Natural History of Hepatitis C Virus

It is estimated that in the United States there are approximately 4.5 million people antibody positive for hepatitis C. The natural history of hepatitis C is difficult to characterize. There are a number of reasons for this difficulty including various methods of looking at the history as well as the variable rate of progression in many cohorts of patients. It takes between 5-12 weeks after exposure for a person to seroconvert so the antibody can be found in the blood. However, it takes 1-2 weeks for the RNA of the virus to be found in the bloodstream. Research has found the rate of progression to cirrhosis may be as high as 30% of patients after 20 years of infection to as low as 4% of infected patients.

Phases of the Hep C Virus

Generally speaking, the majority of patients in the acute phase (the first six months after exposure), have little or no symptoms making it difficult to identify patients in that phase. Sixty to eighty-five percent of patients who are antibody positive will progress to chronic hepatitis C after the acute phase. Studies looking at the characteristics of those who spontaneously cleared the virus with no treatment could not find any significant reasons shared by those patients who spontaneously cleared and those who went on to chronic illness, except gender. Women were more apt to clear the virus. Most patients were asymptomatic, with persistently elevated or fluctuating liver enzymes. However, some patients never have elevated liver enzymes and this may signify a more benign course of disease. Overall the progression of hepatitis C virus is usually slow and variable.

For those patients who report symptoms early on in the disease, the most frequently reported are fatigue and lack of stamina. Some patients, especially as the disease progresses, have extra-hepatic manifestations. These may include type 2 diabetes, arthritis, skin diseases such as porphyria cutanea tarda and lichen planus. Glomerulonephritis and nephrotic syndrome are seen, as well. Dry eyes are often an annoying and uncomfortable problem.

The course of hepatitis C virus is variable. There are some factors that make progression of the disease more likely. Drinking alcohol is a factor that can be modified by encouraging patients to stop drinking or if they cannot stop, encourage them to cut down. There is no safe level of alcohol for a patient with liver disease. Patients who have fatty liver are more likely to progress. Eating a healthy low fat diet is helpful. Factors that cannot be modified are gender, age at infection, and duration of infection. Males are more likely to have progressive disease as are people who acquire the virus after the age of 40. And of course, alcohol consumption plays a very big part in the rate of progression and will increase the chance of becoming cirrhotic. Studies have shown that men over the age of 40 who drink alcohol, have a mean time of progression to cirrhosis of 13 years. Women who are infected before 40 years of age who are non-drinkers progressed to cirrhosis over 42 years. Many people will never progress to cirrhosis.

Understadning the Risk for Liver Disease

Between 20 and 30% of patients will develop cirrhosis over a couple of decades. Cirrhosis causes portal hypertension and this may lead to bleeding varices especially in the esophagus. This is a life-threatening condition. Ascites, a buildup of fluid in the abdomen is also a symptom of late stage disease. This may lead to spontaneous bacterial peritonitis which is an infection of the ascitic fluid. Another sequela of late stage cirrhosis is a condition where the body has lost the ability for the blood to clot. This causes easy bruising and spontaneous bleeding. Lastly, people with cirrhosis are at increased risk for hepatocellular carcinoma.

It is estimated that the number of cases of cirrhosis will approach 900,000 by the year 2030. It is also expected that liver-related deaths will triple to 40,000 patients per year in the same time frame. The good news is that the new direct acting antivirals are now curing the vast majority of patients. Hopefully this will stem the tide of liver-related morbidity and mortality and decrease the number of liver transplants that are needed.

The natural history of hepatitis C is quite complex and the story is still unfolding. There are a myriad of factors that relate to progression and outcome of this virus. Individual characteristics such as age, sex, race, and genetic makeup, along with behavioral characteristics, metabolic factors, and other viruses that affect patients all play a role in the natural history.

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