Occult hepatitis B virus infection: clinical implications in tuberculosis treatment.

Occult hepatitis B virus infection (OBI) is characterized by the absence of HBsAg and persistence of the virus genome (HBV-DNA) in liver tissue and/or blood. OBI has been reported in several clinical contexts. However, the clinical significance of OBI in tuberculosis (TB) treatment is unknown. We investigated the OBI prevalence and its impact on the risk of drug-induced liver injury (DILI) during TB treatment. This was a prospective cohort study with one hundred patients who were treated for TB from 2008 to 2015. Laboratory, clinical and demographic data of TB patients were extracted from medical records. Based on HBV-DNA testing of serum samples, an OBI prevalence of 12% was established; almost half of these patients had both anti-HBc and anti-HBs serological markers. Low CD4+ cell counts have been shown to be a risk factor for OBI among TB patients co-infected with HIV (P=.036). High DILI incidence was observed in this study. A multivariable Cox proportional hazard model was conducted and identified OBI (HR 2.98, 95% CI 1.30-6.86) as the strongest predictor for DILI when adjusted to CD4+ cell count (HR 0.38, 95% CI 0.17-0.90), ALT before TB treatment (HR 1.37, 95% CI 0.81-2.32) and TB extrapulmonary clinical form (HR 2.91, 95% CI 1.75-7.21). The main aim of this study was to highlight DILI as a clinical outcome during treatment of TB patients with OBI. Therefore, HBV-DNA testing should be considered routinely in monitoring DILI, and also in other clinical implications associated with OBI, reduce morbidity and mortality.

Dealing with initial inconclusive serological results for chronic Chagas disease in clinical practice.

Most guidelines for Chagas disease recommend the performance of two serological tests in order to detect it. However, inconclusive results may arise from this strategy. The aim was to describe whether serological follow-up together with the patient's clinical characteristics could clarify the outcome of patients with initial inconclusive test results. In this retrospective case series, all results of Chagas disease serological tests and outpatient visits recorded from 2004 to 2008 were screened for inclusion. The inclusion criterion was clinical suspicion of chronic Chagas disease and the exclusion criteria were previous diagnosis of Chagas disease, suspicion of acute Chagas disease, and serological tests with no corresponding medical evaluation. A total of 1,732 patients were analyzed. Chronic Chagas disease prevalence was 21.1%. After the initial set of serological tests, 2.9% of patients had inconclusive test results. Most of these patients had definite diagnosis after clinical follow-up and the repetition of serological tests in a new blood sample. Loss to follow-up while partaking in the diagnostic investigation reached 17.7%. The prevalence of initial inconclusive serological tests for chronic Chagas disease is low. Clinical evaluations and follow-up clarify the definite diagnosis. Noncompliance to follow-up is a frequent problem. Strategies to reduce inconclusive results and noncompliance are discussed.

The roles of GSTM1 and GSTT1 null genotypes and other predictors in anti-tuberculosis drug-induced liver injury.

WHAT IS KNOWN AND OBJECTIVE: Anti-tuberculosis drugs (ATD), although highly effective, often cause liver injury. Glutathione S-transferases (GST) play a crucial protective role in the detoxifying mechanisms of drugs. Several studies have investigated the genetic null variants of GSTM1 and GSTT1 as possible risk factors for ATD-induced liver injury; however, those findings are inconsistent. We investigated GSTM1 and GSTT1 null genotypes in Brazilian patients with tuberculosis (TB), adjusting for other possible predictors of ATD-induced liver injury. METHODS: This was a prospective cohort study with patients who were treated for TB from 2006 to 2011. GSTM1 and GSTT1 gene deletions were analysed from genomic DNA by polymerase chain reaction (PCR). Demographic, clinical and laboratory data were extracted from medical records and possible predictors of liver injury were evaluated. RESULTS AND DISCUSSION: This study enrolled 177 patients. Anti-tuberculosis drugs-induced liver injury incidence was 33.3%. Hepatitis B infection (HBV) and increased alanine aminotransferase (ALT) baseline were significant predictors. Neither GSTM1 nor GSTT1 null genotypes were associated with ATD-induced liver injury; nevertheless, the comparison among four different liver toxicity grades showed that GSTM1 non-null genotype was significant more frequent among the higher grades of liver toxicity. WHAT IS NEW AND CONCLUSION: GSTM1 and GSTT1 null genotypes do not seem to play important roles in ATD-induced liver injury in Brazilians. However, there was evidence that GSTM1 polymorphisms were possibly related to the intensity of toxicity. Active HBV and initial high ALT could predict ATD-induced liver injury.

Can hepatitis B virus infection predict tuberculosis treatment liver toxicity? Development of a preliminary prediction rule.

BACKGROUND: Liver toxicity due to tuberculosis (TB) treatment is a frequent cause of treatment interruption, and may sometimes lead to a change in therapy to a less potent regimen. OBJECTIVE: To estimate the risk of hepatotoxicity in patients with or without hepatitis B virus (HBV) infection receiving TB treatment and to develop a clinical prediction rule. DESIGN: A prospective observational follow-up was conducted. Data from 154 patients who underwent TB treatment were analysed. Crude risk ratios were estimated and a Cox proportional hazards model was fit. RESULTS: The mean follow-up time was 187 days. Crude risk ratios showed that ethnicity, human immunodeficiency virus infection, multiple sexual partners, highly active antiretroviral treatment, and clinical forms of TB were possible predictors of liver toxicity. HBV infection and other sexually transmitted diseases showed considerable relative risk, although not statistically significant. The Cox proportional hazards model identified the following predictors of hepatotoxicity: White ethnicity, multiple sexual partners, high baseline alanine transferase and clinical forms of TB. Active HBV, indicated by the detection of surface antigen HBV, could predict hepatotoxicity, although with low precision. CONCLUSION: Using this information, we were able to apply a score and draw a nomogram to estimate survival probabilities and median times to event for each patient.