Table E13Evidence table of the studies that examined the association between changes in intermediate outcomes to predict treatment effectiveness (n=4)

Surrogates Outcomes
Decompensation
(Liver failure)
CirrhosisHCCLiver-related mortalityAll cause mortality
Chronic hepatitis B Interferon alpha vs. untreated127
ALT normalization during treatment*RR 0.24 (.10–.59)RR 0.24 (.08–.69)
HBV DNA detectable end of treatment
Worsening histology
Change in HBeAg status
HBsAg seroconversion
Drug Resistance
HBeAg positive chronic hepatitis B Interferon alpha 2a vs. untreated128
ALT normalization during treatment
HBV DNA detectable during/ end of treatment§OR 1.58 (1.12– 2.25)
Worsening histology
Change in HBeAg status
HBsAg seroconversion
Drug resistance
HBeAg positive chronic hepatitis B All treated with peginterferon alpha 2a or 2b129
Lamivudine plus peginterferon alpha 2b vs. lamivudine117
ALT normalization during treatment
HBV DNA detectable at end of treatment#OR 3.08 (0.44– 22.7)
Worsening histology&RR 5.56 (1.12– 27.62)
Loss of HBeAg end of treatmentORˆ 0.6 (0.03–9.01)
O% 0.81 (0.09– 7.64)
HBsAg seroconversion
Drug Resistance
*

Adjusted for age, cirrhosis at baseline and interferon alpha treatment. Combined endpoint of decompensation includes ascites, jaundice, encephalopathy, portal hypertensive bleeding and HCC & 2 point increase in modified HAI on serial liver biopsies. Combined clinical outcome of ‘Liver complications’ reported including decompensated cirrhosis and HCC. Multivariate analysis, adjusted for ‘other risk factors.’

§

HBV DNA pattern1 (always or frequently > 10 pg/ml). OR from multivariate analysis adjusted for age, HBeAg at baseline and interferon alpha treatment for composite end point of ‘disease progression’ defined as progression to cirrhosis, decompensation or HCC.

4

HBV DNA ≥10 copies/ml at 24 weeks after end of treatment. Unadjusted OR; calculated from frequencies reported in table.

ˆ

Unadjusted OR calculated from reported frequencies for cohort of patients treated with lamivudine plus peginterferon alpha-2b

%

Unadjusted OR calculated from reported frequencies for cohort of patients treated with lamivudine alone

From: Appendix E Tables and Figures

Cover of Management of Chronic Hepatitis B
Management of Chronic Hepatitis B.
Evidence Reports/Technology Assessments, No. 174.
Wilt TJ, Shamliyan T, Shaukat A, et al.

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