Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study

Angela Chau,Masatoshi Ishigami,Seng Gee Lim,Akito Nozaki,Toru Ishikawa,Yuichiro Eguchi,Yong Kyun Cho,Keigo Kawashima,Takanori Suzuki,Sung Eun Kim,Dae-Won Jun,Mindie H Nguyen,Hiroshi Abe,Jae Yoon Jeong,Takanori Ito,Ramsey Cheung,Haruki Uojima,Eileen L Yoon,Makoto Chuma,Jihyun An,Daniel Q Huang,Hirokazu Takahashi,Hyoung Su Kim,Tsunamasa Watanabe,Soung Won Jeong,Sang Bong Ahn,Sebastián Marciano,Yasuhito Tanaka,Joseph Hoang ,Huy N Trinh ,Yao–Chun Hsu ,Ming‐Lung Yu ,Chung‐Feng Huang ,Chia‐Yen Dai ,Jee‐Fu Huang ,Wan‐Long Chuang ,Cheng‐Hao Tseng ,Adrián Gadano ,Manabu Maeda ,Hongseob Oh ,Ming‐Lun Yeh ,Pei‐Chien Tsai ,Kaori Inoué ,Jae‐Jun Shim

doi:10.1016/j.cgh.2023.09.002

Abstract

It is unclear if there may be sex differences in response to nucleos(t)ide analogs including virologic response (VR), biochemical response (BR), complete response (CR), and hepatocellular carcinoma (HCC) incidence among hepatitis B patients. We compared nucleos(t)ide analog treatment outcomes by sex. We performed a retrospective cohort study of 3388 treatment-naïve adult hepatitis B patients (1250 female, 2138 male) from the Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus consortium who initiated therapy with either entecavir or tenofovir from 22 sites (Argentina, Korea, Japan, Taiwan, and the United States). We used propensity-score matching to balance background characteristics of the male and female groups and competing-risks analysis to estimate the incidence and subdistribution hazard ratios (SHRs) of VR, BR, CR, and HCC. Females (vs males) were older (52.0 vs 48.6 y); less likely to be overweight/obese (49.3% vs 65.7%), diabetic (9.9% vs 13.1%), or cirrhotic (27.9% vs 33.0%); and had a lower HBV DNA level (5.9 vs 6.0 log10 IU/mL) and alanine aminotransferase level (91 vs 102 IU/L) (all P < .01). However, after propensity-score matching, relevant background characteristics were balanced between the 2 groups. Females (vs males) had similar 5-year cumulative VR (91.3% vs 90.3%; P= .40) and HCC incidence rates (5.1% vs 4.4%; P= .64), but lower BR (84.0% vs 90.9%; P < .001) and CR (78.8% vs 83.4%; P= .016). Males were more likely to achieve BR (SHR, 1.31; 95% CI, 1.17-1.46; P < .001) and CR (SHR, 1.16; 95% CI, 1.03-1.31; P= .016), but VR and HCC risks were similar. Sex differences exist for treatment outcomes among hepatitis B patients. Male sex was associated with a 16% higher likelihood of clinical remission and a 31% higher likelihood of biochemical response than females, while virologic response and HCC incidence were similar between the 2 groups.

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