Background: Mycobacterium tuberculosis (TB) infection of the liver, known as hepatic TB, is an extrapulmonary manifestation of TB. Hepatic TB has become more prevalent, likely as a result of the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic. We sought to review case series to characterize the epidemiology, pathophysiology, clinical features, diagnosis, and treatment of hepatic TB and to comment on the impact of HIV co-infection on these characteristics. Methods: We conducted a systematic literature search in PubMed and ScienceDirect for articles pertaining to hepatic TB with human subjects from 1960 to July 2013.

ObjectiveTo determine if urinary lipoarabinomannan (LAM) may serve as a biomarker to monitor antituberculosis (TB) therapy response, and whether LAM results before and after treatment are predictive of patient outcomes.DesignProspective cohort.SettingOutpatient referral clinic and tertiary hospital in South Africa.ParticipantsAdults (≥18 years) with ≥2 TB-related symptoms (cough, fever, weight loss, night sweats) for ≥2 weeks being initiated on anti-TB therapy.InterventionsOn enrolment, we obtained urine and nebulised sputum specimens, offered HIV testing and started participants on anti-TB therapy for ≥6 months. We collected urine samples after the 2-month intensive treatment phase and at the completion of anti-TB therapy. Positive LAM results were graded from 1 (low) to 5 (high). Participants were followed for >3 years.Outcome measuresThe primary outcome was change in urine LAM results during anti-TB therapy. The secondary outcome was all-cause mortality.ResultsAmong 90 participants, 57 (63%) had culture-confirmed pulmonary TB. Among the 88 participants tested, 82 (93%) were HIV-infected with median CD4 168/mm3 (IQR 89–256/mm3). During anti-TB therapy, the percentage of LAM-positive participants decreased from baseline to 2 months (32% to 16%), and from baseline to 6-months (32% to 10%) (p values <0.005). In multivariate longitudinal analyses, urine LAM positivity and grade decreased among those with culture-confirmed pulmonary TB (p<0.0001), and had no change in sputum culture-negative participants. At the 2-month visit, participants with positive laboratory-based LAM or rapid LAM with ≥2+ grade had a significantly greater risk of mortality. In analyses adjusted for age, sex, baseline Karnofsky score and HIV status, participants with a rapid LAM ≥2+ grade after 2 months of anti-TB therapy had a 5.6-fold (95% CI 1.2 to 25.2) greater risk of mortality.ConclusionsRapid urine LAM testing may be a valuable tool to monitor anti-TB therapy response and to assess prognosis of patients being treated for pulmonary TB in HIV-endemic regions.

We sought to determine if urine lipoarabinomannan (LAM) would improve diagnosis of pulmonary TB. We enrolled consecutive adults presenting with ≥2 TB-related symptoms, obtained one induced sputum sample for smear microscopy (AFB) and mycobacterial culture, and performed urine LAM testing (DetermineTM TB LAM, Alere). We used culture-confirmed pulmonary TB as the gold standard, and compared accuracy with area under receiver operating characteristic curves (AUROC). Among 90 participants, 82 of 88 tested (93%) were HIV-infected with a median CD4 168/mm3 (IQR 89–256/mm3). Diagnostic sensitivities of urine LAM and sputum AFB were 42.1% (95% CI 29.1–55.9%) and 21.1% (95% CI 11.4–33.9%), and increased to 52.6% (95% CI 39.0–66.0%) when combined. Sensitivity of LAM increased significantly among participants with a lower Karnofsky Performance score, anemia, hypoalbuminemia, and higher C-reactive protein. Combining LAM with AFB had an AUROC = 0.68 (95% CI 0.59–0.77), significantly better than AFB alone (AUROC=0.58; 95% CI 0.51–0.64). The combination of LAM and AFB was significantly better than AFB alone among patients with Karnofsky Performance score ≤90, hemoglobin ≤10 g/dL, albumin ≤25 g/L, C-reactive protein ≥25 mg/L, or CD4 <200/mm3. Urine LAM testing may be most beneficial among patients with functional impairment, elevated inflammatory markers, or greater immunosuppression.

Affordable, sensitive, and scalable technologies are needed for monitoring antiretroviral treatment (ART) success with the goal of eradicating HIV-1 infection. This review discusses use of Sanger sequencing and next generation sequencing (NGS) methods for HIV-1 drug resistance (HIVDR) genotyping, focusing on their use in resource limited settings (RLS). Sanger sequencing remains the gold-standard method for detecting HIVDR mutations of clinical relevance but is mainly limited by high sequencing costs and low-throughput. NGS is becoming a more common sequencing method, with the ability to detect low-abundance drug-resistant variants and reduce per sample costs through sample pooling and massive parallel sequencing. However, use of NGS in RLS is mainly limited by infrastructure costs. Given these shortcomings, our review discusses sequencing technologies for HIVDR genotyping, focusing on common in-house and commercial assays, challenges with Sanger sequencing in keeping up with changes in HIV-1 treatment programs, as well as challenges with NGS that limit its implementation in RLS and in clinical diagnostics. We further discuss knowledge gaps and offer recommendations on how to overcome existing barriers for implementing HIVDR genotyping in RLS, to make informed clinical decisions that improve quality of life for people living with HIV.