Disease Course and Outcomes
The first six months of HCV infection encompass the acute phase.12 Because it passes with few, if any signs or symptoms in most cases, this stage of the illness is usually dismissed by the patient. About 15‒25% of adults with acute HCV infection may develop clinical symptoms. The symptomatic onset ranges from 3 to 12 weeks after exposure.13,14 Symptoms, if they occur, can include fever, fatigue, tenderness in the liver area, nausea or decreased appetite, and jaundice.12,13
Approximately 75‒85% of HCV-infected persons will progress to chronic HCV infection.13
The chronic phase is generally established when HCV genetic material (RNA) persists in the patient's serum for 6 months or more.13,14
Numerous factors appear to affect the likelihood of developing chronic HCV infection. Females are more likely to clear the virus, for example, as are people who develop jaundice during the acute phase. In contrast, the virus is prone to persisting in patients co-infected with HIV.13,14
Although the disease is transmittable during the chronic phase through blood, chronic HCV infection is usually either asymptomatic or has only non-specific symptoms such as fatigue or depression.15
While elevations of alanine transaminase (ALT)—a liver enzyme that increases in response to liver cell death13—may be observed, ALT testing is commonly used to monitor disease progression or liver function recovery after treatment, rather than in the diagnosis of HCV infection or disease.
Importantly, although chronic hepatitis C infection is generally thought of as primarily affecting the liver, it can manifest as health problems throughout the body. Chronic hepatitis C can give rise to insulin resistance and diabetes, autoimmune conditions, and some non-liver cancers, such as lymphoma. Recent studies revealed associations between HCV infection and cardiovascular, kidney, and central nervous system diseases.1 About three-quarters of those with chronic hepatitis C develop these non-liver manifestations.16
Within the first 20 years of infection, advanced liver disease may develop. During this timeframe, roughly 10‒15% of patients develop cirrhosis of the liver—the replacement of healthy liver tissue by dysfunctional fibrous tissue and nodules.13,14
Up to 4% of patients with HCV-related liver cirrhosis develop liver cancer each year.17 Liver cancer may be suspected in someone with advanced HCV-related liver cirrhosis who experiences sudden weight loss, elevated liver function tests, or pain or fullness in the right upper abdomen.18
More than a third of liver transplants are a consequence of hepatitis C.19,20 Although five-year survival following transplant is good (up to 85%), hepatitis C patients who receive liver transplants can have a recurrence of the infection.20,21
Iron Overload and HCV
HCV-induced oxidative stress appears to disrupt iron balance by suppressing levels of a hormone called hepcidin, which is a regulator that helps control iron absorption.22-24 Low hepcidin levels lead to increased iron accumulation in the liver24,25; this is common in HCV.26-28 Excess iron in the liver may, in turn, create more oxidative stress, causing liver injury and fibrosis.29,30
In a study of the impact of iron overload on oxidant/antioxidant systems, scientists found evidence that the HCV core protein inhibits iron-induced activation of antioxidants in the liver, exacerbating oxidative stress, which could facilitate the development of liver cancer.31 Hepatic iron depletion has been postulated to decrease the risk of hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C.23
Phlebotomy (ie, therapeutic bloodletting) to reduce iron levels significantly improves liver enzyme levels in HCV patients32 and yields histological improvements33 as well as increased response to interferon treatment.34-36 Additional findings suggest iron depletion may lower the risk of developing hepatocellular carcinoma.37
At a minimum, most hepatitis C patients should avoid supplements containing iron and seek to reduce dietary sources of iron such as red meat. Vitamin C facilitates iron absorption while calcium and green tea impede it. Hepatitis C patients should take vitamin C at a different time than when eating iron-rich foods.