Determinants of drug-resistant tuberculosis: analysis of 11 countries.

SETTING: Eleven countries/territories. OBJECTIVES: Global information on the determinants of drug-resistant tuberculosis (TB) based on representative data is not available. We therefore studied the relationship between demographic characteristics, prior TB treatment, and human immunodeficiency virus (HIV) infection with anti-tuberculosis drug resistance. METHODS: Population-based representative data on new and previously treated patients with TB collected within an international drug resistance surveillance network. RESULTS: Of 9,615 patients, 8,222 (85.5%) were new cases of TB and 1,393 (14.5%) were previously treated cases. Compared with new cases, previously treated cases were significantly more likely to have resistance to one (OR = 2.5,95% CI 2.1-3.0; P < 0.001), two (OR = 4.6, 95%CI 3.7-5.6; P < 0.001), three (OR = 11.5, 95%CI 8.6-15.3; P < 0.001), and four (OR = 18.5, 95% CI 12.0-28.5; P < 0.001) drugs. An approximately linear increase in the likelihood of having multidrug-resistant tuberculosis (MDR-TB) was observed as the total time (measured in months) of prior anti-tuberculosis treatment increased (P < 0.001, chi2 for trend). In multivariate analysis, prior TB treatment for 6-11 months (OR = 7.6, 95% CI 2.6, 22.4; P < 0.001) and > or = 12 months (OR 13.7, 95% CI 4.5-41.6; P < 0.001), but not HIV positivity, was associated with MDR-TB. CONCLUSION: This study shows that prior but ineffective treatment is a strong predictor of drug resistance, and that HIV is not an independent risk factor for MDR-TB. The association between length of treatment and drug resistance may reflect longer treatment as a result of treatment failure in patients with drug resistance; it may also reflect irregular prior treatment for TB, leading to drug resistance.     

HIV testing among tuberculosis patients in the era of antiretroviral therapy: a population-based study in Brazil.

SETTING: Rio de Janeiro, Brazil, a city with 29862 cases of tuberculosis (TB) reported between January 1995 and June 1998. OBJECTIVES: To evaluate the counseling and testing practices for human immunodeficiency virus (HIV) infection among TB patients, and to identify the patient characteristics associated with HIV screening as antiretroviral therapy was introduced. DESIGN: Cross-sectional study of patients with TB who were reported to the health department and who initiated anti-TB treatment. The main outcome measure was screened versus not screened for HIV. RESULTS: The proportion of TB patients who received HIV screening increased from January 1995 through June 1998 (P < 0.001). Among young adults aged 20-49 years with TB, the independent predictors of HIV screening were a diagnosis of both pulmonary and extrapulmonary TB (odds ratio [OR] = 2.4, 95% confidence interval [CI] 2.1-2.8); TB meningitis (OR = 13.5, 95%CI 6.5-31.5); disseminated TB (OR = 8.2, 95%CI 5.3-12.9); lymphatic TB (OR = 5.6, 95%CI 4.7-6.6); and male sex (OR = 1.4, 95%CI 1.3-1.6). Patients with newly diagnosed TB who were women, lived in a low income neighborhood (OR = 0.7, 95%CI, 0.6-0.7), and sought TB treatment in their own residential neighborhood (OR = 0.3, 95%CI 0.3-0.4) were less likely to receive HIV counseling and testing. CONCLUSION: Health care providers in Rio de Janeiro selectively offered HIV counseling and testing to persons they perceived to be at risk for HIV and those with advanced stages of TB. HIV counseling and testing should be expanded and offered to all TB patients.     

TB prevention in HIV clinics in New York City.

SETTING: Ten hospital-based human immunodeficiency virus (HIV) clinics in New York City. OBJECTIVE: To evaluate tuberculosis (TB) prevention in HIV clinics based on the prevalence and incidence of TB and the efficacy of preventive therapy with isoniazid (INH). DESIGN: The medical records of 2393 HIV-infected patients with a first clinic visit in 1995 were reviewed retrospectively. Deaths and TB cases through December 1997 were ascertained through a match with the TB and AIDS registries. RESULTS: At first visit, 92 patients (4%) had a history of TB, 98 (4%) were being treated for TB, and six (<1%) were diagnosed with TB. During follow-up, 23 cases were diagnosed, an incidence of 0.53 per 100 person-years (py) (95%CI 0.34-0.77). Among 439 tuberculin skin test (TST) positive patients, the incidence of TB/100 py was 1.63 (95%CI 0.27-5.02) in patients with no INH, 1.28 (95%CI 0.40-2.98) in patients with <12 months of INH, and 1.06 (95%CI 0.38-2.28) in patients with 12 months of INH. The incidence/100 py was 0.0 (95%CI 0.0-0.78) in TST-negative patients and 0.37 (95%CI 0.09-0.95) in anergic patients. The relative risk of TB was 0.65 (95%CI 0.14-4.56) in TST-positive patients with 12 months of INH (vs. none). CONCLUSIONS: The benefits of TB prevention efforts in these HIV clinics from 1995 to 1997 were limited because most TB occurred before the first clinic visit. Methods for reaching HIV-infected patients earlier should be identified.     

Does antiretroviral treatment reduce case fatality among HIV-positive patients with tuberculosis in Malawi?

SETTING: Thyolo district, Malawi. OBJECTIVES: To report on 1) case fatality among human immunodeficiency virus (HIV) positive tuberculosis (TB) patients while on anti-tuberculosis treatment and 2) whether antiretroviral treatment (ART) initiated during the continuation phase of TB treatment reduces case fatality. DESIGN: Retrospective cohort analysis. METHODS: Comparative analysis of treatment outcomes for TB patients registered between January and December 2004. RESULTS: Of 983 newly registered TB patients receiving diagnostic HIV testing, 658 (67%) were HIV-positive. A total of 132 (20%) patients died during the 8-month course of anti-tuberculosis treatment, of whom 82 (62%) died within the first 2 months of treatment when ART was not provided (cumulative incidence 3.0, 95%CI 2.5-3.6 per 100 person-years). A total of 576 TB patients started the continuation phase of anti-tuberculosis treatment, 180 (31%) of whom were started on ART. The case-fatality rate per 100 person-years was not significantly different for patients on ART (1.0, 95%CI 0.6-1.7) and those without ART (1.2, 95%CI 0.9-1.7, adjusted hazard ratio 0.86, 95%CI 0.4-1.6, P = 0.6) CONCLUSIONS: ART provided in the continuation phase of TB treatment does not have a significant impact on reducing case fatality. Reasons for this and possible measures to reduce high case fatality in the initial phase of TB treatment are discussed.     

HTLV-1 infection is frequent among out-patients with pulmonary tuberculosis in northern Lima, Peru.

SETTING: Tuberculosis (TB) and human T-lymphotropic virus 1 (HTLV-1) are frequent in Peru. The prevalence of HTLV-1 among Peruvian TB patients is unknown. OBJECTIVE: To determine the prevalence of HTLV-1, HTLV-2 and the human immunodeficiency virus (HIV) in out-patients with TB and to compare HTLV-1-infected patients with seronegative patients. DESIGN: Cross-sectional study including subjects aged 18-65 years diagnosed with smear-positive pulmonary TB at health centres in northern Lima from November 2004 to August 2005. HTLV and HIV screening was performed using enzyme-linked immunosorbent assay; HTLV-1 and HTLV-2 were confirmed using line immunoassay. RESULTS: There were 311 participants with a median age of 29 years; 173 (56%) were men. HTLV-1 prevalence was 5.8% (18/311, 95%CI 3.2-8.4) and HIV prevalence was 1.3% (4/304, 95%CI 0.4-3.3). HTLV-2 was not diagnosed. In comparison with HIV- and HTLV-seronegative patients, HTLV-1-infected subjects were older (median age 44 vs. 28, P < 0.001) and were more likely to have been born in the southern Andes (OR 4.4, 95%CI 1.6-11.9). They were also more likely to report a history of TB deaths in the family (OR 5.4, 95%CI 1.7-16.8) and had more sputum smear results graded as 3+ (OR 4.1, 95%CI 1.5-11.2). CONCLUSION: HTLV-1 screening among Peruvian TB patients is important. Because 3+ sputum smears are frequent and mortality is high among relatives, families of HTLV-1/TB-positive cases merit special attention.     

Prevalence of M. tuberculosis infection and tuberculosis disease among HIV-infected people in Spain.

OBJECTIVE: To study the prevalence of Mycobacterium tuberculosis infection (MTBI) and past/current tuberculosis (TB) among human immunodeficiency virus (HIV) infected persons in Spain. DESIGN: Longitudinal study conducted between 2000 and 2003 at 10 HIV hospital-based clinics. Data were drawn from clinical records. Associations were measured using odds ratios (ORs) and their 95% confidence intervals (95%CI). RESULTS: Of the 1242 persons who met the eligibility criteria, most were male (75%), aged <40 years (75%) and unemployed (40%). HIV infection occurred through intravenous drug use (53%), heterosexual sex (29%) and sex between men (16%). In the initial evaluation, 315 subjects had evidence of MTBI: 84 (6.8%) had a history of TB, 23 (1.8%) current TB and 208 (16.8%) latent tuberculosis infection (LTBI). MTBI was associated with male sex, age 30-49 years, contact with a TB case, homelessness, poor education, and negatively with CD4 <100 cells/mm(3). Among subjects with MTBI, past/current TB was associated with retirement/disability (OR 6, 95%CI 1.6-22.5), CD4 <200 cells/mm(3) (OR 9.7, 95%CI 3.8-24.6), viral load >55,000 copies (OR 5.3, 95%CI 1.4-20.0), and negatively, with skilled work (OR 0.4, 95%CI 0.1-1.0) or administrative/managerial/professional work (OR 0.05, 95%CI 0.01-0.4). CONCLUSION: Social context has an impact on the effectiveness of HIV and TB control programmes even in industrialised countries with free access to health care.     

Drug-resistant tuberculosis and HIV in Ukraine: a threatening convergence of two epidemics?

OBJECTIVE: To investigate anti-tuberculosis (TB) drug resistance rates in Donetsk Oblast, Ukraine, and to explore the association between the epidemics of human immunodeficiency virus (HIV) and multidrug-resistant TB (MDR-TB). METHODS: All consecutive newly diagnosed and previously treated patients with sputum smear-positive TB presenting to all TB units in Donetsk Oblast over 12 months were invited to take part in the study. A total of 1293 and 203 patients with TB were tested for HIV and MDR-TB in the civilian and penitentiary sectors, respectively. RESULTS: Of those enrolled for the study, 307 were HIV-positive, 379 had MDR-TB, and 97 had MDR-TB and HIV co-infection. MDR-TB rates in the civilian sector were respectively 15.5% (95%CI 13.1-17.8) and 41.5% (95%CI 36.4-46.5) in newly diagnosed and previously treated TB patients. Among prisoners, MDR-TB rates were 21.8% (95%CI 12.4-31.2) in new cases and 52.8% (95%CI 43.9-61.7) in previously treated TB cases. HIV status was significantly associated with MDR-TB (OR 1.7, 95%CI 1.3-2.3). CONCLUSIONS: High MDR-TB rates and a positive association between MDR-TB and HIV epidemics were found in Donetsk Oblast. Urgent measures to improve HIV prevention, control of drug-resistant TB and collaboration between HIV and TB control activities need to be implemented without further delay.     

Recurrent tuberculosis and its risk factors: adequately treated patients are still at high risk.

Recurrent tuberculosis (TB) poses significant threats, including drug resistance, to TB control programs. However, recurrence and its causes, particularly in the era of epidemic human immunodeficiency virus (HIV), have not been well described. We systematically searched published material for studies reporting on recurrent TB following completion of standard treatment regimens to provide data on the issue. A total of 32 studies were reviewed. Among controlled trials, the overall recurrence rates (per 100,000 person-years) were respectively 3,010 (95%CI 2,230-3,970) and 2,290 (95%CI 1,730-2,940) at 6 and 12 months after treatment completion. Recurrence rates were higher among observational studies compared to controlled trials and in countries with high versus low background TB incidence. TB recurrence (%) was higher among HIV-infected (6.7, 95%CI 5.9-7.6) than non-HIV-infected individuals (3.3, 95%CI 2.8-3.9). Factors independently associated with recurrence in the literature included residual cavitation, greater area of involved lung tissue, positive sputum culture at 2 months of treatment and HIV infection. Among those with HIV infection, recurrent TB was associated with a low initial CD(4) count and receiving less than 37 weeks of anti-tuberculosis treatment. We argue that adequately treated patients are still at high risk for recurrent disease and should be considered in case-finding strategies. Moreover, those with multiple risk factors may benefit from modification of standard treatment.     

Factors associated with an increased case-fatality rate in HIV-infected and non-infected South African gold miners with pulmonary tuberculosis.

SETTING: A gold mining company in the Free State Province, South Africa. AIM AND DESIGN: A retrospective cohort study to investigate factors associated with an increased case-fatality rate (CFR) at 6 months in human immunodeficiency virus (HIV) positive and negative tuberculosis (TB) patients. RESULTS: Between April 1993 and March 1997, there were 2236 men with culture-confirmed pulmonary TB in whom HIV status and treatment outcome were known. The overall CFR within the first 6 months of therapy was low (3.6%). After adjusting for confounding factors, HIV infection (OR 15.0, 95%CI 7.4-30.6), self-presentation compared to detection by the active radiological screening programme (OR 5.6, 95%CI 2.6-12.2) and presence of silicosis (OR 3.0, 95%CI 1.4-6.3) were significantly associated with an increased CFR. Opportunistic infections accounted for 56.2% (36/64) of deaths in HIV-positive men. Cryptococcal disease accounted for 75% (27/36) of deaths from opportunistic infections. CONCLUSION: HIV infection and silicosis are both powerful risk factors for TB and are associated with an increased risk of death. Strategies aimed at reducing these two risk factors within the workforce could reduce TB incidence and mortality. In settings with functional DOTS programmes and sufficient resources, expanding the DOTS programme to include active case detection should be explored as a means of reducing TB prevalence and mortality.     

Adverse drug reactions associated with first-line anti-tuberculosis drug regimens.

BACKGROUND: Standard treatment of active tuberculosis (TB) consists of isoniazid (INH), rifampin (RMP), pyrazinamide (PZA) and ethambutol (EMB). Although this regimen is effective in treating active TB, it is associated with many adverse drug reactions (ADRs) and poses a significant challenge to completion of treatment. OBJECTIVES: To examine the incidence of major ADRs and risk factors associated with first-line anti-tuberculosis medications. METHODS: This study evaluated patients receiving treatment for active TB from a population-based database (2000-2005). The nature of the ADRs, likelihood of association with the study medications and severity were evaluated. RESULTS: A total of 1061 patients received treatment, of whom 318 (30%) had at least one major ADR. The overall incidence of all major ADRs was 7.3 events per 100 person-months (95%CI 7.2-7.5): 23.3 (95%CI 23.0-23.7) when on all four first-line drugs, 13.6 (95%CI 13.3-14.0) when on RMP, INH and PZA, and 2.4 (95%CI 2.3-2.6) when on INH and RMP. Adjusted hazard ratio (HR) revealed that combination regimens containing PZA, females, subjects aged 35-59 and >or=60 years, baseline aspartate aminotransferase >or=80 U/l and drug resistance were associated with any major event. CONCLUSIONS: First-line anti-tuberculosis drugs are associated with significant ADRs. There are several risk factors associated with the development of ADRs, including exposure to regimens containing PZA.     

Hepatocellular carcinoma in Saudi Arabia: role of hepatitis B and C infection

BACKGROUND AND AIM: To estimate the risk of hepatocellular carcinoma (HCC) in non-alcoholic patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, 118 patients who were admitted to a regional hospital in Saudi Arabia were compared with 118 age- and sex-matched healthy individuals. RESULTS: The prevalence of HBsAg in HCC patients (67%; 95% confidence interval (CI): 57.7-75.3) was significantly higher than the rate (6.7%; 95%CI: 3.0-12.9) in the controls (OR: 28.4; 95%CI: 12.6-63.9; P < 0.001). There was a high risk of HCC in the presence of HBsAg alone (OR: 34.3; 95%CI: 14.8-79.1, P < 0.001) and anti-HCV alone (OR: 12.2; 95%CI: 3.2-47.2; P < 0.001). Although HBV and HCV were independent risk factors in the development of HCC, there was no interactive relationship between the two viruses. Dual infections occurred in only 3.4% and were associated with only a moderate increase in the risk of HCC (OR: 14.6; 95%CI: 1.57-135.9). In 24.6% of the cases no virus was identified as the etiologic factor. CONCLUSION: Hepatitis B virus constitutes a major risk factor and HCV contributes a less significant role in the development of HCC. The ongoing program of HBV vaccination may significantly decrease the prevalence of HBV-associated HCC in this population.     

Contribution of reinfection to recurrent tuberculosis in South African gold miners

SETTING: A gold mine in South Africa. OBJECTIVE: To investigate incidence and risk factors for tuberculosis (TB) recurrence and the relative contribution of reinfection and relapse to recurrence. DESIGN: Prospective cohort study. METHODS: Employees cured of a first episode of culture-positive TB were followed up for recurrence, which was classified as reinfection or relapse by restriction fragment length polymorphism using an insertion sequence (IS) 6110 probe. RESULTS: Among 609 patients, 57 experienced recurrence during a median follow-up period of 1.02 years, corresponding to a recurrence rate of 7.89 per 100 person-years (py). The culture positive recurrence rate was 5.79/100 py, and was higher in human immunodeficiency virus (HIV) infected patients (8.86/100 py in HIV-infected vs. 3.35/100 py in non-HIV-infected). Among HIV-infected patients, the risk of culture-positive recurrence was higher with decreasing CD4 count (compared with CD4 < 200, hazard ratios for recurrence among individuals with CD4 200-500 and CD4 > 500 were 0.40 [95%CI 0.14-1.09] and 0.14 [95%CI 0.02-1.10], respectively, Ptrend = 0.01). IS6110 genotyping was available on both the initial and subsequent isolate for 16/42 (38%, 14 HIV-infected) patients with culture-positive recurrence, and showed reinfection in 11 (69%). CONCLUSION: HIV-infected gold miners, particularly those who are more immunosuppressed, are at higher risk of TB recurrence. TB control strategies need to take into account reinfection as an important cause of recurrent TB.     

结核病与艾滋病低流行地区MTB/HIV双重感染患者发现模式的效果评价

目的 回顾性分析上海市近10年在结核病患者与HIV/AIDS人群中对HIV抗体和活动性结核病双向筛查的数据,评价MTB/HIV双重感染患者发现模式的效果,为进一步完善相关政策提供依据。 方法 通过《中国结核病信息管理系统》收集2012—2020年结核病患者(68155例)HIV抗体检测结果及结核病诊断、治疗相关资料;通过《结核菌/艾滋病病毒双重感染防治管理工作年度报表》收集2012—2020年HIV/AIDS人群接受结核病相关检查情况。采用线性回归模型评价筛查阳性率随年度的变化趋势,并计算年度变化百分比(APC)和需筛查人数(NNS),评价筛查效果;采用单因素方差分析和多因素logistic回归分析评价2012—2019年上海市长宁区、浦东新区10769例肺结核患者中HIV阳性的影响因素。 结果 2012—2020年上海市累积发现MTB/HIV双重感染患者308例,其中新确诊HIV感染者64例,占全部MTB/HIV双重感染患者的20.78%。2012—2020年间,结核病患者中HIV抗体检测阳性率由2.42%(32/1322)下降到0.50%(20/3995),总体呈下降趋势(APC=-16.64,t=-7.007,P<0.001);HIV/AIDS人群中活动性结核病确诊率由1.02%(50/4912)下降到0.21%(25/11878),同样呈下降趋势(APC=-14.27,t=-4.038,P=0.005)。多因素logistic回归分析显示,男性[OR(95%CI)=5.386(2.306~12.581)],年龄36~75岁[36~45、46~55、56~65、66~75岁OR(95%CI)值分别为26.243(3.230~213.244)、32.736(3.993~268.358)、20.309(2.482~166.144)、13.461(1.692~107.059)],在结核病治疗过程中死亡[OR(95%CI)=14.875(3.192~69.312)],并发肺外结核[OR(95%CI)=3.451(1.607~7.409)]是MTB/HIV双重感染的危险因素。 结论 上海市目前采取的 MTB/HIV双重感染患者发现模式取得了较好的效果,结核病患者的HIV阳性率和HIV/AIDS人群的活动性结核病确诊率均迅速下降。男性、年龄36~75岁、在治疗过程中死亡、并发肺外结核是MTB/HIV双重感染的危险因素。     

Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients

AIM: To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico.METHODS: We investigated the presence of OHBI in 49 HIV-1+/HBsAg- patients. Hepatitis B virus (HBV) DNA was analyzed using nested PCR to amplify the Core (C) region and by real-time PCR to amplify a region of the S and X genes. The possible associations between the variables and OHBI were investigated using Pearson’s χ² and/or Fisher’s exact test.RESULTS: We found that the frequency of OHBI was 49% among the group of 49 HIV-1+/HBsAg- patients studied. The presence of OHBI was significantly associated with the HIV-1 RNA viral load [odds ratio (OR) = 8.75; P = 0.001; 95%CI: 2.26-33.79] and with HIV-antiretroviral treatment with drugs that interfere with HBV replication (lamivudine, tenofovir or emtricitabine) (OR = 0.25; P = 0.05; 95%CI: 0.08-1.05).CONCLUSION: The OHBI frequency is high among 49 Mexican HIV-1+/HBsAg- patients and it was more frequent in patients with detectable HIV RNA, and less frequent in patients who are undergoing HIV-ARV treatment with drugs active against HBV.     

Meta-analysis on the association of TIRAP S180L variant and tuberculosis susceptibility

The missense variant S180L in TIRAP (Toll-interleukin-1 receptor domain-containing adaptor protein) gene is implicated in attenuating TLRs signal transaction and may affect individual response to Mycobacterium tuberculosis infection. Several studies investigated the association between TIRAP S180L and risk of tuberculosis (TB), but the results were controversial. In this study, we quantitatively synthesized nine studies relevant to the association between TIRAP S180L polymorphism and TB risk with total 6584 TB cases and 7294 controls using meta-analysis. We found that the variant allele Leu180 and heterozygous genotype Ser/Leu were not significantly associated with risk of TB (allelic OR = 0.99, 95%CI: 0.88-1.11; Ser/Leu vs Ser/Ser: OR = 0.99, 95%CI: 0.87-1.13) with heterogeneity P values > 0.05. In subgroup analysis, none of the significant associations were observed for S180L and TB risk in Africans (allelic OR = 0.58, 95%CI: 0.29-1.61; heterozygous OR = 0.65, 95%CI: 0.32-1.32) or Asians (allelic OR = 1.30, 95%CI: 0.97-1.74; heterozygous OR = 1.17, 95%CI: 0.84-1.65) or risk of pulmonary tuberculosis (PTB) (allelic OR = 0.92, 95%CI: 0.69-1.22; heterozygous OR = 0.98, 95%CI: 0.86-1.12). This meta-analysis indicates that TIRAP S180L polymorphism is unlikely to substantially contribute to TB susceptibility.     

Defaulting from anti-tuberculosis treatment in a teaching hospital in Rio de Janeiro, Brazil.

SETTING: Few studies have investigated factors associated with defaulting from anti-tuberculosis (TB) therapy in hospital settings. OBJECTIVE: To identify the factors associated with defaulting from treatment among TB in-patients in Rio de Janeiro city, Brazil. DESIGN: Case-control study. METHODS: All study participants initiated anti-tuberculosis treatment in a teaching hospital. A defaulting case was defined as a person who did not return for anti-tuberculosis medications after 60 days. Cases and controls were interviewed by a trained health care worker using a standardized form. RESULTS: From 1 January to 31 December 1997, 228 TB cases were registered. After a review of the medical records, 39 were excluded. Household visits were performed in 189 patients; 46 subjects were identified as cases and 117 as controls. Defaulting from anti-tuberculosis treatment was observed in 66 cases (28.9%) before and in 46 (20.2%) after a home visit. After multivariate analysis, the strongest predictors of defaulting from treatment were: 1) returning card not provided (OR 0.099; 95%CI 0.008-1.2; P = 0.07), 2) not feeling comfortable with a doctor (OR 0.16; 95%CI 0.33-0.015; P = 0.001), and 3) blood pressure not measured (OR 0.072; 95%CI 0.036-0.79; P = 0.024). CONCLUSIONS: In this hospital, the factors associated with defaulting from anti-tuberculosis treatment highlight the necessity for a structured TB Control Program. It is expected that the implementation of such a program, pursuing specific approaches, should enhance completion of anti-tuberculosis treatment and cure.     

Hepatotoxicity of tuberculosis chemotherapy under general programme conditions in Singapore.

SETTING: The Singapore Tuberculosis (TB) Control Unit, a high volume national referral centre. OBJECTIVES: To determine the incidence, clinical course and outcome of TB drug-induced hepatitis (DH) and the risk factors associated with DH under general programme conditions. DESIGN: A retrospective review of adult patients started on TB treatment in 1998. RESULTS: There were 55 cases of DH in the cohort of 1036 patients treated in 1998. The median time to diagnosis of DH was 38 days. Factors significantly associated with DH were abnormal baseline transaminases/ bilirubin (OR 2.1, 95%CI 1.1-4.3, P = 0.02), age >60 years (OR 1.97, 95%CI 1.14-3.34, P = 0.01) and female sex (OR 1.9, 95%CI 1.07-3.4, P = 0.02). Ethnicity, self-reported alcohol consumption and body weight were not associated with development of DH. All three patients with fatal DH had received pyrazinamide-containing regimens. Treatment was re-introduced in 48 patients and successfully completed in 45 patients. The median time to reinstitution of TB treatment was 23 days. CONCLUSION: The incidence of TB drug-induced hepatitis was 5.3%. Age >60 years, abnormal baseline transaminase/bilirubin levels and female sex were risk factors associated with the development of TB drug-induced hepatitis.     

Hepatic steatosis in hepatitis B virus infected patients: meta-analysis of risk factors and comparison with hepatitis C infected patients

Background and Aims: Although hepatic steatosis (HS) has an association with hepatitis C virus (HCV) infection, an association with hepatitis B virus (HBV) is controversial. We performed a meta‐analysis to evaluate HS prevalence and risk factors, in HBV infection. Methods: Standard guidelines for performance of meta‐analyses were followed. Studies with HS assessed by histology were included. Pooled odd ratios (OR) and standardized mean differences (SMD) were obtained with the random‐effects model and DerSimonian‐Laid method. Results: Seventeen out of 21 studies were included, comprising 4100 HBV infected patients. Overall HS prevalence was 29.6%. Eight studies also included 945 HCV infected patients, showing decreased risk of HS in HBV versus HCV patients (OR 0.55, 95%CI [0.45–0.67], P < 0.001). In HBV, HS positively associated with male gender (OR 1.74, 95%CI [1.28–2.38], P < 0.001), body mass index (SMD 2.17, 95%CI [1.23, 3.11], P < 0.001), obesity (OR 6.59, 95%CI [3.51–12.257], P = 0.003), diabetes (OR 2.62, 95%CI [1.37–4.00], P = 0.004), glycemia (SMD 0.84, 95%CI [0.00, 1.67], P = 0.049), triglycerides (SMD 1.18, 95%CI [0.48, 1.89], P = 0.001), cholesterol (SMD 0.88, 95%CI [0.31, 1.45], P = 0.003), moderate alcohol consumption (OR 1.54, 95%CI [1.10–2.15], P = 0.011) and negatively with HBV DNA (SMD ?74.12, 95%CI [?82.93, ?65.31], P < 0.001). HS had no association with aminotransferases, HBeAg, genotype or hepatic histology, necroinflammation or fibrosis. Conclusion: HS in HBV seems to be as frequent as in the general population, and lower than in HCV infected patients, relating to metabolic factors but not with hepatic histology severity. A puzzling strong negative association between viral load and HS, may even suggest a protective effect of the virus on HS.     

Risk factors for new onset diabetes mellitus after liver transplantation: A meta-analysis

AIM: To determine the risk factors for new-onset diabetes mellitus(NODM) after liver transplantation by conducting a systematic review and meta-analysis.METHODS: We electronically searched the databases of MEDLINE, EMBASE and the Cochrane Library from January 1980 to December 2013 to identify relevant studies reporting risk factors for NODM after liver transplantation. Two authors independently assessed the trials for inclusion and extracted the data. Discrepancies were resolved in consultation with a third reviewer. All statistical analyses were performed with the Rev Man5.0 software(The Cochrane Collaboration, Oxford, United Kingdom). Pooled odds ratios(OR) or weighted mean differences(WMD) with 95% confidence intervals(CIs) were calculated using either a fixed effects or a random effects model, based on the presence(I2 50%) or absence(I2 50%) of significant heterogeneity. RESULTS: Twenty studies with 4580 patients were included in the meta-analysis, all of which were retrospective. The meta-analysis identified the following significant risk factors: hepatitis C virus(HCV) infection(OR = 2.68; 95%CI: 1.92-3.72); a family history of diabetes(OR = 1.69, 95%CI: 1.09-2.63, P 0.00001); male gender(OR = 1.53; 95%CI: 1.24-1.90; P 0.0001); impaired fasting glucose(IFG; OR = 3.27; 95%CI: 1.84-5.81; P 0.0001); a family history of diabetes(OR = 1.69; 95%CI: 1.09-2.63; P = 0.02); use of tacrolimus(OR = 1.34; 95%CI: 1.03-1.76; P = 0.03) and body mass index(BMI)(WMD = 1.19, 95%CI: 0.69-1.68, P 0.00001). Other factors, such as hepatitis B virus infection and alcoholism, were not found to be associated with the incidence of NODM.CONCLUSION: The study showed that HCV infection, IFG, a family history of diabetes, male gender, tacrolimus and BMI are risk factors for NODM after liver transplantation.     

Hepatitis B or C viral infection and risk of pancreatic cancer: A meta-analysis of observational studies

AIM: To investigate if there is an association between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the risk of pancreatic cancer. METHODS: All relevant studies published before 11 October, 2012 were identified by a systematic search of MEDLINE, EMBASE, BIOSIS Previews and the Cochrane Library databases and with cross-referencing. The observational studies that reported RR or OR estimates with 95%CIs for the association between HBV or HCV and pancreatic cancer were included. A random-effects model was used to summarize meta-analytic estimates. The Newcastle-Ottawa quality assessment scale was applied to assess the quality of the methodology in the included studies. RESULTS: A total of 8 eligible studies were selected for meta-analysis. Overall, chronic hepatitis B and inactive hepatitis B surface antigen (HBsAg) carrier state (HBsAg positive) had a significantly increased risk of pancreatic cancer with OR of 1.20 (95%CI: 1.01-1.39), especially in the Chinese population (OR = 1.30, 95%CI: 1.05-1.56). Past exposure to HBV (possible occult HBV infection) had an increased OR of pancreatic cancer risk (OR = 1.24, 95%CI: 1.05-1.42), especially among those patients without natural immunity [anti hepatitis B core (HBc) positive/hepatitis B surface antibody (anti HBs) negative], with OR of 1.67 (95%CI: 1.13-2.22). However, past exposure to HBV with natural immunity (anti-HBc positive/anti-HBs positive) had no association with pancreatic cancer development, with OR 0.98 (95%CI: 0.80-1.16), nor did the HBV active replication (hepatitis B e antigen positive status), with OR 0.98 (95%CI: 0.27-1.68). The risk of pancreatic cancer among anti-HBs positive patients was significantly lower than among anti-HBs negative patients (OR = 0.54, 95%CI: 0.46-0.62). Past exposure to HCV also resulted in an increased risk of pancreatic cancer (OR = 1.26, 95%CI: 1.03-1.50). Significant between-study heterogeneity was observed. Evidence of publication bias for HBV/HCV infection-pancreatic cancer association was not found.