Extent of liver inflammation in predicting response to interferon α & Ribavirin in chronic hepatitis C patients: a cohort study.
BACKGROUND
Liver inflammation due to HCV infection leads to fibrosis, which is an independent predictor of treatment response to interferon therapy in Chronic Hepatitis C (CHC) patients. This relationship has not been studied for liver inflammation on pretreatment liver biopsy and End of Treatment Response (ETR). ALT is a less invasive test than liver biopsy for measuring liver inflammation. Aim of this study was to compare ETR to Interferon α (recombinant Interferon) & Ribavirin in CHC patients having higher and lower grades of liver inflammation and to determine the diagnostic accuracy of pretreatment ALT for grades of liver inflammation.


METHODS
A retrospective cohort of 876 naïve CHC patients, who completed Interferon α & Ribavirin for 24 weeks, was studied for ETR. Pretreatment grade of inflammation on liver biopsy was taken as the exposure variable. It was classified as high if there was moderate or severe and low if there was minimal or mild. Multivariable logistic regression modeling was performed. Diagnostic accuracy of pretreatment ALT for liver inflammation grades was determined by computing Area Under the Receiver Operator Curve (AUROC).


RESULTS
Of all patients, 672 having diagnostic liver biopsy and ETR available were analyzed. Among them, 103 had high and 569 had low grades of liver inflammation. Mean age was 36.9 (SD 9.1) years, with patients with high grades being older than those with low grades inflammation (p = 0.03). High grades of liver inflammation was associated with ETR (RR 1.17, 95% CI 1.12-1.18) adjusting for age, Total Leukocyte count (TLC) and pretreatment levels of ALT, irrespective of liver fibrosis. This relation remained significant for 'bridging fibrosis and cirrhosis' and not for 'no' or 'portal fibrosis'. AUROC of pretreatment ALT for males and females was moderately accurate for severe inflammation compared to minimal inflammation and less accurate for high grades compared to low grades.


CONCLUSIONS
ETR in patients with higher grades of liver inflammation was 17% higher than those with lower grades irrespective of fibrosis and 9% higher for bridging fibrosis and cirrhosis. Pretreatment ALT was moderately accurate for severe inflammation only on liver biopsy in both males and females.
Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan. shirin.mirza.eb0806@student.aku.edu
Shirin
S
Mirza
Amna Rehana
AR
Siddiqui
Saeed
S
Hamid
Muhammad
M
Umar
Shaheena
S
Bashir
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000998:Antiviral Agents; D015415:Biomarkers; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin; D000410:Alanine Transaminase