Cirrhosis

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Cirrhosis is an advanced form of liver disease that has many causes, not just hepatitis C (HCV). Alcoholism, hepatitis B, fatty liver disease and other conditions can cause cirrhosis. It is usually irreversible, and in advanced stages, the only treatment is liver transplant. In the US, HCV infection is the most common cause of chronic liver disease, and the most common reason for liver transplantation. Cirrhosis is characterized by the formation of scar tissue (called fibrosis) which replaces liver tissue.

Classification of cirrhosis

Cirrhosis, has two phases, compensated and decompensated. Compensated cirrhosis means that the liver is still functioning relatively well. In fact, a person with compensated cirrhosis may be asymptomatic. Decompensated cirrhosis means that the liver is not functioning well.

There is a lot of variability in how cirrhosis can affect an individual. In some people, cirrhosis can remain compensated for a long time. In others, cirrhosis becomes decompensated quickly. For the majority of people, cirrhosis will go back and forth from compensated to decompensated for years. 1,2

How does HCV cause fibrosis and cirrhosis?

Generally, when a virus enters the body, it needs to find a place where it can reproduce or replicate in order to survive. HCV prefers liver cells (hepatocytes) in order to replicate. When HCV enters a liver cell, it uses genetic material (RNA) in that cell to help it reproduce and generate copies of itself. It releases these new copies into the bloodstream, and they travel to other liver cells to begin the cycle of replication again. The process of reproduction inside a liver cell can result in cell damage or destruction. Additionally, the immune response that the body launches against the virus can also result in cell damage or destruction. Either way, this damage or destruction of cells eventually results in formation of scar tissue or fibrosis. As fibrosis progresses, areas of scarring become interconnected, and the texture of the liver changes. With extensive fibrosis (cirrhosis), blood is no longer able to flow through the liver and liver function becomes significantly impaired. 1

What is my risk for developing cirrhosis?

Studies have found that up to 50% of people with chronic HCV infection eventually develop cirrhosis.3,4

In a person with chronic HCV, cirrhosis typically develops gradually. About 20% to 30% of people with chronic HCV infection will develop cirrhosis over a 20- to 30-year period. 5

What are the symptoms of cirrhosis?

For the majority of people, cirrhosis develops silently, without symptoms. However, a person with chronic HCV who develops cirrhosis has a greater chance of experiencing the symptoms of liver disease than someone with chronic HCV without cirrhosis.5

The early symptoms of compensated cirrhosis may include:

  • Fatigue
  • Loss of appetite
  • Weight loss
  • Weakness

As cirrhosis advances, the symptoms may include :

  • Jaundice (yellowing in the skin or whites of eyes)
  • Itchy skin (pruritus)
  • Muscle cramping
  • Spider veins
  • Swelling (edema) in the lower extremities (feet and legs)
  • Difficulty taking a full breath
  • Feeling full in the belly area
  • Nausea

Three serious complications may occur with decompensated cirrhosis:

  • Portal hypertension causing varices
  • Ascites
  • Hepatic encephalopathy

Other general symptoms throughout the body can result from loss of liver function due to cirrhosis, reflecting the important role of the liver in maintain a range of basic body functions.

What are the complications associated with cirrhosis?

Advanced cirrhosis is associated with a range of complications, many resulting from loss of liver function, reflecting the important role of the liver in maintaining basic body functions. Many of these complications can be controlled with medication. However, because they are manifestations of end-stage liver disease, the only curative treatment is liver transplant. 2

Ascites. The most common complication of advanced (or decompensated) cirrhosis is called ascites, which is the retention of fluid in the abdominal cavity. This fluid retention can cause the abdomen to become quite swollen and uncomfortable. Ascites occurs because of multiple factors, all interfering with the liver’s ability to regulate fluid balance. This complication is associated with increased risk for infection because retained fluid can come in contact with bacteria transported from the intestine to the liver.

Edema. In addition to retention of fluid in the abdominal cavity (ascites), loss of the ability to regulate fluid balance can result in peripheral edema, affecting the hands, legs, and feet.

Hormonal problems. Because the liver is responsible for producing some male and female sexual hormones and regulating levels of others, impaired liver function can result in hormonal imbalances. This can lead to swelling of breast tissue (gynecomastia ) and hypogonadism, resulting in impotence, loss of sexual drive, and infertility in men and irregular menstruation in women.

Bleeding problems. The liver produces many different proteins responsible for functions throughout the body. Included among these are proteins involved in blood coagulation (clotting), including fibrinogen, prothrombin, and several different clotting factors. As the liver loses function, production of these coagulation substances decreases, resulting in greater risk for bleeding throughout the body.

Hepatic encephalopathy. Hepatic encephalopathy is a brain disorder that results from toxins entering the brain. With decompensated cirrhosis, the liver loses its ability to filter toxins out of the blood and these toxins may be transported to the brain. Hepatic encephalopathy may result in memory problems, difficulty concentration, mood changes, sleep disturbances, confusion, or coma..

Portal hypertension. Portal hypertension occurs when fibrosis blocks the flow of blood through the liver, causing increased pressure in the liver’s blood circulation system. Portal hypertension can cause blood to back up in the spleen, an organ that stores red and white blood cells and platelets. Enlargement of the spleen is called splenomegaly. Portal hypertension can cause many serious problems, such as ascites and varices (enlarged veins).

Pruritis. The liver produces a substance called bile that is used in digestion of fat. With cirrhosis, bile can get into the skin and cause itching (pruritis).

Varices. With cirrhosis, blood is prevented from entering and leaving the liver. This can result in a stretching and weakening of blood vessels, called varices, in the esophagus, stomach, and other areas in the digestive tract.

Kidney failure. Severely impaired liver function is associated with kidney damage and may lead to kidney failure.

What are the risk factors that increase the chance of developing cirrhosis with HCV?

In a person with HCV, several risk factors can increase the chances of developing cirrhosis. These include1,2,6:

  • Drinking alcohol. Drinking large amounts of alcohol over a long period of time can increase the chances of developing cirrhosis.
  • Increasing age. People over the age of 50 years are at higher risk of developing cirrhosis.
  • Fatty liver disease. A disease called steatosis where fat is deposited in the liver cells, increases risk for cirrhosis.
  • Gender. Men with HCV appear to progress to cirrhosis more quickly than women.
  • Co-infection with HIV. HCV/HIV co-infection is associated with increased risk for developing cirrhosis.
  • Immune system dysfunction. A weakened or malfunctioning immune system may increase the risk of cirrhosis.
  • Uncontrolled, elevated blood sugar. There is some evidence that people who have insulin resistance or diabetes are at greater risk for developing cirrhosis.
  • Presence of another type of liver disease (e.g., hemochromatosis)

How is cirrhosis diagnosed?

Damage to the liver is evaluated using results obtained from a liver biopsy or another noninvasive procedure. These results determine the grade or stage of liver fibrosis. There are various scoring systems, depending on which procedure is used. The Metavir scoring system is the most common one used when a liver biopsy is performed. A fibrosis score from 0 to 4 is used to stage the extent of fibrosis and grade the degree of inflammation.1

Metavir scoring system

0 No scarring
1 Minimal scarring
2 Scarring has occurred and extends outside the areas in the liver that contain blood vessels
3 Bridging fibrosis is spreading and connecting to other areas that contain fibrosis
4 Cirrhosis or advanced scarring of the liver

Laboratory testing can also be useful in identifying cirrhosis in a person with HCV. Elevations in bilirubin or decreases in albumin or platelets may suggest cirrhosis. Liver function tests do not accurately reflect liver damage caused by HCV. Elevated liver enzymes (alanine transaminase [ALT] and aspartate transaminase [AST]) do not correlate with the degree of fibrosis or cirrhosis.

Imaging studies of the abdominal area, typically using ultrasound, may sometimes detect changes in the liver indicative of cirrhosis and help to evaluate possible complications of cirrhosis.

Learn more about liver biopsy and laboratory tests for HCV and liver disease.

view references
  1. Goldberg E, Chopra S. Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis. Uptodate. Runyon BA, Travis AC, eds. Accessed at: www.uptodate.com. 2014.
  2. Goldberg E, Chopra S. Cirrhosis in adults: Overview of complications, general management, and prognosis. Uptodate. Runyon BA, Travis AC, eds. Accessed at: www.uptodate.com. 2014.
  3. Tong MJ, el-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med 1995;332:1463-6.
  4. Yano M, Kumada H, Kage M, et al. The long-term pathological evolution of chronic hepatitis C. Hepatology 1996;23:1334-40.
  5. Chopra S. Clinical manifestations and natural history of chronic hepatitis C virus infection. Uptodate. Di Bisceglie AM, Bloom A, eds. Accessed at: www.uptodate.com. 2014.
  6. Sheth SG, Chopra S. Epidemiology, clinical features, and diagnosis of nonalcoholic fatty liver disease in adults. Uptodate. Lindor KD, Travis AC, eds. Accessed at: www.uptodate.com. 2014.
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