A histopathological study of the effects of 6-month versus 12-month interferon alpha-2b therapy in chronic hepatitis C.
OBJECTIVE
Interferon therapy has been shown to have beneficial effects in chronic hepatitis C, but the optimal duration of treatment has not been clearly defined. The aims of this study were: (a) to perform a detailed histological comparison of the effects of a 6-month and a 12-month treatment using the Knodell score as well as a recently proposed grid of analysis, (b) to determine possible histological predictive factors of response to therapy, and (c) to attempt to relate histological and biochemical modifications.


METHODS
Liver biopsies obtained before and 18 months after beginning of treatment were therefore compared in 26 patients treated for 6 months, and in 34 patients treated for 12 months.


RESULTS
Six months of treatment induced a significant decrease in periportal (p = 0.02) and intralobular (p = 0.004) hepatocyte necrosis. The same items were improved in the 12-month-treated patients but, in addition, portal inflammation (p = 0.01), bile duct lesions (p = 0.03), lymphoid aggregates (p = 0.002) and fibrosis (p = 0.008) were also improved, according to the Knodell score. Low scores for fibrosis, steatosis and cholangiolar proliferation on the pretreatment liver biopsy could be considered predictive factors for alanine aminotransferase normalization at 6 months. There was no relationship between biochemical response and modification of fibrosis.


CONCLUSIONS
Our results suggest that: (a) a decrease in fibrosis might be detected only after a 12-month interferon treatment, and (b) initial fibrosis, cholangiolar proliferation and steatosis are predictive of a lack of biochemical response. The absence of a relation between biochemical response and evolution of fibrosis implies that the evaluation of treatments in chronic hepatitis C should always include a detailed histopathological study.
Ziol
M
M
Services d'Anatomie et de Cytologie Pathologiques et d'Hépatologie, Hôpital Henri Mondor, Créteil, France.
Nhieu
J T
JT
Roudot-Thoraval
F
F
Métreau
J M
JM
Deugnier
Y
Y
Dhumeaux
D
D
Zafrani
E S
ES
D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002455:Cell Division / Q000187:drug effects; D002908:Chronic Disease; D005218:Fat Necrosis / Q000473:pathology / Q000628:therapy; D005500:Follow-Up Studies; D006526:Hepatitis C / Q000201:enzymology / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000473:pathology / Q000628:therapy; D009336:Necrosis; D011237:Predictive Value of Tests; D011994:Recombinant Proteins; D012044:Regression Analysis; D016896:Treatment Outcome; D005723:gamma-Glutamyltransferase / Q000097:blood
D000998:Antiviral Agents; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase