Using Antitubercular drugs for

Tuberculosis in patients with

Chronic Liver diseases
Pratap Sagar Tiwari, MD
DM RESIDENT, BIR HOSPITAL, NAMS, NEPAL
Introduction
• It is quite evident that more than 90 % of TB are reactivation of their latent form that
usually present in pts 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 TB is much higher in cirrhotic population when compared to
normal population.
• A study conducted in Western India showed that the prevalence rate was 15 X higher
than in the general population[2].
• Another study from India showed that there is nearly 5Xhigher prevalence of TB in
cirrhosis pts (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.
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 ↑ 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.
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 pts
of Asian origin, so ethnicity and environment seems to play a role as well.
• 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]

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.
References are at the end of the slides
Studies on hepatotoxicity of ATT drugs in
combination therapy

References are at the end of the slides

Studies on hepatotoxicity of ATT drugs in
combination therapy

References are at the end of the slides

Risk Factors
• Treating TB with drugs among which many are hepatotoxic, in CLD pts who
are already in immunodeficient state and moreover have these RFs poses a
great challenge.
• RX of TB in DLC is challenging because RX is a double-edged sword. RX 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 pts with CLD when some appropriate
measures are applied.
Principle of Safe ATT Therapy in CLD

1. Monitoring
2. Modification
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 RX,[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.
Modification:

• Two hepatotoxic drugs REGIME: Most preferred regime

— 9 HRE
Regimes without pyrazinamide (Z)
— 2 HRSE + 6 HR
— 6–9 ZRE Regime without isoniazid (H)
• One hepatotoxic drug REGIME:
2 HRE + 7 HR [1]
— 2 SHE + 10 HE Most preferred regime
• No hepatotoxic drugs REGIME:
— 18–24 SEO.

1. American thoracic society, CDC, infectious disease society of America. Treatment of

WHO 4th ed: TB treatment Guideline tuberculosis. Morbidity and mortality weekly report: recommendations and
reports.2003;52(RR-11):1–77.
 Modification:

However, in some situations like early CLD, the pt 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.
1. Sonika U. Tuberculosis and liver disease: management issues. Tropical Gastroenterology 2012;33(2):102–106
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.

2 HZEO + 10 HEO
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.
 • The American Thoracic Society (ATS) guidelines advise the use of E+O+ cycloserine +
capreomycin or aminoglycoside for 18-24 mo if the pt has LC with HE[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.
Summary of the existing classifications of anti-tuberculosis drugs (1
and 2) and possible future evolutions based on recent evidence (3)
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
Summary of the existing classifications of anti-tuberculosis drugs (1
and 2) and possible future evolutions based on recent evidence (3)
Definition of hepatotoxicity
• The definition of hepatotoxicity in pts with CLD 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 RX withdrawal
and to avoid dangerous continuation of ATT 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
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
• All confounding factors like superimposed acute viral hepatitis and
recidivism towards alcohol should be investigated.
• Usually, AT 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)
 Development of nausea, vomiting, Complete full ATT
ATDT ESTABLISHED
abdominal pain, jaundice Stop temporary
drugs

Stoppage of all Similarly introduce

hepatotoxic drugs Isoniazid if
LFT every 3-7 d required

Wait for AST/ALT Increase by 150 mg

Start/Continue 2-3
and Bilirubin to Restart with 150 every 7-14 d till
non hepatotoxic
return to baseline mg/d rifampicin full dose (450
drug
or < 2ULN mg/d)

Continue 2-3 non Rifampicin

hepatotoxic drug tolerated
• If a second episode of ATDT occurs after full institution of ATT, all hepatotoxic
drugs should be stopped and extended duration ATT 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.
 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
END OF SLIDES
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.
References to slide: RISK FACTORS
1. 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 : 916-9.
2. Singh J, Arora A, Garg PK, Thakur VS, Pande JN, Tandon RK. Antituberculosis treatment-induced hepatotoxicity: role of predictive factors. Postgrad Med J 1995; 71 : 359-
62
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.
9. Ohkawa K, Hashiguchi M, Ohno K, Kiuchi C, Takahashi S, Kondo S, et al. Risk factors for antituberculous chemotherapyinduced hepatotoxicity in Japanese pediatric
patients. Clin Pharmacol Ther 2002; 72 : 220-6.
10. Singla R. Evaluation of risk factors for antituberculosis treatment induced hepatotoxicity. Indian J Med Res 132, July 2010, pp 81-86
11. Anand AC, Seth AK, Paul M, Puri P. Risk factors of hepatotoxicity during anti-tuberculosis treatment. MJAFI 2006; 62 : 45-9.
12. [No authors listed]. Controlled clinical trial comparing a 6-month and a 12-month regimen in the treatment of pulmonary tuberculosis in the Algerian Sahara Algerian
Working Group/British Medical Research Council cooperative study. Am Rev Respir Dis 1984; 129 : 921-8.
13. Shakya R, Rao BS, Shrestha B. Incidence of hepatotoxicity due to antitubercular medicines and assessment of risk factors. Ann Pharmacother 2004; 38 : 1074-9.
14. Pande JN, Singh SP, Khilnani GC, Khilnani S, Tandon RK. Risk factors for hepatotoxicity from antituberculosis drugs: a case-control study. Thorax 1996; 51 : 132-6.
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.
17. Buchanan N, Eyberg C, David MD. Isoniazid pharmacokinetics in kwashiorkor. S Afr Med J 1979; 56 : 299-300.
Adenosine deaminase level in tuberculous peritonitis among pts with underlying liver cirrhosis

• Using 27 U/L as the cut-off value of ADA, the SN and SP were 100% and
93.3%, respectively, for detecting TBP in LC patients.[1]
• Thought to be caused by the concomitant immunocompromised status and
dilutional phenomenon in advanced liver disease[2].
• In addition, cirrhotic pts always have a low protein level in ascites, and the
correlation between total protein and ADA activity has been discussed in
several studies[2,3,4].

1. Liao YJ. Adenosine deaminase activity in tuberculous peritonitis among patients with underlying liver cirrhosis. World J Gastroenterol. 2012 Oct 7; 18(37): 5260–5265.
2. Hillebrand DJ, Runyon BA, Yasmineh WG, Rynders GP. Ascitic fluid adenosine deaminase insensitivity in detecting tuberculous peritonitis in the United States. Hepatology.
1996;24:1408–1412.
3. Bhargava DK, Gupta M, Nijhawan S, Dasarathy S, Kushwaha AK. Adenosine deaminase (ADA) in peritoneal tuberculosis: diagnostic value in ascitic fluid and serum. Tubercle.
1990;71:121–126.
4. Fernandez-Rodriguez CM, Perez-Arguelles BS, Ledo L, Garcia-Vila LM, Pereira S, Rodriguez-Martinez D. Ascites adenosine deaminase activity is decreased in tuberculous ascites with
low protein content. Am J Gastroenterol. 1991;86:1500–1503.
• PURPOSE: To determine DX features of TBP in the absence and presence of CLD.
• PATIENTS AND METHODS: 34 pts with TBP (13 without [Group I] and 21 with CLD
[Group II] and 26 controls with cirrhosis and uninfected ascites (Group III) .
G1: N=13 GII: N=21 GIII: N=26
• RESULTS: TBP without CLD TBP with CLD Without TBP
Ascitic fluid protein was > 25 g/L 100 % 70 % 0%
SAAG was > 11 g/L 0% 71 % 96 %
Ascitic fluid LDH 100 % 84 % 0%

• In Groups I and II combined, ascitic fluid acid-fast stain was negative in all but MTB culture was
positive in 45% (10/22); peritoneal nodules occurred in 94% (31/33), granulomas in 93%
(28/30), and positive peritoneal M tb culture in 63% (10/16).
• CONCLUSIONS: In pts with suspected TBP, AFP> 25 g/L, SAAG < 11 g/L and LDH> 90 U/L
have high SN for the disease. With coexistent CLD, a lower protein level and high SAAG
• Try regimens that atleast contain one of either isoniazid or rifampicin because they
are the most potent antitubercular drugs.
Isoniazid: effective against both intra and extracellular organisms.
• Very less incidence of clinical hepatitis when used alone as hepatotoxic drug( 0.6%)
• Most reactions are idiosyncratic so doesnot recur when rechallenged.
Rifampicin: Early bactericidal activity against rapidly growing bacilli.
• No studies on single use hepatotoxic profile.
• Can cause jaundice only without hepatocellular damage.
• Rarely causes centrilobular necrosis leading to cholestasis .
• can potentiate hepatotoxicity of other antitubercular drugs
Pyrazinamide: Weak bactericidal but greatest activity against dormant bacilli.
• Safety data unknown
• Introduction: There is paucity of data on tuberculosis and antituberculous
therapy (ATT) induced hepatotoxicity in pts with CLD.
• Aim: To study demographic, clinical characteristics of tuberculosis, pattern of
DILI and treatment responses to ATT in pts with liver cirrhosis.
• Material and method: All cases of LC diagnosed with tuberculosis (TB)
between January 2010 and June 2013 were enrolled.
• DILI was defined as follows (1) an AST/ALT value exceeding 3 X ULN if the
baseline level was normal (<40 IU/L), or an AST/ALT exceeding 2 times the
baseline level if the baseline level was abnormal and an absolute increase in
serum bilirubin >2 mg/dl from baseline.

Sharma P. Clinical and Biochemical Profile of Tuberculosis in Patients with Liver Cirrhosis. JCEH 2015;5(1):8–13
Baseline Characteristics of Patients with Cirrhosis
and Tuberculosis (n = 67).

Sharma P. Clinical and Biochemical Profile of Tuberculosis in Patients with Liver Cirrhosis. JCEH 2015;5(1):8–13
 Clinical and Radiographic Characteristics of Patients
with TB with Cirrhosis

Sharma P. Clinical and Biochemical Profile of Tuberculosis in Patients with Liver Cirrhosis. JCEH 2015;5(1):8–13
 Regimens of Anti-TB Treatment and Toxicity

Sharma P. Clinical and Biochemical Profile of Tuberculosis in Patients with Liver Cirrhosis. JCEH 2015;5(1):8–13
 • Results: Patients with Child's status A (n = 7) received 4 drugs (RHEZ) and
could tolerate well even during follow up without any drug induced toxicity.
In rest of pts commonest regimen followed was combination of drugs (RHEO,
n = 32) followed by RHE (n = 11).
• DILI occurred in 35% started with either RHEO, HEO and REO.
• Median time of onset of DILI was 12 days (4–34) days. There was no DILI
related death during hospital stay or follow up.
• Conclusions: Extrapulmonary TB is common in patients with cirrhosis and
DILI is common in Child B and C with combination of rifampicin and isoniazid
regimen.
Sharma P. Clinical and Biochemical Profile of Tuberculosis in Patients with Liver Cirrhosis. JCEH 2015;5(1):8–13