symptomatic, depending on whether their cirrhosis is clinically compensated or decompensated. In compensated cirrhosis, patients are usually asymptomatic, and their disease is detected incidentally by labs, physical exams, or imaging. One of the common findings is mild to moderate elevation in aminotransferases or gamma-glutamyl transpeptidase with possible enlarged liver or spleen on the exam. On the other hand, patients with decompensated cirrhosis usually present with a wide range of signs and symptoms arising from a combination of liver dysfunction and portal hypertension. The diagnosis of ascites, jaundice, hepatic encephalopathy, variceal bleeding, or hepatocellular carcinoma in a patient with cirrhosis signifies the transition from a compensated to a decompensated phase of cirrhosis. Other cirrhosis complications include spontaneous bacterial peritonitis and hepatorenal syndrome, which occur in patients who have ascites.

Multiple Organs Affected

Gastrointestinal

Portal hypertension can cause ascites, hepatosplenomegaly, and prominence of the periumbilical abdominal veins, resulting in caput medusa. Esophageal varices are another complication of cirrhosis secondary to increased blood flow in the collateral circulation, with a mortality rate of at least 20% at 6 weeks after a bleeding episode. [10]  Patients with alcoholic cirrhosis are at increased risk of small bowel bacterial overgrowth and chronic pancreatitis, and patients with chronic liver disease have a higher rate of gallstone formation. [11] [12]

Hematologic

Anemia can occur due to folate deficiency, hemolytic anemia (spur cell anemia in severe alcoholic liver disease), and hypersplenism. There can be pancytopenia due to hypersplenism in portal hypertension, impaired coagulation, disseminated intravascular coagulation, and hemosiderosis in cirrhosis patients due to different causes.

Patients with cirrhosis are prone to develop hepatorenal syndrome secondary to systemic hypotension and renal vasoconstriction, causing the underfilling phenomenon. Splanchnic vasodilation in cirrhosis leads to decreased effective blood flow to the kidneys, activating the renin-angiotensin-aldosterone system, leading to sodium and water retention and renal vascular constriction. [13]  However, this effect is not enough to overcome the systemic vasodilation caused by cirrhosis, leading to renal hypoperfusion and worsened by renal vasoconstriction with the endpoint of renal failure. [14]

Manifestations of cirrhosis include hepatopulmonary syndrome, portopulmonary hypertension, hepatic hydrothorax, decreased oxygen saturation, ventilation-perfusion mismatch, reduced pulmonary diffusion capacity, and hyperventilation.

Spider nevi, central arterioles surrounded by multiple smaller vessels resembling a spider, are seen in cirrhosis patients secondary to hyperestrogenemia. Liver dysfunction leads to a sex hormone imbalance, causing an increased estrogen-to-free testosterone ratio and the formation of spider nevi. [15]  Palmar erythema is another skin finding that is seen in cirrhosis and is also secondary to hyperestrogenemia. Jaundice is a yellowish discoloration of the skin and mucous membranes seen when the serum bilirubin is greater than 3 mg/dL and in decompensated cirrhosis.

Patients with alcoholic liver cirrhosis can develop hypogonadism and gynecomastia. The pathophysiology is multifactorial, mainly due to the hypersensitivity of estrogen and androgen receptors seen in cirrhotic patients. Hypothalamic pituitary dysfunction has also been implicated in the development of these conditions. [16]  Hypogonadism can lead to decreased libido and impotence in males with loss of secondary sexual characteristics and feminization. Women can develop amenorrhea and irregular menstrual bleeding, as well as infertility.

Nail Changes

Clubbing, hypertrophic osteoarthropathy, and the Dupuytren contracture are seen. Other nail changes include azure lunules (Wilson disease), Terry nails, and Muehrcke nails.

Fetor hepaticus (sweet, musty breath smell due to high levels of dimethyl sulfide and ketones in the blood) and asterixis (flapping tremor when the arms are extended and the hands are dorsiflexed) are both features of hepatic encephalopathy that can be seen in cirrhosis. [17]  Cirrhosis can lead to hyperdynamic circulation, reduced lean muscle mass, muscle cramps, and umbilical herniation. Physical examination in patients with cirrhosis may reveal stigmata of chronic liver disease (spider telangiectasias, palmar erythema, Dupuytren contractures, gynecomastia, testicular atrophy), signs of portal hypertension (ascites, splenomegaly, caput medusae, Cruveilhier-Baumgarten murmur- epigastric venous hum), signs of hepatic encephalopathy (confusion, asterixis, and fetor hepaticus), and other features such as jaundice, bilateral parotid enlargement, and scant chest/axillary hair.

Lab Findings

Aminotransferases are usually mildly to moderately elevated, with aspartate aminotransferase (AST) greater than alanine aminotransferase (ALT); however, normal levels do not exclude cirrhosis. [18]  In most forms of chronic hepatitis (except alcoholic hepatitis), the AST/ALT ratio is less than 1. As chronic hepatitis progresses to cirrhosis, there is a reversal of this AST/ALT ratio. Alkaline phosphatase (ALP), 5'- nucleotidase, and gamma-glutamyl transferase (GGT) are elevated in cholestatic disorders. Prothrombin time (PT) is elevated due to coagulation factor defects and bilirubin, while albumin is low as the liver synthesizes it, and its functional capacity decreases. Thus, serum albumin and PT are true indicators of synthetic hepatic function. Normochromic anemia is seen; however, macrocytic anemia can be seen in alcoholic liver cirrhosis. Leukopenia and thrombocytopenia are also seen secondary to sequestration by the enlarged spleen and alcohol suppression effect on the bone marrow. [19]  Immunoglobulins, especially the gamma fraction, are usually elevated due to impaired clearance by the liver. [20]

Specific Labs to Investigate Newly Diagnosed Cirrhosis

Serology and PCR techniques for viral hepatitis and autoimmune antibodies (anti-nuclear antibodies [ANA], anti-smooth muscle antibodies (ASMA), anti-liver-kidney microsomal antibodies type 1 (ALKM-1) and serum IgG immunoglobulins) for autoimmune hepatitis and anti-mitochondrial antibody for primary biliary cholangitis may be ordered. Ferritin and transferrin saturation for hemochromatosis, ceruloplasmin, and urinary copper for Wilson disease, Alpha 1-antitrypsin level, and protease inhibitor phenotype for alpha 1-antitrypsin deficiency, and serum alpha-fetoprotein for hepatocellular carcinoma (HCC) are other useful tests.

Imaging and Liver Biopsy

Several imaging modalities are used alongside labs to help diagnose cirrhosis. These include ultrasound, CT, MRI, and transient elastography (fibroscan). Ultrasonography is a cheap, noninvasive, and available modality for evaluating cirrhosis. It can detect nodularity and increased echogenicity of the liver, which are seen in cirrhosis; however, it is nonspecific as these findings can also be seen in fatty liver. [21]  It can also determine the ratio of the caudate lobe width to the right lobe width, which usually increases in cirrhosis. [22]  Moreover, it is a useful screening tool for HCC in cirrhotic patients. Duplex Doppler ultrasonography helps to assess the patency of hepatic, portal, and mesenteric veins. CT and MRI, in contrast, can detect HCC and vascular lesions, with MRI being superior to CT. [23]  MRI can also be used to detect the level of iron and fat deposition in the liver for hemochromatosis, steatosis, and biliary obstruction if an MRC (magnetic resonance cholangiography) is obtained.[24] [25] MRI, however, is expensive and not readily available. Transient elastography (fibroscan) is a noninvasive method that uses high-velocity ultrasound waves to measure liver stiffness, which correlates with fibrosis. In cirrhosis, a colloid liver spleen scan using technetium-99m sulfur colloid may show increased colloid uptake in the bone marrow and spleen compared to the liver. The presence of varices in the esophagus or stomach on esophagogastroduodenoscopy (EGD) suggests portal hypertension. A liver biopsy is the gold standard for diagnosing cirrhosis and assessing the disease's degree of inflammation (grade) and fibrosis (stage). See Image . Cirrhosis, Portal Space in Fibrous Septa. Reticulin stain 4×.

Nevertheless, it can miss the diagnosis at times due to sampling errors. [24]  The diagnosis of cirrhosis by biopsy requires the presence of fibrosis and nodules. The nodular pattern can be micronodular, macronodular, or mixed with the micronodular pattern, representing an independent risk factor for elevated hepatic venous pressure gradient (HVPG) and more severe disease. [24]  Noninvasive tests using direct and indirect serum markers detect patients with significant fibrosis/cirrhosis from patients with no/mild fibrosis. [25] [26] [27]

• Treatment / Management

Damage to the liver is permanent. Nevertheless, further injury to the liver should be avoided to halt the progression of the disease. General management to prevent chronic liver disease includes avoidance of alcohol, vaccination for HBV and HCV, good nutrition with a balanced diet, weight reduction, and early treatment of precipitating factors like dehydration, hypotension, and infections (see Image. Schistosomiasis Infection). This is achieved by routine monitoring of volume status, kidney function, varices development, and progression to HCC. Specific therapy usually targets the etiology, including antiviral medications in viral hepatitis, steroids and immunosuppressant agents in autoimmune hepatitis, ursodeoxycholic acid and obeticholic acid in primary biliary cholangitis, copper chelation in Wilson disease, and iron chelation and phlebotomy in hemochromatosis. Weight loss of at least 7% is beneficial in NASH, and alcohol abstinence is crucial in alcoholic cirrhosis. [28]

• Differential Diagnosis

The differential diagnosis for hepatic cirrhosis includes the following:

• Acute fatty liver of pregnancy
• Amanita phalloides mushroom poisoning
• Acetaminophen poisoning
• Bacillus cereus toxin
• Fructose intolerance
• Galactosemia
• HELLP(hemolysis, elevated liver enzymes, low platelets) syndrome of pregnancy
• Hemorrhage viruses (Ebola virus, Lassa virus, Marburg virus)
• Idiopathic drug reaction
• Neonatal iron storage diseases
• Tyrosinemia

Predictive models for the prognosis of cirrhosis estimate the 10-year survival in patients with compensated cirrhosis at 47%, but this drops to 16% once a decompensating event occurs. The Child-Turcotte-Pugh (CTP) scoring or classification uses serum albumin, bilirubin, PT, ascites, and hepatic encephalopathy to classify patients with cirrhosis into classes A, B, and C. 1 and 2-year survival rates for these classes are 100% and 85% (A), 80% and 60% (B), and 45% and 35% (C). The model for end-stage liver disease (MELD) score is another model used to predict the short-term mortality of patients with cirrhosis. It uses serum bilirubin, creatinine, and INR to predict mortality within the next 3 months. [29]  Based on the MELD score (more recently, the MELDNa score), the priority of organ allocation for liver transplantation for patients with cirrhosis is adjudicated in the US. [29]  Liver transplantation is indicated in decompensated cirrhosis that does not respond to medical treatment. The 1-year and 5-year survival rates after liver transplantation are approximately 85% and 72%, respectively. Recurrence of the underlying liver disease can occur after a transplant. [30]  Long-term side effects of immunosuppressant drugs are another cause of morbidity in transplant patients.

• Complications

Complications accompanying hepatic cirrhosis can include:

• Portal hypertension
• Edema in the abdomen and lower extremities
• Splenomegaly
• Hepatic encephalopathy [31]
• Deterrence and Patient Education

While patient lifestyle changes cannot cure cirrhosis, these behavioral modifications can prevent or at least delay disease progression and provide symptomatic relief. Modifiable lifestyle factors include:

• Eliminating ethanol consumption
• Avoid raw seafood and shellfish
• possible low-sodium diet to reduce water retention
• Vaccinations for pneumonia, influenza, and hepatitis
• Regulate protein intake according to their doctor's directions
• Some doctors will recommend a vitamin and mineral supplement
• Pearls and Other Issues

Hepatocellular Carcinoma

HCC is the most common primary cancer in the liver, and its incidence is increasing. [32]  Cirrhosis secondary to HBV and HCV is the most common risk factor. [32]  Routine monitoring of cirrhotic patients for the development of HCC is recommended, with at least 6 monthly screenings using abdominal ultrasonography. [2]

• Enhancing Healthcare Team Outcomes

An interprofessional team that includes a hepatologist, gastroenterologist, liver surgeon, pathologist, infectious disease specialist, primary care provider, and internist is best for treating and preventing liver cirrhosis. All healthcare workers should follow patients with liver dysfunction from any cause because it can quickly become irreversible. Liver cirrhosis is associated with many systemic complications that can cause death. A liver transplant is not always an option because of the shortage of donors.

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• Comment on this article.

Schistosomiasis Infection. Under a magnification of 500X, this photomicrograph of a liver tissue specimen revealed signs of a schistosomiasis infection. This included a histopathologic finding known as pipe stem cirrhosis, which occurs when schistosomes (more...)

Cirrhosis, Liver. Reticulin stain enhances the fibrous septa dividing the hepatic nodules, ×4 magnification. Contributed by F Farci, MD

Liver Cirrhosis, Reticulin Stain 4× Contributed by F Farci, MD

Cirrhosis, Portal Space in Fibrous Septa. Reticulin stain 4×. Contributed by F Farci, MD

Liver Cirrhosis, Trichrome Stain, 4× Contributed by F Farci, MD

Disclosure: Bashar Sharma declares no relevant financial relationships with ineligible companies.

Disclosure: Savio John declares no relevant financial relationships with ineligible companies.

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• Cite this Page Sharma B, John S. Hepatic Cirrhosis. [Updated 2022 Oct 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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• Food Allergy
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• Heptologist In Delhi
• Liver transplant
• Alcoholic Liver Cirrhosis

Alcoholic liver cirrhosis is a late stage of fibrosis of the liver caused by many forms of liver diseases and conditions, such as chronic alcoholism. A person diagnosed with an alcoholic liver case may start from having fatty liver disease, then alcoholic hepatitis, and ultimately develop alcoholic cirrhosis. Hence, alcoholic liver cirrhosis stages in three levels. The diagnosed liver cirrhosis can be of two types :

• Compensated cirrhosis – when symptoms are not noticeable
• Uncompensated cirrhosis- when the symptoms can be noticed

The most common alcoholic liver causes are:

• Chronic alcohol consumption
• Chronic hepatitis
• Fatty liver disease
• Iron buildup in the body or hemochromatosis
• Copper accumulated in the liver (Wilson’s disease)
• Cystic fibrosis
• Biliary Atresia
• Inherited sugar metabolism or digestive disorders
• Infection like syphilis

Many other factors like the destruction of bile ducts(Primary Biliary Cirrhosis) or leaky gut also called, increased intestinal permeability are cofactors for the development of alcoholic liver cirrhosis.

Now, let us have a look at alcoholic liver cirrhosis symptoms:

• Food pipe problems
• Portal hypertension
• Swelling in legs (oedema) and abdomen (ascites)
• Bleeding in mouth
• Confusion, poor memory, loss of appetite
• Patchy red skin on palms (erythema)

Food pipe problem is also known as esophageal varices. Kidney failure and hypersplenism are other complications that happen due to this medical condition. If the symptoms are not taken seriously, then this deficient liver may arise a life-threatening situation. Hence, a person needs to keep a track of these indicators as if these signs are caught early and treated, it may slow down the progression of the disease.

How to treat alcoholic liver cirrhosis:

The first and foremost step in treatments is to help the patient to cease alcohol consumption. Medications like corticosteroids, calcium channel blockers, insulin can also be prescribed by the doctor as per the alcoholic liver care plan. Hepatologists may advise the patient to follow an alcoholic liver disease diet inclusive of fiber and protein. If the condition of the patient gets worsened, then the hepatologist may have to suggest a liver transplant surgery.

Dr. Nivedita Pandey is one of the best liver specialist doctors in Patna, Bihar. She is a well-renowned liver specialist doctor in Delhi, the best stomach doctor in Patna, the best gastroenterologist in Jammu, and a notable stomach doctor in Faridabad. Now, you can sway off all your gastroenterological worries online by booking an online gastroenterologist consultation with one of the best hepatologists in India. She is a liver specialist in Delhi NCR, one of the finest gastroenterologists in Jhansi and Jammu, and an acidity specialist doctor in Patna. Dr. Pandey’s gastroenterologist live chat has also helped people in several ways.

Case Review

This alcoholic liver case study presents a patient with liver cirrhosis. A 43-year-old man was brought into the hospital with a complaints of loss of appetite, abdominal distention, and arrhythmia. He also experienced itchy skin and blood in the stool. The patient’s family rushed him into the hospital, and he was in a half-conscious state. The patient was taken to the emergency room for evaluation. As told by the family, he had a past medical history and was a heavy alcohol consumer. This alcoholic liver case history consisted of various medical ailments like fatty liver, asthma, tuberculosis, malnutrition, hypertension, and hepatitis C. The patient had a heart attack three years back and stented for the same. Due to his health conditions, he was on several medications. In the emergency room, when the patient was under observation by a stomach specialist doctor in Patna and her team, they were able to diagnose from his symptoms that it was alcoholic liver cirrhosis. The patient went for a few scans including, a liver function test, liver ultrasound, and endoscopy along with CT, blood test, and urine tests.

Case Discussion

Though most of the liver cirrhosis causes remain unknown, with the help of her team, the best liver doctor and specialist in Patna was able to find out the reason for this one. The liver cirrhosis caused in this case was due to the medical history of the patient. His scans came out to be reasonably sound, and a liver biopsy was conducted to confirm the severity and type of liver disease. There were problems in his blood and urine culture, and they were taken care of by the team. His liver appeared swollen in the reports. There were certain other problems seen in his ultrasound and endoscopy. The crew decided to start with the treatment while keeping him under observation for the next 72 hours.

Clinical Symptoms

He was initially confused and was not able to respond or hear properly. According to the condition reported by his family i.e.- appetite loss, memory loss, and confusion were some other clinical symptoms of alcoholic liver cirrhosis. When the doctor talked to the family of the patient, she was able to get a clearer picture. The patient complained about acute abdominal pain. When Dr. Pandey, one of the best doctors in Patna for the stomach, observed the patient and talked to him, she noticed bleeding in his mouth. This further helped doctors to eliminate all doubts, and after looking at the lab results, they made out it was alcoholic liver cirrhosis.

The first and foremost management required when treating the alcoholic liver cirrhosis case is calming the patient down. The liver specialist with the help of her fellow doctors was able to counsel the patient and explain his medical condition to the family. After a complete diagnosis, the patient was taken to the ICU as he was under observation. The doctor prescribed him antioxidant drugs and insulin to control any future problems while treating the present one. The doctor is the best gastroenterologist in Faridabad, Delhi, and Patna, and she handled the situation well before any further complications. The patient got his discharge in due time and was sent back home in a healthy and sound condition.

1.   Which Group of People are More Likely to get diagnosed with alcoholic liver cirrhosis?

A person who has drunk heavily for a long time is more prone to acquire this disease. Women are also at risk for this medical disease due to the absence of many enzymes which break down alcohol particles.

Consider consulting the best gastroenterologist in India , Dr. Nivedita Pandey who is also well known for her nutritional counselling services and teleconsultation services. She is also famous for her care from afar service. You can also find her as the best liver specialist doctor in Patna, Bihar or hepatologist in Patna or the best doctor for hepatitis b in Patna , a gastroenterologist in Faridabad , the best gastro doctor in Delhi, NCR , a gastroenterologist In Uttarakhand , a liver specialist in Jhansi , best gastroenterologist in Jammu take advantage of the online gastroenterology consultation to gastroenterologist live chat and receive the best treatment that your body deserves!

2.   Is liver cirrhosis cancer?

No, liver cirrhosis is not a type of cancer. If a person has alcoholic liver cirrhosis, he/she has an increased risk of liver cancer.

3.   Is liver cirrhosis a hereditary disease?

Negative, alcoholic liver cirrhosis is not a hereditary disease, rather it is a type of an acquired disease.

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• Case Report
• Open access
• Published: 09 September 2024

Robot-assisted laparoscopic hepatectomy for hepatocellular carcinoma with Fontan-associated liver disease: a world-first case report

• Takuma Ishikawa 1 ,
• Shinji Itoh   ORCID: orcid.org/0000-0003-0382-2520 1 ,
• Takeo Toshima 1 ,
• Shohei Yoshiya 1 ,
• Yuki Bekki 1 ,
• Norifumi Iseda 1 ,
• Yuriko Tsutsui 1 ,
• Ichiro Sakamoto 2 ,
• Kotaro Abe 2 &
• Tomoharu Yoshizumi 1  

Surgical Case Reports volume  10 , Article number:  210 ( 2024 ) Cite this article

Metrics details

Fontan-associated liver disease (FALD) encompasses hepatic complications following the Fontan procedure, ranging from fibrosis to hepatocellular carcinoma (HCC). Despite advancements in surgical techniques and perioperative care, robot-assisted laparoscopic hepatectomy (RALH) for HCC in patients with FALD has not been previously reported owing to concerns about the Fontan circulation.

Case presentation

We present the first case of RALH for recurrent HCC in a 45-year-old man after the Fontan procedure. The preoperative evaluation confirmed good cardiac function. The procedure involved meticulous monitoring and management of central venous pressure and was successfully completed with minimal blood loss. Postoperative recovery was uneventful. With thorough preoperative cardiac assessment and close collaboration between cardiologists and anesthesiologists, RALH can be safely performed in selected patients with FALD.

Conclusions

Even if a patient has a history of FALD, RALH can be safely performed in selected patients under appropriate conditions.

Liver complications after undergoing the Fontan procedure (FP) are classified as Fontan-associated liver disease (FALD) [ 1 ]. The first report of FALD was by Stanton et al. in 1981 when cirrhosis was found in an autopsy case who died of a fatal arrhythmia 21 months after the FP [ 2 ]. FALD is a severe complication, particularly in adult patients who have undergone the FP [ 3 ]. FALD encompasses a range of hepatic abnormalities, from mild fibrosis to cirrhosis and hepatocellular carcinoma (HCC), and is associated with benign and malignant liver lesions [ 4 ]. The pathophysiology of FALD is complex, involving hemodynamic and inflammatory factors [ 3 ]. Recently, the long-term prognosis after the FP has been improving owing to advances in procedures and postoperative management [ 5 ]. As a result, the number of patients diagnosed with FALD, a late complication of liver fibrosis and cirrhosis leading to HCC, is increasing.

Robot-assisted surgery is rapidly gaining popularity in many surgical fields, because it is precise, minimally invasive surgery with enhanced stereoscopic magnification enabling full dexterity [ 6 ]. The first report of robot-assisted laparoscopic hepatectomy (RALH) in the world was made by Giulianotti in 2003 [ 7 ]. Several limitations and drawbacks to conventional laparoscopy exist, including limited movement, the inability to perform high-precision sutures, unnatural positions for the surgeon, and flat vision. Robotic surgery can overcome the limitations of conventional laparoscopy. The goal is for this type of minimally invasive surgery to be available to more patients [ 7 ].

Despite the known benefits of RALH, its results have never been reported after the FP. The limitations of RALH in FALD are related primarily to the adverse effects of pneumoperitoneum on the Fontan circulation due to increasing intra-abdominal and intrathoracic pressure, rising pulmonary and systemic resistance, and cardiac preload and output reduction, which can be fatal [ 8 ]. Moreover, severe portal hypertension may cause a high risk of bleeding during liver resection [ 9 ]. To the best of our knowledge, this report is the first case of RALH for HCC after the FP.

We present the case of a 45-year-old man with HCC recurrence. The patient had a history of tricuspid atresia and underwent a Blalock–Taussig–Thomas shunt procedure at the age of 3, an FP at the age of 6, and total cavopulmonary bypass conversion, atrial septal defect creation, right atrium maze procedure, and implantation of a permanent pacemaker lead at the age of 26. At age 42, the patient had elevated alpha-fetoprotein levels, and a detailed examination revealed HCC. Lap-assisted partial resection of segment 3 of the liver was performed. Pathological findings indicated a moderate to poorly differentiated HCC with trabecular and pseudoglandular patterns of 2.5 × 1.9 cm. This was classified as vp1, vv1, va0, b0, im0, and the peritumoral liver tissue showed stage F3 cirrhosis according to the new Inuyama classification [ 10 ]. No malignant cells were found in the surgical margins (R0 resection).

During follow-up, HCC recurrence was suspected in segment 5 of the liver on computed tomography (CT) 25 months postoperatively. CT hepatic arteriography/CT arterial portography revealed a reticular pattern of decreased enhancement in the hepatic parenchyma, indicative of changes due to congestive liver. An 8 mm arterially enhanced nodule was observed with corona-like enhancement in segment 5 of the liver ( Fig.  1 a ) and a lack of portal blood flow, consistent with findings of HCC ( Fig.  1 b ). The tumor was located on the edge of segment 5, and the nearest branch of the Glisson 5 was not within the planned resection margin ( Fig.  1 c, d ).

Abdominal computed tomography arteriography and arterial portography. a 8 mm arterially enhanced nodule with corona-like enhancement was observed in segment 5 of the liver (yellow arrowhead). b Same nodule exhibited poor portal blood flow (yellow arrowhead). c Position of the tumor is indicated in the 3D images (yellow arrowhead). d 3D images show that the tumor was located on the edge of segment 5 (yellow arrowhead) and branch of the Glisson 5 (orange arrowhead)

Preoperative information included a height of 164 cm and a weight of 57.1 kg (body mass index, 21.1). Blood testing showed the following results: aspartate transaminase, 35 U/L; alanine transaminase, 56 U/L; albumin, 4.2 mg/dL; total bilirubin, 0.9 mg/ dL; prothrombin time-international normalized ratio, 1.08; and platelet count, 12.8 × 104/μL. Alpha-fetoprotein and des-gamma-carboxy prothrombin were elevated to 11.1 ng/mL and 7538 mAU/mL, respectively. Type IV collagen 7S was slightly elevated to 6.0 ng/mL, but other markers of liver fibrosis were normal (hyaluronic acid, 39 ng/mL; mac-2-binding protein glycosylation isomer, 0.34 cutoff index). Negative results were obtained for hepatitis B virus surface antigen and hepatitis C virus antibody, and the patient had no history of heavy alcohol consumption. The indocyanine green (ICG) retention rate at 15 min was 15.9%. The Child–Pugh classification was A. Echocardiography demonstrated good single right ventricular function and no obstruction in the Fontan circulation. Cardiac function tests showed an ejection fraction of 61%, central venous pressure (CVP) of 10–14 mmHg, pulmonary artery pressure of 17 mmHg, and pulmonary capillary wedge pressure of 11 mmHg. Pulmonary and renal functions were normal. Oxygen saturation in room air was 96%. The systolic blood pressure was approximately 90 mmHg.

Robot-assisted laparoscopic partial resection of S5 was planned to address the recurrent HCC after a multidisciplinary discussion with the cardiologist and anesthesiologist. Warfarin 2 mg was discontinued and replaced with heparin. Two days before the surgery, 12.5 mg of ICG was administered intravenously to the patient. After induction of general anesthesia, a central venous catheter was inserted into the right internal jugular vein for intraoperative monitoring of CVP. A transesophageal echocardiogram was also placed. Management was performed by monitoring cardiac output and its variations using a FloTrac sensor ® . The cardiovascular medications used in this case were dobutamine, vasopressin, furosemide, ephedrine, and phenylephrine.

Surgical procedure

The patient was placed in the supine position. A small incision was made in the subumbilical area, and an access port was placed to induce pneumoperitoneum. A pneumoperitoneum was started at a pressure of 8 mmHg while carefully monitoring vital signs. The liver showed a rough surface consistent with cirrhosis, and a small amount of ascites was observed. Adhesions between the abdominal wall and omentum were noted. The lesion in S5 was visibly protruding ( Fig.  2 a ) . The second port was placed 20 cm away from the tumor, and the third port was positioned 7 cm away in the lower right abdomen. An assistant port (12 mm) was placed 7 cm away between the second and third ports. To add additional ports, it was necessary to perform adhesiolysis within the abdominal cavity. Adequate visualization of the tumor had been achieved, and it was deemed feasible to resect the marginal tumor with four ports. We performed intraperitoneal manipulation using four ports and a minimal number of instruments. ( Fig.  2 b ) .

Operative findings. a Surgery was performed by the insertion of four ports: one subumbilical for the camera (8 mm), one working trocar in the right lateral flank (8 mm), one working trocar in the lower right abdomen position (8 mm), and one assistant port between the second and third ports (12 mm). b Lliver showed a rough surface consistent with cirrhosis. The tumor in S5 was visibly protruding (yellow arrowhead). c Tumor in S5 was revealed using indocyanine green fluorescence for confirmation. d Robot-assisted laparoscopic S5 partial hepatectomy resections were performed

The patient cart was rolled in and docked from the right side. The falciform ligament was not divided. Adhesions were dissected to allow for liver resection. Adhesions around the hepatoduodenal ligament were observed. Furthermore, since the lesion was small and located on the surface of segment 5, we refrained from forcibly Pringle maneuver. The resection line was set to ensure adequate margins. Although the gallbladder was located near the tumor, we were able to secure clear resection margins for the tumor, thus preserving the gallbladder. Liver parenchymal transection was performed using the crush-clamp technique with intraoperative ICG fluorescence to confirm the tumor margins (Fig.  2 c). Small, exposed vessels on the transection surface were coagulated and divided as necessary. The specimen was extracted (Fig.  2 d). Intra-abdominal lavage was performed, and hemostasis was confirmed. A 15 Fr drain was placed through the 8 mm port on the right side of the abdomen. The robotic docking was released, and the patient cart was rolled out (console time was 54 min). The specimen was extracted through the umbilical incision. After confirming the tumor was at a sufficient distance from the resection margin, the incision was closed ( Fig.  3 ) . The operation duration was 111 min, with minimal blood loss.

Macroscopic findings of the resected tissue specimen. a Elastic soft nodule was found in liver segment 5. b On the cut surface, there was a yellowish-white tumor measuring 0.8 cm × 0.8 cm

Histological findings

A well to moderately differentiated HCC with compact, trabecular, and pseudoglandular patterns of 0.6 × 0.6 cm was classified as vp1, vv0, va0, b0, im0. The peritumoral liver tissue showed stage F4 cirrhosis according to the new Inuyama classification [ 10 ] No malignant cells were found in the surgical margins (R0 resection).

Postoperative course

Postoperatively, the patient was managed in the intensive care unit. Owing to low blood pressure, norepinephrine was administered. On the first postoperative day, the drain was removed as its condition was unremarkable. Norepinephrine was discontinued, and the patient was transferred to the general ward and began oral intake. On the second postoperative day, heparin therapy was initiated. On the third postoperative day, oral warfarin was resumed. CT on the sixth postoperative day revealed no issues. Heparin therapy was discontinued on the seventh postoperative day. The patient was discharged on the eighth postoperative day. One year after surgery, the patient has not had HCC recurrence.

We presented a case of robotic-assisted laparoscopic liver resection in a patient with FALD where reoperation was necessary due to HCC recurrence. No reports of robotic-assisted laparoscopic liver resection for HCC with FALD exist. Liver dysfunction arising from FALD causes liver fibrosis, cirrhosis, and HCC, even in young patients [ 11 ]FALD is caused by excessive hepatic congestion due to high CVP and results from fibrosis of the sinusoids and portal tracts. The progression of FALD depends on the duration after the FP and hepatic venous pressure [ 12 ]. It has been reported that FALD progresses to cirrhosis 11–15 years after the FP, with cumulative incidence rates of cirrhosis of 56.6% and 97.9% at 20 and 30 year post-FP, respectively [ 13 ]. The annual incidence of HCC in FALD is estimated to be between 1.5% and 5.0% [ 14 ].

Many cases of HCC arising from FALD are treated non-surgically because of poor liver function, making surgical resection unfeasible [ 9 ]]. However, recent advancements in surgical techniques and perioperative management have made safe hepatectomy possible in open and laparoscopic surgery [ 14 , 15 ] Laparoscopic hepatectomy for HCC arising from FALD has often been avoided owing to the difficulty in controlling venous bleeding caused by high CVP and challenges in anesthesia management [ 16 ].

Robot-assisted laparoscopic surgery in patients with Fontan circulation is considered disadvantageous, because the venous return may be compromised by insufflation of carbon dioxide (CO₂) into the abdomen, use of the reverse Trendelenburg position, and positive pressure ventilation [ 14 , 15 , 17 ]. Furthermore, CO₂ absorption from the peritoneum increases the partial pressure of CO₂ in the blood, raising pulmonary vascular resistance. CO₂ in the abdominal cavity might be sucked into the injured hepatic veins, causing pulmonary embolism. The Pringle maneuver does not adversely affect the Fontan circulation during laparoscopic hepatectomy [ 14 ]. On the other hand, inferior vena cava clamping can easily induce hypotension in the Fontan circulation [ 5 ]. In this case, the patient was placed in the reverse Trendelenburg position, and the CVP was controlled at approximately 10 mmHg during the surgery. The preoperative CVP in the previous surgery was 19 mmHg, and the CVP was controlled at approximately 15 mmHg during the surgery. In the current surgery, the patient was managed by the cardiology department preoperatively, with the preoperative CVP ranging from 10 to 14 mmHg and the intraoperative CVP controlled at 10 mmHg. In case of FALD, minimally invasive surgery, particularly RALH, was considered candidate only when the lesion was small, located on the surface of anterolateral segments, and did not involve major blood vessels, and the Fontan circulation was maintained despite a low CVP. Furthermore, this case involved reoperation, and compared to laparoscopic surgery, the advantages of RALH were considered beneficial for performing precise tasks, such as adhesiolysis, in confined spaces. However, a disadvantage of RALH was the time required to convert to open surgery, which was crucial in cases involving FALD. The indication for RALH in patients with FALD must be carefully determined through close communication with cardiologists and anesthesiologists.

RALH has several disadvantages compared with conventional laparoscopic hepatectomy, including prolonged operation time and increased total cost [ 18 , 19 ]. However, RALH offers several advantages over conventional laparoscopic hepatectomy, including enhanced visualization, improved surgical dexterity, ease of dissection and suturing, and stable camera control. [ 20 , 21 ]. Comparisons between robotic and laparoscopic hepatectomies indicate that both methods are equally safe and feasible in terms of blood loss, transfusion rates, and postoperative complications [ 22 ]. Nevertheless, robotic surgery has a higher rate of performing major hepatectomies in a minimally invasive manner [ 22 ]. In addition, during robotic-assisted laparoscopic surgery, the timing of conversion to open surgery must always be considered because of the risk of intraoperative bleeding and the likelihood of vital sign changes in patients with FALD. Therefore, hepatectomy for HCC arising from FALD requires stricter criteria than conventional hepatectomy. Such criteria may include preoperative CVP to predict the likelihood of intraoperative bleeding from hepatic veins. To establish such criteria, data should be accumulated on patients with FALD by creating a large-scale, nationwide database. In this surgery, the tumor was located on the liver surface; therefore, we were able to perform the hepatectomy relatively easily. In the future, reports on hepatectomy for tumors in the deep liver parenchyma will also be necessary.

In conclusion, our report suggests that RALH for patients with HCC and Fontan circulation can be safely performed in selected patients with sufficient cardiac reserves. A long time has passed since the FP was first performed, and the cases of HCC with congested liver cirrhosis are expected to increase in the future. In addition, because of congestive cirrhosis and carcinogenesis at a young age, recurrence of HCC may be unavoidable. RALH is a desirable minimally invasive surgery for reoperation and maintaining postoperative quality of life. More case reports on RALH for patients with HCC and Fontan circulation are warranted.

We successfully performed RALH in a patient with FALD. To safely perform RALH for HCC in patients who have undergone the FP, thorough preoperative cardiac function assessments, careful decision-making, and close communication between cardiologists and anesthesiologists are necessary.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Carbon dioxide

Computed tomography

• Central venous pressure
• Fontan-associated liver disease
• Fontan procedure
• Hepatocellular carcinoma

Indocyanine green

• Robot-assisted laparoscopic hepatectomy

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Acknowledgements

We would like to thank Editage ( www.editage.jp ) for English language editing.

This study was not supported by any funding.

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Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1 Maidashi, Higashi-Ku, Fukuoka-Shi, Fukuoka, 812-0054, Japan

Takuma Ishikawa, Shinji Itoh, Takeo Toshima, Shohei Yoshiya, Yuki Bekki, Norifumi Iseda, Yuriko Tsutsui & Tomoharu Yoshizumi

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Ichiro Sakamoto & Kotaro Abe

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Study conception: SI. Writing: TI. Final approval of the article: all authors. Accountability for all aspects of the work: all authors.

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Correspondence to Shinji Itoh .

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Progressive familial intrahepatic cholestasis type 4: a case report

• Mohamed Abdelmalak Abokandil 1 ,
• Saber Waheeb 1 , 2 ,
• Wessam Zaghloul 1 , 2 ,
• Manal Abdelgawad 1 , 2 ,
• Mona Abdelhady 2 ,
• Mohamed Mansy 1 , 3 &
• Mostafa Kotb   ORCID: orcid.org/0000-0002-2558-3551 1 , 2  

Journal of Medical Case Reports volume  18 , Article number:  434 ( 2024 ) Cite this article

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Progressive familial intrahepatic cholestasis is an autosomal recessive genetic disorder that manifests primarily with jaundice and pruritus and can progresses from persistent cholestasis to cirrhosis and late childhood liver failure. Classically, progressive familial intrahepatic cholestasis is classified into three subtypes: 1, 2, and 3 and results from a defect in a biliary protein responsible for bile formation and circulation in the liver. In the last decade and with the increased use of genetic testing, more types have been known.

Case presentation

A 6-month-old Afrocentric boy presented with progressive jaundice and pruritus that started since the age of 2 months. He was thoroughly investigated to be finally diagnosed as progressive familial intrahepatic cholestasis type 4. A low-fat diet, ursodeoxycholic acid, fat-soluble vitamins, and cholestyramine were started. He showed initial improvement then had refractory pruritus and impaired quality of life. He underwent surgical biliary diversion at the age of 1 year with marked improvement of manifestations.

Owing to the increased technology of genetic testing, more clinical subtypes of progressive familial intrahepatic cholestasis were diagnosed other than the classical three types. Surgical management using biliary diversion could be beneficial and delays or may even obviate the need for liver transplantation.

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Introduction

Progressive familial intrahepatic cholestasis (PFIC) is a group of rare autosomal recessive genetic disorders involving defects in bile acid secretion or transport. There are a wide spectrum of manifestations ranging from neonatal cholestasis, recurrent cholestasis, refractory pruritus, growth failure, childhood liver failure, and portal hypertension to advanced end-stage liver disease [ 1 , 2 ]. Classically, PFIC is classified into three subtypes: PFIC1, PFIC2, and PFIC3 according to the timing of their discovery. PFIC1 (Byler’s disease) involves FIC1 deficiency due to mutations in the ATPase phospholipid transporting 8B1 (ATP8B1) gene. PFIC2, which is the most common subtype involves a defective or deficient severe bile salt export pump (BSEP) caused by a mutation in the ATP-binding cassette subfamily B member 11 (ABCB11) gene. PFIC3 is due to multidrug resistance protein 3 (MDR3) deficiency resulting from a mutation in the ABCB4 gene [ 3 , 4 , 5 ].

With the advancements in genetic analyses, newer subtypes are being discovered. PFIC4 was first reported in 1991 by Gumbiner et al . [ 6 , 7 ]. In PFIC4, there is deficiency in a protein called tight junction protein 2 (TJP2) or zona occludens 2 due to mutation in the tight junction protein 2 (TJP2) gene. This results in reduced integrity of the canalicular membrane and reflux of bile acids into hepatocytes, with their deleterious effect in potentiating hepatocyte damage and cholestasis [ 7 , 8 ]. TJP2 has a widespread expression, including the respiratory and central nervous systems [ 8 ].

Clinically, cases with PFIC4 can present with mild anicteric pruritus, recurrent cholestasis, or severe progressive liver disease [ 4 , 8 ]. Extrahepatic manifestations in the form of neurological and respiratory symptoms can be present in these cases [ 7 ]. Similar to PFIC2, there is increased risk of progression to hepatocellular carcinoma (HCC) in PFIC4 [ 7 , 9 , 10 ]. Thus, early diagnosis, treatment, and close follow-up is mandatory.

Investigations in PFIC4 typically show elevated total and direct serum bilirubin with low to normal serum gamma glutamyl transferase (GGT). Liver enzymes are elevated in these cases as well as serum bile acids [ 7 ]. Liver histopathology classically reveals canalicular cholestasis along with a variable degree of fibrosis and giant cell transformation. Electron microscopy shows elongated tight junctions and a lack of the densest part of the zona occludens [ 11 ]. Molecular genetic diagnosis is considered the test of choice in diagnosing PFIC type as it is noninvasive unlike liver biopsy. This can be done using next-generation sequencing (NGS) [ 12 ]. Whole-exome (WES) or whole-genome (WGS) sequencing can be done in cases with negative targeted gene analysis.

Genetic counseling for parents is crucial as it is an autosomal recessive disorder. Nutritional management with providing adequate calories [125–140% of the recommended dietary allowances ( RDA)], protein (2–3 g/kg daily), and a low-fat diet is crucial. Supplementation of medium-chain triglycerides (MCT) and fat-soluble vitamins is recommended [ 13 ]. Regular monitoring of growth parameters and nutritional deficiencies is important as those cases are liable for growth failure.

Pruritus is the most devastating manifestation in PFIC. It can affect the quality of life. Local skin emollients, ursodeoxycholic acid (UDCA), cholestyramine, antihistamines, rifampicin, naltrexone, and sertraline are used to control pruritus [ 14 ]. Some cases respond well to these medications. Others can have deterioration in liver status or refractory itching despite drug therapy, necessitating biliary diversion or liver transplantation [ 15 ].

Biliary diversion (BD) procedures aim at the diversion of bile from the intestine, reducing the reabsorption of bile through enterohepatic circulation [ 16 ]. This reduces the accumulation of bile acids. BD has good results in the alleviation of refractory pruritus in PFIC1 and 2 [ 17 ]. Its role in the newer variants of PFIC is not yet well known. We report a case with PFIC4 who had refractory pruritus for which he underwent surgical biliary diversion.

A 6-month-old Afrocentric boy presented to our institute with a 3-month history of progressive generalized jaundice and persistent pruritus. History revealed that the parents were cousins. No family history of cholestasis or hepatic disease was reported. On clinical examination, the patient was markedly icteric and pale. His growth parameters were affected; weight −1.8 standard deviation (SD), length −1.5 SD, and mid upper arm circumference 12 cm, despite being within the normal range at birth (weight 0.7 SD and length 0.9 SD). He had marked hepatomegaly, but no splenomegaly or ascites. He had scratch marks allover his body, especially around in his face. His urine was dark.

His investigations showed direct hyperbilirubinemia along with elevation of liver enzymes and serum bile acids. On the other hand, gamma-glutamyl transpeptidase (GGT), serum albumin, and coagulation profiles were within normal ranges (Table  1 ). At this stage, biliary atresia and other causes of obstructive jaundice in this age group such as PFIC, Alagille syndrome, and inspissated bile syndrome were considered. Percutaneous ultrasound (US)-guided liver biopsy revealed marked pseudoglandular transformation of almost all of the hepatocytes with canalicular cholestasis, florid ductular proliferation, and mild ductopenia (Fig.  1 A and B). Thus, PFIC was the prime consideration.

A , B Prominent pseudoglandular transformation and canalicular cholestasis (arrows). Hematoxylin and eosin stain ( A ×100, B ×200). C Diagrammatic illustration of the operation performed. D , E Marked improvement of jaundice and growth

The patient was on nutritional management with adequate calories and proteins in addition to MCT. He was on high doses of vitamin D (2000 units/day) based on his serum vitamin D level. He also received the recommended daily doses of vitamins A and E. UDCA dose was escalated according to clinical and laboratory findings. Cholestyramine was added in maximum doses with initial control of pruritus, then became nonbeneficial.

Whole-exome sequencing was done to detect the exact genetic mutation. A homozygous pathogenic variant in TJP2 was identified, which was consistent with the diagnosis of progressive familial intrahepatic cholestasis type 4 (OMIM: 615878). The patient continued on his nutritional and medical management till 1 year of age; however, he still had growth failure and worsening of pruritus with evident scarring and impaired quality of life.

The patient was scheduled for partial internal diversion. On exploration, the gallbladder was found to be dilated with thickened wall. A 15-cm-long jejeunal segment was isolated with its blood supply, 40 cm from the duodenojejunal junction, and passed retrocoloic for anastomosis with the gallbladder. The proximal stump was closed and side-to-side jejunocolic anastomosis was done, while the distal end was anastomosed with the transverse colon in an end-to-side fashion. Restoration of the bowel continuity was done by end-to-end jejunojejunal anastomosis (Fig.  1 C).

Postoperatively, the patient was doing well after 18 months of follow-up with marked drop in the level of total and direct bilirubin, improvement in the growth pattern (weight 0.9 SD, length 0.5 SD) and relief of pruritus (Fig.  1 D, E).

PFIC type 4 represents a new entity of PFIC that evolved after the advances in genetic testing. The exact incidence of PFIC4 is not well known due to the limited number of studies, which are mostly case reports or small case series [ 7 ]. PFIC1 and PFIC 2 usually occur in early infancy and are caused by a mutation in the ATP8B1 and ABCB11 genes, respectively. They are characterized by having a normal level of GGT, compared to PFIC3, that occurs in adolescents due to a mutation in the ABCB4 gene and has high GGT levels [ 1 , 2 ]. In PFIC4, there is a mutation in the TJP2 gene, which is a member of the membrane-associated guanylate kinase homolog family, located on the long arm of chromosome 9. It encodes a protein called tight junction protein 2 (TJP2). This encoded protein is an integral component of the tight junction barrier in epithelial and endothelial cells, which are crucial for proper assembly of tight junctions. Deficiency of TJP2 protein results in reduced integrity of the canalicular membrane and reflux of bile acids through the intercellular spaces into the hepatocytes, causing liver damage and progressive cholestasis [ 8 , 18 ]. All homozygous mutations cause deficient TJP2 protein and complete loss of function. Missense and frame deletion lead to milder disease due to residual TJP2 protein expression [ 19 , 20 ].

Medical treatment for PFIC4 using UDCA (10–30 mg/kg/day), fat-soluble vitamins, MCT, and cholestyramine (240–400 mg/kg/day) can be effective in some cases [ 14 , 21 ]. Surgery is indicated if there is intractable pruritus despite optimum treatment. Other indications include failure to thrive and nutritional deficiencies. Sambrotta et al . reported 12 cases with PFIC4; 9 cases (75%) required liver transplantation (LT) while 2 had portal hypertension [ 19 ]. On the other hand, Zhang et al . reported 7 cases and none of them required LT; all of them responded well to medical treatment [ 20 ].

Biliary diversion in PFIC is indicated for children who do not yet have advanced fibrosis or liver cirrhosis. [ 15 ] Regardless of the adopted technique, the main aim is to interfere with enterohepatic recirculation of bile salt leading to bile salt pool depletion; hence, pruritus decreases and the progression to cirrhosis is delayed. This can be achieved either by anastomosis of the biliary tract to the outside skin using a jejunal loop as a conduit as a stoma (external drainage) or to the intestines (internal drainage). The latter has now gained ground and can be performed by anastomosing the gall bladder via a jejunal (cholecystojejunocolic), ileal (cholecystojejunocolic), appendix (cholecystoappendicocolic) conduit to the colon or directly between gall bladder and antireflux loop of colon (cholecystocolocolic anastomosis) [ 22 ].

Concerning biliary diversion surgeries, a meta-analysis yielded a 60% incidence of pruritus relief and only a 27% need for liver transplantation [ 23 ]. They also found that partial internal biliary diversion using a chole-cystojejunocolic approach has lower complications and liver transplantation requirement than partial extrabiliary diversion using appendix or jejunum [ 23 ].

Conclusions

Owing to the advances in genetic testing, more clinical subtypes of PFIC have been diagnosed, other than the classical three types. Surgical management using biliary diversion could be beneficial and could delay or even obviate the need for liver transplantation. The CARE Checklist has been completed by the authors for this case report, attached as supplementary material.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Mohamed Abdelmalak Abokandil, Saber Waheeb, Wessam Zaghloul, Manal Abdelgawad, Mohamed Mansy & Mostafa Kotb

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M. Abokandil, M. Abdelgawad, and S. Waheeb made and confirmed the diagnosis, provided the details of the case, and contributed to the design of the report. M. Abdelhady provided the pathological diagnosis. W. Zaghloul, M. Mansy, and M. Kotb drafted the manuscript. All authors read and approved the final version of the manuscript.

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Abokandil, M.A., Waheeb, S., Zaghloul, W. et al. Progressive familial intrahepatic cholestasis type 4: a case report. J Med Case Reports 18 , 434 (2024). https://doi.org/10.1186/s13256-024-04662-5

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DOI : https://doi.org/10.1186/s13256-024-04662-5

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Hev infection in the context of prior hbv-related liver injury: case series.

1. Introduction

2. case series, 3. materials and methods, 4. discussions, 5. conclusions, author contributions, institutional review board statement, informed consent statement, data availability statement, acknowledgments, conflicts of interest.

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Share and Cite

Olariu, M.-C.; Filipescu, M.-C.; Pauna, A.M.; Simoiu, M.; Borcan, A.M. HEV Infection in the Context of Prior HBV-Related Liver Injury: Case Series. Infect. Dis. Rep. 2024 , 16 , 888-893. https://doi.org/10.3390/idr16050070

Olariu M-C, Filipescu M-C, Pauna AM, Simoiu M, Borcan AM. HEV Infection in the Context of Prior HBV-Related Liver Injury: Case Series. Infectious Disease Reports . 2024; 16(5):888-893. https://doi.org/10.3390/idr16050070

Olariu, Mihaela-Cristina, Mihai-Cezar Filipescu, Andreea Marilena Pauna, Madalina Simoiu, and Alina Maria Borcan. 2024. "HEV Infection in the Context of Prior HBV-Related Liver Injury: Case Series" Infectious Disease Reports 16, no. 5: 888-893. https://doi.org/10.3390/idr16050070

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