ATT induced liver injury is very common with anti tubercular drugs as tuberculosis is one of the most common infection in india. Management of att liver injury is very important in medicine and is elaborated here.
Interstitial lung disease is a general category that includes many different lung conditions. All interstitial lung diseases affect the interstitium, a part of the lungs' anatomic structure.
Some of the types of interstitial lung disease include:
Interstitial pneumonia: Bacteria, viruses, or fungi may infect the interstitium of the lung. A bacterium called Mycoplasma pneumonia is the most common cause.
Idiopathic pulmonary fibrosis : A chronic, progressive form of fibrosis (scarring) of the interstitium. Its cause is unknown.
Nonspecific interstitial pneumonitis: Interstitial lung disease that's often present with autoimmune conditions (such as rheumatoid arthritis or scleroderma).
Austin Journal of Clinical Cardiology is an open access, peer reviewed, scholarly journal dedicated to publish articles in all areas of cardiology and angiology. The aim of the journal is to provide a forum for cardiologists, researchers, physicians, and other health professionals to find most recent advances in the areas of cardiology and cardiovascular diseases.
Austin Journal of Clinical Cardiology accepts original research articles, review articles, case reports, clinical images and rapid communication on all the aspects of cardiology and circulatory system.
Austin Journal of Clinical Cardiology strongly supports the scientific upgradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group also brings universally peer reviewed journals under one roof thereby promoting knowledge sharing, mutual promotion of multidisciplinary science.
Austin Journal of Clinical Cardiology is an open access, peer reviewed, scholarly journal dedicated to publish articles in all areas of cardiology and angiology
ATT induced liver injury is very common with anti tubercular drugs as tuberculosis is one of the most common infection in india. Management of att liver injury is very important in medicine and is elaborated here.
Interstitial lung disease is a general category that includes many different lung conditions. All interstitial lung diseases affect the interstitium, a part of the lungs' anatomic structure.
Some of the types of interstitial lung disease include:
Interstitial pneumonia: Bacteria, viruses, or fungi may infect the interstitium of the lung. A bacterium called Mycoplasma pneumonia is the most common cause.
Idiopathic pulmonary fibrosis : A chronic, progressive form of fibrosis (scarring) of the interstitium. Its cause is unknown.
Nonspecific interstitial pneumonitis: Interstitial lung disease that's often present with autoimmune conditions (such as rheumatoid arthritis or scleroderma).
Austin Journal of Clinical Cardiology is an open access, peer reviewed, scholarly journal dedicated to publish articles in all areas of cardiology and angiology. The aim of the journal is to provide a forum for cardiologists, researchers, physicians, and other health professionals to find most recent advances in the areas of cardiology and cardiovascular diseases.
Austin Journal of Clinical Cardiology accepts original research articles, review articles, case reports, clinical images and rapid communication on all the aspects of cardiology and circulatory system.
Austin Journal of Clinical Cardiology strongly supports the scientific upgradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group also brings universally peer reviewed journals under one roof thereby promoting knowledge sharing, mutual promotion of multidisciplinary science.
Austin Journal of Clinical Cardiology is an open access, peer reviewed, scholarly journal dedicated to publish articles in all areas of cardiology and angiology
Case #1.
Azathioprine에 의한 심한 골수부전 환자를 소개 하였습니다.
실제로 소개드린 첫번째 문헌(GUT)에 의하면 골수 억제의 부작용은 초기 치료 기간에 집중되어 있지만 전 치료 기간에 발생될 수 있는 것으로 되어 있습니다. 문헌들에 의하면 TPMT 활성이 저하된 환자에게 많이 발생하고 투여 전 TPMT 활성을 검사 한 후 치료를 시작 하여야 한다는 내용들이 많습니다. 그러나 TPMT 검사는 고가에 오랜 검사기간이 걸리는 검사입니다(비보험 225,750원, 20일). 또한 슬라이드에 소개드린 두번째 문헌(DDS)에는 스크리닝 검사의 효용성에 대하여 회의적인 결과를 보고 하였습니다.
면역 억제제 투여시 첫 약물로써 가장 간단하게 투여할 수 있는 이뮤란(Azathioprine)이라는 이름의 약물 역시도 주의하며 투여 해야 할 약물 이라 생각 됩니다. 심각한 혈액학적 합병증의 발생률은 약 6% 정도로 보고되고 있으며, 류마티스질환 치료 하시는 분들 역시도 오랜 치료기간 한두번의 경험을 할 수 있는 정도라고 합니다. 사용을 안할 수 없는 약물인 만큼 투여 전 환자와 보호자에게 발생 가능한 부작용에 대한 충분한 설명이 필요 하다고 생각 합니다.
Case #2.
Hepatic enz. elevation 주소로 오신 분이고, non-A, non-B hepatitis로써 ANA 검사상 high titer 소견을 보였습니다. 그런데 ANA 보고시 간과할 수 있는 ANA pattern이 'Discrete speckled' 로 보고되고 Anti Centromere Ab. 양성소견 이었습니다. 다시 병력 청취 하였더니 Raynaud disease가 의심 되었던 case 입니다. ANA 검사 결과를 볼때 titer 뿐 아니라 pattern도 챙겨 보아야 한다는 교훈을 얻었던 case 입니다.
Edward B. Garon, MD, MS, Jamie E. Chaft, MD, and Matthew D. Hellmann, MD, prepared useful Practice Aids pertaining to lung cancer management for this CME/MOC/CE activity titled "Improving Patient Outcomes With Cancer Immunotherapies Throughout the Lung Cancer Continuum: State of the Science and Implications for Practice." For the full presentation, monograph, complete CME/MOC/CE information, and to apply for credit, please visit us at http://bit.ly/2ATq0qp. CME/MOC/CE credit will be available until November 21, 2019.
Meta-Analysis of Traditional Chinese Medicine Injection Combined with Paclita...semualkaira
To investigate the effect of traditional Chinese medicine injection combined with paclitaxel, cisplatin or carboplatin chemotherapy regimen (TP Chemotherapy Regimen) on lung cancer.
Meta-Analysis of Traditional Chinese Medicine Injection Combined with Paclita...semualkaira
To investigate the effect of traditional Chinese medicine injection combined with paclitaxel, cisplatin or carboplatin chemotherapy regimen (TP Chemotherapy Regimen) on lung cancer.
A protocol presentation I created during my training at KEMH. Disease was ulcerative colitis. Suggestions made by expert evaluating this have not been incorporated.
Cupping therapy is a promising modality to be used as a complementary therapy for chronic diseases. It may improve the symptoms and quality of life of patients. There is a need for more studies regarding the efficacy and safety of cupping therapy in the treatment of chronic diseases to build a solid scientific evidence regarding this topic.
This is a slide presentation for MBBS students. a brief overview of hemochromatosis, an iron overload condition. overview of hemochromatosis, pathophysiology, clinical features, approach, and management
Liver transplantation; notes of DM/DNB/SpecialistsPratap Tiwari
Liver transplantation; extensive notes of DM/DNB/Specialists. This was my notes for my exam compiled from several sources, credit goes to original authors. This is just for quick revision
This is a lecture note for 5th-semester MBBS students. Lecture notes on hepatology, liver disease, and liver abscess. Introduction to a liver abscess, pyogenic liver abscess, causes, approach and management of liver abscess.
This is a lecture note for 5th semester MBBS students. Lecture notes on hepatology, liver disease, alcoholic liver disease, alcohol-related liver disease, portal hypertension, hepatic encephalopathy, and acute liver failure. Introduction to acute liver failure, causes, approach, and management of acute liver failure .
This is a lecture note for 5th semester MBBS students. Lecture notes on hepatology, liver disease, alcoholic liver disease, alcohol-related liver disease, portal hypertension, and hepatic encephalopathy. Introduction to hepatic encephalopathy, causes, differentials, approach, and management of hepatic encephalopathy .
This is a lecture note for 5th semester MBBS students. Lecture notes on hepatology, liver disease, alcoholic liver disease, alcohol-related liver disease, alcoholic hepatitis, portal hypertension, ascites. Introduction to ascites and management of ascites.
This is a lecture note for 5th semester MBBS students. Lecture notes on hepatology, liver disease, alcoholic liver disease, alcohol-related liver disease, portal hypertension, ascites. Introduction to ascites and management of ascites.
brief lecture notes for 5th sem MBBS, on portal hypertension and varices. Introduction to portal hypertension and esophageal and gastric varices and management of variceal bleeding.
Chronic liver disease, lecture presentation for 5th sem MBBS students. Introduction to chronic liver disease, notes on liver fibrosis, alcoholic hepatitis, liver histology and overview.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Are There Any Natural Remedies To Treat Syphilis.pdf
Antitubercular agents in TB patients with Chronic Liver disease (CLD)
1. Using Antitubercular drugs for
Tuberculosis in patients with
Chronic Liver diseases
Pratap Sagar Tiwari, MD (Internal Medicine)
DM HEPATOLOGY, BIR HOSPITAL, NAMS, NEPAL
2. Introduction
• It is quite evident that more than 90 percent of tuberculosis are reactivation of
their latent form that usually present in patients with some level of
immunodeficient or immunosuppressed state.
• So, Cirrhosis being itself an immunodeficient state[1], it would be aggreable to
state that prevalence of tuberculosis is much higher in cirrhotic population when
compared to normal population.
• A study conducted in Western India showed that the prevalence rate was 15
times higher than in the general population[2].
• Another study from India showed that there is nearly five times higher
prevalence of TB in cirrhosis patients (8.1%) compared to the general population
(1.6%), with pulmonary TB being the commonest form[3].
1. Cho YJ, Lee SM, Yoo CG, Kim YW, Han SK, Shim YS, Yim JJ. Clinical characteristics of tuberculosis in patients with liver cirrhosis. Respirology. 2007;12:401–405.
2. Saigal S, Nandeesh HP, Agarwal SR, Misra A, Jain SK, Sarin SK. High prevalence and profile of tuberculosis in chronic liver disease patients. Gastroenterology. 1998;114:A38.
3. Baijal R, Praveenkumar HR, Amarapurkar DN, Nagaraj K, Jain M. Prevalence of tuberculosis in patients with cirrhosis of liver in western India. Trop Doct. 2010;40:163–164.
3. Drug induced hepatotoxicity: ATT
• Anti-TB chemotherapy containing isoniazid (H), rifampicin (R) and
pyrazinamide (Z) has proved to be highly effective but hepatotoxic and the
risk further increases when these drugs are combined.
• The development of DIH during chemotherapy for TB is one of the most
common reason leading to interruption of therapy.
• Wide variations have been found in the incidence of hepatotoxic reactions
from different countries, with the reported incidence being 3 % in the
USA[1], 4 % in the UK[1], 11 % in Germany[2], 13 % in HK[3], 36 % in
Japan[4], 26 % in Taiwan[4] and 8-36 % in India[5,6].
1. Ormerod LP, Skinner C, Wales J. Hepatotoxicity of antituberculosis drugs. Thorax 1996; 51 : 111-3.
2. Garg PK, Tandon RK. Antituberculosis treatment induced hepatotoxicity. In: Sharma SK, Mohan A, editors. Tuberculosis 2nd ed. New Delhi: Jaypee Brothers Medical Publishers;
2009.p. 783-95.
3. Lauterburg BH, Smith CV, Todd EL, Mitchell JR. Pharmacokinetics of the toxic hydrazino metabolites formed from isoniazid in humans. J Pharmacol Exp Ther 1985; 235 : 566-70.
4. Ellard GA, Mitchison DA, Girling DJ, Nunn AJ, Fox W. The hepatic toxicity of isoniazid among rapid and slow acetylators of the drug. Am Rev Respir Dis 1978; 118 : 628-9.
5. Parthasarthy R, Sarma GR, Janardhanam B, Ramachandran P, Santha T, Sivasubramania S, et al. Hepatic toxicity in south Indian patients during treatment of tuberculosis with short-
course regimens containing isoniazid, rifampicin and pyrazinamide. Tubercle 1986; 67 : 99-108.
6. Mehta S. Malnutrition and drugs: clinical implications. Dev Pharmacol Ther 1990; 15 : 159-65.
4. Risk Factors
• Why only some pts who receive anti-TB drugs develop hepatitis is not clear. Even
from the incidence datas, it can be derived that hepatotoxicity occurs more in
patients of Asian origin, so ethnicity and environment seems to play a role aswell.
• Several studies have searched for host factors, or genetic factors such as HLA
typing[1], cytochrome P450 2E1[2] or acetylator status[3].
RISK FACTORS
Advance age[4-10] Women [4,6,12,13] Extrapulmonary TB [10,11]
Greater disease severity on chest radiograph [10,14].
Poor nutritional status [9,10,15,16]. PEM[17], MAC < 20 cm and hypoalbuminaemia [10]
References are at the end of the slides
Now it is noteworthy to state that patients with cirrhosis already have some of these risk factors like advanced age, poor
nutritional status and hypoalbuminemia.
5. Studies on hepatotoxicity of ATT drugs in
combination therapy
References are at the end of the slides
6. Studies on hepatotoxicity of ATT drugs in
combination therapy
References are at the end of the slides
7. Risk Factors
• Treating a tuberculosis with drugs among which many are hepatotoxic, in
CLD patients who are already in immunodeficient state and moreover have
these risk factors poses a great challenge.
• Treatment of TB in decompensated cirrhosis is challenging because
treatment is a double-edged sword. Treatment may lead to hepatotoxicity
and progressive TB may lead to liver decompensation.
• However the real picture is not scary as I have just explained. Anti-
tubercular drugs can be safely used in these patients with CLD when some
appropriate measures are applied.
9. Monitoring
• LFT should be carried out before initiating ATT, for baseline levels[1] as it has
been seen that pts with abnormal baseline ATs levels are at ↑ risk of
developing hepatic injury eventually.[2]
• These should be repeated twice weekly for the first 2 wks followed by wkly
monitoring till the end of 2 months and then monthly till the end of the RX.[3]
• If the serum AT is >3 X normal before the initiation of treatment,[4] the
modified regimens should be considered.
1. American Thoracic Society and Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med.
2000;161:S221–47.
2. Teleman MD, Chee CB, Earnest A , Wang YT . Hepatotoxicity of tuberculosis chemotherapy under general programme conditions in Singapore. Int J Tuberc Lung Dis.2002;6:699–705.
3. Saukkonen JJ, Cohn DL, Jasmer RM, Schenker S, Jereb JA, Nolan CM, et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med.
2006;174:935–52.
1 Note that TB itself may involve the liver and cause abnormal liver function.
10. Modification:
• Two hepatotoxic drugs REGIME:
— 9 HRE
— 2 HRSE + 6 HR
— 6–9 ZRE
• One hepatotoxic drug REGIME:
— 2 SHE + 10 HE
• No hepatotoxic drugs REGIME:
— 18–24 SEO.
WHO 4th ed: TB treatment Guideline
Regimes without pyrazinamide (Z)
Regime without isoniazid (H)
2 HRE + 7 HR
1. American thoracic society, CDC, infectious disease society of America. Treatment of
tuberculosis. Morbidity and mortality weekly report: recommendations and
reports.2003;52(RR-11):1–77.
[1]
Most preferred regime
Most preferred regime
11. Modification:
1. Sonika U. Tuberculosis and liver disease: management issues. Tropical Gastroenterology 2012;33(2):102–106
However, in some situations like early CLD, the patient will obviously fall under CLASS A despite relatively
preserved function, so in such situations,it isn’t necessary to stick to CPA OR B, First line drugs HRZE can be
initiated with close monitoring. Moreover at times, it is better to deal case by case basis. For eg Though
Pyrazinamide is a weak bactericidal but its stong sterilizing properties may prove to be beneficial while
treating tb.
12. A study on hepatotoxic drug regime containing Z
• The regime containing H+Z+E+O for 2 months followed by H+E+O for 10 months
was found to be less hepatotoxic and better tolerated than rifampicin containing
regimes.[1]
• 26.6% pts on regimen (2 HRE + 7 HR ) developed hepatotoxicity as compared to
none on regimen B (2 HZEO + 10 HEO )(P = 0.043).[1] [N=31]
• Hepatotoxicity was diagnosed if ALT increased > 5X from the baseline or to > 400 IU/L, or if bilirubin increased by > 2.5
mg/dL from the baseline.
1. Saigal S, Agarwal SR, Nandeesh HP, Sarin SK. Safety of an ofloxacin-based antitubercular regimen for the treatment of
tubrculosis in patients with underlying chronic liver disease: a preliminary report. J Gastroenterol Hepatol.
2001;16:1028–32.
2 HZEO + 10 HEO
13. • The American Thoracic Society (ATS) guidelines advise the use of E+O+ cycloserine
+ capreomycin or aminoglycoside for 18-24 mo if the patient has liver cirrhosis
with encephalopathy[1].
Proposed regimens are: [2]
(1) REO ± Aminoglycoside for 9-12 mo
(2) HEO ± Aminoglycoside for 9-12 mo
(3) EO ± Aminoglycoside for 12-24 mo.
Note: Role of aminoglycosides may be limited due to ↓ renal reserve in these pts.
The role of streptomycin is slowly being eliminated and it is also not included in
proposed regime for future (see next slide).
1. American Thoracic Society. CDC; Infectious Diseases Society of America. Treatment of tuberculosis. MMWR
Recomm Rep. 2003;52:1–77.
14. Summary of the existing classifications of anti-tuberculosis drugs (1
and 2) and possible future evolutions based on recent evidence (3)
15. Summary of the existing classifications of anti-tuberculosis drugs (1
and 2) and possible future evolutions based on recent evidence (3)
Jose A. Caminero, Anna Scardigli. Classification of antituberculosis drugs: a new proposal based on the most recent
evidence.European Respiratory Journal 2015 46: 887-893
16. Summary of the existing classifications of anti-tuberculosis drugs (1
and 2) and possible future evolutions based on recent evidence (3)
17. Definition of hepatotoxicity
• The definition of hepatotoxicity in pts with liver diseases is controversial,
because of difficulty in defining the influence of the natural evolution of
the underlying liver disease.
• There is a need to define better the level of AST/ALT and serum bilirubin
at which to consider hepatotoxicity to avoid unnecessary treatment
withdrawal and to avoid dangerous continuation of antitubercular
therapy when hepatotoxicity has set in.
• Although it is generally recommended that therapy be interrupted when AT
levels ↑ to 3-5 X ULN, this limit has not been defined in pts with AT values
already elevated before starting therapy[1].
1. Lew W, Pai M, Oxlade O, Martin D, Menzies D. Initial drug resistance and tuberculosis treatment outcomes: systematic review and meta-analysis. Ann Intern Med 2008; 149: 123-
134
18. Definition of hepatotoxicity
• Schenker et al[1] reported that elevations in the ALT and/or AST levels to
50-100 IU/L more than the baseline levels might define toxicity.
• In a study by Saigal et al[2], hepatotoxicity was diagnosed if ALT/AST levels
↑ to >5X of the baseline level, or >400 IU/L, or if the bilirubin ↑ by 2.5
mg/dL after exclusion of superimposed acute hepatitis.
1. Schenker S, Martin RR, Hoyumpa AM. Antecedent liver disease and drug toxicity. J Hepatol 1999; 31: 1098-1105
2. Saigal S, Agarwal SR, Nandeesh HP, Sarin SK. Safety of an ofloxacin-based antitubercular regimen for the treatment of tuberculosis in patients with underlying chronic liver
disease: a preliminary report. J Gastroenterol Hepatol 2001; 16: 1028-1032
19. • All confounding factors like superimposed acute viral hepatitis and
recidivism towards alcohol should be investigated.
• Usually, transaminase elevation falls back to baseline after stopping the
drugs.
• When the initial antitubercular regimen has been interrupted due to
hepatotoxicity, it is reasonable to go either of the 2 ways a: modified
regime or b: reintroduction one at a time (BTS/ATS)
1. Schenker S, Martin RR, Hoyumpa AM. Antecedent liver disease and drug toxicity. J Hepatol 1999; 31: 1098-1105
2. Saigal S, Agarwal SR, Nandeesh HP, Sarin SK. Safety of an ofloxacin-based antitubercular regimen for the treatment of tuberculosis in patients with underlying chronic liver
disease: a preliminary report. J Gastroenterol Hepatol 2001; 16: 1028-1032
20. ATDT ESTABLISHED
Stoppage of all
hepatotoxic drugs
Continue 2-3 non
hepatotoxic drug
Wait for AST/ALT
and Bilirubin to
return to baseline
or < 2ULN
Complete full ATT
Stop temporary
drugs
Similarly introduce
Isoniazid if
required
Start/Continue 2-3
non hepatotoxic
drug
Increase by 150 mg
every 7-14 d till
full dose (450
mg/d)
Restart with 150
mg/d rifampicin
Development of nausea, vomiting,
abdominal pain, jaundice
LFT every 3-7 d
Rifampicin
tolerated
21. • If a second episode of ATDT occurs after full institution of antitubercular
therapy, all hepatotoxic drugs should be stopped and extended duration
antitubercular therapy with no potentially hepatotoxic drugs should be
provided OR the last drug added should be stopped.
• One advise is to start with R because it is less likely than H or Z to cause
hepatotoxicity and is the most effective agent [1,2].
• In pts who have experienced jaundice but tolerate the reintroduction of R
and H, it is advisable to avoid Z.
1. American Thoracic Society, CDC, Infectious Diseases Society of America. Treatment 7. of tuberculosis. Morbidity and Mortality Weekly Report: Recommendations and Reports,
2003,52(RR-11):1–77.
2. Saukkonen JJ et al. An official ATS statement: hepatotoxicity of antituberculosis 8. therapy. American Journal of Respiratory and Critical Care Medicine, 2006, 174:935–952.
22. Prevention of ATDH
• N-Acetyl cysteine (NAC) has been shown in one study to prevent ATT-induced
hepatotoxicity[1].
• In that RCT, 60 new TB pts aged ≥ 60 years were randomized into two groups. In
Group Ⅰ (n = 32), the drug regimen included daily doses of HRZE. Pts in Group Ⅱ
(n = 28) were treated with the same regimen and NAC.
• The mean values of AT were significantly higher in group Ⅰ than in group Ⅱ
(with NAC) after 1 and 2 wk of treatment[1]. Hepatotoxicity occurred in 12 pts with
(37.5%) group I and none in group II.
• This study proved that NAC protects against antitubercular-drug-induced
hepatotoxicity.
• A hepatoprotective effect of silymarin on ATDH has been shown in rats[2].
1. Baniasadi S, Eftekhari P, Tabarsi P, Fahimi F, Raoufy MR, Masjedi MR, Velayati AA. Protective effect of N-acetylcysteine on antituberculosis drug-induced hepatotoxicity. Eur J
Gastroenterol Hepatol 2010; 22: 1235-1238
2. Tasduq SA, Peerzada K, Koul S, Bhat R, Johri RK. Biochemical manifestations of anti-tuberculosis drugs induced hepatotoxicity and the effect of silymarin. Hepatol Res 2005; 31:132-
135
24. References to slide: Studies on hepatotoxicity
61. Døssing M, Wilcke JT, Askgaard DS, Nybo B. Liver injury during antituberculosis treatment: an 11-year study. Tuber Lung Dis. 1996;77:335–340.
62. Ormerod LP, Horsfield N. Frequency and type of reactions to antituberculosis drugs: observations in routine treatment. Tuber Lung Dis. 1996;77:37–42.
63. Tost JR, Vidal R, Caylà J, Díaz-Cabanela D, Jiménez A, Broquetas JM. Severe hepatotoxicity due to anti-tuberculosis drugs in Spain. Int J Tuberc Lung Dis. 2005;9:534–540.
64. van Hest R, Baars H, Kik S, van Gerven P, Trompenaars MC, Kalisvaart N, Keizer S, Borgdorff M, Mensen M, Cobelens F. Hepatotoxicity of rifampin-pyrazinamide and isoniazid preventive therapy and tuberculosis treatment. Clin Infect Dis.
2004;39:488–496.
65. Teleman MD, Chee CB, Earnest A, Wang YT. Hepatotoxicity of tuberculosis chemotherapy under general programme conditions in Singapore. Int J Tuberc Lung Dis. 2002;6:699–705.
66. Fernández-Villar A, Sopeña B, Fernández-Villar J, Vázquez-Gallardo R, Ulloa F, Leiro V, Mosteiro M, Piñeiro L. The influence of risk factors on the severity of anti-tuberculosis drug-induced hepatotoxicity. Int J Tuberc Lung Dis. 2004;8:1499–1505.
67. Pukenyte E, Lescure FX, Rey D, Rabaud C, Hoen B, Chavanet P, Laiskonis AP, Schmit JL, May T, Mouton Y, et al. Incidence of and risk factors for severe liver toxicity in HIV-infected patients on anti-tuberculosis treatment. Int J Tuberc Lung Dis.
2007;11:78–84.
68. Schaberg T, Rebhan K, Lode H. Risk factors for side-effects of isoniazid, rifampin and pyrazinamide in patients hospitalized for pulmonary tuberculosis. Eur Respir J. 1996;9:2026–2030.
69. Saigal S, Agarwal SR, Nandeesh HP, Sarin SK. Safety of an ofloxacin-based antitubercular regimen for the treatment of tuberculosis in patients with underlying chronic liver disease: a preliminary report. J Gastroenterol Hepatol. 2001;16:1028–
1032.
70. Breen RA, Miller RF, Gorsuch T, Smith CJ, Schwenk A, Holmes W, Ballinger J, Swaden L, Johnson MA, Cropley I, et al. Adverse events and treatment interruption in tuberculosis patients with and without HIV co-infection. Thorax. 2006;61:791–794.
71. Huang YS, Chern HD, Su WJ, Wu JC, Chang SC, Chiang CH, Chang FY, Lee SD. Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis. Hepatology. 2003;37:924–930.
72. Sharma SK, Balamurugan A, Saha PK, Pandey RM, Mehra NK. Evaluation of clinical and immunogenetic risk factors for the development of hepatotoxicity during antituberculosis treatment. Am J Respir Crit Care Med. 2002;166:916–919.
73. Ungo JR, Jones D, Ashkin D, Hollender ES, Bernstein D, Albanese AP, Pitchenik AE. Antituberculosis drug-induced hepatotoxicity. The role of hepatitis C virus and the human immunodeficiency virus. Am J Respir Crit Care Med. 1998;157:1871–
1876.
74. Sharifzadeh M, Rasoulinejad M, Valipour F, Nouraie M, Vaziri S. Evaluation of patient-related factors associated with causality, preventability, predictability and severity of hepatotoxicity during antituberculosis [correction of antituberclosis]
treatment. Pharmacol Res. 2005;51:353–358.
75. Pande JN, Singh SP, Khilnani GC, Khilnani S, Tandon RK. Risk factors for hepatotoxicity from antituberculosis drugs: a case-control study. Thorax. 1996;51:132–136.
48. Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, Menzies D. Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. Am J Respir Crit Care Med. 2003;167:1472–1477.
38. Park WB, Kim W, Lee KL, Yim JJ, Kim M, Jung YJ, Kim NJ, Kim DH, Kim YJ, Yoon JH, et al. Antituberculosis drug-induced liver injury in chronic hepatitis and cirrhosis. J Infect. 2010;61:323–329.
25. References to slide: RISK FACTORS
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3. Garg PK, Tandon RK. Antituberculosis treatment induced hepatotoxicity. In: Sharma SK, Mohan A, editors. Tuberculosis 2nd ed. New Delhi: Jaypee Brothers Medical Publishers; 2009.p. 783-95.
4. Ormerod LP, Horsfield N. Frequency and type of reactions to antituberculosis drugs: observations in routine treatment. Tuber Lung Dis 1996; 77 : 37-42.
5. Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, Menzies D. Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. Am J Respir
Crit Care Med 2003; 167 : 1472-7.
6. Dossing M, Wilcke JT, Askgaard DS, Nybo B. Liver injury during antituberculosis treatment: an 11-year study. Tuber Lung Dis 1996; 77 : 335-40.
7. Teleman MD, Chee CB, Earnest A, Wang YT. Hepatotoxicity of tuberculosis chemotherapy under general programme conditions in Singapore. Int J Tuberc Lung Dis 2002; 6 : 699-705.
8. Hwang SJ, Wu JC, Lee CN, Yen FS, Lu CL, Lin TP, et al. A prospective clinical study of isoniazid-rifampicinpyrazinamide-induced liver injury in an area endemic for hepatitis B. J Gastroenterol
Hepatol 1997; 12 : 87-91.
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15. Singh J, Garg PK, Tandon RK. Hepatotoxicity due to antituberculosis therapy: clinical profile and reintroduction of therapy. J Clin Gastroenterol 1996; 22 : 211-4.
16. Krishnaswamy K, Prasad CE, Murthy KJ. Hepatic dysfunction in undernourished patients receiving isoniazid and rifampicin. Trop Geogr Med 1991; 43 : 156-60.
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