Combination antiretroviral therapy (cART) was associated with more improvements than declines in liver fibrosis score in HIV-infected patients with or without hepatitis coinfections, according to a study.
Liver disease is a leading cause of non-Aids morbidity and mortality in individuals living with HIV, especially patients who are coinfected with hepatitis C virus (HCV) or hepatitis B virus (HBV). While liver fibrosis can result from HIV infection alone, the presence of HCV or HBV accelerates its progression. Previous studies have demonstrated conflicting results on the effect of cART on liver fibrosis. Some studies have shown improvement in liver fibrosis scores; others have shown decline, particularly in HIV/HCV co-infected cohorts.
Dr Yingying Ding, of Shanghai China's Fudan University, and colleagues undertook a retrospective cohort study of HIV-infected patients treated with cART from 2004 to 2016. Patients with HIV alone as well as patients co-infected with HBV and/or HCV were included in the cohort. Ultimately, 3,900 patients met the criteria for inclusion in the analysis.
The researchers classified the patients into 3 categories using the Fibrosis-4 (FIB-4) index, an inexpensive, noninvasive marker of liver fibrosis (class 1, <1.45; class 2, 1.45˗3.25; class 3, >3.25). They then determined which patients changed from baseline to a lower or higher FIB-4 class in at least 2 subsequent measurements and showed how demographic variables, disease characteristics, medication regimens, and laboratory values were associated with these changes.
Results showed that 52.6% of patients in class 2 and 74.2% of patients in class 3 improved to a lower class, while 12.8% of patients in class 1 and 5% of patients in class 2 progressed to a higher class. Older age, male, Dai ethnicity, injection drug use, HCV co-infection, and tenofovir therapy were negatively associated with improvement to lower classes; a class 3 status at baseline and time-updated increases in CD4 count from baseline were positive predictors. For progression to higher classes, older age, male, Jingpo ethnicity, and HCV co-infection were positive predictors, while baseline CD4 count and class 2 status at baseline were negative predictors.
A decreased risk of mortality was noted in class 3 patients who improved to a lower class. "This suggests that reductions in liver fibrosis score in patients with severe liver fibrosis would provide survival benefit for them," wrote the authors. "Therefore, special attention should be given to those without significant reductions in liver fibrosis shortly after treatment, and their treatments should be reviewed and may be revised."
"Several clinical implications emerged from this study," the investigators concluded. "First, cART initiation particularly at early stage is associated with an overall reduction in liver fibrosis in HIV-infected patients with and without hepatitis co-infections. Second, most improvements of liver fibrosis associated with treatment occur shortly after treatment, thus for those without significant reductions in liver fibrosis shortly after treatment, their treatments should be reviewed and may be revised. Third, the hepato-toxicity associated with cART should be monitored from treatment initiation until the end of treatment [and] special attention should be given to those who are older, male, (and) co-infected with HCV.”
Abstract
We examined the effect of combination antiretroviral therapy (cART) on liver fibrosis among HIV-infected patients with or without Hepatitis B (HBV) or C virus (HCV) co-infection. This was a retrospective cohort study of HIV-infected patients receiving cART during 2004–2016. Liver fibrosis was assessed using Fibrosis-4 (FIB-4) score with 3 classifications: Class 1, < 1.45; Class 2, 1.45˗3.25; Class 3, > 3.25. Of 3,900 participants, 68.6% were HIV mono-infected, 5.3% were HIV/HBV co-infected, 23.8% were HIV/HCV co-infected and 2.3% were HIV/HBV/HCV co-infected. Participants received follow-up treatment (median was 3.3 years). Improvement to a lower class was observed in Class 2 (52.6%) and Class 3 (74.2%), respectively. Progression to a higher class was observed in 12.8% and 5.0% in Class 1 and Class 2, respectively and with a median time of 5.7 months. For improvement to lower classes, older age, male, Dai ethnicity, injection drug use, HCV co-infection, and tenofovir for treatment were negative predictors, but in Class 3 of FIB-4 and time-updated increases in CD4 count from baseline was positive predictors. For progression to higher classes, older age, male, Jingpo ethnicity and HCV co-infection, were positive predictors, while baseline CD4 count and in Class 2 of FIB-4 were negative predictors. Improvement to lower class linked with decreased mortality risk among patients in Class 3. Early cART initiation for HIV-infected patients with and without hepatitis co-infections may mitigate or slow down some of liver fibrosis, but special attention should be given to those who are older, male, co-infected with HCV.
Authors
Yingying Ding, Song Duan, Runhua Ye, Yuecheng Yang, Shitang Yao, Jibao Wang, Dongdong Cao, Xing Liu, Lin Lu, Manhong Jia, Zunyou Wu, Na He
[link url="http://www.infectiousdiseaseadvisor.com/hivaids/art-improves-liver-fibrosis-in-hiv/article/631071/"]Infectious Disease Advisor material[/link]
[link url="http://onlinelibrary.wiley.com/doi/10.1111/jvh.12658/abstract"]Journal of Viral Hepatitis abstract[/link]