Chronic hepatitis C: diagnosis

Laboratory diagnostics of chronic hepatitis C

At the time of referral, serum transaminase activity rarely exceeds the upper limit of normal by 6 times, on average it is approximately 3 times higher than normal. Serum transaminase activity does not reflect the degree of changes in the liver; it can be normal with repeated determination, despite significant morphological changes. However, if it is more than 10 times higher than the upper limit of normal, this suggests the presence of chronic hepatitis with necrotic and inflammatory changes.

Serum albumin and bilirubin levels are usually normal at presentation and increase slightly over time. Prothrombin levels are unchanged.

The serum HCV-RNA concentration is essential for assessing contagiousness and monitoring treatment outcomes. Quantitative methods such as branched-chain DNA (rDNA) assays are used in diagnostics but have low sensitivity. Their results require confirmation by PCR. If HCV-RNA is present in the blood, liver biopsy will usually reveal changes. Serum HCV-RNA concentrations exceeding 10 ⁵ molecular equivalents (copies) per ml are observed in the active phase of the disease and coincide with peaks in transaminase activity.

Serum anti-core-HCV IgM can serve as a criterion for assessing the effectiveness of treatment.

If possible, the genotype of the virus should be determined. Type 1b is associated with a more severe course, poor response to antiviral drugs, relapse after liver transplantation, and the possibility of developing cancer. Type 4 is characterized by resistance to antiviral treatment.

In the differential diagnosis of chronic hepatitis C with autoimmune chronic hepatitis, especially when IFN therapy is being considered, blood should be tested for autoantibodies.

For early detection of hepatocellular carcinoma in patients with liver cirrhosis, especially in men over 40 years of age, the level of serum alpha-fetoprotein is determined every 6 months and an ultrasound of the liver is performed.

Histological examination of the liver

The histological picture is not pathognomonic, but characteristic changes are often revealed. A distinctive feature are lymphoid aggregates or follicles in the portal tracts, which can be either isolated or part of inflammatory changes in the portal tracts. The core of the aggregates consists of B cells in combination with many T helpers/inducers and is surrounded by a ring formed mainly of T suppressors of cytotoxic lymphocytes. In terms of cellular composition, these aggregates resemble primary lymphoid follicles in the lymph nodes. Their formation is not accompanied by manifestations of the autoimmune process. The degree of involvement of the bile ducts in different series of studies was different. Interstitial hepatitis occurs in a mild form, although it is usually accompanied by intralobular cellular infiltration. Fatty degeneration is detected in 75% of cases, its mechanism is unclear. The picture of mild chronic hepatitis is characteristic. Chronic hepatitis may be associated with liver cirrhosis, or histological examination reveals a picture of inactive liver cirrhosis. The changes are not associated with the duration of the disease or the activity of serum transaminases at presentation. Liver biopsy plays an important role in clarifying the diagnosis and assessing the activity and stage of the disease. Repeated biopsies are apparently justified only in the case of scientific research, otherwise there is no need for them.

HCV-RNA can be detected in liver tissue using PCR.

Immunological diagnostics of chronic hepatitis C

Approximately 5% of patients with autoimmune hepatitis have a false-positive anti-HCV test, and approximately 10% of patients with hepatitis C have circulating autoantibodies. However, these conditions are fundamentally different. The clinical picture of hepatitis C does not change in the presence of autoantibodies.

An association has been found between HCV infection and a positive LKM I test. This may be due to the presence of cross-antigenic determinants in chronic HCV infection and autoimmune chronic active hepatitis with LKM 1, although detailed analysis has shown that these determinants are different from each other. There are clinical differences between these two types of hepatitis. HCV infection usually affects older men and those with a low LKM I titer.

Anti-GOR are autoantibodies against host proteins found in LKM 1-positive patients with chronic hepatitis C. They have no clinical significance.

Autoimmune hepatitis can be initiated by interferon in patients with chronic HCV infection. It is impossible to predict this by the level of autoantibodies before treatment. Autoimmune hepatitis is manifested by sudden increases in the activity of serum transaminases and autoantibody titers. Immunosuppressive therapy is effective.

The detection of autoantibodies in patients with anti-HCV and HCV-RNA may lead to difficulties in choosing treatment: immunosuppressive therapy, which is responded to by patients with true chronic autoimmune hepatitis, or antiviral therapy for those infected with HCV.

Comparative characteristics of autoimmune hepatitis and chronic hepatitis C

Indicator	Autoimmune hepatitis	Hepatitis C
Age	Young and middle	Any
Floor	Predominantly female	Uniform distribution
AsAT activity:
10 times higher than normal	Usually	Rarely
"fluctuates"	Very rarely	Usually
HCV-RNA	Absent	Present
Contact with blood	Absent	Often
Response to corticosteroids	Rapid decrease in serum transaminase activity	Absent or weak

Differential diagnosis of chronic hepatitis C

It is necessary to exclude the role of all possible hepatotoxic drugs in the development of the disease.

There should be no markers for hepatitis B. However, in some patients with chronic hepatitis B, with very low, undetectable titers of HBsAg and HBV DNA, an erroneous diagnosis of hepatitis C is possible.

Chronic autoimmune hepatitis is indicated by very high activity of serum transaminases and gamma globulin levels in combination with high titers of autoantibodies in the serum.

Wilson's disease should be excluded.

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