Liver Cirrhosis: Understanding the Causes, Pathophysiology, and Treatment Approaches

Liver cirrhosis is a chronic, progressive condition involving long-term liver damage, scar tissue formation (fibrosis), and distortion of the liver's normal structure. This process gradually declines liver function and carries a risk of serious, life-threatening complications such as liver failure, esophageal variceal bleeding, and hepatocellular carcinoma (HCC). It is the leading cause of morbidity and mortality due to chronic liver disease worldwide.

Etiology

Liver cirrhosis can be caused by several factors, including inflammatory, toxic, metabolic, and autoimmune factors. Some of the main causes include:

a. Alcoholic Fatty Liver Disease (ALFD)

The early stage of liver disease caused by excessive alcohol consumption, characterized by fat accumulation in liver cells (hepatocytes). Although it often does not cause obvious symptoms, ALFD is an important condition because it can develop into more serious forms of liver disease such as alcoholic hepatitis, fibrosis, and cirrhosis if alcohol consumption continues.

b. Non-Alcohol Fatty Liver Disease (NAFLD)

Nonalcoholic fatty liver disease (NAFLD) is a condition of fat accumulation in the liver that occurs in individuals who do not consume alcohol or consume only small amounts. It is one of the most common chronic liver diseases worldwide and is closely associated with metabolic syndrome, including obesity, type 2 diabetes, and dyslipidemia. NAFLD typically does not exhibit symptoms in its early stages. However, if left untreated, it can progress to nonalcoholic steatohepatitis (NASH), liver fibrosis, and even cirrhosis.

c. Non-Alcoholic Steatohepatitis (NASH)

Non-alcoholic steatohepatitis (NASH) is an advanced form of non-alcoholic fatty liver disease (NAFLD). It is characterized by fat accumulation in the liver, as well as inflammation and damage to liver cells (hepatocytes). NASH can progress to fibrosis, cirrhosis, and even hepatocellular carcinoma, a type of liver cancer.

d. Infeksi Virus Hepatitis B dan C Kronis

Chronic hepatitis B and C are long-term liver infections caused by the hepatitis B virus (HBV) or the hepatitis C virus (HCV) that last more than six months. Both viruses often present no symptoms initially, but can progress to cirrhosis, liver failure, or liver cancer.

Pathogenesis and Pathophysiology of Cirrhosis

Liver cirrhosis is the final stage of chronic liver damage caused by various factors, including viral hepatitis, long-term alcohol consumption, and fat accumulation in the liver (nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, or NAFLD/NASH). Cirrhosis begins when the liver experiences continuous damage, prompting the body to attempt to repair it. However, these repair efforts are imperfect, resulting in the formation of scar tissue (fibrosis) that replaces healthy liver tissue.

Over time, this fibrosis spreads, causing structural changes in the liver, including in the sinusoids, which are the small blood vessels where blood flows. Typically, blood from the digestive tract flows through the liver for processing. In cirrhosis, however, this flow is obstructed because scar tissue causes blood vessels to become stiff and narrow. Consequently, blood pressure in the portal vein system increases, a condition known as portal hypertension.

This pressure causes blood to take shortcuts through blood vessels in the stomach and esophagus. These vessels become swollen and fragile, forming varicose veins. If these varicose veins rupture, serious bleeding can result. Additionally, high pressure causes fluid to build up in the abdomen (ascites) and enlarges the spleen.

Conversely, impaired blood flow and damaged liver tissue disrupt the liver's functions, such as filtering toxins, producing proteins (like albumin and blood clotting factors), and aiding metabolism. These changes cause symptoms such as easy bruising, swelling, and jaundice (yellowing of the skin and eyes). They also cause hepatic encephalopathy, which is confusion due to toxin buildup in the brain, such as ammonia. These changes also have systemic effects. The body tries to adapt by retaining salt and water due to reduced blood flow perception, which causes swelling (edema). The heart works harder and the blood vessels in other organs, particularly in the digestive tract, dilate.

Complications of Cirrhosis

The downstream effects of cirrhosis and portal hypertension include:

• General poisoning, feeling sick, tired, and confused

• Decreased immunity, healing, and recovery

• Fluid leakage from veins, causing swelling in your body

• Hormonal imbalance and deficiency

• Digestive problems, malabsorption, and malnutrition

• Mild cognitive impairment and motor dysfunction

Life-threatening complications of cirrhosis and portal hypertension may include:

• Gastrointestinal varices and gastrointestinal bleeding

• Spontaneous bacterial peritonitis

• Kidney failure (hepatorenal syndrome)

• Respiratory failure (hepatopulmonary syndrome)

• Chronic liver failure

• Liver cancer (HCC)

Diagnosis of Cirrhosis

The diagnosis of cirrhosis involves a combination of clinical examination, laboratory tests, imaging, and biopsy if necessary. The aim is to assess liver damage, identify the cause of cirrhosis, and determine the severity of the disease.

1. Blood test (laboratory)

Blood tests are used to evaluate liver function and look for signs of damage or complications of cirrhosis. Here are some important parameters:

• Liver Enzymes (SGOT/SGPT). These are typically elevated in the early stages of liver damage but may be normal or low in advanced cirrhosis because damaged liver cells can no longer produce the enzymes.

• Albumin and Total Protein. These tend to be low because the liver cannot produce them in sufficient quantities.

• Bilirubin. Levels increase, indicating impaired bile excretion leading to jaundice (icterus).

• Complete Blood Count. Typically shows a decrease in platelets (thrombocytopenia), anemia, and leukopenia, especially if there is splenomegaly (hypersplenism).

• Prothrombin Time (PT INR). Results are typically prolonged because the liver fails to produce clotting factors.

• Mac-2 Banding Protein Glycosylation Isomer (M2BPGi). A non-invasive test to measure fibrosis levels; M2BPGi levels increase significantly with the progression of liver fibrosis, including cirrhosis.

2. Imaging Examination

Imaging is performed to view the structure of the liver, detect fibrosis, and complications such as ascites or varices. Commonly used methods include:

• Ultrasound (Abdominal Ultrasound): This is typically used as an initial examination to reveal changes in liver shape, a rough surface, an enlarged spleen, and the presence of ascites fluid.

• Elastography (FibroScan): This test measures liver stiffness, which reflects the degree of fibrosis. It is widely used to assess cirrhosis without the need for a biopsy.

• CT scan or MRI: These are used to assess liver structure in greater detail and to monitor complications such as liver cancer (HCC) or portal vein thrombosis.

3. Liver biopsy

A liver biopsy is the gold standard for directly evaluating the extent of damage and fibrosis. During the procedure, a small liver tissue sample is taken with a needle and examined under a microscope. Since this test is invasive, there is a risk of bleeding, and it is not always necessary.

Management

• Cirrhosis therapy aims to halt disease progression, manage complications, and consider liver transplantation in advanced cases.

• Lifestyle modifications: Stop alcohol consumption, follow a balanced low-salt diet

• Specific therapies, such as:

• Antivirals (for hepatitis B/C)

• Corticosteroids or immunomodulators (for autoimmune hepatitis)

• Regular monitoring: Through blood tests or ultrasound every 6 months for early detection of HCC

• Liver transplantation: The best option for patients with decompensated cirrhosis or end-stage liver failure

Liver cirrhosis is a chronic liver disease characterized by the formation of scar tissue due to various causes such as chronic hepatitis, excessive alcohol consumption, and fatty liver disease. This condition often develops without symptoms and is only detected when it has become severe. Although it cannot be cured, cirrhosis can be managed through early detection, treatment based on the cause, and lifestyle changes. K-LAB Medical Center offers the M2BPGi test, which can help assess the extent of liver damage non-invasively. Early detection and management are crucial to prevent serious complications and maintain the patient's quality of life. Remember to always undergo regular health check-ups and consult with your doctor.

Source

• NCBI – Cirrhosis – 2009

• NCBI – Hepatic Cirrhosis – 2022

• NCBI – Nonalcoholic Fatty Liver – 2023

• NCBI – Diagnosis and Management of Cirrhosis – 2024

• Cleveland Clinic – Cirrhosis of the Liver - 2023