The influence of risk factors on the severity of anti-tuberculosis drug-induced hepatotoxicity.

BACKGROUND: Hepatotoxicity is one of the most serious adverse effects of anti-tuberculosis drugs (ATD). Although many risk factors have been associated with ATD-induced hepatotoxicity, their influence on hepatitis severity has not been studied systematically. OBJECTIVES: To evaluate whether the presence of hepatotoxicity risk factors (advanced age, chronic liver disease, abuse of alcohol or other drugs or malnutrition) influences the severity of ATD-induced hepatotoxicity. DESIGN: A prospective cohort study of 471 active tuberculosis patients treated with isoniazid, rifampicin and pyrazinamide and followed in a tuberculosis clinic between January 1998 and July 2002. Incidence of hepatotoxicity and its severity according to the presence or absence of ATD-induced hepatitis risk factors was evaluated. RESULTS: The incidence of ATD-induced hepatotoxicity (serum transaminase > 3 x the upper limit of normal [ULN]) was 18.2% (42/231 patients) in the risk factor group and 5.8% (14/240 patients) in the non-risk factor group (OR 3.5; 95% CI 1.9-6.7; P < 0.001). Severe hepatotoxicity (transaminase > 10 x ULN) occurred in 6.9% (16/231) of the risk factor group and in 0.4% (1/240) (OR 17.7; 95% CI 2.3-135; P < 0.001) of the group without risk factors. CONCLUSIONS: ATD-induced hepatitis is significantly more frequent and more severe in patients with hepatotoxicity risk factors.     

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.     

A prospective study of antituberculous drug-induced hepatotoxicity in an area endemic for liver diseases

Purpose   Identification of risk factors associated with antituberculosis drug-induced hepatotoxicity (anti-TB-DIH) is important, especially in endemic area for TB and liver disease. This study assessed the incidence and risk factors of anti-TB-DIH in upper Egyptian patients treated for active pulmonary and extra-pulmonary TB. Methods  A total of 100 consecutive TB patients were prospectively followed up both clinically and biochemically before and during their course of anti-TB therapy with daily doses of isoniazid, rifampin, ethambutol, and pyrazinamide, or streptomycin. Results  Anti-TB-DIH developed in 15 (15%) patients within 15–60 days (median: 30 days) from the onset of therapy. Liver function normalized in 10 (60%) patients within 2 weeks from cessation of therapy. No recurrence of DIH was observed after reintroduction of therapy. Only 1 patient died from fulminant hepatic failure despite discontinuation of all anti-TB drugs. By univariate analysis, patients with anti-TB-DIH had more pre-existing liver disease (P = 0.024; OR: 3.60; 95% CI: 1.16–11.18), lower body mass index (BMI; P = 0.037; OR: 3.73; 95% CI: 1.04–10.56), lower serum albumin (P = 0.035; OR: 3.31; 95% CI: 1.04–10.56), and more extensive disease (P = 0.033; OR: 3.50; 95% CI: 1.11–11). Age, gender, raised baseline transaminases level, inclusion of pyrazinamide, and inactive hepatitis B or C carrier state were not significant risk factors of DIH. Using multivariate regression analysis, only pre-existing liver disease and lower BMI of 20 kg/m² or less were independent predictors of DIH (P = 0.024 and P = 0.047, respectively). Conclusion   Anti-TB-DIH is not uncommon, needs early recognition and treatment, and is more in patients with pre-existing liver disease and low BMI.     

艾滋病合并结核病患者抗结核治疗中肝损伤情况调查

目的 了解艾滋病合并结核病(HIV/TB)患者在标准化抗结核治疗中肝损伤的发生情况及对预后的影响.方法 对361例HIV/TB患者在抗结核治疗最初2月内(强化期)肝损伤发生率、程度、预后情况进行总结,并随机抽取382例抗HIV阴性结核病患者做对照.结果 HIV/TB组肝损伤总发生率为40.2％,严重肝损伤发生率为10.8％,因肝损伤更改抗结核方案为14.4％,治疗失败率为7.8％;HIV阴性组肝损伤总发生率为21.7％、严重肝损伤率为4.5％、更改抗结核方案者为5.2％、治疗失败率为0.8％,两组比较有统计学意义.结论 AIDS/TB患者抗结核治疗中易发生肝损伤,严重肝损伤患者增多,需更改治疗方案.     

Molecular epidemiology of tuberculosis in the Bata and Malabo districts of Equatorial Guinea.

SETTING: Bata and Malabo districts, Equatorial Guinea, 1 March 1999 to 28 February 2001. OBJECTIVE: To study the molecular epidemiology of tuberculosis (TB). RESULTS: During the study period, 429 patients were diagnosed with TB in the Bata and Malabo districts. A positive culture was obtained in 206 (48%) TB patients, with RFLP analysis being performed in 185 (89.8%). Ninety-two different patterns were identified. Single patterns were found in 71 strains (38.3%) and the remaining 114 strains (61.6%) were classified into 21 clusters (of 2 to 25 patients). In addition, 37 of the typing strains were resistant to one or more anti-tuberculosis drugs, and 30 were included in clusters (81%), with 21 low level isoniazid (MIC < or = 1 microg/ml) resistance strains in the same cluster. Statistical analysis showed that resistance to anti-tuberculosis drugs (OR 3.1; 95% CI 1.2-7.6; P = 0.014), and positive smear results (4+ grade smear) (OR 4.3; 95% CI 1.5-12; P = 0.005), were significantly more frequent among patients with clustered strains. No epidemiological links were related to clustering. CONCLUSIONS: The level of clustering (61.6%) observed suggests a high degree of recent transmission and a predominance of determined patterns of Mycobacterium tuberculosis strains among the population of Equatorial Guinea.     

Predictive factors of hyperlipidemia in HIV-infected subjects receiving lopinavir/ritonavir

We studied 382 multiexperienced HIV-infected patients followed up for > or =3 months after starting lopinavir/ritonavir (LPV/r) to identify the factors predicting hypertriglyceridemia and high non-HDL cholesterol levels (triglycerides > or =200 mg/dl and/or non-HDL cholesterol > or =190 mg/dl) after 6 and 12 months of LPV/r exposure. The predictors of hypertriglyceridemia were higher baseline triglyceride levels [OR: 2.28 (95% CI: 1.67-3.12) for each additional 100 mg/dl; p = 0.001], the total duration of antiretroviral treatment [OR: 1.26 (95% CI: 1.12-1.41) for each additional year; p = 0.01], CDC stage C (OR: 2.06; 95% CI: 1.24-3.88; p = 0.02), and male gender (OR: 2.52; 95% CI: 1.42-4.74; p = 0.02); intravenous drug abusers seem less likely to develop the event (OR: 0.52; 95% CI: 0.37-0.92; p = 0.03). The predictors of high non-HDL cholesterol levels were higher baseline levels [OR: 3.92 (95% CI: 1.92-6.24) for each additional 100 mg/dl; p = 0.001) and the combination of NRTIs and NNRTIs with LPV/r (OR: 1.83; 95% CI: 1.10-3.69; p = 0.03). The 75 patients stopping LPV/r showed a significant reduction in median triglyceride and non-HDL cholesterol levels after 3 months of 39 mg/dl and 20 mg/dl (p = 0.01 for both), respectively. Patients with high triglyceride and non- HDL cholesterol levels at the start of LPV/r treatment are at higher risk of developing hyperlipidemia.     

CYP2E1和NAT2基因多态性与抗结核药物诱导的药物性肝损伤关系的荟萃分析

目的明确细胞色素氧化酶P450 2E1(cytochrome P450 2E1,CYP2E1)和N-乙酰基转移酶-2(N-acetyltransferase-2,NAT2)基因多态性与抗结核药诱导的药物性肝损伤(anti-tuberculosis drug-induced hepatotoxicity,ATDH)之间的关系。方法计算机检索Medline/Pubmed、EMBASE、Web of Science数据库和Cochrane图书馆中所有有关CYP2E1基因多态性与ATDH关系的研究文献。根据文献纳入及排除标准筛选文献,并对文献进行质量评价。采用OR及95%CI作为分析疗效的统计量。采用Revman 5.0软件统计分析。结果共计纳入研究文献9篇,入选2049例研究对象。CYP2E1基因Pst I/Rsa I多态性中,c1/c1型比c1/c2和c2/c2型有更高的ATDH发生率(OR=1.38,95%CI:1.08~1.77,P=0.01);在Dra I多态性中各型之间无差异(OR=0.78,95%CI:0.51~1.18,P=0.23)。与携带NAT2快速或中速乙酰化的c1/c1型人群比较,携带NAT2慢速乙酰化的c1/c1型人群具有更高的ATDH风险(OR=3.10,P0.0001)。结论 CYP2E1基因c1/c1型是ATDH发生的风险因素,且合并慢速乙酰化的NAT2基因型时可进一步增加ATDH发生率。     

Evaluation of clinical parameters to predict Mycobacterium tuberculosis in inpatients

BACKGROUND: Respiratory isolation has been recommended for all patients with suspected tuberculosis (TB) to avoid transmission to other patients and health care personnel. In implementing these guidelines, patients with and without TB are frequently isolated, significantly increasing hospital costs. The objective of this study was to derive a clinical rule to predict the need for respiratory isolation of patients with suspected TB. METHODS: To identify potential predictors of the need for isolation, 56 inpatients with sputum cultures positive for TB were retrospectively compared with 56 controls who were isolated on admission to the hospital based on clinically suspected TB but whose sputum cultures tested negative for TB. Variables analyzed included TB risk factors, clinical symptoms, and findings from physical examination and chest radiography. RESULTS: Multivariate analysis revealed that the following factors were significantly associated with a culture positive for TB: presence of TB risk factors or symptoms (odds ratio [OR], 7.9 [95% confidence interval (CI), 4.4-24.2]), a positive purified protein derivative tuberculin test result (OR, 13.2 [95% CI, 4.4-40.7]), high temperature (OR, 2.8 [95% CI, 1.1-8.3]), and upper-lobe disease on chest radiograph (OR, 14.6 [95% CI, 3.7-57.5]). Shortness of breath (OR, 0.2 [95% CI, 0.12-0.53]) and crackles noted during the physical examination (OR, 0.29 [95% CI, 0.15-0.57]) were negative predictors of TB. A scoring system was developed using these variables. A patient's total score of 1 or higher indicated the need for respiratory isolation, accurately predicting a culture positive for TB (98% sensitivity [95% CI, 95%-100%]; 46% specificity [95% CI, 33%-59%]). CONCLUSION: Among inpatients with suspected active pulmonary TB, a prediction rule based on clinical and chest radiographic findings accurately identified patients requiring respiratory isolation.     

Risk factors for hepatotoxicity associated with rifampin and pyrazinamide for the treatment of latent tuberculosis infection: experience from three public health tuberculosis clinics.

SETTING: Three municipal tuberculosis (TB) clinics. OBJECTIVES: Reports of liver injury in patients treated with a 2-month regimen of daily rifampin and pyrazinamide (2RZ) for latent TB infection have raised concern about its safety. We aimed to evaluate the safety and tolerability of 2RZ and identify risk factors for hepatotoxicity. METHODS: We reviewed charts of adults started on 2RZ between 1999 and 2001. Cases with grade 3 hepatotoxicity (AST or ALT >5.0-20.0 x upper limit of normal) and grade 4 hepatotoxicity (AST or ALT >20.0 x upper limit of normal) were identified. RESULTS: Of 148 patients prescribed 2RZ, 85 (57.4%) completed therapy. Grade 3 or 4 hepatotoxicity occurred in 14 patients (eight grade 4 cases). In multivariate analysis, hepatotoxicity was associated with female sex (odds ratio [OR] 4.1; 95% confidence interval [CI] 1.2-14.3) and with presumed recent infection (recent tuberculin skin test conversion or contact with a TB case) (OR 14.3; 95%CI 1.8-115), but not with alcohol use, illicit drug use, age, race, or pyrazinamide dose. CONCLUSIONS: Hepatotoxicity occurred in a high proportion of patients prescribed 2RZ, and was more common among females and those with recent infection. Caution is warranted in using 2RZ in populations where its safety has not been established.     

Genetic polymorphisms of manganese superoxide dismutase, NAD(P)H:quinone oxidoreductase, glutathione S-transferase M1 and T1, and the susceptibility to drug-induced liver injury

BACKGROUND/AIMS: Drug metabolizing enzymes may be related to drug-induced liver injury (DILI). Manganese superoxide dismutase (MnSOD), NAD(P)H:quinone oxidoreductase (NQO1), and glutathione S-transferase (GST) are important drug metabolizing enzymes. We aimed to elucidate the relationship between genetic polymorphisms of these enzymes and the susceptibility to DILI. METHODS: A total of 115 patients with DILI and 115 drug-, sex-, and age-matched controls were enrolled. Their genetic polymorphisms of MnSOD, NQO1, GSTM1, and GSTT1 were assayed. RESULTS: Sixty-three (54.8%) of DILI patients were incriminated to anti-tuberculosis drugs. Subjects with a mutant C allele (T/C or C/C genotype) of MnSOD had a higher risk of DILI than those with MnSOD T/T genotype, both in overall drugs studied (adjusted OR: 2.44, 95% C.I.: 1.38-4.30, P=0.002), and in sub-category of anti-tuberculosis drugs (adjusted OR: 2.47, 95% C.I.: 1.13-5.39, P=0.02). In addition, subjects carrying GSTM1 null genotype had increased risk of anti-tuberculosis DILI (adjusted OR: 2.23, 95% C.I.: 1.07-4.67, P=0.03). CONCLUSIONS: The MnSOD mutant C allele may increase the susceptibility to DILI, and GSTM1 null genotype may be related to anti-tuberculosis drug-induced hepatotoxicity. Determination of the MnSOD and GSTM1 genotypes may help identify patients at high risk for DILI.     

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.     

Effect of anti-tuberculosis therapy on liver function of pulmonary tuberculosis patients infected with hepatitis B virus

AIM: To observe the effect of anti-tuberculosis therapy on liver function of pulmonary tuberculosis patients with hepatitis B virus (HBV) infection, and to compare the differences of liver function by two treatments of anti-tuberculosis. METHODS: Forty-seven TB patients with HBV infection and 170 TB patients without HBV infection were divided into HPBE(S) and HLAMKO treatment groups. Liver function tests before and after the treatments were performed once in 2 wk or monthly, and their clinical manifestations were recorded. RESULTS: The rate of hepatotoxicity occurred in 26 (59%) TB patients with HBV during anti-TB treatment, higher than that in 40 (24%) TB patients without HBV. Hepatotoxicity occurred in 66 out of 217 patients, and the incidence of liver dysfunction was 46.1% in HPBE(S) group, significantly higher than that in HLAMKO group (12.7%) (P<0.01). CONCLUSION: TB patients with HBV should choose HLAMKO treatment because of fewer hepatotoxicity.     

Response to empirical anti-tuberculosis treatment in patients with sputum smear-negative presumptive pulmonary tuberculosis

BACKGROUND: In many cases, physicians initiate anti-tuberculosis (TB) treatment based only on symptoms or radiographic findings without confirmation of pulmonary TB by acid-fast bacilli (AFB) smear. It has not been well known which clinical characteristics could be used as predictors for positive culture or real TB in patients with sputum smear-negative presumptive pulmonary TB. OBJECTIVE: We tried to elucidate treatment outcomes in patients with sputum smear-negative presumptive pulmonary TB and to find predictors of positive culture results. METHODS: We reviewed data of the patients who had been treated as presumptive TB with negative AFB smear on the basis of clinical and radiographic features from December 1998 to December 2000 at a university hospital in Korea. We reviewed medical records and radiographs of patients and analyzed possible predictors for positive culture. RESULTS: One hundred and one patients were enrolled. Among them, pulmonary TB was confirmed by culture in 32 patients (31%). Thirty-one (96.9%) out of 32 culture-positive patients showed clinical or radiographic improvement as did 50 (72.5%) out of 69 culture-negative patients. The predictor for a positive culture result is the presence of patchy consolidation in an initial radiograph (p = 0.025; OR 2.89; 95% CI 1.14-7.28). CONCLUSIONS: The empirical anti-TB treatment in patients with sputum smear-negative presumptive pulmonary TB was effective and adequate, especially presented with patchy consolidation in initial chest radiographs in Korea.     

Impact of country of origin on drug-resistant tuberculosis among foreign-born persons in British Columbia.

SETTING: Provincial tuberculosis (TB) services, British Columbia, Canada. OBJECTIVES: To estimate the risk of drug resistance among foreign-born TB patients and to identify risk factors associated with drug resistance. DESIGN: Using the provincial TB database, we examined all culture-positive foreign-born TB patients for the years 1990-2001. The risk of having a drug-resistant isolate was estimated according to country and region of origin. RESULTS: Of 1940 foreign-born patients identified, 247 (12.7%, 95%CI 11.3-14.3) cases had isolates resistant to at least one of the first-line drugs, with 160 (8.3%) isolates showing monoresistance, 24 (1.2%) multidrug resistance (resistance to at least isoniazid and rifampin) and 63 (3.3%) polyresistance (resistance to two or more drugs, excluding MDR). Country-specific analysis showed that immigrants from Vietnam (adjusted OR 2.12, 95%CI 1.37-3.27) and the Philippines (adjusted OR 1.71, 95%CI 1.10-2.66) had a significantly higher risk of resistance than other immigrants. In addition, the risk was the highest for younger TB patients and patients with reactivated disease (adjusted OR 2.12, 95%CI 1.09-4.09). CONCLUSION: The risk of drug resistance was the highest among foreign-born patients from Vietnam and the Philippines. These findings should assist clinicians in prescribing and tailoring anti-tuberculosis regimens for immigrants more appropriately.     

Extensively drug-resistant tuberculosis in South Korea: risk factors and treatment outcomes among patients at a tertiary referral hospital.

BACKGROUND: Extensively drug-resistant (XDR) tuberculosis (TB) is a major public health threat in South Korea. METHODS: We analyzed baseline epidemiological data for 250 patients enrolled in an ongoing prospective observational study of TB at a large tertiary referral hospital in South Korea. RESULTS: Twenty-six subjects with XDR TB were identified; all were patients who had previously received TB therapy. Cumulative previous treatment duration (range, 18-34 months; odds ratio [OR], 5.6; 95% confidence interval [CI], 1.0-59), number of previously received second-line anti-TB drugs (OR, 1.3; 95% CI, 1.1-1.5), and female sex (OR, 3.2; 95% CI, 1.1-8.3) were significantly associated with XDR TB in crude analyses. After controlling for other factors in a multivariable model, cumulative previous treatment duration remained significantly associated with XDR TB (OR, 5.8; 95% CI, 1.0-61). Subjects with XDR TB were more likely to produce culture-positive sputum at 6 months, compared with patients with non-multidrug resistant TB (risk ratio, 13; 95% CI, 5.1-53). Kanamycin resistance was found to be predictive of 6-month culture positivity after adjustment for ofloxacin and streptomycin resistance (risk ratio, 3.9; 95% CI, 1.9-11). CONCLUSIONS: XDR TB was found to be associated with the cumulative duration of previous treatment with second-line TB drugs among subjects in a tertiary care TB hospital. Patients with XDR TB were more likely to not respond to therapy, and successful conversion of sputum culture results to negative was correlated with initial susceptibility to both fluoroquinolones and kanamycin but not to streptomycin.     

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.     

Acute renal failure in hospitalized patients with HIV: risk factors and impact on in-hospital mortality

BACKGROUND: Kidney disease is an increasingly important complication of HIV. OBJECTIVES: To examine the incidence and predictors of acute renal failure before and after the introduction of HAART, and the impact of acute renal failure on in-hospital mortality in the post-HAART era. METHODS: Adults hospitalized in acute care hospitals in New York State during 1995 (pre-HAART) or 2003 (post-HAART) were identified from the state Planning and Research Cooperative System database. HIV status was defined by primary or secondary diagnosis code. The impact of HIV and HAART on the incidence of acute renal failure and mortality, and the impact of acute renal failure on mortality, was assessed using chi analysis and multivariate regression. RESULTS: There were 52,580 HIV-infected patients discharged from hospital in 1995 and 25,114 in 2003. Compared with uninfected patients, HIV-infected patients had an increased incidence of acute renal failure in both the pre-HAART [adjusted odds ratio (OR), 4.62; 95% confidence interval (CI), 4.30-4.95] and post-HAART eras (adjusted OR, 2.82; 95% CI, 2.66-2.99). In the post-HAART cohort, acute renal failure was associated with traditional predictors such as age, diabetes mellitus, and chronic kidney disease, as well as acute or chronic liver failure or hepatitis coinfection (P < 0.001 for all comparisons). Acute renal failure was associated with mortality among HIV-infected patients in the post-HAART era (OR, 5.83; 95% CI, 5.11-6.65). CONCLUSIONS: Acute renal failure remains common among hospitalized patients with HIV and is associated with chronic kidney disease, liver disease, and increased mortality.     

Drug-induced liver injury in hospitalized HIV patients: high incidence and association with drugs for tuberculosis

Background. The evaluation of liver disease in HIV patients is cumbersome because may result from a number of different causes. The aim of this retrospective study was to estimate the incidence of severe drug induced liver injury (DILI) in a group of HIV inpatients and investigate potential risk factors.Material and methods. We performed a retrospective analysis of data from HIV-infected patients hospitalized between August 2010 and August 2011 in a tertiary hospital in São Paulo, Brazil. Severe hepatotoxicity was defined as grade 3 (5.1 to 10 × ULN) or 4 (> 10 × ULN) of ALT and AST levels. Factors analyzed included demographics, infection with hepatitis viruses, alcohol history and use of hepatotoxic drugs prior to or during hospital admission.Results. A total of 149 patients with HIV were hospitalized during the study period. The majority were male over 42 years of age and 82 (55%) were taking HAART initiated prior to admission. Mean CD4 counts were 164 cells/mm³. Thirty three patients (22.1%) developed severe DILI during hospital stay, which had a mean duration of 26 days. Factors associated with severe DILI in the multivariate analysis were abnormal baseline ALT levels [OR 2.02 (95%CI 1.13-3.59); p = 0.017] and tuberculosis therapy [OR 2.31 (95% CI 1.27-4.19); p = 0.006]. In conclusion, in this group of HIV patients admitted to a tertiary hospital in Brazil, we found a high incidence (22.1%) of severe DILI. The use of anti-tuberculosis drugs and baseline liver injury were independent factors associated with severe DILI during hospital stay.     

Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is common in severely obese subjects and can progress to cirrhosis and liver failure. Predicting advanced or progressive disease may help in selecting patients for liver biopsy and assist the development of therapeutic options. METHODS: Liver biopsies were taken at laparoscopic obesity surgery in 105 consecutive patients. The clinical and biochemical variables were analyzed for correlation with specific histologic features. RESULTS: Twenty-six patients (25%) were found to have nonalcoholic steatohepatitis (NASH), and 11 (42%) of these had advanced fibrosis. A raised index of insulin resistance (odds ratio [OR] 9.3, 95% confidence interval [CI] 3.4-26), systemic hypertension (OR 5.2, 95% CI 2.0-13.5), and raised alanine aminotransferase (OR 8.6, 95% CI 3.1-23.5) were independent predictors of NASH. A combination of 2 or 3 of these predictors allows a sensitivity of 0.8 and specificity of 0.89 for NASH. Alcohol consumption was associated with a reduction in NASH (OR 0.35, 95% CI 0.12-1.00) and diabetes (OR 0.18, 95% CI 0.047-0.67). CONCLUSION: Insulin resistance and systemic hypertension, features of the metabolic syndrome, are independently associated with advanced forms of NAFLD. Moderate alcohol consumption seems to reduce the risk of NAFLD in the severely obese, possibly by reducing insulin resistance.