Expression of microRNA-3620 in blood plasma and its clinical significance in patients with anti-tuberculosis drug-induced hepatotoxicity / 中华传染病杂志

Objective To investigate the expression of microRNA (miRNA)-3620 in the plasma of patients with anti-tuberculosis drug-induced hepatotoxicity (ATDH).Methods A total of 35 patients with ATDH and 35 non-ATDH paired individuals were included in this study.Plasma miRNA-3620 levels were detected using real-time Polymerase chain reaction.Comparison between two groups was done with t test.Receiver operation characteristic (ROC) curve analysis was performed to determine the diagnostic value of miRNA-3620 in ATDH.Results The relative expression of plasma miRNA-3620 of patients with ATDH and non-ATDH were 1.65±1.43 and 0.71±0.45, respectively, with significantly statistical difference (t=3.703, P<0.01).The cut off value of miRNA-3620 expression was 1.15 and the area under ROC curve were 0.71(95% CI: 0.43-1.45).Based on this cutoff value, the sensitivity and specificity of miRNA-3620 in diagnosing ATDH were 60.0% and 82.9%, respectively;the positive predictive value was 77.8% and the negative predictive value was 67.4%.Twenty-one ATDH cases and 29 non-ATDH cases was correctly diagnosed, with the accuracy of 71.4%.Conclusion The expression of miRNA-3620 in plasma is significantly increased in ATDH patients.

Evaluation of risk factors for antituberculosis treatment induced hepatotoxicity.

Background & objectives: Antituberculosis (anti-TB) drug induced hepatotoxicity (DIH) is the most common side effect leading to interruption of therapy. Wide variations have been found in the reported incidence of hepatotoxicity during short-course chemotherapy. Several risk factors for hepatotoxicity have been suggested in previous studies. We undertook a prospective case-control study to assess the role of these putative risk factors in the development of DIH in patients receiving anti-TB treatment. Methods: One hundred and seventy five consecutive cases with a diagnosis of anti-TB DIH were compared with 428 consecutive controls who took anti-TB drugs for the full duration of chemotherapy without clinical or biochemical evidence of hepatitis. Cases positive for markers of acute viral hepatitis were carefully excluded. Cases and controls were compared with respect to age, sex, site of tuberculosis, radiological extent of disease on chest radiograph, body mass index (BMI), mid-arm circumference (MAC) and liver function at baseline which included serum bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), serum total protein and serum albumin. Results: Univariate logistic regression revealed that the risk of developing DIH was greater in older patients. Significantly greater percentage of cases had extrapulmonary tuberculosis (TB) (P<0.01). Also, a significantly higher percentage of cases had moderate to far advanced disease severity on chest radiograph (P<0.01). On multivariate logistic regression, the adjusted odds were significant (P<0.01) for age >35 yr, MAC <20 cm and hypoalbuminaemia (albumin <3.5 g/dl). Interpretation & conclusions: Older age, poor nutritional status including baseline hypoalbuminaemia were independent predictors of occurrence of anti-TB DIH. Clinicians should be vigilant for occurrence of hepatotoxicity in this high risk group.

Multi-drug resistant extra-pulmonary tuberculosis in a HIV negative patient.

A 25 year-old, HIV seronegative male presented with bilateral cervical lymphadenopathy with cold abscesses and sinus formation, peripancreatic lymphadenopathy and hypodense lesions in the spleen. Culture of pus aspirated from the cold abscess in the neck grew M.tuberculosis resistant to Rifampicin, Isoniazid, Ciprofloxacin and Para-aminosalicylic acid. In a resource-limited setting, he was treated with Ethambutol (E), Pyrazinamide (Z), Ethionamide (Eth), Cycloserine (Cyc), and Ofloxacin (Ofl). While on treatment, he developed drug induced hepatotoxicity; Z and Eth were stopped and clofazimine was added to the regimen. Subsequently, he developed splenic abscess and clofazimine induced generalized pigmentation of the body including tongue. After eighteen months of treatment, lymphadenopathy and splenic lesions regressed significantly. Thus, present case highlights several important basic principles of management of MDR-TB such as procuring tissue for microbiological testing, judicious use of imaging modalities, careful monitoring for adverse drug reactions, intercurrent infections and the need for pretreatment counselling for ensuring compliance and completion of treatment.