Time course of histological changes in patients with a sustained biochemical and virological response to corticosteroid withdrawal therapy for chronic hepatitis B.
OBJECTIVE
Although biochemical and virological responses to corticosteroid withdrawal therapy for chronic hepatitis B have been extensively studied, long term changes in liver histology have not been well documented.


METHODS
We retrospectively analyzed 45 paired liver biopsy specimens taken before and after treatment from 40 patients who persistently showed biochemical remission and an absence of HBe antigen (RIA) for up to 20 yr.


RESULTS
The grading scores for necroinflammatory and fibrotic activity in the liver specimens decreased significantly after corticosteroid withdrawal therapy. Histological scores graded according to Knodell's components improved significantly in every category after corticosteroid withdrawal therapy. However, inflammatory cell infiltrates remained within the liver for long periods. The disappearance rate of necroinflammation in the periportal, lobular, and portal regions of the liver were 25%, 7.4%, and 7.4%, respectively, at yr 5 after therapy, and were 84.4%, 78.2%, and 58.7%, respectively, at yr 10 after therapy. The cumulative disappearance rate, calculated using the Kaplan-Meier method, was significantly lower for portal inflammation than for periportal necroinflammation.


CONCLUSIONS
Our results show that: 1) despite clinical remission of chronic hepatitis B virus infection, long periods are needed for histological resolution of necroinflammation in the liver; and 2) by a Cox proportional hazard analysis of the factors contributing to histopathological disappearance of disease-related inflammation, the degree of fibrosis of liver biopsy specimens from pretherapy patients was the most statistically significant factor (p = 0.049).
Arase
Y
Y
Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan.
Ikeda
K
K
Murashima
N
N
Chayama
K
K
Tsubota
A
A
Koida
I
I
Suzuki
Y
Y
Saitoh
S
S
Kobayashi
M
M
Kobayashi
M
M
Kumada
H
H
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001706:Biopsy; D016001:Confidence Intervals; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology* / Q000821:virology; D008103:Liver Cirrhosis / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D009336:Necrosis; D016017:Odds Ratio; D011239:Prednisolone / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012074:Remission Induction; D012189:Retrospective Studies; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D011239:Prednisolone; D000410:Alanine Transaminase