What is cirrhosis and what are its common causes?

Cirrhosis Definition and Causes

Cirrhosis is an end-stage form of chronic liver disease characterized by the gradual replacement of healthy liver tissue with annular fibrosis, destroying the architecture of the liver parenchyma and blocking intrahepatic portal blood flow, leading to portal hypertension and hepatic dysfunction. 1

Definition and Pathophysiology

• Cirrhosis represents the final pathological outcome of various chronic liver diseases, where ongoing injury initiates a dysregulated wound healing response resulting in abnormal connective tissue production and deposition 2
• The process begins with fibrosis development in the space of Disse that progressively matures and enlarges over time, typically starting in the centrilobular region and extending toward the portal tract 2
• As the disease progresses, regenerative nodules form surrounded by fibrous bands, which is the histological hallmark of cirrhosis 3
• This architectural distortion leads to increased intrahepatic resistance to portal flow, which is the primary factor in the development of portal hypertension 2

Common Causes of Cirrhosis

Viral Hepatitis

• Hepatitis B and C are major causes of cirrhosis worldwide 1
• Globally, approximately 54% of cirrhosis cases are attributed to HBV infection and 31% to HCV infection 1
• In Africa and East Asia, hepatitis B accounts for about 60% of cases, while in Western countries, hepatitis C is the predominant viral cause 1
• HBV-related risk factors for progression to cirrhosis include HBeAg seropositivity, high viral load, and genotype C 1
• HCV genotype 1b has been associated with increased risk of progression to cirrhosis and HCC 1

Alcohol-Related Liver Disease

• Chronic alcohol abuse is a leading cause of cirrhosis globally 1
• In some European countries, alcohol accounts for 40-50% of cirrhosis cases 1
• The risk of developing cirrhosis increases with the amount and duration of alcohol consumption 4

Metabolic Causes

• Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasingly recognized as major causes of cirrhosis 1, 5
• NAFLD affects approximately 19% of the US adult population, corresponding to an estimated 28.8 million adults 1
• Obesity, diabetes, and metabolic syndrome are risk factors for NAFLD progression to cirrhosis 1
• NASH is becoming a common cause of cryptogenic cirrhosis (cirrhosis of unknown etiology) in Western countries 1

Genetic and Autoimmune Causes

• Hereditary hemochromatosis can lead to cirrhosis in up to 45% of cases, usually with a background of cirrhosis 1
• Alpha-1-antitrypsin deficiency is a well-documented cause of cirrhosis 1
• Wilson's disease can lead to cirrhosis, but only in the presence of advanced liver disease 1
• Autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis can progress to cirrhosis 1

Other Causes

• Aflatoxin B1 exposure (from fungal contamination of food) is an important co-factor for cirrhosis and HCC development in parts of Africa and Asia 1
• Drug-induced liver injury can lead to cirrhosis in some cases 1
• Cryptogenic cirrhosis (unknown etiology) accounts for 3-30% of cirrhosis cases 1

Disease Progression and Complications

• Cirrhosis evolves from an asymptomatic compensated phase to a symptomatic decompensated phase 2, 5
• Decompensation is characterized by complications including ascites, variceal hemorrhage, hepatic encephalopathy, and jaundice 2
• Portal hypertension drives the development of gastroesophageal varices, present in 30-40% of patients with compensated cirrhosis and up to 85% with decompensated cirrhosis 2
• Hepatocellular carcinoma (HCC) is a serious complication of cirrhosis, with an annual incidence of 1-8% in cirrhotic patients 1
• Systemic inflammation and circulatory dysfunction contribute to multi-organ failure in advanced disease 2

Diagnosis

• Diagnosis is based on clinical features, laboratory tests, imaging studies, and sometimes liver biopsy 4, 6
• Noninvasive assessment includes serum markers, elastography techniques, and conventional imaging 1
• Morphologic features of cirrhosis on imaging include liver surface nodularity, atrophic right lobe, hypertrophied caudate lobe, and narrow hepatic veins 1
• Liver biopsy remains the reference standard for diagnosis but is increasingly being replaced by noninvasive methods 4, 6

Prognosis and Management

• The Child-Pugh and Model for End-stage Liver Disease (MELD) scores help assess disease severity and prognosis 4
• Management focuses on treating the underlying cause, preventing progression, and managing complications 5
• Liver transplantation remains the only curative option for selected patients with advanced disease 3
• Recent advances in understanding cirrhosis pathophysiology have led to improved management and quality of life 3