Gilbert's syndrome and antiviral therapy of hepatitis C.
Treatment of chronic hepatitis C with type I interferons and ribavirin can be associated with exacerbation of hepatitis and sometimes liver decompensation. We report two patients with chronic hepatitis C virus infection who experienced a severe increase of bilirubin levels of up to 17 times upper the limit of normal value in the absence of deterioration of hepatic function during therapy with pegylated-interferon and ribavirin. A genetic disposition for Gilbert's syndrome explained the adverse events and permitted a continuation of therapy leading to a sustained clearance of chronic hepatitis C infection. Since one patient jaundiced already during a lead-in treatment period with ribavirin monotherapy we suggest that hyperbilirubinaemia during combination therapy is primarily caused by ribavirin rather than by effects of interferon alpha on UDP-glucuronosyltransferase activities. Of note, both patients recovered from their initial unconjugated hyperbilirubinemia despite continuation of ribavirin therapy, which indicates that compensatory mechanisms leading to a normalization of UGT1A1 activity are likely.
Deterding
Katja
K
Dept. of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Grüngreiff
Kurt
K
Lankisch
Tim O
TO
Potthoff
Andrej
A
Bahr
Matthias J
MJ
Manns
Michael P
MP
Wedemeyer
Heiner
H
Strassburg
Christian P
CP
D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005878:Gilbert Disease / Q000139:chemically induced* / Q000175:diagnosis / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced* / Q000175:diagnosis / Q000235:genetics; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b