Characteristics and risk factors for antituberculosis drug-induced liver injury in a cohort of patients with cirrhosis in a tertiary referral university teaching hospital in Thailand
, , , , , and | Apr 30, 2019
About this article
Article Category: Original article
Published Online: Apr 30, 2019
Page range: 65 - 74
DOI: https://doi.org/10.1515/abm-2019-0003
Keywords
© 2018 Passisd Laoveeravat et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.
Figure 1
Baseline characteristics of cirrhotics receiving 3 hepatotoxic antituberculosis drugs (isoniazid, rifampin, and pyrazinamide)
| Characteristics | ATDILI | Non-ATDILI | |
|---|---|---|---|
| (n = 6) | (n = 31) | ||
| Age (years), mean ± SD (range) | 54 ± 13 (39–69) | 54 ± 13 (25–89) | 0.65 |
| Male, n (%) | 5 (83%) | 21 (68%) | 0.65 |
| Cause of cirrhosis, n (%) | |||
| HBV | 0 (0%) | 6 (19%) | 0.24 |
| HCV | 2 (33%) | 5 (16%) | 0.32 |
| Alcohol | 1 (17%) | 12 (39%) | |
| Alcohol consumption, n (%) | |||
| Comorbid conditions, n (%) | |||
| HIV | 3 (50%) | 4 (13%) | 0.07 |
| DM | 1 (17%) | 12 (39%) | 0.39 |
| CKD and ESRD | 1 (13%) | 7 (23%) | 0.57 |
| CTP class, n (%)* | 0.12 | ||
| A | 0 (0%) | 8 (28%) | |
| B | 6 (100%) | 16 (55%) | |
| C | 0 (0%) | 5 (17%) | |
| CTP score, median (range)** | 8 (7–9) | 7 (5–13) | |
| MELD score, median (range)*** | 12.4 (10.2–14.5) | 12.4 (6.4–23.5) | 0.51 |
| Baseline laboratory results, median (range) | |||
| Total bilirubin, mg/dL | 1.2 (0.4–2.6) | 1.2 (0.3–7.0) | 0.67 |
| AST, U/L | 47 (18–67) | 44 (12–406) | 0.46 |
| ALT, U/L | 24 (9–41) | 26 (1–181) | 0.48 |
| ALP, U/L | 213 (143–362) | 130 (48–615) | 0.33 |
| White blood cell count/mL | 12,010 (7,010–23,310) | 7,830 (3,580–18,900) | 0.06 |
Characteristics of tuberculosis in the study cohort
| Features | n (%) |
|---|---|
| Organs of tuberculosis infection† | |
| Pulmonary | 40 (64%) |
| Extrapulmonary | 6 (10%) |
| Disseminated (≥2 organs involved) | 17 (27%) |
| Diagnostic methods for tuberculosis‡ | |
| Biopsy | 12 (19%) |
| PCR | 20 (31%) |
| AFB smear | 18 (28%) |
| CT imaging | 1 (2%) |
| Chest x-ray imaging | 10 (16%) |
| Clinical diagnosis | 3 (5%) |
Baseline characteristics of study patients
| Characteristic | ATDILI (n = 6) | non-ATDILI (n = 58) | |
|---|---|---|---|
| Age (years), mean ± SD (range) | 54 ± 13 (39–69) | 55 ± 13 (25–89) | 0.86 |
| Male, n (%) | 5 (83%) | 40 (69%) | 0.66 |
| Cause of cirrhosis, n (%) | |||
| HBV | 0 (0%) | 13 (22%) | 0.33 |
| HCV | 2 (33%) | 11 (19%) | 0.59 |
| Alcohol | 1 (17%) | 20 (35%) | 0.65 |
| Comorbid conditions, n (%) | |||
| HIV | 3 (50%) | 5 (9%) | 0.02 |
| DM | 1 (17%) | 17 (29%) | 0.67 |
| CKD and ESRD | 0 (0%) | 8 (14%) | <0.001 |
| CTP class, n (%)† | 0.054 | ||
| A | 0 (0%) | 16 (30%) | |
| B | 6 (100%) | 26 (48%) | |
| C | 0 (0%) | 12 (22%) | |
| CTP score, median (range)‡ | 8 (7–9) | 7 (5–13) | 0.66 |
| MELD score, median (range)§ | 12.4 (10.2–14.5) | 11.7 (6.4–29.1) | 0.76 |
| Number of hepatotoxic ATDs, n (%) | 0.09 | ||
| 1 | 0 (0%) | 3 (5%) | |
| 2 | 0 (0%) | 24 (41%) | |
| 3 | 6 (100%) | 31 (53%) | |
| Pyrazinamide in initial ATDs | 6 (100%) | 31 (53%) | 0.04 |
| Baseline laboratory results, median (range) | |||
| Total bilirubin, mg/dL | 1.2 (0.4–2.6) | 1.3 (0.3–7.0) | 0.61 |
| AST, U/L | 47 (18–67) | 44 (9–406) | 0.54 |
| ALT, U/L | 24 (9–41) | 23 (1–181) | 0.55 |
| ALP, U/L | 213 (143–362) | 131 (48–615) | 0.13 |
| Albumin, g/dL | 2.9 (1.9–3.0) | 2.9 (1.5–4.2) | 0.25 |
| Creatinine, mg/dL | 0.7 (0.3–1.4) | 0.8 (0.4–8.8) | 0.41 |
| Hemoglobin, g/dL | 9.0 (7.7–9.8) | 10.0 (7.0–15.2) | 0.14 |
| Platelet count/mL | 265,000 (27,000–334,000) | 152,000 (64,000–511,000) | 0.44 |
| White blood cell count/mL | 12,010 (7,010–23,310) | 6,375 (1,610–18,900) | 0.01 |
| INR | 1.3 (1.2–1.4) | 1.3 (0.9–2.5) | 0.94 |
Initial antituberculosis regimen according to Child–Turcotte–Pugh class
| Initial antituberculosis drugs regimen (number of patients) | |||
|---|---|---|---|
| Three hepatotoxic drugs | Two hepatotoxic drugs | One hepatotoxic drug | |
| CTP class A (n = 16) | IRZE (8) | IRE (7) | IEOS (1) |
| CTP class B (n = 32) | IRZE (21), IRZES (1) | IRE (6), IREO (1), IREOS (1), IREL (1) | IE (1) |
| CTP class C (n = 12) | IRZE (5) | IRE (5) | IEOS (1), REO (1) |
| Not classified (n = 4) | IRZE (2) | IRE (2) | – |
Characteristics of cirrhotic patients diagnosed with antituberculosis drug-induced liver injury (ATDILI). Bold numbers indicate laboratory value that met the criteria for ATDILI diagnosis.
| Patient No. Sex, age (years) | Etiology of cirrhosis | CTP score | HIV status (CD4 cells/ mm3) | Site of tuberculosis | AST/ALT/ALP/ TB at baseline | AST/ALT/ALP/TB at ATDILI diagnosis | Duration to ATDILI (days) | Initial ATD regimen | Subsequent regimen | Vital status at the end of treatment | Time to improvement of LFTs after ATDILI diagnosis |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1. Male, 68 | Cryptogenic | 8 | HIV- | Meningitis | 25/28/173/2.6 | 153/105/153/1.2 | IRZE | IR | Alive | N/A | |
| 2. Male, 54 | Cryptogenic | 8 | HIV- | Peritoneal | 34/12/330/1.6 | 515/228/347/4.1 | IRZE | IEO | Alive | N/A | |
| 3. Female, 39 | Cryptogenic | 8 | HIV- | Lung | 18/9/213/0.5 | 125/118/171/9.9 | 66 | IRZE | EO | Alive | 7 mo. |
| 4. Male, 69 | Alcohol | 7 | HIV+ (8) | Lung | 60/41/143/0.8 | 461/281/195/3.5 | 13 | IRZE | IRE | Alive | 2 mo. |
| 5. Male, 47 | HCV | 9 | HIV+ (448) | Lung | 66/32/362/0.4 | 180/62/202/7.32 | 15 | IRZE | OS | Dead at 1 week after ATDILI diagnosis due to liver failure | Dead |
| 6. Male, 44 | HCV | 8 | HIV+(156) | Lung | 67/20/78/2.4 | 230/57/292/3.5 | 51 | IRZE | EO | Alive | 2 mo. |
Comparison of drug-induced liver injury risk factors for each of Child–Turcotte–Pugh score
| CTP class A | CTP class B | CTP class C | |
|---|---|---|---|
| Encephalopathy | None | Grade 1–2 | Grade 3–4 |
| ATDILI, n (%) | 6 (100%) | 0 | 0 |
| Ascites | None | Mild to moderate | Severe |
| ATDILI, n (%) | 2 (33%) | 1 (17%) | 3 (50%) |
| Bilirubin, mg/dL | <2 | 2–3 | >3 |
| ATDILI, n (%) | 6 (100%) | 0 | 0 |
| Albumin, g/dL | >3.5 | 2.8–3.5 | <2.8 |
| ATDILI, n (%) | 0 | 0 | 6 (100%) |
| INR | <1.7 | 1.7–2.3 | >2.3 |
| ATDILI, n (%) | 6 (100%) | 0 | 0 |