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Hepatitis C Treatment
Once therapy has been started, the likelihood of a sustained virologic response can be predicted based upon the virologic response at 12 weeks of therapy and probably even earlier. Week 12 HCV RNA drops by > 2 logs Week 12 HCV RNA does not drop by > 2 logs Treat for 48 weeks then do HCV RNA level (and again at 72 weeks to get SVR) Consider stopping HCV RNA detected at 24 weeks HCV RNA not detected at 24 weeks Treatment failed HCV RNA at 48 weeks to get SVR Pegylated interferon: Better and better tolerated than standard interferon Effective for patients who failed prior interferon- based treatment Ribavirin: Ribavirin = nucleoside analog: inhibits replication of RNA viruses.. Mechanism: Depletes intracellular triphosphate pools by direct inhibition of inosine monophosphate dehydrogenase Inhibits 5'-cap structure of viral mRNA and viral-dependent RNA polymer - ases Alters balance between proinflamm - tory (Th1-like) and antiinflammatory (Th2-like) cytokines. Induces mutations into viral RNA. Primary ribavirin monotherapy not useful as viraemia not improved Combination therapy with pegylated interferon is preferred (better than interferon monotherapy) Combination most effective in relapsers after initial response to interferon alpha monotherapy Disease course during corticoster - oid use Increases viral load, but ALT decreases Short term course probably has no effect, and long term course may need liver biopsy Goals and long-term benefits of treatment Eradicate HCV RNA- redicted by achieve - ment of a SVR (absence of HCV RNA by PCR 6m after stopping treatment). Genotype 2 or 3 — Peginterferon + ribavirin (400mg bd) for 24 weeks Genotypes 1 and 4 : Peginterferon + ribavirin for 48 weeks. Modify treatment depending upon the response. Early virologic response=EVR Genotype’s 1 and 4
Factors Associated With a response to interferon and ribavarin: Genotype 2/3>1;Viral load. Younger age;Lower body weight. No bridging fibrosis/cirrhosis. No significant (>33 %) steatosis. No diabetes mellitus. Being African American. Contraindications: - Uncontrolled depressive illness (controlled illness not a C/I). - Renal, heart, or lung transplant recipients. - Any condition known to be exacerbated by interferon and ribavirin (eg Autoimmune hepatitis). - Untreated hyperthyroidism. - Pregnant or unwilling/unable to comply with adequate contraception. - Severe concurrent disease such as severe hypertension, heart failure, significant coronary artery disease, poorly controlled diabetes, obstructive pulmonary disease. - Younger than 3. - Known hypersensitivity to HCV drugs. Patients to Consider Treatment In: - Persistently normal ALT values (especially if acquired HCV <35 yrs old/ Male/not Tee total/ no minimal fibrosis on liver biopsy (minimal in 25% with normal ALT/ abnorm in 70%)- 40% will get a rise in ALT. - Failed prior treatment (incl. relapser) with either interferon alone or with ribavirin, or peginterferon given alone. - Drug/ alcohol abusers willing to join a substance abuse program. - Liver biopsy evidence of either no or only mild fibrosis (portal fibrosis: Metavir score <2; Ishak score <3). - Acute hepatitis C. - Coinfection with HIV. < Age 18. - Chronic renal disease (on or not on haemodialysis). - Decompensated cirrhosis. - Recipient of a liver transplant. Absolute Indications: >18 years of age. - Abnormal serum ALT values. - Liver biopsy with chronic hepatitis with significant fibrosis (more than portal fibrosis (Metavir score =2, or Ishak score =3). - Compensated liver disease (total serum bilirubin <1.5 g/dL; INR <1.5; albumin >3.4 g/dL; platelet count >75,000 k/mm(3); and no evidence of hepatic encephalopathy or ascites). - Acceptable hematological and biochemical indices (hemoglobin >13 g/dL for men and >12 g/dL for women; neutrophil count >1.5 k/mm(3); creatinine < 1.5 mg/dL). - Willing to be treated and to conform to treatment requirements. Relapsers after interferon monotherapy —Give combination therapy with ribavirin (1000 to 1200 mg/day) plus pegylated interferon. Nonresponders to interferon monotherapy —Give a trial of combination therapy if tolerated interferon monotherapy and have moderate to advanced histologic features- reponse likely to be bad Nonresponders to standard interferon ribavirin combination therapy — Options are: a) observation,b) Enrollment into a study c) Trial of 48 weeks of pegylated interferon plus ribavirin.- 20% response rate. Nonresponders to pegylated interferon ribavirin combination therapy — Observe or re-treat depending on situation Special Considerations
Written by Dr Sebastian Zeki
