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Co-infection with hepatitis B virus among tuberculosis patients is associated with poor outcomes during anti-tuberculosis treatment.

ABSTRACT: BACKGROUND:Tuberculosis (TB) and chronic Hepatitis B virus (HBV) infection are common in China. Fist-line anti-TB medications often produce drug-induced liver injury (DILI). This study sought to investigate whether TB patients with chronic HBV co-infection are more susceptible to liver failure and poor outcomes during anti-TB treatment. METHODS:Eighty-four TB patients developed DILI during anti-TB treatment and were enrolled, including 58 with chronic HBV co-infection (TB-HBV group) and 26 with TB mono-infection (TB group). Clinical data and demographic characteristics were reviewed. The severity of DILI and incidences of liver failure and death were compared. Risk factors of clinical outcomes were defined. RESULTS:The patterns of DILI were similar in both groups. Compared with patients in the TB group, patients in the TB-HBV group who did not receive anti-HBV therapy before anti-TB treatment were more susceptible to Grade-4 severity of DILI (36.2% vs. 7.7%, P?= 0.005), liver failure (67.2% vs. 38.5%, P?= 0.013) and poor outcomes (37.9% vs. 7.7%, P?= 0.005). Age?>?50 years (48.1% vs. 22.6%, P?= 0.049), cirrhosis (50.0% vs. 15.4%, P?= 0.046) and total bilirubin >?20 mg/dl (51.6% vs. 14.8%, P?= 0.005) were independent risk factors for the rate of death in the TB-HBV group, and HBV DNA >?20,000 IU/ml had borderline significance (44.1% vs. 20.8%, P?= 0.081). In the TB-HBV group, nucleos(t)ide analogues as rescue therapy were not able to reduce short-term death (33.3% vs. 36.8%, P?= 0.659) once liver failure had occurred. CONCLUSIONS:Patients on anti-TB therapy with chronic HBV co-infection are more susceptible to developing liver failure and having poor outcomes during anti-TB treatment. Regular monitoring of liver function and HBV DNA level is mandatory. Anti-HBV treatment should be considered in those with high viral levels before anti-TB treatment.

SUBMITTER: Chen L

PROVIDER: S-EPMC6029116 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Co-infection with hepatitis B virus among tuberculosis patients is associated with poor outcomes during anti-tuberculosis treatment.

Chen Lubiao L Bao Dujing D Gu Lin L Gu Yurong Y Zhou Liang L Gao Zhiliang Z Huang Yuehua Y

BMC infectious diseases 20180703 1

<h4>Background</h4>Tuberculosis (TB) and chronic Hepatitis B virus (HBV) infection are common in China. Fist-line anti-TB medications often produce drug-induced liver injury (DILI). This study sought to investigate whether TB patients with chronic HBV co-infection are more susceptible to liver failure and poor outcomes during anti-TB treatment.<h4>Methods</h4>Eighty-four TB patients developed DILI during anti-TB treatment and were enrolled, including 58 with chronic HBV co-infection (TB-HBV grou ...[more]

PMID: 29970037

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Project description:Viral diversity is an important feature of hepatitis C virus (HCV) infection and an important predictor of disease progression and treatment response. HIV/HCV co-infection is associated with enhanced HCV replication, increased fibrosis, and the development of liver disease. HIV also increases quasispecies diversity of HCV structural genes, although limited data are available regarding the impact of HIV on non-structural genes of HCV, particularly in the absence of direct-acting therapies. The genetic diversity and presence of drug resistance mutations within the RNA-dependent RNA polymerase (NS5B) gene were examined in 3 groups of women with HCV genotype 1a infection, including those with HCV mono-infection, antiretroviral (ART)-naïve women with HIV/HCV co-infection and CD4 cell count <350 cells/mm3, and ART-naïve women with HIV/HCV co-infection and CD4 cell count ?350 cells/mm3. None had ever been treated for HCV infection. There was evidence of significant diversity across the entire NS5B gene in all women. There were several nucleotides and amino acids with distinct distributions across the three study groups, although no obvious clustering of NS5B sequences was observed based on HIV co-infection or CD4 cell count. Polymorphisms at amino acid positions associated with resistance to dasabuvir and sofosbuvir were limited, although the Q309R variant associated with ribavirin resistance was present in 12 individuals with HCV mono-infection, 8 HIV/HCV co-infected individuals with CD4 <350 cells/mm3, and 12 HIV/HCV co-infected individuals with CD4 ?350 cells/mm3. Previously reported fitness altering mutations were rare. CD8+ T cell responses against the human leukocyte antigen (HLA) B57-restricted epitopes NS5B2629-2637 and NS5B2936-2944 are critical for HCV control and were completely conserved in 44 (51.8%) and 70 (82.4%) study participants. These data demonstrate extensive variation across the NS5B gene. Genotypic variation may have a profound impact on HCV replication and pathogenesis and deserves careful evaluation.

Project description:OBJECTIVE:The role of ribavirin (RBV) in the treatment of recent hepatitis C virus (HCV) (acute/early chronic) is unclear, particularly in HIV-infected individuals. This study evaluated early virological decline during recent HCV therapy in HIV-uninfected individuals receiving pegylated interferon (PEG-IFN) monotherapy and HIV-infected individuals receiving PEG-IFN/RBV. DESIGN:The Australian Trial in Acute Hepatitis C was a nonrandomized prospective study of patients with recent HCV. METHODS:All participants received PEG-IFN (24 weeks); HCV/HIV participants also received RBV. Early HCV RNA decline was assessed among adherent participants (?80% PEG-IFN, ?80% treatment). Logistic regression identified predictors of rapid virological response (RVR) (<10 IU/ml). RESULTS:Of 109 treated, 82% were adherent (HCV, n=57; HCV/HIV, n=32). Overall, RVR was 51% (HCV: 55% vs. HCV/HIV: 43%; P=0.323). Factors independently associated with RVR included duration of infection less than 26 weeks, HCV RNA below 5.6 log(10) IU/ml at baseline and HCV genotype 2/3 infection. Between baseline and week 12, mean decline in HCV RNA was greater in HCV/HIV participants (PEG-IFN/RBV) compared to HCV participants (PEG-IFN) (4.19 vs. 3.32 log(10) IU/ml; P=0.029). Greater HCV RNA decline was observed in those treated with RBV, particularly amongst those with an estimated duration of infection at least 26 weeks and those with unfavourable IL28B genotypes. Adherent HIV-uninfected and infected participants had similar early virological response (76 vs. 90%; P=0.102) and sustained virological response (63 vs. 75%; P=0.253), respectively. RVR was highly predictive of sustained virological response (adjusted odds ratio 4.09; 1.49, 11.25). CONCLUSION:The results of this study suggest a potential benefit for PEG-IFN and RBV combination therapy in maximizing virological responses in HCV/HIV participants with recent HCV, particularly those with a longer duration of HCV infection and unfavourable IL28B genotypes.

Dataset Information

Co-infection with hepatitis B virus among tuberculosis patients is associated with poor outcomes during anti-tuberculosis treatment.

Publications

Co-infection with hepatitis B virus among tuberculosis patients is associated with poor outcomes during anti-tuberculosis treatment.

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