Liver Cirrhosis

What is liver cirrhosis?

It is a chronic disease that affects the liver as a result of persistent damage over several years, leading to a reduction or complete loss of its functions (liver failure), which are essential for life. These functions include protein production, detoxification and drug metabolism, glucose storage, cholesterol and bile production, synthesis of clotting factors, and storage of iron, fat-soluble vitamins (A, D, and K), vitamin B12, and minerals (zinc, copper, and magnesium). When this occurs, the liver’s repair process replaces normal tissue with scar tissue (fibrosis), forming nodules that alter the organ’s structure.

Causes

The most common causes of liver cirrhosis in Brazil and worldwide are related to chronic alcohol abuse, hepatitis B and C, and non-alcoholic fatty liver disease (NAFLD).

• alcoholic cirrhosis: Excessive, daily, and prolonged alcohol consumption (60 g/day for men and 40 g/day for women) can lead to the development of permanent liver damage
• viral hepatitis (B, C, and Delta):
  • hepatitis B infection resolves in about 80% of cases, unlike hepatitis C, which progresses to chronic form in 80% of cases. Currently, there are effective medications for treating hepatitis C, with cure rates exceeding 90%. It is expected that in the coming years, cirrhosis caused by hepatitis C will decrease significantly
  • hepatitis Delta occurs in patients already infected with the hepatitis B virus and is relatively common in the northern region of Brazil
• non-alcoholic fatty liver disease (NAFLD): Obesity, type 2 diabetes, dyslipidemia (elevated cholesterol and triglycerides), hypothyroidism, severe malnutrition, and certain medications can also lead to fat accumulation in the liver (hepatic steatosis), which in more advanced stages may progress to steatohepatitis, fibrosis, and cirrhosis

Other Causes

• metabolic diseases: resulting from congenital metabolic disorders that primarily affect children or young adults, such as galactosemia, tyrosinemia, Wilson’s disease, hemochromatosis, alpha-1 antitrypsin deficiency, among others
• cystic fibrosis
• primary sclerosing cholangitis
• primary biliary cirrhosis
• drug- or medication-induced hepatitis
• autoimmune hepatitis
• cryptogenic cirrhosis (of unknown cause): approximately 10% to 20% of cirrhosis cases remain with an undetermined etiology
• hepatic vein thrombosis

Complications of the Disease

• portal hypertension: All blood from the digestive system (stomach, intestines, pancreas) and the spleen must pass through the liver before reaching the rest of the body. The veins from these organs drain into a single large liver vein called the portal vein. When cirrhosis is established, structural changes in the liver increase pressure in the portal vein, initiating a process known as portal hypertension. This leads to the formation of varices in the esophagus, stomach, and rectum, which, if large, can cause serious gastrointestinal bleeding. Additionally, along with reduced protein production by the diseased liver, it contributes to the development of ascites (fluid accumulation in the abdomen)
• hepatic encephalopathy: These are potentially reversible neuropsychiatric changes characterized by personality alterations and impaired cognition, motor function, and consciousness level, due to the liver’s inability to metabolize neurotoxins (such as ammonia). Symptoms can range from mild mental changes to drowsiness, disorientation, or coma in serious cases
• splenomegaly (enlarged spleen): The spleen helps remove old blood cells. Each time blood flows through the spleen, throusands of cells are removed to make room for recently produced red blood cells, platelets and leucocytes . In portal hypertension, blood flow from the spleen to the liver becomes congested, causing the spleen to retain blood longer and remove more blood cells than necessary. This leads to anemia, thrombocytopenia, and leukopenia—a condition known as hypersplenism
• hepatorenal syndrome: A type of kidney failure that occurs due to liver failure, without structural damage to the kidneys. It typically appears in advanced stages of cirrhosis
• hepatopulmonary and portopulmonary syndromes:
• hepatopulmonary syndrome affects about one-third of patients with decompensated cirrhosis and is defined by a triad: liver disease, intrapulmonary vascular dilation, and arterial hypoxemia (low blood oxygen). The only effective treatment is liver transplantation
• portopulmonary hypertension occurs in patients with cirrhosis and portal hypertension, leading to increased pressure in the pulmonary artery and resulting in right-sided heart failure. It is a serious condition that may be treated with specific medications depending on severity
• hepatocellular carcinoma (primary liver cancer): Patients with cirrhosis have about a 30% chance of developing hepatocellular carcinoma, especially when cirrhosis is caused by hepatitis B, hepatitis C, NAFLD, alcohol, or hemochromatosis. The curative treatment is liver transplantation
• bacterial infections: These are serious complications in cirrhotic patients and require early recognition and immediate targeted treatment, as they significantly impact survival. Studies show that 32–34% of cirrhotic patients develop bacterial infections upon admission or during hospitalization, and this rate increases to 45% in the presence of gastrointestinal bleeding. The most common infections include spontaneous bacterial peritonitis, urinary tract infections, pneumonia, and skin and soft tissue infections
• malnutrition and sarcopenia: In cirrhosis, nutrient absorption is impaired due to reduced bile flow and intestinal edema, decreased hepatic storage of water-soluble vitamins and micronutrients, and reduced hepatic and muscular metabolism caused by increased cytokines and hormonal imbalances (insulin, glucagon, thyroid hormones). This leads to severe malnutrition and often irreversible sarcopenia (muscle loss)

Symptoms

• asymptomatic, or with nonspecific symptoms such as fatigue, tiredness, and anorexia (loss of appetite)
• swelling: leg edema, fluid accumulation in the abdomen (ascites) and lungs (pleural effusion)
• jaundice: yellowing of the skin and eyes
• hormonal changes: women may stop menstruating; men may experience sexual impotence, gynecomastia (enlarged breasts), reduced axillary and pubic hair, and testicular atrophy
• bruising and spontaneous bleeding
• palmar erythema: reddening of the palms
• clubbing: nails become more curved, giving the fingers a drumstick-like appearance

Diagnosis and Treatment

In most cases, the diagnosis is made through medical history, physical examination, blood tests, and upper abdominal ultrasound. Liver biopsy is indicated in specific cases. The curative treatment for cirrhosis is liver transplantation (LT), in which the cirrhotic liver is replaced (with a whole liver in the case of a deceased donor, or a portion of it in the case of a living donor transplant). LT is indicated for patients who have disease complications that do not respond to clinical treatment or who have liver cancer.

Prevalence of Cirrhosis in Brazil and Worldwide

As of 2015, cirrhosis affected approximately 2.8 million people worldwide and was responsible for 1.3 million deaths. Among these, alcohol was the cause of 348,000 cases, hepatitis C of 326,000, and hepatitis B of 371,000. However, cirrhosis due to NAFLD (non-alcoholic fatty liver disease) has also been increasing in recent years. In Brazil, there is no precise estimate of the disease’s prevalence. It is known that cirrhosis accounts for around 40,000 hospital admissions and a mortality rate of 12.6 per 100,000 inhabitants.

By Einstein Editorial Board