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Cirrhosis

Updated : June 11, 2024





Background

Cirrhosis is the final stage in chronic liver diseases, and it means the common outcome of various liver diseases. The term cirrhosis was coined by Laennec in the year 1826 whereby cirrhosis was from the Greek word “scirrhus” implying to the orange-brown tawny liver colour noticed during autopsy. 

Structurally, cirrhosis is defined by the presence of fibrosis as well as regenerative nodules alteration in the normal architecture of liver. The development of cirrhosis can range from weeks to decades, with conditions such as chronic hepatitis C, taking about forty years to cause cirrhosis. 

Hepatic fibrosis refers to the accumulation of extracellular matrix molecules including collagen, glycoproteins and proteoglycans in the liver and is considered as a reversible process in response to liver injury. However, cirrhosis is usually a non-reversible condition for which persons suffering from this disease cannot receive a cure. Some of the complications of cirrhosis are portal hypertension, ascites, hepatorenal syndrome, and hepatic encephalopathy. 

The histological features of cirrhosis are frequently not reflected in the clinical manifestations. Some of the patients are unlikely to present with significant clinical symptoms and can have near normal life expectancy while others present with complication and manifestations of ESRD with a poor prognosis. Symptoms may be due to decreased liver synthetic capacity (for example, coagulopathy), decreased ability to detoxify compounds (for example, hepatic encephalopathy), or develop complications from portal hypertension (for example, variceal bleed). 

Later in August 2012, the CDC revised the guidelines by recommending a one-time blood test for hepatitis C virus (HCV) infection for those people whose age falls between 1945 and 1965, and these people comprise of three-fourth of all those with chronic HCV infections in the United States. This changed testing could yield approximately 808,600 more people with chronic HCV. The individuals that have been identified should undergo screening for alcohol abuse, and if positive, should be enrolled in prevention or treatment services. 

Epidemiology

Liver disease and cirrhosis result in about 35,000 deaths per year in the United States of America; cirrhosis ranks ninth among the leading causes of mortalities in the country and contributes to 1.2% of all U.S. deaths. Some people are diagnosed with the disease during their Middle Ages or at the early stage of the fifth or sixth decade of life. The prevalence of NAFLD and NASH rises with time, and therefore the occurrence of cirrhosis is expected to rise. Liver disease and cirrhosis result in about 35,000 deaths per year in the United States of America; cirrhosis ranks ninth among the leading causes of mortalities in the country and contributes to 1. Twice as many people died from an overdose in one year than from HIV/AIDS in an entire year, representing 2% of all U.S. deaths. Some people are diagnosed with the disease during their middle ages or at the early stage of the fourth, fifth, or sixth decade of life. The prevalence of NAFLD and NASH rises with time, and therefore the occurrence of cirrhosis is expected to rise. 

Furthermore, approximately 2000 people die every year in the United States due to FHF or fulminant hepatic failure. FHF can be due to viral hepatitis such as hepatitis A, B and others, drugs such as acetaminophen, toxins for example Amanita phalloides, the yellow death – cap mushroom, autoimmune hepatitis, Wilson disease, and many others. Cryptogenic etiology encompasses one-third of FHF cases. The mortality of FHF ranges between 50-80% but can be reduced if the patient undergoes a liver transplant. 

Cirrhosis is the fourteenth leading cause of death in the world, and the fourth in Europe. The estimated worldwide population with NAFLD is 25.2%. 

Anatomy

Pathophysiology

  • There are several acute and chronic conditions that result in persistent inflammation in the liver including viral hepatitis B &C, alcoholic liver disease and nonalcoholic steatohepatitis (NASH). 
  • Hepatocyte damage results to inflammation and formation of cytokines and ROS that further cause hepatocyte damage and apoptosis. 
  • Remote hepatocytes stimulate HSCs activation, thus causing fibrosis and derangement of the normal liver architecture. 
  • Hepatocytes undergo regeneration and create strange nodules of Proliferating Liver cells. 
  • In the liver, fibrotic tissue along with regenerative nodules produce pressure on the hepatic vasculature and result in portal hypertension and collateral vessels. 
  • Functional liver is lost and this results in the formation of coagulopathy, hypoalbuminemia, jaundice and hepatis encephalopathy. 
  • These are portal hypertension, ascities, hepatorenal syndrome, hepatic encephalopathy and hepatocellular carcinoma. 

Etiology

The causes of cirrhosis of the liver may include different types of chronic hepatic illnesses. In the past alcoholic liver disease was the most frequent cause of cirrhosis among the population in the United States. However, recent studies revealed that hepatitis C has become the leading cause of chronic hepatitis and cirrhosis in the country. 

Another main cause of cirrhosis is nonalcoholic fatty liver disease (NAFLD) that can present itself as cryptogenic cirrhosis. In this study 60%of patients with cryptogenic cirrhosis had risk factors associated with NAFLD including obesity, diabetes, and hypertriglyceridemia. As the duration of hepatic fibrosis increases, steatosis can decrease; this can lead to difficulty in distinguishing NAFLD by histological examination. Treatment options in relation to NAFLD include flavonoids since they have been identified to impact general pathophysiologic pathways of NAFLD including lipid metabolic processes, insulin resistance, inflammation, and oxidative stress possibly in the future. 

Thus, NAFLD impacts one-third of Americans, while 2-3% of them have NASH which is defined as the accumulation of fat in the hepatocytes with inflammation and fibrosis. It is estimated that 4 to 10% of the patients with NASH will develop cirrhosis. It has been predicted that both NAFLD and NASH will significantly affect population health in the United States of America. 

The most common causes of cirrhosis in the United States are:The most common causes of cirrhosis in the United States are: 

Hepatitis C (26%) 

Alcoholic liver disease (21%) 

Co-infection with both Hepatitis C plus alcoholic liver disease (15%). 

Cryptogenic causes (18%) – NAFLD is a primary etiology of many of those. 

Hepatitis B (15%) which commonly occurs along with hepatitis D. 

Miscellaneous causes (5%) 

Genetics

Prognostic Factors

Etiology of Cirrhosis: 

The cause of cirrhosis, for instance, may be viral hepatitis, alcoholic liver disease, or Non-Alcoholic Fatty Liver Disease; these influence the advancement of the disease and its management. For instance, continued alcohol intake in alcoholic liver disease or poorly controlled diabetes in NAFLD may lead to a poorer prognosis. 

Severity of Liver Disease: 

Child-Pugh Score: This scoring system estimates the degree of cirrhosis from five clinical parameters and includes bilirubin, albumin, prothrombin time (INR), ascites, and hepatic encephalopathy. The obtained scores are grouped into the classes A (mild), B (moderate) and C (severe) with higher score corresponding to worse prognosis. 

Model for End-Stage Liver Disease (MELD) Score: The MELD score incorporates serum bilirubin, creatinine, and INR to estimate the mortality point in patients. 

Presence and Severity of Complications: 

Portal Hypertension: The presence of factors such as variceal bleeding, ascites, and spontaneous bacterial peritonitis also affects prognosis. 

Hepatic Encephalopathy: Recurrent or severe encephalopathy signifies poor liver function and has direct implications on prognosis. 

Hepatorenal Syndrome: The progression of hepatorenal syndrome is lethal in many cases. 

Clinical History

Age Groups and Causes of Hepatitis C Children and Adolescents:  

Causes: Genetic conditions like Wilson’s disease, alpha-1 antitrypsin deficiency, biliary atresia, or metabolic disorders. 

Presentation: Growth retardation, jaundice, hepatomegaly, splenomegaly, developmental delays, and portal hypertension.  

Young Adults (20 to 40 years):  

Causes: Autoimmune hepatitis, hepatitis B and C, alcohol-related liver disease, NAFLD, and inherited metabolic diseases. 

Presentation: Fatigue, jaundice, right upper quadrant pain, pruritus, hepatomegaly, and early signs of portal hypertension.  

Middle-aged Adults (40 to 60 years):  

Causes: Chronic hepatitis C, alcoholic liver disease, NAFLD/NASH, primary biliary cholangitis, and hemochromatosis. 

Presentation: Ascites, hepatic encephalopathy, worsening portal hypertension, bleeding varices, jaundice, muscle wasting, and gynecomastia.  

Older Adults (60+ years):  

Causes: Long-standing hepatitis C, alcohol-related liver disease, NAFLD, primary biliary cholangitis, and secondary causes like cardiac cirrhosis. 

Physical Examination

General Appearance 

Cachexia: Muscle wasting and weight loss. 

Jaundice: Yellowing of the skin and sclera. 

Pallor: May indicate anemia. 

Skin 

Spider Angiomata: Small, spider-like blood vessels visible on the skin, typically found on the upper body. 

Palmar Erythema: Reddening of the palms. 

Clubbing: Enlargement of the distal fingers. 

Caput Medusae: Dilated veins around the umbilicus due to portal hypertension 

Age group

Associated comorbidity

Alcohol Use  

Obesity and Metabolic Syndrome  

Autoimmune Conditions 

Associated activity

Acuity of presentation

Chronic Presentation: Fatigue, anorexia, weight loss, weakness, mild jaundice, spider angiomata, palmar erythema and mild ascites. 

Acute Presentation: Rapid onset jaundice, severe ascites, hepatic encephalopathy, gastrointestinal bleeding, sepsis and renal dysfunction. 

Differential Diagnoses

  • Nonalcoholic Fatty Liver Disease (NAFLD) / Nonalcoholic Steatohepatitis (NASH) 
  • Alcoholic Liver Disease 
  • Chronic Viral Hepatitis (Hepatitis B and C) 
  • Primary Biliary Cholangitis 
  • Wilson’s Disease 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Management of Underlying Cause: Manage the cause of cirrhosis such as hepatitis B or C, alcoholism, or fatty liver diseases to avoid the progress of the disease in the liver. 

Symptom Management and Complications: 

  • Ascites: Sodium restriction, diuretics (e. g. Na + pumping, spironolactone, furosemide), paracentesis for symptomatic purposes. 
  • Variceal Bleeding: Beta-blockers (e.g., propranolol) to decrease portal pressure, endoscopic band ligation or sclerotherapy to manage bleeding varices. 
  • Hepatic Encephalopathy: Lactulose to decrease blood ammonia level, antibiotics (for instance, rifaximin) to alter the flora in GI tract. 
  • Hepatorenal Syndrome: Vasoconstrictors such as terlipressin, administering albumin, liver transplantation. 
  • Hepatocellular Carcinoma: Imaging/clinical monitoring such as ultrasound or MRI; potentially curative therapy i. e. resection or ablation, or liver transplantation. 

Nutritional Support: High calorie and moderate protein diet; high fiber and low carbohydrates meal plan; vitamin consumption particularly A, D, E, K among other foods. 

Alcohol Cessation: In alcohol-related cirrhosis, therefore, it is essential to maintain complete alcohol abstinence. 

Liver Transplantation: Used and indicated in cases of severe liver cirrhosis and liver dysfunction or hepatoma. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Use of a non-pharmacological approach for treating Cirrhosis

Nutritional Therapy: Maintaining good nutrition by taking enough calories in their diet and reasonable amount of protein. Low sodium intake, usually below 2000 milligrams per day, is essential in the management of this condition accompanied by fluid retention such as ascites. Most importantly vitamins A, D, E, and K since they’re fat soluble and therefore may be lacking in the body because of poor liver function. 

Alcohol Abstinence: It is mandatory for the patients with cirrhosis assumed to be alcohol induced to stop taking alcohol to minimize damage and progression of the disease. 

Fluid Management: 

Ascites Management: Avoidance of high fluid intake and diuretics (such as spironolactone, furosemide and the like) with the help of a physician to address problems with accumulation of fluids. 

Hydration: Supervision of sufficient hydration levels, especially during the periods of dehydration and/or electrolyte abnormalities. 

Exercise and Physical Activity: Physical exercise is recommended in cirrhosis to enhance muscle power and functional capacity within these patients. It also assists in retaining bone mass and preventing possible complications such as osteoporosis. 

Psychosocial Support: Psychotherapy and support groups are beneficial for patients with cirrhosis as they can learn how to deal with the mental health issues related to the condition. It may also help with regards to concerns on compliance to treatment and preventive measures focus. 

Comprehensive Approaches in Managing Hepatic Fibrosis

Reduction of Hepatic Inflammation: Modulate and decrease further inflammation across the liver, may involve therapy with anti-inflammatory substances or drugs that can lower levels of cytokines like IL-6, IL-8, TNF-α. 

Inhibition of Stellate Cell Activation: In addition, prevent or inhibit the activation of stellate cells into collagen producing myofibroblasts. This could include drugs designed to inhibit signaling pathways that contribute to stellate cell activation, for example, TGF-beta1. 

Modulation of Fibrogenic Activities: Target cytokines involved in fibrogenesis with specific emphasis on collagen producing cytokines (e. g., blockage of TGF-beta 1 signaling pathways or other fibro pro cytokines). 

Promotion of Matrix Degradation: Increase the breakdown of the stored extracellular matrix components such as collagens, glycoproteins through promoting matrix metalloproteinases or other enzymes responsible for turnover of matrix. 

Antifibrotic Agents: Conduct research and coordinate the production of drugs to treat or prevent hepatic fibrosis. This may include new generations of small molecule inhibitors or antibodies that selectively targeting certain fibrotic mediators or other strategies. 

Comprehensive Management Strategies for Portal Hypertension

The management of portal hypertension is based on reduction of portal pressure, preventing complications such as variceal bleeding and addressing disease processes that have led to increased portal venous pressure. Here are the key aspects based on the provided information: 

Non-selective beta-blockers (NSBBs): Beta-blockers such as propranolol or nadolol are administered for controlling portal pressure by reducing splanchnic blood flow and cardiac output, respectively. They are most useful in avoiding variceal hemorrhage in the patients with cirrhosis of liver. 

Endoscopic therapy: For each patient with esophageal varices or other varices prone to bleeding, endoscopic treatment in the form of band ligation or sclerotherapy is employed to eradicate varices to minimize risk of bleeding. 

Transjugular intrahepatic portosystemic shunt (TIPS): This is a procedure that requires the establishment of a shunt somewhere between the portal vein and the hepatic vein to relieve the pressure within the portal system. It effectively reduces the portal pressure; however it is indicated to carefully select candidates since it may provoke such complications as hepatic encephalopathy. 

Management of underlying liver disease: Addressing the cause is necessary, for example, organizing the treatment of cirrhosis with the help of measures preventing inflammation and fibrosis progression. This involves identifying and treating alcohol consumption, treating infections experienced in the liver, and preventing diseases ailing the liver. 

Variceal screening and surveillance: Endoscopic surveillance should be performed at regular intervals, at least once in 6 months to identify these varices before they rupture. It also includes assessing the risk level needed to be observed from certain patient profiles such as portal pressure measurements and liver function, among others. 

Risk of Hepatic Encephalopathy in Cirrhosis

Hepatic encephalopathy is another complication that can be diagnosed in some patients with cirrhosis and is traditionally defined as a neuropsychiatric disorder associated with personality changes, intellectual deterioration and reduced level of consciousness. It typically requires the diversion of portal blood into systemic circulation; however, this can be seen in patients without cirrhosis but who have had portocaval shunt surgery. 

Pathogenesis 

Several theories have been proposed to explain the pathogenesis of hepatic encephalopathy: 

Altered Brain Energy Metabolism: Patients may develop alterations in brain energy metabolism and a compromise in the integrity of the blood-brain barrier, which facilitates the entry of neurotoxins into the central nervous system. 

Neurotoxins: Some neurotoxins consist of short-chain fatty acids, mercaptans, false transmitters such as tyramine and octopamine, ammonia and gamma aminobutyric acid (GABA). 

Ammonia Hypothesis: Ammonia synthesised in the GI tracts from the degradation of diverse products by bacterial action is generally neutralized in the liver. Ammonia is not actually metabolized in liver diseases or in portosystemic shunting, thus the levels of the formed go up in the systemic circulation. Neurotoxic effects of ammonia can be: displacement of transport of amino acids, water, and electrolytes across neuronal membranes; and abolition of synaptic potentials. 

Role of Ursodeoxycholic Acid in treating Cirrhosis

Ursodeoxycholic acid or ursodiol is a naturally occurring bile acid that is mainly prescribed for the management of specific cholestatic liver diseases. It is most useful when employed in the early phases and with defining pathophysiological disorders. 

UDCA works by: 

Minimizing the impact of bile acids on liver cells. 

Reducing liver bile acid content and enhancing bile output. 

Anti-inflammatory and immunomodulatory effects. 

Preventing apoptotic cell death of liver cells. 

Indications 

UDCA is primarily indicated for: 

Primary Biliary Cholangitis (PBC): This is the initial treatment and has been found to correct liver function tests and survival excluding transplantation. 

Primary Sclerosing Cholangitis (PSC): However, there is evidence of its off-label use in PSC where the benefits of corticosteroids are not as well-defined. 

Intrahepatic Cholestasis of Pregnancy: Depending on the type of hepatitis and stage of the disease, it can help to less symptoms and stimulate the function of the liver. 

Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH): It is not a first-line treatment; however, some evidence has been found that point toward it being useful. 

Use of Intervention with a procedure in treating Cirrhosis

  • Transjugular Intrahepatic Portosystemic Shunt (TIPS): TIPS is a procedure that involves creating a shunt (a connection) between the portal vein and hepatic vein to reduce portal hypertension.  
  • Variceal Band Ligation: This endoscopic procedure is used to treat esophageal varices, which can cause life-threatening bleeding. Rubber bands are placed around the varices to induce their regression and reduce the risk of bleeding.  
  • Sclerotherapy: Sclerotherapy is another endoscopic procedure used for variceal bleeding. A sclerosing agent is injected directly into the varices to cause their contraction and scarring, preventing further bleeding.  
  • Liver Transplantation: Liver transplantation is the ultimate intervention for end-stage cirrhosis when complications become life-threatening and irreversible.   

Use of phases in managing Cirrhosis

  • Primary Prevention: Primary prevention focuses on addressing risk factors and preventing the development of liver disease and cirrhosis.  
  • Screening and Early Detection: Early detection of liver disease and cirrhosis is crucial for timely intervention. Regular monitoring of individuals with known risk factors (e.g., chronic viral hepatitis, alcohol abuse, metabolic syndrome).  
  • Medical Management: Manage complications, such as ascites, hepatic encephalopathy, and variceal bleeding.  
  • Pharmacological Therapy: Reduce portal hypertension and prevent variceal bleeding e.g., beta-blockers, endoscopic band ligation.  

Medication

 

torsemide 

Indicated for hepatic cirrhosis
The initial once daily oral dose is 5 to 10 mg in conjunction with an aldosterone antagonist or a potassium-sparing diuretic
the dosage can be enhanced, by doubling it, till the desirable diuretic outcome is attained
Doses exceeding 40 mg have not undergone thorough investigation



torsemide 

Indicated for hepatic cirrhosis
The initial once daily oral dose is 5 to 10 mg in conjunction with an aldosterone antagonist or a potassium-sparing diuretic
The dosage can be enhanced, by doubling it, till the desirable diuretic outcome is attained
Doses exceeding 40 mg have not undergone thorough investigation



 
 

Media Gallary

Cirrhosis

Updated : June 11, 2024




Cirrhosis is the final stage in chronic liver diseases, and it means the common outcome of various liver diseases. The term cirrhosis was coined by Laennec in the year 1826 whereby cirrhosis was from the Greek word “scirrhus” implying to the orange-brown tawny liver colour noticed during autopsy. 

Structurally, cirrhosis is defined by the presence of fibrosis as well as regenerative nodules alteration in the normal architecture of liver. The development of cirrhosis can range from weeks to decades, with conditions such as chronic hepatitis C, taking about forty years to cause cirrhosis. 

Hepatic fibrosis refers to the accumulation of extracellular matrix molecules including collagen, glycoproteins and proteoglycans in the liver and is considered as a reversible process in response to liver injury. However, cirrhosis is usually a non-reversible condition for which persons suffering from this disease cannot receive a cure. Some of the complications of cirrhosis are portal hypertension, ascites, hepatorenal syndrome, and hepatic encephalopathy. 

The histological features of cirrhosis are frequently not reflected in the clinical manifestations. Some of the patients are unlikely to present with significant clinical symptoms and can have near normal life expectancy while others present with complication and manifestations of ESRD with a poor prognosis. Symptoms may be due to decreased liver synthetic capacity (for example, coagulopathy), decreased ability to detoxify compounds (for example, hepatic encephalopathy), or develop complications from portal hypertension (for example, variceal bleed). 

Later in August 2012, the CDC revised the guidelines by recommending a one-time blood test for hepatitis C virus (HCV) infection for those people whose age falls between 1945 and 1965, and these people comprise of three-fourth of all those with chronic HCV infections in the United States. This changed testing could yield approximately 808,600 more people with chronic HCV. The individuals that have been identified should undergo screening for alcohol abuse, and if positive, should be enrolled in prevention or treatment services. 

Liver disease and cirrhosis result in about 35,000 deaths per year in the United States of America; cirrhosis ranks ninth among the leading causes of mortalities in the country and contributes to 1.2% of all U.S. deaths. Some people are diagnosed with the disease during their Middle Ages or at the early stage of the fifth or sixth decade of life. The prevalence of NAFLD and NASH rises with time, and therefore the occurrence of cirrhosis is expected to rise. Liver disease and cirrhosis result in about 35,000 deaths per year in the United States of America; cirrhosis ranks ninth among the leading causes of mortalities in the country and contributes to 1. Twice as many people died from an overdose in one year than from HIV/AIDS in an entire year, representing 2% of all U.S. deaths. Some people are diagnosed with the disease during their middle ages or at the early stage of the fourth, fifth, or sixth decade of life. The prevalence of NAFLD and NASH rises with time, and therefore the occurrence of cirrhosis is expected to rise. 

Furthermore, approximately 2000 people die every year in the United States due to FHF or fulminant hepatic failure. FHF can be due to viral hepatitis such as hepatitis A, B and others, drugs such as acetaminophen, toxins for example Amanita phalloides, the yellow death – cap mushroom, autoimmune hepatitis, Wilson disease, and many others. Cryptogenic etiology encompasses one-third of FHF cases. The mortality of FHF ranges between 50-80% but can be reduced if the patient undergoes a liver transplant. 

Cirrhosis is the fourteenth leading cause of death in the world, and the fourth in Europe. The estimated worldwide population with NAFLD is 25.2%. 

  • There are several acute and chronic conditions that result in persistent inflammation in the liver including viral hepatitis B &C, alcoholic liver disease and nonalcoholic steatohepatitis (NASH). 
  • Hepatocyte damage results to inflammation and formation of cytokines and ROS that further cause hepatocyte damage and apoptosis. 
  • Remote hepatocytes stimulate HSCs activation, thus causing fibrosis and derangement of the normal liver architecture. 
  • Hepatocytes undergo regeneration and create strange nodules of Proliferating Liver cells. 
  • In the liver, fibrotic tissue along with regenerative nodules produce pressure on the hepatic vasculature and result in portal hypertension and collateral vessels. 
  • Functional liver is lost and this results in the formation of coagulopathy, hypoalbuminemia, jaundice and hepatis encephalopathy. 
  • These are portal hypertension, ascities, hepatorenal syndrome, hepatic encephalopathy and hepatocellular carcinoma. 

The causes of cirrhosis of the liver may include different types of chronic hepatic illnesses. In the past alcoholic liver disease was the most frequent cause of cirrhosis among the population in the United States. However, recent studies revealed that hepatitis C has become the leading cause of chronic hepatitis and cirrhosis in the country. 

Another main cause of cirrhosis is nonalcoholic fatty liver disease (NAFLD) that can present itself as cryptogenic cirrhosis. In this study 60%of patients with cryptogenic cirrhosis had risk factors associated with NAFLD including obesity, diabetes, and hypertriglyceridemia. As the duration of hepatic fibrosis increases, steatosis can decrease; this can lead to difficulty in distinguishing NAFLD by histological examination. Treatment options in relation to NAFLD include flavonoids since they have been identified to impact general pathophysiologic pathways of NAFLD including lipid metabolic processes, insulin resistance, inflammation, and oxidative stress possibly in the future. 

Thus, NAFLD impacts one-third of Americans, while 2-3% of them have NASH which is defined as the accumulation of fat in the hepatocytes with inflammation and fibrosis. It is estimated that 4 to 10% of the patients with NASH will develop cirrhosis. It has been predicted that both NAFLD and NASH will significantly affect population health in the United States of America. 

The most common causes of cirrhosis in the United States are:The most common causes of cirrhosis in the United States are: 

Hepatitis C (26%) 

Alcoholic liver disease (21%) 

Co-infection with both Hepatitis C plus alcoholic liver disease (15%). 

Cryptogenic causes (18%) – NAFLD is a primary etiology of many of those. 

Hepatitis B (15%) which commonly occurs along with hepatitis D. 

Miscellaneous causes (5%) 

Etiology of Cirrhosis: 

The cause of cirrhosis, for instance, may be viral hepatitis, alcoholic liver disease, or Non-Alcoholic Fatty Liver Disease; these influence the advancement of the disease and its management. For instance, continued alcohol intake in alcoholic liver disease or poorly controlled diabetes in NAFLD may lead to a poorer prognosis. 

Severity of Liver Disease: 

Child-Pugh Score: This scoring system estimates the degree of cirrhosis from five clinical parameters and includes bilirubin, albumin, prothrombin time (INR), ascites, and hepatic encephalopathy. The obtained scores are grouped into the classes A (mild), B (moderate) and C (severe) with higher score corresponding to worse prognosis. 

Model for End-Stage Liver Disease (MELD) Score: The MELD score incorporates serum bilirubin, creatinine, and INR to estimate the mortality point in patients. 

Presence and Severity of Complications: 

Portal Hypertension: The presence of factors such as variceal bleeding, ascites, and spontaneous bacterial peritonitis also affects prognosis. 

Hepatic Encephalopathy: Recurrent or severe encephalopathy signifies poor liver function and has direct implications on prognosis. 

Hepatorenal Syndrome: The progression of hepatorenal syndrome is lethal in many cases. 

Age Groups and Causes of Hepatitis C Children and Adolescents:  

Causes: Genetic conditions like Wilson’s disease, alpha-1 antitrypsin deficiency, biliary atresia, or metabolic disorders. 

Presentation: Growth retardation, jaundice, hepatomegaly, splenomegaly, developmental delays, and portal hypertension.  

Young Adults (20 to 40 years):  

Causes: Autoimmune hepatitis, hepatitis B and C, alcohol-related liver disease, NAFLD, and inherited metabolic diseases. 

Presentation: Fatigue, jaundice, right upper quadrant pain, pruritus, hepatomegaly, and early signs of portal hypertension.  

Middle-aged Adults (40 to 60 years):  

Causes: Chronic hepatitis C, alcoholic liver disease, NAFLD/NASH, primary biliary cholangitis, and hemochromatosis. 

Presentation: Ascites, hepatic encephalopathy, worsening portal hypertension, bleeding varices, jaundice, muscle wasting, and gynecomastia.  

Older Adults (60+ years):  

Causes: Long-standing hepatitis C, alcohol-related liver disease, NAFLD, primary biliary cholangitis, and secondary causes like cardiac cirrhosis. 

General Appearance 

Cachexia: Muscle wasting and weight loss. 

Jaundice: Yellowing of the skin and sclera. 

Pallor: May indicate anemia. 

Skin 

Spider Angiomata: Small, spider-like blood vessels visible on the skin, typically found on the upper body. 

Palmar Erythema: Reddening of the palms. 

Clubbing: Enlargement of the distal fingers. 

Caput Medusae: Dilated veins around the umbilicus due to portal hypertension 

Alcohol Use  

Obesity and Metabolic Syndrome  

Autoimmune Conditions 

Chronic Presentation: Fatigue, anorexia, weight loss, weakness, mild jaundice, spider angiomata, palmar erythema and mild ascites. 

Acute Presentation: Rapid onset jaundice, severe ascites, hepatic encephalopathy, gastrointestinal bleeding, sepsis and renal dysfunction. 

  • Nonalcoholic Fatty Liver Disease (NAFLD) / Nonalcoholic Steatohepatitis (NASH) 
  • Alcoholic Liver Disease 
  • Chronic Viral Hepatitis (Hepatitis B and C) 
  • Primary Biliary Cholangitis 
  • Wilson’s Disease