Hepatitis C: Treatment: Management and Determination of Response

Determining drugs and dosage:

o combination therapy with interferon and ribavirin is treatment of choice,
o ribavirin alone is not effective and should not be used,
o monotherapy with interferon may be necessary if there are contradictions to ribavirin,
o usual dose of interferon is 3 million units subcutaneously three times a week,
o starting dose of interferon may be less if platelets are low, (below 80,000)
o dose of interferon may be gradually increased if started at less than 3 million units three times a week while monitoring the platelets,
o dose of ribavirin is weight related, 1200 mg a day in divided doses twice a day if weight is over 75 kilograms, dose of 1000 mg a day in divided doses twice a day if weight is below 75 kilograms
o ribavirin should be taken with food

Dose alteration during therapy:

o experience required in managing patients since the disease is complex and the side effects of treatment so wide and sometimes subtle
o if platelets fall below 70,000 the dose of interferon should be reduced to 2 million units three times a week,
o if platelets fall below 60,000 the dose of interferon should be reduced to 1 million units three times a week,
o if platelets fall below 50,000 interferon should be stopped,
o if the WBC count falls below 1,500 the dose of interferon should be reduced to 2 million units three times a week,
o if the WBC count falls below 1,000 interferon should be stopped,
o if the hemoglobin falls below 100 mg the ribavirin dose should be reduced by 50%,
o if the hemoglobin falls below 85 gm the ribavirin should be discontinued,
o patients with a cardiac history should only be treated by a specialist.

Management of associated conditions:

o headache or fever may be treated with small doses of acetaminophen, the maximum amount recommended is 1000 milligrams a day,
o muscle pain may be treated with ketoprofen or ibuprofen,
o depression may be treated with anti-depressants,
o menopausal symptoms may be treated with low dose estrogens,
o anxiety may be treated with benzodiazepines

Indications to stop treatment:

o development of inter-current bacterial infection,
o occurrence of any cardiac symptoms such as angina, arrhythmia’s, etc.,
o development of significant depression including suicidal thoughts,
o progressive weight loss,
o development of significant quto-immune disease,
o platelets falling below 50,000,
o hemoglobin falling below 80 grams,
o development of any signs of hepatic decompensation or hepatic failure.

Determination of a response:

o response is defined as:
­ normalization of serum AST and ALT
­ a negative HCV RNA
­ absence of inflammation at liver biopsy
­ resolution of symptoms

The aim of treatment is a SUSTAINED response:

o a sustained response is determined six months after completion of therapy,
o a number of patients who have an end of treatment response will relapse,
o a relapse usually occurs within the first six months after completion of therapy,
o patients achieving a sustained response at six months after completion of therapy usually maintain a sustained response for two years and possibly indefinitely.

Post treatment monitoring:

o check serum AST and ALT at three months post treatment,
o check serum AST, ALT and HCV RNA at six months post therapy,
o check serum AST and ALT at 12 and 24 months post therapy,
o if serum AST and ALT rise above normal check HCV RNA.

Predictors of a Favourable response:

o while there are predictors of a favourable response, patients should still be treated since there is still a percentage of patients who will still respond. (Newsletter Volume 1, Number 4)
­ early normalizations of enzymes
­ rapidity of fall of HCV RNA
­ negative HCV RNA at four months
­ subtypes 2 and 3
­ minimal fibrosis on liver biopsy

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