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Zheng SM, Lin N, Tang SH, Yang JY, Wang HQ, Luo SL, Zhang Y, Mu D. Isolated hepatic tuberculosis associated with portal vein thrombosis and hepatitis B virus coinfection: A case report and review of the literature. World J Clin Cases 2021; 9:9310-9319. [PMID: 34786418 PMCID: PMC8567534 DOI: 10.12998/wjcc.v9.i30.9310] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Revised: 08/09/2021] [Accepted: 09/08/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND While tuberculosis (TB) itself is a common disease, isolated TB of the liver is a rare entity. Tubercular involvement of the liver is more commonly a part of a disseminated disease of the hepatic parenchyma. In contrast, isolated hepatic TB spread through the portal vein from the gastrointestinal tract is seldom encountered in clinical practice, with only a few sporadic cases and short series available in the current literature. Vascular complications, such as portal vein thrombosis (PVT), have rarely been reported previously.
CASE SUMMARY A 22-year-old man was hospitalized with complaints of a 3-mo history of fever and weight loss of approximately 10 kg. He had a 10-year hepatitis B virus (HBV) infection in his medical history. Contrast-enhanced computed tomography (CECT) confirmed hepatosplenomegaly, with hypodensity of the right lobe of the liver and 2.1 cm thrombosis of the right branch of the portal vein. A liver biopsy showed epithelioid granulomas with a background of caseating necrosis. Ziehl-Nelson staining showed acid-fast bacilli within the granulomas. The patient was diagnosed with isolated hepatic TB with PVT. Anti-TB therapy (ATT), including isoniazid, rifapentine, ethambutol, and pyrazinamide, was administered. Along with ATT, the patient was treated with entecavir as an antiviral medication against HBV and dabigatran as an anticoagulant. He remained asymptomatic, and follow-up sonography of the abdomen at 4 mo showed complete resolution of the PVT.
CONCLUSION Upon diagnosis of hepatic TB associated with PVT and HBV coinfection, ATT and anticoagulants should be initiated to prevent subsequent portal hypertension. Antiviral therapy against HBV should also be administered to prevent severe hepatic injury.
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Affiliation(s)
- Shu-Mei Zheng
- Department of Gastroenterology and Hepatology, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Ning Lin
- Department of Clinical Nutrition, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Shan-Hong Tang
- Department of Gastroenterology and Hepatology, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Jia-Yi Yang
- School of Medical Imaging, Nanjing Medical University, Nanjing 211166, Jiangsu Province, China
| | - Hai-Qiong Wang
- Department of Gastroenterology and Hepatology, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Shu-Lan Luo
- Department of Gastroenterology and Hepatology, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Yong Zhang
- Department of Gastroenterology and Hepatology, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Dong Mu
- Department of Gastroenterology and Hepatology, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
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Behzadifar M, Heydarvand S, Behzadifar M, Bragazzi NL. Prevalence of Hepatitis C Virus in Tuberculosis Patients: A Systematic Review and Meta-Analysis. Ethiop J Health Sci 2019; 29:945-956. [PMID: 30700963 PMCID: PMC6341432 DOI: 10.4314/ejhs.v29i1.17] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background Infection with Hepatitis C Virus (HCV) increases the hepatotoxicity of anti-tuberculosis drugs. The purpose of this systematic review and meta-analysis is to determine the prevalence of HCV infection in patients with tuberculosis (TB). Methods PubMed/MEDLINE, ISI/Web of Sciences, CINAHL, EMBASE, the Cochrane Library and Scopus were searched from January 2000 to March 2018. The overall prevalence of HCV in patients with TB was calculated using the random-effect model with 95% confidence interval (CI). To evaluate heterogeneity, I2 test was used. Egger's regression test was utilized to check publication bias. Results Twenty-one articles were selected for the final analysis based on the inclusion/exclusion criteria. A total of 15,542 patients with TB participated in the studies. The overall prevalence of HCV infection in patients with TB was 7% [95%CI: 6–9]. Subgroup analysis revealed that diagnostic test (P=0.0039), geographical background (P=0.0076) and gender distribution (P=0.0672) were statistically significant moderators. Men had a higher risk for HCV than women (Odds Ratio, OR=2.02; 95%CI: 1.28–3.18). Conclusion The results of this study highlighted the importance of screening HCV in TB patients. Knowing whether HCV is present or not in these patients can be helpful in effectively treating them.
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Affiliation(s)
- Meysam Behzadifar
- Hepatitis Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Sanaz Heydarvand
- Bahrami Pediatric Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Behzadifar
- Health Management and Economics Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Nicola Luigi Bragazzi
- School of Public Health, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
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Teschke R, Danan G. Diagnosis and Management of Drug-Induced Liver Injury (DILI) in Patients with Pre-Existing Liver Disease. Drug Saf 2017; 39:729-44. [PMID: 27091053 DOI: 10.1007/s40264-016-0423-z] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The relationship between drugs and pre-existing liver disease is complex, particularly when increased liver tests (LTs) or new symptoms emerge in patients with pre-existing liver disease during drug therapy. This requires two strategies to assess whether these changes are due to drug-induced liver injury (DILI) as a new event or due to flares of the underlying liver disease. Lacking a valid diagnostic biomarker, DILI is a diagnosis of exclusion and requires causality assessment by RUCAM, the Roussel Uclaf Causality Assessment Method, to establish an individual causality grading of the suspected drug(s). Flares of pre-existing liver disease can reliably be assessed in some hepatotropic virus infections by polymerase chain reaction (PCR) and antibody titers at the beginning and in the clinical course to ascertain flares during the natural course of the disease. Unfortunately, flares cannot be verified in many other liver diseases such as alcoholic liver disease, since specific tests are unavailable. However, such a diagnostic approach using RUCAM applied to suspected DILI cases includes clinical and biological markers of pre-existing liver diseases and would determine whether drugs or underlying liver diseases caused the LT abnormalities or the new symptoms. More importantly, a clear diagnosis is essential to ensure effective disease management by drug cessation or specific treatment of the flare up due to the underlying disease.
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Affiliation(s)
- Rolf Teschke
- Division of Gastroenterology and Hepatology, Department of Internal Medicine II, Klinikum Hanau, Leimenstrasse 20, 63450, Hanau, Germany. .,Academic Teaching Hospital of the Medical Faculty, Goethe University Frankfurt/Main, Frankfurt/Main, Germany.
| | - Gaby Danan
- Pharmacovigilance Consultancy, Paris, France
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Saito Z, Kaneko Y, Kinoshita A, Kurita Y, Odashima K, Horikiri T, Yoshii Y, Seki A, Seki Y, Takeda H, Kuwano K. Effectiveness of hepatoprotective drugs for anti-tuberculosis drug-induced hepatotoxicity: a retrospective analysis. BMC Infect Dis 2016; 16:668. [PMID: 27835982 PMCID: PMC5105306 DOI: 10.1186/s12879-016-2000-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Accepted: 10/29/2016] [Indexed: 01/20/2023] Open
Abstract
Background The effectiveness of hepatoprotective drugs for DIH (drug induced hepatotoxicity) during tuberculosis treatment is not clear. We evaluated the effectiveness of hepatoprotective drugs by comparing the period until the normalization of hepatic enzymes between patients who were prescribed with the hepatoprotective drugs after DIH was occurred and patients who were not prescribed with the hepatoprotective drugs. Methods During 2006–2010, 389 patients with active tuberculosis were included in this study. DIH was defined as elevation of peak serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) of more than twice the upper limit of normal (ULN). We divided the patients into the severe (peak serum AST and/or ALT elevation of >5 times the ULN), moderate (peak serum AST and/or ALT elevation of >3 to ≤5 times the ULN), and mild DIH groups (peak serum AST and/or ALT elevation of >2 to ≤3 times the ULN). We compared the average period until the normalization of hepatic enzymes between patient subgroups with and without hepatoprotective drugs (ursodeoxycholic acid: UDCA, stronger neo-minophagen C: SNMC, and glycyrrhizin). Results In the severe group, there was no significant difference in the average period until the normalization between subgroups with and without hepatoprotective drugs (21.4 ± 10.8 vs 21.5 ± 11.1 days, P = 0.97). In the mild group, the period was longer in the subgroup with hepatoprotective drugs than that without hepatoprotective drugs (15.7 ± 6.2 vs 12.4 ± 7.9 days, P = 0.046). Conclusion Regardless of the severity, hepatoprotective drugs did not shorten the period until the normalization of hepatic enzymes.
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Affiliation(s)
- Zenya Saito
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae-shi, Tokyo, 201-8601, Japan.
| | - Yugo Kaneko
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae-shi, Tokyo, 201-8601, Japan
| | - Akira Kinoshita
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae-shi, Tokyo, 201-8601, Japan
| | - Yusuke Kurita
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae-shi, Tokyo, 201-8601, Japan
| | - Kyuto Odashima
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae-shi, Tokyo, 201-8601, Japan
| | - Tsugumi Horikiri
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae-shi, Tokyo, 201-8601, Japan
| | - Yutaka Yoshii
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Aya Seki
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae-shi, Tokyo, 201-8601, Japan
| | - Yoshitaka Seki
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae-shi, Tokyo, 201-8601, Japan
| | - Hiroshi Takeda
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae-shi, Tokyo, 201-8601, Japan
| | - Kazuyoshi Kuwano
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
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Lin HS, Cheng CW, Lin MS, Chou YL, Chang PJ, Lin JC, Ye JJ. The clinical outcomes of oldest old patients with tuberculosis treated by regimens containing rifampicin, isoniazid, and pyrazinamide. Clin Interv Aging 2016; 11:299-306. [PMID: 27042029 PMCID: PMC4795580 DOI: 10.2147/cia.s95411] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Objectives To investigate the clinical characteristics, adverse drug reactions, and outcomes of the oldest old patients (aged ≥80 years) with tuberculosis (TB) treated with rifampicin, isoniazid, and pyrazinamide (RIP)-containing regimens. Design A retrospective chart review study. Setting A 1,200-bed tertiary teaching hospital in southwest Taiwan. Participants We conducted a retrospective observational study between January 1, 2005 and December 31, 2011. Seven hundred adult patients (aged ≥18 years) with TB treated with RIP-containing anti-TB regimens were reviewed, including 161 oldest old patients. Outcome measures Clinical outcomes included clinical responsiveness and microbiological eradication. Adverse outcomes included drug-induced hepatitis, and other symptoms included gastrointestinal upset (eg, abdominal pain, vomiting, diarrhea, or dyspepsia), skin rash, joint pain, and hyperuricemia. Results Compared with the non-oldest old adult patients, the oldest old patients more frequently had hepatitis (P=0.014), gastrointestinal upset (P=0.029), and unfavorable outcomes (P<0.001). In a multivariate analysis, hepatitis during treatment (adjusted odds ratio: 3.482, 95% confidence interval: 1.537–7.885; P<0.003) and oldest old age (adjusted odds ratio: 5.161, 95% confidence interval: 2.294–11.613; P<0.010) were independent risk factors for unfavorable outcomes. In the oldest old patients with hepatitis, rifampicin use was more common in the favorable outcome group than in the unfavorable outcome group (100% vs 37.5%; P=0.001). Conclusion The oldest old age and hepatitis during RIP treatment were associated with unfavorable outcomes. For the oldest old patients with TB having hepatitis during treatment, rifampicin rechallenge and use might benefit the treatment outcome.
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Affiliation(s)
- Huang-Shen Lin
- Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital, Chia-Yi, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chun-Wen Cheng
- Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Ming-Shyan Lin
- Division of Cardiology, Chang Gung Memorial Hospital, Yunlin, Taiwan
| | - Yen-Li Chou
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital, Chia-Yi, Taiwan
| | - Pey-Jium Chang
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jing-Chi Lin
- Division of Allergy and Immunology and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chia-Yi, Taiwan
| | - Jung-Jr Ye
- Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
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Sun Q, Zhang Q, Gu J, Sun WW, Wang P, Bai C, Xiao HP, Sha W. Prevalence, risk factors, management, and treatment outcomes of first-line antituberculous drug-induced liver injury: a prospective cohort study. Pharmacoepidemiol Drug Saf 2016; 25:908-17. [PMID: 26935778 DOI: 10.1002/pds.3988] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2015] [Revised: 01/10/2016] [Accepted: 02/03/2016] [Indexed: 12/17/2022]
Abstract
PURPOSE Antituberculosis drug-induced liver injury (ATDILI) is one of the most deleterious side effects associated with chemotherapy against tuberculosis (TB). In this study, our objective was to determine the incidence, risk factors, and management of ATDILI and analyze its impact on the treatment outcome in patients receiving standard anti-TB chemotherapy. METHODS A prospective cohort study of ATDILI prevalence was conducted in 938 enrolled patients of the 1426 TB cases in Shanghai from March 2011 to September 2012. Patients were followed up until February 2014. Univariate and multivariate logistic regression analyses were used to determine the risk factors of ATDILI. Successful therapeutic outcome, rates of drug resistance conversion, sputum smear/culture conversion, and lung cavity closure were analyzed. RESULTS Hepatitis B surface antigen/hepatitis B e antigen-positive hepatitis B carriers, complicated with systemic lupus erythematosus, albumin ≤ 25 g/L, and chronic alcoholism were independent risk factors for ATDILI. Of the 121 cases with ATDILI (incidence rate of 12.9%), 84 (69.4%) used modified anti-TB therapy after recovery of liver function. Compared with the non-ATDILI group, patients with ATDILI exhibited remarkably decreased lung cavity closure rate (84.6% vs. 93.0%, P < 0.001) along with significantly reduced sputum smear/culture conversion rate (85.4% vs. 94.0%, P < 0.001). CONCLUSIONS Our findings indicated that 12.9% patients developed ATDILI during standard anti-TB therapy, resulting in poor therapeutic outcome. Hepatitis B carriers with systemic lupus erythematosus, albumin ≤ 25 g/L, and chronic alcoholism manifested increased risks for ATDILI. Copyright © 2016 John Wiley & Sons, Ltd.
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Affiliation(s)
- Qin Sun
- Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.,Department of Respiratory and Critical Care Medicine, Changhai Hospital, the Second Military Medical University, Shanghai, China
| | - Qing Zhang
- Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jin Gu
- Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Wen-Wen Sun
- Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Peng Wang
- Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Chong Bai
- Department of Respiratory and Critical Care Medicine, Changhai Hospital, the Second Military Medical University, Shanghai, China
| | - He-Ping Xiao
- Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Wei Sha
- Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
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Kim WS, Lee SS, Lee CM, Kim HJ, Ha CY, Kim HJ, Kim TH, Jung WT, Lee OJ, Hong JW, You HS, Cho HC. Hepatitis C and not Hepatitis B virus is a risk factor for anti-tuberculosis drug induced liver injury. BMC Infect Dis 2016; 16:50. [PMID: 26833347 PMCID: PMC4736472 DOI: 10.1186/s12879-016-1344-2] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Accepted: 01/12/2016] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND The risk of anti-tuberculosis (TB) drug-induced liver injury (DILI) in patients with chronic viral hepatitis (CVH) is not clear. The aim of this study was to investigate incidence and risk factors associated with TB DILI in CVH and non-CVH patients. METHODS Retrospectively, a total of 128 CVH patients who received anti-TB medication from January 2005 to February 2014 were reviewed. Among these, 83 patients had hepatitis B virus (HBV), 41 patients had hepatitis C virus (HCV) and 4 patients were dual hepatitis B and hepatitis C virus co-infected (HBV + HCV) with 251 non-CVH patients who received anti-TB medication selected as the controls. There were no human immunodeficiency virus co-infected patients. Risk factors for DILI were analyzed using cox regression analysis. RESULTS The incidence of DILI was significantly higher in the HCV group (13/41 [31.7%], p < 0.001) and HBV + HCV groups (3/4 [75.0%], p = 0.002) compared to the control group (25/251 [10.0%]). The incidence of transient liver function impairment in the hepatitis B virus group was higher than in the control group (18/83 [21.7%] vs. 27/251 [10.8%] p = 0.010), but not in DILI (11/83 [13.3%] vs. 25/251 [10.0%], p = 0.400). In total patients, HCV, HBV + HCV co-infection, older age, and baseline liver function abnormality were independent factors of DILI. CONCLUSIONS It is recommended to carefully monitor for DILI in patients with HCV or HBV/HCV co-infection, older age, and baseline liver function abnormality.
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Affiliation(s)
- Wan Soo Kim
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Gangnam-ro 79, Jinju, Gyeognam, 660-702, South Korea.
| | - Sang Soo Lee
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Gangnam-ro 79, Jinju, Gyeognam, 660-702, South Korea.
| | - Chang Min Lee
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Gangnam-ro 79, Jinju, Gyeognam, 660-702, South Korea.
| | - Hong Jun Kim
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Gangnam-ro 79, Jinju, Gyeognam, 660-702, South Korea.
| | - Chang Yoon Ha
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Gangnam-ro 79, Jinju, Gyeognam, 660-702, South Korea.
| | - Hyun Jin Kim
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Gangnam-ro 79, Jinju, Gyeognam, 660-702, South Korea.
| | - Tae Hyo Kim
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Gangnam-ro 79, Jinju, Gyeognam, 660-702, South Korea.
| | - Woon Tae Jung
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Gangnam-ro 79, Jinju, Gyeognam, 660-702, South Korea.
| | - Ok Jae Lee
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Gangnam-ro 79, Jinju, Gyeognam, 660-702, South Korea.
| | - Jeong Woo Hong
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Gangnam-ro 79, Jinju, Gyeognam, 660-702, South Korea.
| | - Hyun Seon You
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Gangnam-ro 79, Jinju, Gyeognam, 660-702, South Korea.
| | - Hyun Chin Cho
- Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Palyong-ro, 158, MasanHoiwon-gu, Chang-Won, Republic of Korea.
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Nooredinvand HA, Connell DW, Asgheddi M, Abdullah M, O’Donoghue M, Campbell L, Wickremasinghe MI, Lalvani A, Kon OM, Khan SA. Viral hepatitis prevalence in patients with active and latent tuberculosis. World J Gastroenterol 2015; 21:8920-8926. [PMID: 26269682 PMCID: PMC4528035 DOI: 10.3748/wjg.v21.i29.8920] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2014] [Revised: 02/23/2015] [Accepted: 04/09/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and association with drug induced liver injury (DILI) in patients undergoing anti-tuberculosis (TB) therapy.
METHODS: Four hundred and twenty nine patients with newly diagnosed TB - either active disease or latent infection - who were due to commence anti-TB therapy between September 2008 and May 2011 were included. These patients were prospectively tested for serological markers of HBV, HCV and human immunodeficiency virus (HIV) infections - hepatitis B core antigen (HBcAg), hepatitis B surface antigen (HBsAg), hepatitis B e antigen, IgG and IgM antibody to HBcAg (anti-HBc), HCV IgG antibody and HIV antibody using a combination of enzyme-linked immunosorbent assay, Western blot assay and polymerase chain reaction techniques. Patients were reviewed at least monthly during the TB treatment initiation phase. Liver function tests were measured prior to commencement of anti-TB therapy and 2-4 wk later. Liver function tests were also performed at any time the patient had significant nausea, vomiting, rash, or felt non-specifically unwell. Fisher’s exact test was used to measure significance in comparisons of proportions between groups. A P value of less than 0.05 was considered statistically significant.
RESULTS: Of the 429 patients, 270 (62.9%) had active TB disease and 159 (37.1%) had latent TB infection. 61 (14.2%) patients had isolated anti-HBc positivity, 11 (2.6%) were also HBsAg positive and 7 (1.6%) were HCV-antibody positive. 16/270 patients with active TB disease compared to 2/159 patients with latent TB infection had markers of chronic viral hepatitis (HBsAg or HCV antibody positive; P = 0.023). Similarly the proportion of HBsAg positive patients were significantly greater in the active vs latent TB infection group (10/43 vs 1/29, P = 0.04). The prevalence of chronic HBV or HCV was significantly higher than the estimated United Kingdom prevalence of 0.3% for each. We found no association between DILI and presence of serological markers of HBV or HCV. Three (5.3%) patients with serological markers of HBV or HCV infection had DILI compared to 25 (9.5%) patients without; P = 0.04.
CONCLUSION: Viral hepatitis screening should be considered in TB patients. DILI risk was not increased in patients with HBV/HCV.
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Shin HJ, Kwon YS. Treatment of Drug Susceptible Pulmonary Tuberculosis. Tuberc Respir Dis (Seoul) 2015; 78:161-7. [PMID: 26175767 PMCID: PMC4499581 DOI: 10.4046/trd.2015.78.3.161] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Revised: 03/30/2015] [Accepted: 03/31/2015] [Indexed: 11/24/2022] Open
Abstract
Tuberculosis (TB) remains a major global health problem, and the incidence of TB cases has not significantly decreased over the past decade in Korea. The standard short course regimen is highly effective against TB, but requires multiple TB-specific drugs and a long treatment duration. Recent studies using late-generation fluoroquinolones and/or high-dose rifapentine-containing regimens to shorten the duration of TB treatment showed negative results. Extending the treatment duration may be considered in patients with cavitation on the initial chest radiograph and positivity in sputum culture at 2 months of treatment for preventing TB relapse. Current evidence does not support the use of fixed-dose combinations compared to separate drugs for the purpose of improving treatment outcomes. All patients receiving TB treatment should be monitored regularly for response to therapy, facilitation of treatment completion, and management of adverse drug reactions. Mild adverse effects can be managed with symptomatic therapy and changing the timing of the drug administration, but severe adverse effects require a discontinuation of the offending drugs.
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Affiliation(s)
- Hong-Joon Shin
- Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Korea
| | - Yong-Soo Kwon
- Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Korea
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Abstract
Drug-induced hepatitis (DIH) is one of the major complications among the treatment of patients with tuberculosis (TB); it might even be fatal. This study tries to address the recurrence of DIH with 2 anti-TB regimens. In the retrospective study from 2007 to 2010, 135 TB patients with DIH who were older than 16 years were entered to study. The patients with DIH were randomly treated with a regimen, including isoniazid, rifampin, and ethambutol, plus either ofloxacin or pyrazinamide. The patients were reviewed for occurrence of recurrent DIH. Cure and completed treatment were considered as acceptable treatment outcomes, whereas default of treatment, treatment failure, and death were considered to be unacceptable outcomes. Therefore, 135 subjects with DIH were reviewed, and 23 patients (17%) experienced recurrence of hepatitis (19 cases in the ofloxacin group and 4 cases in the pyrazinamide group). There is no significant difference in recurrence of hepatitis between these 2 groups (P = 0.803). An acceptable outcome was observed in 95 patients (70.4%), and an unacceptable outcome was seen in 14 cases (10.3%). There was no significant difference in outcomes between these 2 regimens (P = 0.400, odds ratio = 1.62, 95% confidence interval, 0.524-4.98). The results of our study suggest that ofloxacin-based anti-TB regimen does not decrease the risk of recurrent DIH. Therefore, adding ofloxacin in the case of DIH is not recommended.
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Agha MA, El-Mahalawy II, Seleem HM, Helwa MA. Prevalence of hepatitis C virus in patients with tuberculosis and its impact in the incidence of anti-tuberculosis drugs induced hepatotoxicity. EGYPTIAN JOURNAL OF CHEST DISEASES AND TUBERCULOSIS 2015. [DOI: 10.1016/j.ejcdt.2014.09.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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Prevalence, drug-induced hepatotoxicity, and mortality among patients multi-infected with HIV, tuberculosis, and hepatitis virus. Int J Infect Dis 2014; 28:95-100. [PMID: 25218771 DOI: 10.1016/j.ijid.2014.06.020] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2014] [Revised: 06/09/2014] [Accepted: 06/27/2014] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVES To investigate the prevalence, incidence of abnormal liver function tests (LFTs), and mortality during anti-TB treatment in patients multi-infected with HIV, tuberculosis (TB), and hepatitis virus (hepatitis B virus (HBV) and hepatitis C virus (HCV)). METHODS Three hundred and sixty-one HIV-positive TB patients were enrolled and divided into an HIV/TB group, HIV/TB/HBV group, and HIV/TB/HCV group; 1013 HIV-negative TB patients were selected randomly as controls. RESULTS One hundred and seventeen (32.4%) HIV-positive TB patients were infected with HBV and/or HCV, compared with 90 (8.9%) HIV-negative TB patients (p=0.000). HIV-positive TB patients had a higher incidence of anti-TB drug-induced hepatotoxicity than HIV-negative TB patients (4.2% vs. 1.0%, odds ratio (OR) 4.348, 95% confidence interval (CI) 1.935-9.769, p=0.000). The incidence of abnormal LFTs in the HIV/TB/HBV group and HIV/TB/HCV group were significantly higher than in the HIV/TB group (40.7% vs. 11.1%, OR 5.525, 95% CI 2.325-13.131, p=0.000; 20.0% vs. 11.1%, OR 2.009, 95% CI 1.057-3.820, p=0.031). A total of 68.4% of patients with HBV-DNA >1.0×10(5) copies/ml and 42.9% of patients with HCV-RNA >1.0×10(5) copies/ml had abnormal LFTs. Twenty-three (19.7%) patients multi-infected with HIV, TB, and hepatitis virus died during anti-TB treatment. CONCLUSIONS HIV, HBV, and HCV are risk factors for the development of abnormal LFTs and mortality during anti-TB treatment. TB patients co-infected with HIV and hepatitis virus need close follow-up.
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Anti-tuberculosis drug-induced liver injury in Shanghai: validation of Hy's Law. Drug Saf 2014; 37:43-51. [PMID: 24203912 DOI: 10.1007/s40264-013-0119-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
INTRODUCTION The most reliable liver safety signal in a clinical trial is considered to be 'Hy's Law cases' defined as subjects experiencing hepatocellular injury and serum bilirubin elevations with no more likely cause than study drug. However, there is little published data to support the current biochemical criteria for Hy's Law cases or their use to estimate postmarketing risk of severe liver injury. OBJECTIVES The primary objective of this study was to identify and characterize Hy's Law cases in patients treated for tuberculosis (TB). A secondary objective was to identify patient risk factors for drug-induced liver injuries. METHODS We utilized eDISH (evaluation of Drug-Induced Serious Hepatoxicity) to retrospectively analyze data from 517 patients treated for activeTB, a regimen well known to be capable of causing severe hepatotoxicity. RESULTS We identified two Hy's Law cases, which is consistent with the treatment's known risk of liver failure. Despite monthly monitoring, neither Hy's Law case experienced a documented elevation in serum alanine aminotransferase exceeding 10 × upper limits of normal. Hepatoprotectant use and infection with chronic hepatitis B were associated with increased risk of liver injury. CONCLUSIONS Our observations support the current biochemical criteria for Hy's Law cases and their use to estimate postmarketing risk.
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Kang YA. Tuberculosis treatment in patients with comorbidities. Tuberc Respir Dis (Seoul) 2014; 76:257-60. [PMID: 25024718 PMCID: PMC4092156 DOI: 10.4046/trd.2014.76.6.257] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Revised: 03/31/2014] [Accepted: 04/07/2014] [Indexed: 12/03/2022] Open
Abstract
Tuberculosis is a significant infectious problem in elderly patients with comorbidities in Korea. The age-associated diseases such as malignancy and diabetes mellitus may increase the risk of tuberculosis in this population. The medication treatments of tuberculosis in patients with comorbidities can cause adverse reactions to antituberculosis drugs and inadequate treatment responses. Thus, clinicians must carefully monitor the toxicity of antituberculosis therapy and the efficacy of treatment in patients with comorbidities.
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Affiliation(s)
- Young Ae Kang
- Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Kumar N, Kedarisetty CK, Kumar S, Khillan V, Sarin SK. Antitubercular therapy in patients with cirrhosis: Challenges and options. World J Gastroenterol 2014; 20:5760-5772. [PMID: 24914337 PMCID: PMC4024786 DOI: 10.3748/wjg.v20.i19.5760] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 12/31/2013] [Accepted: 01/20/2014] [Indexed: 02/06/2023] Open
Abstract
Tuberculosis (TB) has been a human disease for centuries. Its frequency is increased manyfold in patients with liver cirrhosis. The gold standard of TB management is a 6-mo course of isoniazid, rifampicin, pyrazinamide and ethambutol. Although good results are seen with this treatment in general, the management of patients with underlying cirrhosis is a challenge. The underlying depressed immune response results in alterations in many diagnostic tests. The tests used for latent TB have many flaws in this group of patients. Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis. Frequency of hepatotoxicity is increased in patients with liver cirrhosis, frequently leading to severe liver failure. There are no established guidelines for the treatment of TB in relation to the severity of liver disease. There is no consensus on the frequency of liver function tests required or the cut-off used to define hepatotoxicity. No specific treatment exists for prevention or treatment of hepatotoxicity, making monitoring even more important. A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment.
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Liu YM, Cheng YJ, Li YL, Liu CE, Hsu WH. Antituberculosis treatment and hepatotoxicity in patients with chronic viral hepatitis. Lung 2013; 192:205-10. [PMID: 24292367 DOI: 10.1007/s00408-013-9535-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2013] [Accepted: 11/05/2013] [Indexed: 01/24/2023]
Abstract
BACKGROUND Whether antituberculosis (anti-TB) treatment in patients with chronic viral hepatitis affects the incidence and onset time of drug-induced hepatotoxicity (DIH) is still controversial. The aim of this retrospective study was to find out whether chronic viral hepatitis affects the incidence and onset time of DIH. METHODS All patients diagnosed with active TB and being treated at a tertiary referral hospital between 2002 and 2009 were identified from medical records, from which 553 patients were enrolled in the study. The incidence and onset of DIH in patients with and without chronic viral hepatitis (controls) were compared. RESULTS The incidence of DIH was similar in patients with and without chronic hepatitis (8 % [32/392] vs. 7 % [11/161], P > 0.05). The incidence of transient liver function impairment (TLI) was significantly lower in controls than in chronic hepatitis patients (2 % [9/392] vs. 12 % [20/161], P < 0.001. The mean onset times of DIH in the control, hepatitis B virus (HBV), and hepatitis C virus (HCV) groups were not significantly different (40, 39, and 67 days, respectively, all P > 0.05). The mean onset times of TLI in the control, HBV, and HCV groups were significantly different (23, 48, and 68 days, respectively, all P < 0.05). CONCLUSIONS Liver function impairment during anti-TB therapy in patients with chronic viral hepatitis was due to mostly TLI, with TLI occurring later than in controls. Chronic viral hepatitis had no significant effect on the incidence of DIH.
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Affiliation(s)
- Yuag-Meng Liu
- Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, ROC
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Lewis JH, Stine JG. Review article: prescribing medications in patients with cirrhosis - a practical guide. Aliment Pharmacol Ther 2013; 37:1132-56. [PMID: 23638982 DOI: 10.1111/apt.12324] [Citation(s) in RCA: 130] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2012] [Revised: 11/30/2012] [Accepted: 04/08/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND Most drugs have not been well studied in cirrhosis; recommendations on safe use are based largely on experience and/or expert opinion, with dosing recommendations often based on pharmacokinetic (PK) changes. AIM To provide a practical approach to prescribing medications for cirrhotic patients. METHODS An indexed MEDLINE search was conducted using keywords cirrhosis, drug-induced liver injury, pharmacodynamics (PDs), PKs, drug disposition and adverse drug reactions. Unpublished information from the Food and Drug Administration and industry was also reviewed. RESULTS Most medications have not been adequately studied in cirrhosis, and specific prescribing information is often lacking. Lower doses are generally recommended based on PK changes, but data are limited in terms of correlating PD effects with the degree of liver impairment. Very few drugs have been documented to have their hepatotoxicity potential enhanced by cirrhosis; most of these involve antituberculosis or antiretroviral agents used for HIV or viral hepatitis. Paracetamol can be used safely when prescribed in relatively small doses (2-3 g or less/day) for short durations, and is recommended as first-line treatment of pain. In contrast, NSAIDs should be used cautiously (or not at all) in advanced cirrhosis. Proton pump inhibitors have been linked to an increased risk of spontaneous bacterial peritonitis (SBP) in cirrhosis and should be used with care. CONCLUSIONS Most drugs can be used safely in cirrhosis, including those that are potentially hepatotoxic, but lower doses or reduced dosing frequency is often recommended, due to altered PKs. Drugs that can precipitate renal failure, gastrointestinal bleeding, SBP and encephalopathy should be identified and avoided.
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Affiliation(s)
- J H Lewis
- Division of Gastroenterology and Hepatology, Department of Medicine, Georgetown University Medical Center, Washington, DC 20007, USA.
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Agrawal S, Dhiman RK. Answers to multiple choice questions. J Clin Exp Hepatol 2012; 2:401-6. [PMID: 25755463 PMCID: PMC3940550 DOI: 10.1016/j.jceh.2012.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
| | - Radha K. Dhiman
- Address for correspondence: Radha K. Dhiman, Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
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Abstract
Idiosyncratic drug-induced liver injury (DILI) is an important cause of morbidity and mortality following drugs taken in therapeutic doses. Hepatotoxicity is a leading cause of attrition in drug development, or withdrawal or restricted use after marketing. No age is exempt although adults and the elderly are at increased risk. DILI spans the entire spectrum ranging from asymptomatic elevation in transaminases to severe disease such as acute hepatitis leading to acute liver failure. The liver specific Roussel Uclaf Causality Assessment Method is the most validated and extensively used for determining the likelihood that an implicated drug caused DILI. Asymptomatic elevation in liver tests must be differentiated from adaptation. Drugs producing DILI have a signature pattern although no single pattern is characteristic. Antimicrobial and central nervous system agents including antiepileptic drugs are the leading causes of DILI worldwide. In the absence of a diagnostic test or a biomarker, the diagnosis rests on the evidence of absence of competing causes such as acute viral hepatitis, autoimmune hepatitis and others. Recent studies show that antituberculosis drugs given for active or latent disease are still a major cause of drug-induced liver injury in India and the West respectively. Presence of jaundice signifies a severe disease and entails a worse outcome. The pathogenesis is unclear and is due to a mix of host, drug metabolite and environmental factors. Research has evolved from incriminating candidate genes to genome wide analysis studies. Immediate cessation of the drug is key to prevent or minimize progressive damage. Treatment is largely supportive. N-acetylcysteine is the antidote for paracetamol toxicity. Carnitine has been tried in valproate injury whereas steroids and ursodeoxycholic acid may be used in DILI associated with hypersensitivity or cholestatic features respectively. This article provides an overview of the epidemiology, the patterns of hepatotoxicity, the pathogenesis and associated risk factors besides its clinical management.
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Key Words
- ADR, adverse drug reaction
- AED, antiepileptic drugs
- BSEP, bile salt export pump
- CDS, clinical diagnostic scale
- CIOMS, Council for International Organization of Medical Sciences
- CXR, constitutive androstane receptor
- DIAIH, drug-induced autoimmune hepatitis
- DIALF, drug-induced acute liver failure
- DILI
- DILI, idiosyncratic drug-induced liver injury
- FXR, farnesoid X receptor
- GWAS, genome wide association studies
- HBV, hepatitis B virus
- HIV, human immunodeficiency virus
- INH, isoniazid
- LPS, lipopolysaccharide
- MHC, major histocompatibility complex
- MRP, multi-drug resistance proteins
- NAC, N-acetylcysteine
- NAPQI, N-acetyl-p-benzoquinone imine
- NRH, nodular regenerative hyperplasia
- PXR, pregnane X receptor
- PZA, pyrazinamide
- RIF, rifampicin
- RUCAM, Roussel Uclaf Causality Assessment Method
- TEN, toxic epidermal necrolysis
- UDCA, ursodeoxycholic acid
- causality
- drug-induced
- hepatotoxicity
- liver injury
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Dhiman RK, Saraswat VA, Rajekar H, Reddy C, Chawla YK. A guide to the management of tuberculosis in patients with chronic liver disease. J Clin Exp Hepatol 2012; 2:260-270. [PMID: 25755442 PMCID: PMC3940527 DOI: 10.1016/j.jceh.2012.07.007] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2012] [Accepted: 08/08/2012] [Indexed: 12/12/2022] Open
Abstract
Tuberculosis remains one of the 'Captains of the Men of Death' even today, particularly in the developing world. Its frequency is increased 14-fold in patients with chronic liver diseases (CLD) and liver cirrhosis, more so in those with decompensated disease, probably due to the cirrhosis-associated immune dysfunction syndrome, and case-fatality rates are high. The diagnosis of tuberculosis, particularly the interpretation of the Mantoux test, is also fraught with difficulties in CLD, especially after previous BCG vaccination. However, the greatest challenge in the patient with CLD or liver cirrhosis and tuberculosis is managing their therapy since the best first-line anti-tuberculosis drugs are hepatotoxic and baseline liver function is often deranged. Frequency of hepatotoxicity is increased in those with liver cirrhosis, chronic hepatitis B and chronic hepatitis C, possibly related to increased viral loads and may be decreased following antiviral therapy. If hepatotoxicity develops in those with liver cirrhosis, particularly decompensated cirrhosis, the risk of severe liver failure is markedly increased. Currently, there are no established guidelines for anti-tuberculosis therapy (ATT) in CLD and liver cirrhosis although the need for such guidelines is self-evident. It is proposed that ATT should include no more than 2 hepatotoxic drugs (RIF and INH) in patients with CLD or liver cirrhosis and stable liver function [Child-Turcotte-Pugh (CTP) ≤7], only a single hepatotoxic drug (RIF or INH) in those with advanced liver dysfunction (CTP 8-10) and no hepatotoxic drugs with very advanced liver dysfunction (CTP ≥11). A standard protocol should be followed for monitoring ATT-related hepatotoxicity and for stop rules and reintroduction rules in all these patients, on the lines proposed here. It is hoped that these proposals will introduce uniformity and result in streamlining the management of these difficult patients.
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Affiliation(s)
- Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 160014, India
| | - Harshal Rajekar
- Department of Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Chandrasekhar Reddy
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Yogesh K. Chawla
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
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Abstract
Recent increases in the dosages of the essential antituberculosis agents isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA) for use in children recommended by World Health Organization have raised concerns regarding the risk of hepatotoxicity. Published data relating to the incidence and pathogenesis of antituberculosis drug-induced hepatotoxicity (ADIH), particularly in children, is reviewed. Amongst 12,708 children receiving chemoprophylaxis, mainly with INH, but also other combinations of INH, RMP and PZA only 1 case (0.06%) of jaundice was recorded and abnormal liver functions documented in 110 (8%) of the 1225 children studied. Excluding tuberculous meningitis (TBM) 8984 were children treated for tuberculosis disease and jaundice documented in 75 (0.83%) and abnormal liver function tests in 380 (9.9%) of the 3855 children evaluated. Amongst 717 children treated for TBM, however, jaundice occurred in 72 (10.8%) and abnormal LFT were recorded in 174 (52.9%) of those studied. Case reports document the occurrence of ADIH in at least 63 children. Signs and symptoms of ADIH were frequently ignored in the recorded cases. ADIH can occur in children at any age or at any dosage of INH, RMP or PZA, but the incidence of.ADIH is is considerably lower in children than in adults. Children with disseminated forms of disease are at greater risk of ADIH. The use of the higher dosages of INH, RMP and PZA recently recommended by WHO is unlikely to result in a greater risk of ADIH in children.
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Affiliation(s)
- Peter R Donald
- Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Stellenbosch and Tygerberg Children's Hospital, Tygerberg, South Africa
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Wang JY, Liu CH, Hu FC, Chang HC, Liu JL, Chen JM, Yu CJ, Lee LN, Kao JH, Yang PC. Risk factors of hepatitis during anti-tuberculous treatment and implications of hepatitis virus load. J Infect 2011; 62:448-455. [PMID: 21570123 DOI: 10.1016/j.jinf.2011.04.005] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2011] [Revised: 03/30/2011] [Accepted: 04/17/2011] [Indexed: 12/20/2022]
Abstract
OBJECTIVES Hepatitis during anti-tuberculous treatment (HATT) has been an obstacle in managing patients with tuberculosis (TB). We evaluate the risk factors of HATT and the clinical implications of serum viral loads in those with concomitant hepatitis B or C viruses (HBV/HCV) infection. METHODS We did a prospective study on patients with pulmonary tuberculosis in a medical center. HATT was defined as an increase in serum transaminase level of >3 times the upper limit of normal (ULN) with symptoms, or an increase in serum transaminase level of >5 times ULN without symptoms. RESULTS 360 TB patients were studied. The prevalence of concomitant HBV and HCV infection was 11.7% and 6.7%, respectively. HATT developed in 68 (18.9%). Cox regression analysis revealed that severe chronic kidney disease without hemodialysis, N-acetyltransferase (NAT2) slow acetylator, high initial HBV/HCV viral load, and women in those without HBV/HCV infection were significant predictors of drug-induced HATT, whereas severe chronic kidney disease without hemodialysis and men with high initial HBV/HCV viral load were significantly associated virus-induced HATT. CONCLUSION HBV/HCV viral load interacts with gender and, together with severe chronic kidney disease without hemodialysis and NAT2 slow acetylator, were predictors of HATT. TB patients with these characteristics need close follow-up.
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Affiliation(s)
- Jann-Yuan Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taiwan
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Park WB, Kim W, Lee KL, Yim JJ, Kim M, Jung YJ, Kim NJ, Kim DH, Kim YJ, Yoon JH, Oh MD, Lee HS. Antituberculosis drug-induced liver injury in chronic hepatitis and cirrhosis. J Infect 2010; 61:323-329. [PMID: 20670648 DOI: 10.1016/j.jinf.2010.07.009] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2010] [Revised: 07/11/2010] [Accepted: 07/22/2010] [Indexed: 10/19/2022]
Abstract
OBJECTIVES To evaluate the incidence, risk factors and outcomes for anti-tuberculosis (TB) drug-induced liver injury (DILI) in patients with chronic liver disease including cirrhosis. METHODS A total of 107 patients with chronic liver disease were assessed for anti-TB DILI. Anti-TB DILI was defined as elevation of alkaline phosphatase (ALP), aspartate transaminase, or alanine transaminase, or an increase in Child-Turcotte-Pugh score within 2 months of initiating anti-TB medication. The risk factors for anti-TB DILI were evaluated by multivariate logistic regression analysis. RESULTS Fifty-eight (54%) patients had cirrhosis. Of 93 patients receiving one or more hepatotoxic anti-TB drugs, 18 (17%) experienced DILI: 11 (24%) among 46 patients with chronic hepatitis and 7 (15%) among 46 patients with compensated liver cirrhosis (P = 0.271). Independent risk factors for DILI were female sex, number of hepatotoxic anti-TB drugs administered and baseline ALP levels but not cirrhosis itself. Of the 18 patients with DILI, 13 (72%) successfully completed anti-TB treatment after switching to less hepatotoxic drug regimens. CONCLUSIONS Hepatotoxic anti-TB drugs may be safely used in the patients with chronic liver disease including compensated cirrhosis if number of hepatotoxic drugs used is adjusted appropriately.
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Affiliation(s)
- Wan Beom Park
- Department of Internal Medicine, Seoul National University College of Medicine, 39 Boramae Road, Seoul, Republic of Korea
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Chalasani N, Björnsson E. Risk factors for idiosyncratic drug-induced liver injury. Gastroenterology 2010; 138:2246-59. [PMID: 20394749 PMCID: PMC3157241 DOI: 10.1053/j.gastro.2010.04.001] [Citation(s) in RCA: 234] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2010] [Revised: 04/02/2010] [Accepted: 04/08/2010] [Indexed: 12/13/2022]
Abstract
Idiosyncratic drug-induced liver injury (DILI) is a rare disorder that is not related directly to dosage and little is known about individuals who are at increased risk. There are no suitable preclinical models for the study of idiosyncratic DILI and its pathogenesis is poorly understood. It is likely to arise from complex interactions among genetic, nongenetic host susceptibility, and environmental factors. Nongenetic risk factors include age, sex, and other diseases (eg, chronic liver disease or human immunodeficiency virus infection). Compound-specific risk factors include daily dose, metabolism characteristics, and propensity for drug interactions. Alcohol consumption has been proposed as a risk factor for DILI from medications, but there is insufficient evidence to support this. Many studies have explored genetic defects that might be involved in pathogenesis and focused on genes involved in drug metabolism and the immune response. Multicenter databases of patients with DILI (the United States Drug Induced Liver Injury Network, DILIGEN, and the Spanish DILI registry) are important tools for clinical and genetic research. A genome-wide association study of flucloxacillin hepatotoxicity has yielded groundbreaking results and many similar studies are underway. Nonetheless, DILI is challenging to investigate because of its rarity, the lack of experimental models, the number of medications that might cause it, and challenges to diagnosis.
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Affiliation(s)
- Naga Chalasani
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
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Xia YY, Hu DY, Liu FY, Wang XM, Yuan YL, Tu DH, Chen YX, Zhou L, Zhu LZ, Gao WW, Wang HY, Chen DF, Yang L, He PP, Li XT, He YJ, Sun F, Zhan SY. Design of the anti-tuberculosis drugs induced adverse reactions in China National Tuberculosis Prevention and Control Scheme Study (ADACS). BMC Public Health 2010; 10:267. [PMID: 20492672 PMCID: PMC2893093 DOI: 10.1186/1471-2458-10-267] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2010] [Accepted: 05/21/2010] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND More than 1 million tuberculosis (TB) patients are receiving the standard anti-TB treatment provided by China National Tuberculosis Prevention and Control Scheme (CNTS) in China every year. Adverse reactions (ADRs) induced by anti-TB drugs could both do harm to patients and lead to anti-TB treatment failure. The ADACS aimed to explore ADRs' incidences, prognoses, economical and public health impacts for TB patients and TB control, and build a DNA bank of TB patients. METHODS/DESIGN Multiple study designs were adopted. Firstly, a prospective cohort with 4488 sputum smears positive pulmonary tuberculosis patients was established. Patients were followed up for 6-9 months in 52 counties of four regions. Those suspected ADRs should be checked and confirmed by Chinese State Food and Drug Administration (SFDA). Secondly, if the suspected ADR was anti-TB drug induced liver injury (ATLI), a nested case-control study would be performed which comprised choosing a matched control and doing a plus questionnaire inquiry. Thirdly, health economical data of ADRs would be collected to analyze financial burdens brought by ADRs and cost-effectiveness of ADRs' treatments. Fourthly, a drop of intravenous blood for each patient was taken and saved in FTA card for DNA banking and genotyping. Finally, the demographic, clinical, environmental, administrative and genetic data would be merged for the comprehensive analysis. DISCUSSION ADACS will give an overview of anti-TB drugs induced ADRs' incidences, risk factors, treatments, prognoses, and clinical, economical and public health impacts for TB patients applying CNTS regimen in China, and provide suggestions for individualized health care and TB control policy.
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Affiliation(s)
- Yin Yin Xia
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Dai Yu Hu
- Center for Disease Control and Prevention in Chongqing Municipality, Chongqing, China
| | - Fei Ying Liu
- Center for Disease Control and Prevention in Guangxi Zhuang Autonomous Region, Nanning, China
| | - Xiao Meng Wang
- Center for Disease Control and Prevention in Zhejiang Province, Hangzhou, China
| | - Yan Li Yuan
- Center for Disease Control and Prevention in Jilin Province, Changchun, China
| | - De Hua Tu
- Beijing Institute for Tuberculosis Control, Beijing, China
| | - Yi Xin Chen
- Center for Drug Reassessment, State Food and Drug Administration, Beijing, China
| | - Lin Zhou
- Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Li Zhen Zhu
- Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Wei Wei Gao
- Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Hong Yuan Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Da Fang Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Li Yang
- Department of Health Policy and Management, School of Public Health, Peking University, Beijing, China
| | - Ping Ping He
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Xiao Ting Li
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Ying Jian He
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Feng Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Si Yan Zhan
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
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Tedla Z, Nyirenda S, Peeler C, Agizew T, Sibanda T, Motsamai O, Vernon A, Wells CD, Samandari T. Isoniazid-associated hepatitis and antiretroviral drugs during tuberculosis prophylaxis in hiv-infected adults in Botswana. Am J Respir Crit Care Med 2010; 182:278-85. [PMID: 20378730 DOI: 10.1164/rccm.200911-1783oc] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
RATIONALE Little is known about the incidence of isoniazid-associated hepatitis in HIV-infected Africans who receive both isoniazid preventive therapy (IPT) and antiretroviral therapy (ART). OBJECTIVES To assess the rate of and risk factors for isoniazid (INH)-associated hepatitis in persons living with HIV (PLWH) during IPT. METHODS PLWH recruited for a clinical trial received 6 months of open-label, daily, self-administered INH at public health clinics. At screening PLWH were excluded if they had any cough, weight loss, night sweats, or other illness. Alcohol abuse was defined as meeting any CAGE criterion. INH-associated hepatitis (INH-hepatitis) was defined as having either alanine or aspartate aminotransferase greater than 5.0 times the upper limit of normal regardless of symptoms when INH was not excluded as the cause. MEASUREMENTS AND MAIN RESULTS Of 1,995 PLWH enrolled between 2004 and 2006, 1,762 adhered to at least 4 months of IPT and were analyzed. Nineteen (1.1%) developed hepatitis probably or possibly associated with INH including one death at month 6; 14 of 19 (74%) occurred in months 1-3. Antiretroviral therapy (ART) was received by 480 participants but was not statistically associated with INH-hepatitis (relative risk [RR], 1.56; 95% confidence intervals [CI], 0.62-3.9); those receiving nevirapine had a higher rate (2.0%) than those receiving efavirenz (0.9%; P = 0.34). Although alcohol use did not reach significance (RR, 1.42; 95% CI, 0.57-3.51), meeting at least one CAGE criterion approached statistical significance (RR, 2.37; 95% CI, 0.96-5.84). Neither age greater than 35 years nor the presence of hepatitis B virus core antibody was associated with INH-hepatitis. CONCLUSIONS The observed rates of INH-hepatitis were similar to published data. Six months of IPT, which is recommended by the World Health Organization, was relatively safe in this, the largest cohort of African PLWH. Clinical trial registered with www.clinicaltrials.gov (NCT 00164281).
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Affiliation(s)
- Zegabriel Tedla
- Centers for Disease Control and Prevention, Division of Tuberculosis Elimination, 1600 Clifton Road NE, Mailstop E-10, Atlanta, GA 30333, USA
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Tajiri K, Shimizu Y. Practical guidelines for diagnosis and early management of drug-induced liver injury. World J Gastroenterol 2009. [PMID: 19058303 DOI: 10.3748/wig.14.6774] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The spectrum of drug-induced liver injury (DILI) is both diverse and complex. The first step in diagnosis is a suspicion of DILI based on careful consideration of recent comprehensive reports on the disease. There are some situations in which the suspicion of DILI is particularly strong. Exclusion of other possible etiologies according to the pattern of liver injury is essential for the diagnosis. In patients with suspected DILI, diagnostic scales, such as the Councils for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM) scale, may be helpful for the final diagnosis. Early management of DILI involves prompt withdrawal of the drug suspected of being responsible, according to serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (T-Bil). However, as DILI patients may show resolution of liver injury without discontinuation of the drug, it should be carefully evaluated whether the suspected drug should be discontinued immediately with adequate consideration of the importance of the medication.
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Affiliation(s)
- Kazuto Tajiri
- Department of Gastroenterology and Hematology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan
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Tajiri K, Shimizu Y. Practical guidelines for diagnosis and early management of drug-induced liver injury. World J Gastroenterol 2008; 14:6774-6785. [PMID: 19058303 PMCID: PMC2773872 DOI: 10.3748/wjg.14.6774] [Citation(s) in RCA: 131] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2008] [Revised: 11/05/2008] [Accepted: 11/12/2008] [Indexed: 02/06/2023] Open
Abstract
The spectrum of drug-induced liver injury (DILI) is both diverse and complex. The first step in diagnosis is a suspicion of DILI based on careful consideration of recent comprehensive reports on the disease. There are some situations in which the suspicion of DILI is particularly strong. Exclusion of other possible etiologies according to the pattern of liver injury is essential for the diagnosis. In patients with suspected DILI, diagnostic scales, such as the Councils for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM) scale, may be helpful for the final diagnosis. Early management of DILI involves prompt withdrawal of the drug suspected of being responsible, according to serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (T-Bil). However, as DILI patients may show resolution of liver injury without discontinuation of the drug, it should be carefully evaluated whether the suspected drug should be discontinued immediately with adequate consideration of the importance of the medication.
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Affiliation(s)
- Kazuto Tajiri
- Department of Gastroenterology and Hematology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan
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Tajiri K, Shimizu Y. Practical guidelines for diagnosis and early management of drug-induced liver injury. World J Gastroenterol 2008. [PMID: 19058303 DOI: 10.4748/wjg.14.6774] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The spectrum of drug-induced liver injury (DILI) is both diverse and complex. The first step in diagnosis is a suspicion of DILI based on careful consideration of recent comprehensive reports on the disease. There are some situations in which the suspicion of DILI is particularly strong. Exclusion of other possible etiologies according to the pattern of liver injury is essential for the diagnosis. In patients with suspected DILI, diagnostic scales, such as the Councils for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM) scale, may be helpful for the final diagnosis. Early management of DILI involves prompt withdrawal of the drug suspected of being responsible, according to serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (T-Bil). However, as DILI patients may show resolution of liver injury without discontinuation of the drug, it should be carefully evaluated whether the suspected drug should be discontinued immediately with adequate consideration of the importance of the medication.
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Affiliation(s)
- Kazuto Tajiri
- Department of Gastroenterology and Hematology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan
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Makhlouf HA, Helmy A, Fawzy E, El-Attar M, Rashed HAG. A prospective study of antituberculous drug-induced hepatotoxicity in an area endemic for liver diseases. Hepatol Int 2008; 2:353-60. [PMID: 19669265 PMCID: PMC2716885 DOI: 10.1007/s12072-008-9085-y] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2008] [Accepted: 06/19/2008] [Indexed: 12/02/2022]
Abstract
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.
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Affiliation(s)
- Hoda A. Makhlouf
- Department of Chest Diseases, Faculty of Medicine, Assiut University, Assiut, 71111 Egypt
| | - Ahmed Helmy
- Department of Tropical Medicine & Gastroenterology, Faculty of Medicine, Assiut University, Assiut, 71111 Egypt
- Gastroenterology Section, Department of Medicine MBC 46, King Faisal Specialist Hospital & Research Center, PO Box 3354, Riyadh, 11211 Saudi Arabia
| | - Ehab Fawzy
- Department of Tropical Medicine & Gastroenterology, Faculty of Medicine, Assiut University, Assiut, 71111 Egypt
| | - Madiha El-Attar
- Department of Tropical Medicine & Gastroenterology, Faculty of Medicine, Assiut University, Assiut, 71111 Egypt
| | - Hebat Alla G. Rashed
- Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, 71111 Egypt
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Anti-tuberculosis therapy-induced hepatotoxicity among Ethiopian HIV-positive and negative patients. PLoS One 2008; 3:e1809. [PMID: 18350147 PMCID: PMC2265547 DOI: 10.1371/journal.pone.0001809] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2007] [Accepted: 02/17/2008] [Indexed: 11/19/2022] Open
Abstract
Background To assess and compare the prevalence, severity and prognosis of anti-TB drug induced hepatotoxicity (DIH) in HIV positive and HIV negative tuberculosis (TB) patients in Ethiopia. Methodology/Principal Findings In this study, 103 HIV positive and 94 HIV negative TB patients were enrolled. All patients were evaluated for different risk factors and monitored biochemically and clinically for development of DIH. Sub-clinical hepatotoxicity was observed in 17.3% of the patients and 8 out of the 197 (4.1%) developed clinical hepatotoxicity. Seven of the 8 were HIV positive and 2 were positive for HBsAg. Conclusions/Significance Sub-clinical hepatotoxicity was significantly associated with HIV co-infection (p = 0.002), concomitant drug intake (p = 0.008), and decrease in CD4 count (p = 0.001). Stepwise restarting of anti TB treatment was also successful in almost all the patients who developed clinical DIH. We therefore conclude that anti-TB DIH is a major problem in HIV-associated TB with a decline in immune status and that there is a need for a regular biochemical and clinical follow up for those patients who are at risk.
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Kim YH, Suh GY, Chung MP, Kim H, Kwon OJ, Lim SY, Lim SY, Koh WJ. Treatment of isoniazid-resistant pulmonary tuberculosis. BMC Infect Dis 2008; 8:6. [PMID: 18211720 PMCID: PMC2245946 DOI: 10.1186/1471-2334-8-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2006] [Accepted: 01/23/2008] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Although resistance to isoniazid (INH) is the most common form of drug resistance seen among Mycobacterium tuberculosis isolates, there have been few studies on the efficacy and optimal duration of treatment for patients with INH-resistant tuberculosis (TB). METHODS We evaluated retrospectively the treatment outcomes of 39 patients who were treated for INH-resistant pulmonary TB. The treatment regimens consisted of a 12-month regimen of rifampin (RIF) and ethambutol (EMB), with pyrazinamide (PZA) given during the first 2 months (2HREZ/10RE) (n = 21), a 9-month regimen of RIF and EMB with PZA during the first 2 months (2HREZ/7RE) (n = 5), and a 6-month regimen of RIF, EMB, and PZA (2HREZ/4REZ) (n = 13). After drug susceptibility testing confirmed the INH-resistance of the isolated M. tuberculosis strains, INH was discontinued for all the patients. RESULTS Among the 39 patients, treatment was successfully completed by 36 patients (92%). However, treatment failure occurred, and acquired resistance to other first-line drugs, such as RIF, developed in three patients (8%). Cavitary and bilateral extensive lesions were commonly found in the chest radiographs of the patients who exhibited treatment failure. CONCLUSION These findings underline the seriousness of concerns regarding treatment failure and the development of multidrug-resistant TB in patients with INH-resistant TB following treatment with recommended regimens.
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Affiliation(s)
- Yee Hyung Kim
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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Kuniholm MH, Mark J, Aladashvili M, Shubladze N, Khechinashvili G, Tsertsvadze T, del Rio C, Nelson KE. Risk factors and algorithms to identify hepatitis C, hepatitis B, and HIV among Georgian tuberculosis patients. Int J Infect Dis 2008; 12:51-6. [PMID: 17644020 PMCID: PMC2649965 DOI: 10.1016/j.ijid.2007.04.015] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2006] [Revised: 04/03/2007] [Accepted: 04/09/2007] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVES To determine prevalence, risk factors, and simple identification algorithms for HIV, hepatitis B, and hepatitis C co-infection; factors that may predispose for anti-tuberculosis therapy-induced hepatotoxicity. METHODS We recruited 300 individuals at in-patient tuberculosis hospitals in three cities in Georgia, administered a behavioral questionnaire, and tested for antibody to HIV, hepatitis C (HCV), hepatitis B core antigen (anti-HBc), and the hepatitis B surface antigen (HBsAg). RESULTS Of the individuals tested, 0.7% were HIV positive, 4.3% were HBsAg positive, 8.7% were anti-HBc positive, and 12.0% were HCV positive. In multivariable analysis, a history of blood transfusion, injection drug use, and prison were significant independent risk factors for HCV, while a history of blood transfusion, injection drug use, younger age at sexual debut, and a high number of sex partners were significant risk factors for HBV. Three-questionnaire item algorithms predicted HCV serostatus 74.1% of the time and HBV serostatus 85.2% of the time. CONCLUSIONS Treatment of tuberculosis patients in resource-limited countries with concurrent epidemics of HCV, HBV, and HIV may be associated with significant hepatotoxicity. Serologic screening of tuberculosis patients for HBV, HCV, and HIV or using behavioral algorithms to identify patients in need of intensive monitoring during anti-tuberculosis therapy may reduce this risk.
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Affiliation(s)
- Mark H Kuniholm
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Suite E7133, 615 N. Wolfe St., Baltimore, MD 21205, USA.
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Yun JW, Lim SY, Suh GY, Chung MP, Kim H, Kwon OJ, Cha HS, Koh EM, Koh WJ. Diagnosis and treatment of latent tuberculosis infection in arthritis patients treated with tumor necrosis factor antagonists in Korea. J Korean Med Sci 2007; 22:779-83. [PMID: 17982222 PMCID: PMC2693840 DOI: 10.3346/jkms.2007.22.5.779] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Tumor necrosis factor (TNF) is essential for host defense against Mycobacterium tuberculosis, and the risk of reactivation of latent tuberculosis infection (LTBI) increases with anti-TNF therapy. This study estimated the prevalence of LTBI and evaluated the safety and completion rate of short-course therapy with isoniazid plus rifampin for 3 months to treat LTBI in a cohort of Korean arthritis patients before initiating anti-TNF therapy. We retrospectively studied the files of 112 consecutive patients to evaluate LTBI before starting anti-TNF drugs. Screening tests were performed, including a tuberculin skin test and chest radiography. LTBI treatment was indicated in 41 patients (37%). Of these, three patients refused the LTBI treatment. Of the 38 patients who underwent LTBI treatment, 36 (95%) took isoniazid plus rifampin for 3 months. Six patients (16%) showed transient elevations of liver enzymes during the LTBI treatment. Overall, 35 patients (92%) completed the LTBI treatment as planned. In conclusion, LTBI was diagnosed in one-third of Korean arthritis patients before initiating anti-TNF therapy. A high percentage of these patients completed 3 months of LTBI treatment with isoniazid plus rifampin without serious complications.
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Affiliation(s)
- Jong Wook Yun
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seong Yong Lim
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gee Young Suh
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Man Pyo Chung
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hojoong Kim
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - O Jung Kwon
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hoon-Suk Cha
- Division of Rheumatology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eun-Mi Koh
- Division of Rheumatology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Won-Jung Koh
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Shapiro MA, Lewis JH. Causality assessment of drug-induced hepatotoxicity: promises and pitfalls. Clin Liver Dis 2007; 11:477-505, v. [PMID: 17723916 DOI: 10.1016/j.cld.2007.06.003] [Citation(s) in RCA: 105] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Drug-induced liver injury is the leading cause of acute liver failure in the United States, but the ability to ascribe hepatic injury confidently to a specific drug remains a challenging and often difficult pursuit. This article explores the ongoing challenges inherent in what is currently a clinical process of elimination made in the attempt of assigning causality in drug-induced liver injury. In particular, it points out the shortcomings and pitfalls that often limit the applicability of the causality-assessment methodologies currently in use.
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Affiliation(s)
- Max A Shapiro
- Hepatology Section, Division of Gastroenterology, Georgetown University Hospital, Georgetown University Medical Center, Washington, DC 20007, USA
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Kim SH, Min KU, Lee JH, Kim TH, Sohn JW, Yoon HJ, Shin DH, Ahn MH, Park SS. Two cases of cutaneous paragonimiasis initially presenting with respiratory symptoms. ACTA ACUST UNITED AC 2007. [DOI: 10.1016/j.rmedx.2007.01.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Saukkonen JJ, Cohn DL, Jasmer RM, Schenker S, Jereb JA, Nolan CM, Peloquin CA, Gordin FM, Nunes D, Strader DB, Bernardo J, Venkataramanan R, Sterling TR. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med 2006; 174:935-52. [PMID: 17021358 DOI: 10.1164/rccm.200510-1666st] [Citation(s) in RCA: 672] [Impact Index Per Article: 35.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Drug-induced liver injury (DILI) is a problem of increasing significance, but has been a long-standing concern in the treatment of tuberculosis (TB) infection. The liver has a central role in drug metabolism and detoxification, and is consequently vulnerable to injury. The pathogenesis and types of DILI are presented, ranging from hepatic adaptation to hepatocellular injury. Knowledge of the metabolism of anti-TB medications and of the mechanisms of TB DILI is incomplete. Understanding of TB DILI has been hampered by differences in study populations, definitions of hepatotoxicity, and monitoring and reporting practices. Available data regarding the incidence and severity of TB DILI overall, in selected demographic groups, and in those coinfected with HIV or hepatitis B or C virus are presented. Systematic steps for prevention and management of TB DILI are recommended. These include patient and regimen selection to optimize benefits over risks, effective staff and patient education, ready access to care for patients, good communication among providers, and judicious use of clinical and biochemical monitoring. During treatment of latent TB infection (LTBI) alanine aminotransferase (ALT) monitoring is recommended for those who chronically consume alcohol, take concomitant hepatotoxic drugs, have viral hepatitis or other preexisting liver disease or abnormal baseline ALT, have experienced prior isoniazid hepatitis, are pregnant or are within 3 months postpartum. During treatment of TB disease, in addition to these individuals, patients with HIV infection should have ALT monitoring. Some experts recommend biochemical monitoring for those older than 35 years. Treatment should be interrupted and, generally, a modified or alternative regimen used for those with ALT elevation more than three times the upper limit of normal (ULN) in the presence of hepatitis symptoms and/or jaundice, or five times the ULN in the absence of symptoms. Priorities for future studies to develop safer treatments for LTBI and for TB disease are presented.
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Abstract
INTRODUCTION Tuberculosis continues to be a major cause of morbidity and mortality worldwide. Currently available drugs are effective for treatment of the disease or latent infection, but may cause serious adverse effects. METHODS The authors reviewed the literature for side effects of five first-line antituberculous medications (isoniazid, rifampin, pyrazinamide, ethambutol and streptomycin). Incidence of the major side effects were compiled with particular attention to the incidence of isoniazid hepatotoxicity. RESULTS Hepatotoxicity to isoniazid is a serious problem. Although overall incidence may be decreasing, incidence averaged 9.2 per 1000 patients who were compliant, in multiple studies, with a case fatality rate of 4.7%. The incidence is higher with increasing age. Other serious adverse effects include dermatological, gastrointestinal, hypersensitivity, neurological, haematological and renal reactions. They can lead to drug discontinuation (in up to 10% of patients) or even more serious morbidity or mortality. CONCLUSIONS Side effects to antituberculosis drugs are common, and include hepatitis, cutaneous reactions, gastrointestinal intolerance, haematological reactions and renal failure. These adverse effects must be recognised early, to reduce associated morbidity and mortality.
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Affiliation(s)
- Eric J Forget
- Respiratory Epidemiology Unit, Montreal Chest Institute, McGill University, Montréal, Québec, H2X 2P4, Canada
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