Increased hepatotoxicity among HIV-infected adults co-infected with Schistosoma mansoni in Tanzania: A cross-sectional study

Abstract

IntroductionLittle is known about hepatotoxicity in patients with schistosome and HIV co-infections. Several studies have reported increased liver enzymes and bilirubin levels associated with schistosome infection. We investigated whether HIV-infected adults on antiretroviral therapy who had S. mansoni co-infection had a higher prevalence of hepatotoxicity than those without.Methodology/Principal findingsWe determined the presence and grade of hepatotoxicity among 305 HIV-infected outpatients who had been on medium-term (3–6 months) and long-term (>36 months) antiretroviral therapy in a region of northwest Tanzania where S. mansoni is hyperendemic. We used the AIDS Clinical Trial Group definition to define mild to moderate hepatotoxicity as alanine aminotransferase, alanine aminotransferase, and/or bilirubin elevations of grade 1 or 2, and severe hepatotoxicity as any elevation of grade 3 or 4. We determined schistosome infection status using the serum circulating cathodic antigen rapid test and used logistic regression to determine factors associated with hepatotoxicity. The prevalence of mild-moderate and severe hepatotoxicity was 29.6% (45/152) and 2.0% (3/152) in patients on medium-term antiretroviral therapy and 19.6% (30/153) and 3.3% (5/153) in the patients on long-term antiretroviral therapy. S. mansoni infection was significantly associated with hepatotoxicity on univariable analysis and after controlling for other factors associated with hepatotoxicity including hepatitis B or C and anti-tuberculosis medication use (adjusted odds ratio = 3.0 [1.6–5.8], p = 0.001).Conclusions/SignificanceOur work demonstrates a strong association between S. mansoni infection and hepatotoxicity among HIV-infected patients on antiretroviral therapy. Our study highlights the importance of schistosome screening and treatment for patients starting antiretroviral therapy in schistosome-endemic settings. Additional studies to determine the effects of schistosome-HIV co-infections are warranted.

Effects of schistosomes on host anti-viral immune response and the acquisition, virulence, and prevention of viral infections: A systematic review

“…One study reported that S . mansoni -HIV coinfection was associated with elevated liver transaminases after controlling for other known causes of transaminitis (HBV, HCV, alcohol, medications) in patients on ART [ 88 ]. This suggests that S .…”

“…Schistosomes and HIV virulence. One study reported that S. mansoni-HIV coinfection was associated with elevated liver transaminases after controlling for other known causes of transaminitis (HBV, HCV, alcohol, medications) in patients on ART [88]. This suggests that S. mansoni infection could potentiate direct hepatotoxicity of HIV on hepatocytes [89].…”

Prevalence and Factors Associated With Liver Fibrosis Among Adult HIV-Infected Patients Attending Urban and Rural Care Clinics in Uganda

“…Among Western populations, the prevalence of liver fibrosis among HIV-infected patients was similar to the findings of our study and other studies in SSA, with estimates of 16%–29% [ 20 ]. Antiretroviral therapy has been demonstrated to reduce risk of liver fibrosis via adequate viral suppression [ 8 , 30 ]. In resource-limited settings, rollout of HIV care programs started in urban settings long before their initiation within hard-to-reach areas [ 23 ].…”

Association of schistosomiasis and HIV infections: A systematic review and meta-analysis

“…Figure 2 details the study selection procedure. Of the 364 abstracts identified ( Figure 2 ), 29 focused on HIV and S. haematobium and/or S. mansoni , and 26 were included in the summary ( Brodish and Singh, 2016 ; Downs et al, 2017b ; Colombe et al, 2018 ; Noormahomed et al, 2014 ; Stete et al, 2018 ; Sanyaolu et al, 2016 ; Costiniuk et al, 2012 ; Sadlier et al, 2013 ; Efraim et al, 2013 ; Lar et al, 2016 ; Tegegne et al, 2017 ; Marti et al, 2017 ; Olusegun et al, 2011 ; Kallestrup et al, 2005 ; Mazigo et al, 2014 ; Kleppa et al, 2015 ; Mwanakasale et al, 2003 ; Ndhlovu et al, 2007 ; Kjetland et al, 2006 ; Downs et al, 2012 ; Woodburn et al, 2009 ; Sanya et al, 2015 ; Ssetaala et al, 2015 ; Downs et al, 2011 ; Wall et al, 2018 ) ( Table 1 ): nine reported the association of HIV and schistosomiasis; 11 reported the prevalence of schistosomiasis among people with HIV; and six reported the prevalence of HIV among people with schistosomiasis (one of these papers also reported an odds ratio for the association between schistosomiasis and HIV). One ecological analysis, one mathematical modelling paper and one summary of HIV and schistosomiasis among children were also evaluated.…”