What is cirrhosis?

From the Guidelines

Cirrhosis is a late-stage liver disease characterized by extensive scarring (fibrosis) of the liver tissue, which can lead to serious complications and significantly impact morbidity, mortality, and quality of life. It occurs when healthy liver cells are damaged and replaced by scar tissue over time, disrupting normal liver function and structure 1. This scarring prevents the liver from performing its vital functions, including filtering toxins from the blood, producing proteins for blood clotting, and processing nutrients. Cirrhosis develops gradually, often over years or decades, as a result of chronic liver damage from various causes such as long-term alcohol abuse, viral hepatitis (particularly hepatitis B and C), nonalcoholic fatty liver disease, certain medications, autoimmune diseases, or inherited disorders like hemochromatosis or Wilson's disease.

As cirrhosis progresses, it can lead to serious complications including:

• Portal hypertension (increased blood pressure in the vein system connecting the intestines and liver)
• Fluid accumulation in the abdomen (ascites)
• Bleeding from enlarged veins in the esophagus
• Confusion due to toxin buildup in the brain (hepatic encephalopathy)
• Increased risk of liver cancer While early cirrhosis may cause no symptoms, advanced disease typically presents with fatigue, weakness, loss of appetite, weight loss, nausea, yellowing of the skin (jaundice), itchy skin, and easy bruising. According to a recent study published in Gastroenterology, cirrhosis consists of 3 distinct prognostic stages, including the compensated stage, the stage of decompensation, and a third stage of “further” decompensation 1. Treatment focuses on addressing the underlying cause, preventing further damage, and managing complications, as the scarring itself is generally irreversible without a liver transplant. The use of vasoactive drugs and intravenous albumin is a common approach in the management of cirrhosis, particularly in patients with variceal hemorrhage, ascites, and spontaneous bacterial peritonitis 1.

The clinical and economic burden of cirrhosis is significant, with chronic liver disease being the fourth leading cause of death among adults aged 45–64 years, and accounting for more than 44,000 deaths annually 1. The development of ascites is an important landmark in the natural history of cirrhosis, as it is associated with a 50% mortality over two years, and signifies the need to consider liver transplantation as a therapeutic option 1. Therefore, early diagnosis and treatment of cirrhosis are crucial to improve morbidity, mortality, and quality of life, and to reduce the clinical and economic burden of the disease.

From the Research

Definition of Cirrhosis

• Cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury, which leads to portal hypertension and end-stage liver disease 2.
• It is a pathologic scarring of liver tissue that leads to impaired liver function, resulting from any etiology of chronic liver inflammation 3.
• Cirrhosis is the end result of hepatocellular necrosis that initiates the inflammatory process, and it can be classified by cause, such as alcoholic cirrhosis 4.

Diagnosis and Evaluation

• Cirrhosis often is an indolent disease; most patients remain asymptomatic until the occurrence of decompensation, characterized by ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, or variceal bleeding from portal hypertension 5.
• No serologic or radiographic test can accurately diagnose cirrhosis, and liver biopsy remains the reference standard for diagnosis 3, 5.
• A significant correlation has been demonstrated between persistently elevated liver function tests and biopsy-proven underlying hepatic disease 5.

Pathophysiology and Mechanisms

• Liver fibrosis is the pathological deposition of extracellular matrix rich in fibrillar collagen within the hepatocytes in response to chronic liver injury due to various causes, and it can progress to cirrhosis 6.
• Hepatic stellate cells and myofibroblast activation represent a key event in fibrosis, and macrophages and neutrophils produce inflammatory cytokines and participate in activating hepatic stellate cells 6.
• Multiple pathophysiological mechanisms and cell types are responsible for the progression of liver fibrosis and cirrhosis 6.

Management and Treatment

• Management of underlying diseases has been found to halt the progression, and to an extent, even reverse liver fibrosis, preventing further liver injury and cirrhosis-related complications 3, 6.
• Clinicians should counsel patients about alcohol use, obesity management, and prevention of infection, and drugs with potential for hepatotoxicity should be avoided 3.
• Clinical assessment with laboratory tests and calculation of the Child-Pugh and Model for End-stage Liver Disease (MELD) scores should occur every 6 months, and evaluation for liver transplantation is indicated for patients with a MELD score of 15 or greater, complications of cirrhosis, or hepatocellular carcinoma 3.