Disease Progression

Advanced cirrhosis in a human liver

The symptoms of hepatitis C are sometimes very difficult to recognize. In a significant proportion of patients they are progressive in nature at some stage. They can be very mild, at least in the early stages of infection.

Just like HBV infection, acute infection may frequently be remarkably asymptomatic, but sometimes presents with major symptoms. Fatigue may be prominent. Other symptoms include mild fever, muscle and joint aches, nausea, vomiting, loss of appetite, vague abdominal pain, and sometimes diarrhea. Many cases go undiagnosed because the symptoms are suggestive of a flu-like illness which just comes and goes, or these symptoms are so mild that the patient is unaware of anything unusual. A minority of patients notice dark urine and light colored stools, followed by jaundice in which the skin and whites of the eyes appear yellow. Itching of the skin may be present. Some people may loose 5 to 10 pounds, at least in part due to mal-absorption of food due to disturbed liver functions in addition to diminished appetite.

The most common symptom of chronic disease is fatigue.

Individuals infected with HCV are often identified because they are found to have elevated liver enzymes on blood testing as part of a routine health check-up, or because a hepatitis C antibody is found to be positive at the time of blood donation or insurance check-up. Usually, elevated liver enzymes and a positive antibody test for HCV (anti-HCV) mean that an individual has chronic hepatitis C. We refer further to the section on diagnosis of HCV.

A bigger percentage of patients than previously thought, and in particular the younger, may clear the virus during acute hepatitis C. They have positive anti-HCV test but their HCVRNA disappears. They are identified by HCVRNA absence in the blood when seen years later. If such patients have elevated enzymes, other causes need to be considered.

A mild inflammatory response in which the infected individual is virtually asymptomatic but with potentially a high level of virus in the blood, may continue for years, even decades, before progressing significantly. More than 50-85% of infected individuals develop chronicity. In some 20-30% of patients, this may eventually result in cirrhosis (scarring of the liver tissue), and clinically in end-stage symptomatic liver disease. This appears to take, on average, about 20-30 years to develop. However, up to 1/3 may not develop significant liver damage at all, even after years.

Symptoms of advanced liver disease may include fluid retention in the abdomen (ascites) and legs (peripheral edema), variceal hemorrhage (bleeding from varicose veins in esophagus or stomach), or impaired mental function, subtle with sleep disturbances or full-blown liver coma due to failure of detoxification of the blood by the liver. If the patient with chronic disease turns yellow (jaundice), this tends to be a very concerning symptom with a variety of more serious explanations.

Some patients with cirrhosis (scarring and nodule formation) may clinically do well for years, while others may deteriorate. The risk of liver cell cancer (hepatocellular carcinoma, HCC) increases over time.

Other organ involvement may be associated with hepatitis C infection. This includes thyroid function, painful joint and skin complaints caused by abnormal proteins (cyroglobulins), a disease called porphyria cutanea tarda and associated with disturbed liver metabolism of porphyrins, renal disease albeit rarely major renal function impairment and certain blood disorders.

Importantly, the disease outcome is strongly influenced by co-morbid problems such as alcohol abuse, poorly controlled diabetes, iron accumulation in the liver and severe obesity.