Indications and contraindications for treatment of hepatitis C virus infections

Treatment indications

All patients with chronic hepatitis C virus (HCV) infections are considered prospects for antiviral treatment to prevent progression of liver damage to cirrhosis or hepatocarcinoma. The consensus is that such treatment must entail a combination of interferon alfa and rivabirin. ^1,3 Treatment is indicated for anti-HCV-positive, HCV RNA-positive patients with increased serum aminotransferase levels and for whom there is histological evidence of chronic hepatitis, provided there are no specific contraindications. ⁴ The following should be taken into consideration when deciding whether to initiate treatment: age, comorbidities, extrahepatic manifestations such as cryoglobulinemia and glomerulonephritis, and quality of life.⁵ It is important to note that decisions on whether treatment should be implemented must not be based on the way in which the CHV was acquired or the presence or absence of symptoms. Whether HCV genotypes or HCV RNA levels are valid indicators for treatment is the subject of debate.

Patients with genotypes 2 and 3 may be treated at any stage of the disease because of the high frequency of sustained virological response in these patients.⁶

Patients with liver cirrhosis and hepatitis C who comply with the criteria mentioned previously and who have no clinical history of decompensation such as ascites, bleeding varices, severe malnutrition, or grossly abnormal laboratory indexes are also prospects for treatment.

The decision to initiate a treatment must be made on an individual basis for patients who are older than 65 years, have persistently normal aminotransferase levels, display no histological evidence of fibrosis or portal fibrosis (Metavir 1),⁷ have HIV or HBV coinfection,⁸ or fail to respond to or relapse from treatment with nonpegylated interferon alfa with or without ribavirin. In the last-mentioned instance, it is advisable to obtain histological evidence of the grade of fibrosis or cirrhosis before making a decision.

Hepatitis C patients who are prospects for renal transplantation should undergo treatment prior to transplantation. As frequent adjustments of drug doses are required for patients with chronic renal failure, it is advisable to obtain histological confirmation of the stage of liver disease.⁹

Antiviral treatment of patients awaiting liver transplantation may be considered to stabilize or improve liver function. In liver transplant patients with reinfected grafts, the trend is to initiate treatment at an early stage to prevent the progression of this condition. In such cases, it is necessary to take a liver biopsy. Treatment is often extended for longer than usual. The issue of maintenance therapy with long-term follow-ups is still the subject of research.¹⁰

Treatment of children with hepatitis C should be carried out in controlled clinical studies.

At present, treatment of cases of acute hepatitis C with pegylated interferon or interferon alfa monotherapy is considered justified.¹¹

Contraindications

Treatment is not recommended for hepatitis C patients with clinically decompensated liver cirrhosis. Treatment is contraindicated in the presence of pregnancy, severe depression, significant neuropsychiatric syndromes, alcohol abuse, drug addiction, active autoimmune diseases such as lupus erythematosus, rheumatoid arthritis or psoriasis, severe anemia, liver failure, failure to apply contraceptive measures during treatment, uncompensated dysthyroidism, recent organ transplantation.^12,13

The issues and recommendations of the consensus panel are as follows

1. Who are the ideal prospects for treatment?

Patients who are anti-HCV positive and have persistently elevated ALT levels and viral loads with a diagnosis of chronic hepatitis or liver cirrhosis child A associated to platelet levels higher than 75,000. hemoglobin > 12 g/dL. Patients without preexisting neutropenia and in whom there is an absence of decompensated associated diseases.

The quality of evidence for this recommendation was given a rating of 2

Combined antiviral treatment (Pegylated interferon plus Ribavirin) is contraindicated in instances of:

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  decompensate psychiatric disease,

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  decompensate diabetes mellitus,

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  decompensate arterial hypertension,

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  decompensate hemoglobinopathy,

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  decompensate autoimmune diseases,

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  immunosuppressive treatment (nontransplanted patients),

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  thrombocytopenia (< 50,000 platelets per microliter), and

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  neutropenia (< 750 cells per milliliter).

The quality of evidence for this recommendation was given a rating of 2

Special indications

Patients with neutropenia (< 750 cells per milliliter), thrombocytopenia (< 50,000 platelets per microliter) and other hematological pathologies in transplant and research programs must be treated individually by physicians with experience in the management of such patients.

The quality of evidence for this recommendation was given a rating of 3

Should patients receiving immunosuppressive treatment for pathologies other than liver transplants (e.g., lupus and renal transplants) be considered for treatment?

Such patients should be given the opportunity of treatment. However, they should be treated by physicians with experience in the management of this type of patient.

The quality of evidence for this recommendation was given a rating of 2

Which physicians should treat patients infected with HCV?

Gastroenterologists, internists, infectologists, and hepatologists with experience in the management of these patients.

The quality of evidence for this recommendation was given a rating of 3