Clinical Course/ Natural history

• Acute HCV Infection

Most patients, almost 80%, with acute hepatitis C infections are totally unaware as they have no symptoms at all. The clinical illness in those who seek medical care is similar to that of other types of viral hepatitis, and serologic testing is necessary to detect the exact etiology.

The average incubation period i.e. time from exposure to onset of symptoms, for this virus is 6-7 weeks and the average time from exposure to seroconversion is 8-9 weeks. 

The antibody to HCV (anti-HCV) is positive within 15 weeks in 80% and is present in 97% within six months after exposure.

However, the onset of infection is usually not recognized because symptoms are either vague or non-existent. The symptoms when present are usually mild, often described as flu-like, and tend to wax and wane over time. The patients usually have either jaundice or non-specific symptoms like anorexia, malaise or abdominal pain. 

The course of acute HCV is variable. There are no identified clinical or epidemiologic features, which can predict the course of acute HCV infection. Characteristically, the ALT levels are elevated but they fluctuate over time. Recovery without sequelae is seen only in 15% of the patients and is defined by sustained absence of HCV RNA in serum and normalization of ALT levels. The patients who do recover, do so in the first six to twelve months. However, in 85% of the patients, the ALT levels start to rise again after normalization and indicate progression to chronic disease. Fulminant hepatic failure is rare in acute cases.

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Chronic HCV Infection

Almost 85% of the patients develop chronic HCV infection and the majority of these (60-70%) have persistent or fluctuating ALT elevations indicating active liver disease. In the remaining 30-40% of the chronically infected persons, the ALT levels are normal. Since the ALT levels can fluctuate, a single determination cannot be used to exclude ongoing liver injury, and a long-term follow-up of patients is required to determine their clinical prognosis.

The course of the disease is slow and protracted. It is generally more than 20-30 years after initial infection before clinically evident chronic liver disease can be seen. Patients are usually asymptomatic and are identified during routine screening for physicals and blood donation, etc. Symptoms in chronic HCV infection (if present) are usually mild and the most common is fatigue.

Complications of Chronic HCV infection, seen after 20-30 years are usually:

Cirrhosis – 10-20%

Hepatocellular Carcinoma (HCC) – seen in 1-5% patients after 20-30 years but the incidence in patients with Cirrhosis is higher and is usually 1-4% per year (signifying more active disease) 

Mortality is a rare complication.

HCV infection has also been implicated in the pathogenesis of a number of other diseases e.g.:

Arthritis

Kerato-conjuctivitis sicca

Lichen planus

Autoimmune hepatitis

Porphyria cutanea tarda

Cryoglobulinemia

Glomerulonephritis

Non-hodgkin’s lymphoma

Some factors contributing to the extent and severity of the disease are:

Age - >40 at infection

Alcohol use – even moderate intake of alcohol such as >10g/day enhances disease progression significantly because of its ability to provoke increased viral replication and by its own additive hepatic cellular damage. Clearly, drinking of alcohol should be strongly discouraged

Ethnicity

Geography

Presence of other viral infections like – HIV and HBV

Host immune responses

Inactivation of host tumor suppressor genes(MP6/IGF2R)

Pre-existing liver disease

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Special Consideration in Children and Adolescents

Children at-risk of hepatitis C infection due to exposure to blood or blood products should be considered for screening. In children and adolescents, the primary risk factor for acquiring hepatitis C is percutaneous exposure to contaminated blood and blood products for example: 

Children receiving blood transfusion before 1992 when second generation test to check HCV antibody became available. A transfusion history may not always be documented and should be explored for children who have undergone major surgical procedures such as those for scoliosis and for congenital heart disease, or who have experienced major trauma before 1992.

Children with hemophilia who received clotting factor concentrates before 1987 when viral inactivation measures sufficient to inactivate hepatitis C were introduced.

Children with cancer, history of premature birth, or those with immune deficiency syndromes who received the infected lots of IV immune globulin product - gamma guard between April 1^st 1993 and January 23^rd 1994 - when the contaminated lots were withdrawn from the market.

Other pediatric risk groups for HCV infection include:

Dialysis patients.

Children born to HCV infected mothers - Testing of infants for anti-HCV should be performed after age 12 months, when passively transferred maternal anti-HCV declines below detectable levels. If earlier diagnosis of HCV infection is desired, RT-PCR for HCV RNA may be performed at 1–2 months. Umbilical cord blood should not be used for diagnosis of perinatal HCV infection as it can be contaminated by maternal blood.

Adolescents with high risk behaviors such as IVDA - The most common diagnosis of acute hepatitis in teenagers is acute hepatitis A. However, acute hepatitis B and C should also be considered since the signs and symptoms of all types of viral hepatitis are similar. Sometimes history of a prior transfusion or other high risk exposure may focus attention on HBV and HCV but the history should not always be relied upon as teenagers may be unwilling to divulge a history of drug abuse or high risk sexual behavior while the parent is in the room. Clinicians don’t have to rely on such information to arrive on the correct diagnosis of acute viral hepatitis and testing for the hepatitis panel can give the answers.

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