The incubation period of HCV infection (period prior to onset of clinical symptoms) is highly variable. The most common symptoms are often very mild and may include: fatigue, jaundice, loss of appetite and vague muscular and RUQ discomforts. In very rare instances, fulminant hepatitis can occur, leading to rapid liver failure. However, the majority of cases are asymptomatic for many years.
HCV infection is spontaneously resolved
by the immune system in about 15% to 25% of cases. Currently, more than a million
Americans who were infected remain positive for HCV antibody but have no HCV circulating in their blood. Those with chronic HCV infection are at risk for chronic liver disease. Over time, up to 25% of those with
chronic hepatitis develop a serious condition, such as cirrhosis
or hepatocellular cancer. Cirrhosis greatly increases the risk of developing liver cancer.
Chronic hepatitis: About 80% of those infected with HCV will develop a chronic inflammation of the liver, called chronic persistent hepatitis. Hepatitis is defined as chronic if it persists past 6 months, and indeed it may persist for 30 years or more in people with chronic HCV infection.
Cirrhosis:
Cirrhosis usually develops in those
with HCV after a long period of time (i.e. 20 years or more). 10 to 20% of people with chronic HCV will develop cirrhosis of the liver as
the virus continues to cause necrosis and inflammation. This results in
fibrosis with nodules and scar tissue. The fibrosis and vascular impairment associated with cirrhosis of
the liver interferes with the liver's metabolism of nutrients, detoxification
of the blood, bile production and other functions critical to the functioning
of the body. Abdominal ascites is a common symptom of advancing cirrhosis.
Alcohol effects: Alcohol consumption does not cause hepatitis C, but alcohol speeds the progression of hepatitis C and liver disease. There are no current guidelines as to how much alcohol might be safe to consume, but abstinence from alcohol is the safest course. Certainly heavy intake, more than 3 drinks per day, should always be avoided, and people should remain abstinent throughout anti-viral treatment. Another problem related to alcohol consumption is that antiviral therapy may be ineffective. Also, interferon therapy can be associated with relapse in people with history of alcohol abuse. Interferon therapy should be used with caution in those who recently stopped alcohol abuse, and these patients should be referred to alcohol abuse treatment programs for support during anti-viral treatment.
There are a number of risk factors associated with HCV and the development of HCC.
The mechanism by which HCV causes HCC is not well-understood. Since HCC is highly correlated with cirrhosis, some suggest that HCV is a secondary cause; however, some HCV patients have HCC without underlying cirrhosis. It is believed that the core protein of HCV impedes the natural process of cell death or interferes with the function of a normal inhibitor (tumor suppressor) gene. Thus, the liver cells live and reproduce without normal constraints, resulting in cancer. Commonly, an individual with alcohol-induced cirrhosis has stopped drinking for about 10 years prior to a diagnosis of HCC; actively drinking alcoholics rarely develop HCC. It appears that when the alcoholic stops drinking, the liver cells attempt to regenerate, and during this regeneration, mutations occur.
Cryoglobulinemia:
About 5% of HCV patients develop a combination of joint pain, weakness,
and areas of bleeding into the skin known as cryoglobulinemia. The kidneys
and brain also may be affected.
Psychiatric co-morbidity:
Studies have shown that patients with HCV have a higher prevalence of psychiatric
illness, and patients with severe mental illness have 4 to 9 times the
prevalence of HCV. Interferon treatment has been associated with frequent
adverse affects: affective, anxiety, cognitive, and psychotic symptoms.
Psychiatric symptoms often results in interruption or cessation of treatment,
so pretreatment assessment and ongoing psychiatric follow-up is critical.
A study at a Veteran's Affairs Medical Center showed that of 306 randomly selected HCV patients, a large percentage had psychiatric disorders:
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