Disease Course and Outcomes
The first six months of HCV infection encompass the acute phase (Chakravarty 2010). 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 20% to 30% of adults with acute HCV infection may develop clinical symptoms. The symptomatic onset ranges from 3 to 12 weeks after exposure (Chen 2006; Dooley 2011). Patients may experience fever, fatigue, tenderness in the liver area, nausea or decreased appetite, and jaundice (Chakravarty 2010; Chen 2006).
Approximately 75%-85% of HCV-infected persons will progress to chronic HCV infection (Chen 2006).
The chronic phase is generally established when HCV genetic material (RNA) persists in the patient's serum for 6 months or more (Dooley 2011; Chen 2006).
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 appears to be more likely to persist in patients co-infected with HIV (Chen 2006; Dooley 2011).
Although the disease is transmittable during the chronic phase through blood, HCV carriers may not recognize they have an infection for up to 20 years because symptoms during this time are often mild (NIH-NDDIC 2012).
While elevations of alanine transaminase (ALT) - a liver enzyme that increases in response to liver cell death (Chen 2006) - may be observed, at least one-third of patients may exhibit normal levels (McDonald 2010). Eventually, nonspecific symptoms such as fatigue usually prompt the patient to visit a physician.
Within the first 20 years of infection, advanced liver disease may develop. During this timeframe, roughly 10% to 15% of patients develop cirrhosis of the liver – the replacement of healthy liver tissue by dysfunctional fibrous tissue and nodules (Dooley 2011; Chen 2006).
Up to 4% of patients with HCV-related liver cirrhosis develop liver cancer each year (Cheifetz 2011). Liver cancer may be suspected in someone with advanced HCV-related liver cirrhosis that experiences sudden weight loss, elevation in liver function tests, or pain or fullness in the right upper abdomen (Hepatitis C Technical Advisory Group 2005)
More than a third of liver transplants are a consequence of hepatitis C (Angelico 2011; Gordon 2009). Although five year survival following transplant is good (up to 85%), most hepatitis C patients who receive liver transplants have a recurrence of the virus (Gordon 2009; Narang 2010).
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 (Fujita 2007; Miura 2008; Nishina 2008). Low hepcidin levels lead to increased iron accumulation in the liver (Nishina 2008; De Domenico 2007); this is common in HCV (Girelli 2009; Tsochatzis 2010; Fujinaga 2011). Excess iron in the liver may, in turn, create more oxidative stress, causing liver injury and fibrosis (Price 2009; Fujita 2008).
In a study of the impact of iron overloading on oxidant/antioxidant systems, scientists found evidence that HCV core protein inhibits iron-induced activation of antioxidants in the liver, exacerbating oxidative stress, which could facilitate the development of liver cancer (Moriya 2010). Hepatic iron depletion has been postulated to decrease the risk of hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C (Miura 2008).
Phlebotomy (i.e., therapeutic bloodletting) to reduce iron levels significantly improves liver enzyme levels in HCV patients (Sumida 2007) and yields histological improvements (Sartori 2011) as well as increased interferon efficacy in interferon non-responders (Di Bisceglie 2000; Alexander 2007). A comprehensive review concluded that phlebotomy enhanced patient response to interferon treatment (Desai 2008). Additional findings suggest iron depletion may lower the risk of developing hepatocellular carcinoma (Kato 2007).
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 their vitamin C at a different time than when eating foods with high iron levels.