Revisión sistemática

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The association between CYP2E1 polymorphisms and hepatotoxicity due to anti-tuberculosis drugs: a meta-analysis.

Año 2014
Autores Sheng YJ , Wu G , He HY , Chen W , Zou YS , Li Q - Más
Revista Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
Enlaces Pubmed , DOI

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BACKGROUND:

Although there have been previous studies on the potential association between cytochrome P450 2E1 (CYP2E1) polymorphisms and the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH), the results have generally been controversial.

METHODS:

We searched Medline/PubMed, EMBASE, Web of Science, and the Cochrane Library using the following key words: cytochrome P450 2E1, CYP2E1, polymorphism, tuberculosis and TB. The strength of the association between the CYP2E1 PstI/RsaI and DraI polymorphism and ATDH risk as measured by odds ratios (OR) with 95% confidence intervals (CIs) was studied.

RESULTS:

Compared with the wild genotype (c1/c1), the OR of ATDH was 1.41 (95% CI.: 1.1-1.82, P=0.007) for the PstI/RsaI polymorphism, and 0.78 (95% CI.: 0.51-1.18, P=0.23) for the DraI polymorphism. Compared with individuals with N-acetyltransferase 2 (NAT2) fast or intermediate acetylator genotype and c1/c1 genotype patients who were NAT2 slow acetylators and carried the high activity CYP2E1 c1/c1 genotype had higher risk for ATDH (OR=3.10, P<0.0001).

CONCLUSION:

The present meta-analysis indicates that the CYP2E1 c1/c1 genotype may be a risk factor for ATDH, and the concomitant presence of the slow acetylator NAT2 genotype may further increase this risk.

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Estudio primario

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Herbal hepatoxicity from Chinese skullcap: A case report.

Año 2012
Autores Yang L , Aronsohn A , Hart J , Jensen D
Revista World journal of hepatology
Enlaces Pubmed , DOI

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The use of herbal supplements has increased considerably over the last decade. We report a case of an elderly woman who began taking Move Free Advanced for arthritis, which in addition to glucosamine and chondroitin, contained two herbal ingredients, Chinese skullcap and Black Catechu. Our patient presented with significant cholestasis and hepatitis which significantly improved after discontinuation of the supplement. Since neither the patient nor the treating physician recognized this supplement as a potential hepatotoxin, she resumed taking the supplement and again suffered from considerable hepatotoxicity. Liver biopsy at that time was consistent with acute drug induced liver injury. She, once again, recovered after discontinuation of the supplement. Review of the literature confirms that Chinese skullcap has been implicated as a possible hepatotoxic agent which was demonstrated in this case.

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Detection of hepatotoxicity associated with methotrexate therapy for psoriasis.

Año 1989
Revista Archives of dermatology
Enlaces Pubmed

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To determine whether liver function tests and clinical and demographic information would predict methotrexate-associated hepatotoxicity, we identified 78 patients who had undergone 147 liver biopsies associated with methotrexate therapy for psoriasis. The joint sensitivity of aspartate aminotransferase, alkaline phosphatase, and total bilirubin values in detecting abnormal results from a biopsy specimen obtained after treatment was .86; the predictive value of negative test results was .93. A logistic regression model significantly predicted the presence of abnormal (grade III or higher) liver biopsy specimen results. The concordance index was .92 (perfect, 1.0). Regression coefficients may be used along with information from a specific patient to calculate the predicted probability of an abnormal result from a liver biopsy specimen after treatment. We conclude that this multivariate risk estimation model significantly predicts the likelihood of positive findings from liver biopsy specimens in this patient population. The clinical use of this model awaits further validation.

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Cyclophosphamide hepatotoxicity in a patient with systemic lupus erythematosus.

Año 1982
Autores Bacon AM , Rosenberg SA
Revista Annals of internal medicine
Enlaces Pubmed

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Estudio primario

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Acupuncture may cause hepatotoxicity in patients in climacteric.

Año 2008
Autores Hong L , Chen Z , Zhou X , Han Z , Zhang X , Wu K - Más
Revista Climacteric : the journal of the International Menopause Society
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Estudio primario

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[Probable hepatoxicity from epigallocatecol gallate used for phytotherapy].

Año 2004
Revista Gastroentérologie clinique et biologique
Enlaces Pubmed

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Estudio primario

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Hepatotoxicidad por amoxicilina/ácido clavulánico: caso clínico

Traducción oficial
Año 1999
Revista Rev. méd. Chile
Enlaces Virtual Health Library

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We report a 72 years old diabetic male that, after the use of combined amoxicillin-clavulanic acid, developed pruritus and jaundice. Liver function tests showed serum total bilirubin of 4.3 mg/dL aspartate aminotransferase 140 U/l (normal <35 U/L), alanine aminotransferase 470 U/L (normal <40) and alkaline phosphatases of 400 U/L (normal <100). Serology for hepatitis A, B and C viruses was negative, ERCP showed a normal biliary tree and liver biopsy disclosed a cholestatic hepatitis. Ursodeoxycholic was started to relieve pruritus. Liver function tests improved shortly thereafter, suggesting that this drug may be useful in the treatment of drug induced cholestasis

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Revisión sistemática

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Risk of tyrosine kinase inhibitors-induced hepatotoxicity in cancer patients: a meta-analysis.

Año 2013
Autores Teo YL , Ho HK , Chan A
Revista Cancer treatment reviews
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INTRODUCTION:

Although existing evidence from clinical trials has demonstrated manifestation of hepatic adverse events (AEs) with the use of tyrosine kinase inhibitors (TKIs), overall risks have yet to be reported. Thus we conducted a meta-analysis to determine the risk of hepatotoxicity associated with the use of TKIs, by comparing the occurrence of hepatotoxicity of the TKI arms against that of comparison arms.

METHODS:

A comprehensive literature search of randomized control trials involving TKIs was performed. Only randomized, double-blind and placebo-controlled phase 2 or phase 3 human trials were included. The included studies must involve the comparison of a TKI against placebo, or the comparison of TKI with chemotherapy agent against placebo with the same chemotherapy agent.

RESULTS:

Twelve articles were included in the analysis. There was a significant overall increase in the odds of developing high-grade (grade 3 or above) hepatotoxicity with the use of TKIs compared to the control arms (Pooled OR 4.35, 95% CI 2.96-6.39). The odds of developing all-types all-grades (Pooled OR 2.42, 95% CI 1.52-3.85) and high-grade hepatotoxicity due to elevation in alanine transaminase (Pooled OR 5.22, 95% CI 2.88-9.46), aspartate transaminase (Pooled OR 6.15, 95% CI 3.09-12.25) and total bilirubin (Pooled OR 1.76, 95% CI 0.59-5.24) was higher with the use of TKI than compared to the controls.

DISCUSSION:

This is the first meta-analysis to demonstrate a significantly increased risk of hepatic AEs associated with TKIs use. Clinicians should be aware of this risk and provide close monitoring in patients receiving these therapies.

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Evidence and consequences of spectrum bias in studies of criteria for liver transplant in paracetamol hepatotoxicity.

Año 2008
Autores Ding GK , Buckley NA
Revista QJM : monthly journal of the Association of Physicians
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OBJECTIVE:

In severe paracetamol hepatotoxicity, orthotopic liver transplant (OLT) is a standard treatment in patients judged to have a hopeless prognosis. The most commonly used criteria to make this decision are the King's College Criteria (KCC). We aimed to compare the expected survival for patients who meet the KCC and do not receive transplant and those who receive OLT.

METHODS:

A systematic review of studies of survival in patients who met the KCC according to whether they were transplanted. Data from these studies was extrapolated to compare long-term survival with and without adjustment for Quality of Life.

RESULTS:

The survival of patients meeting KCC and undergoing transplant has not been specifically studied. UK data on transplants for acute liver failure indicate 1 and 10 year survival rates of 65 and 44%, respectively. Survival in those without transplant was documented in 15 studies. The average long-term survival rate was 24.9%. Survival was worse in studies originating in the King's unit (13.8 vs. 30.0%). It was apparent that this may be due to spectrum bias occurring in this much larger unit. There was clear evidence that those with the best prognosis were preferentially transplanted at the Kings liver unit, indicating the criteria may perform significantly worse at predicting death without transplant than previously estimated. Even so, for a 20-year-old meeting KCC, the best estimate of life expectancy with transplant (13.5 years) is no better than without (13.4 years). Adjustment for quality of life made OLT clearly a worse option.

CONCLUSION:

Criteria for OLT that have a much higher positive predictive value (for death without transplant) are required. Such studies must be conducted only on those who would be considered suitable for transplant. Non-orthotopic liver transplant may be a preferred option in such circumstances, although much more data on survival after this procedure are required.

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Age-related risk of hepatotoxicity in the treatment of latent tuberculosis infection: a systematic review.

Año 2010
Autores Kunst H , Khan KS
Revista The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Enlaces Pubmed

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OBJECTIVE:

To determine the age-related risk of hepatotoxicity under currently recommended treatment regimens for latent tuberculosis (TB) infection (LTBI).

METHODS:

A systematic review of the MEDLINE and EMBASE databases (from database inception to 2008) was performed to determine the risk of isoniazid (INH) and/or rifampicin hepatotoxicity in LTBI treatment stratified by patient age. Study selection, study quality assessment and data extraction were performed using piloted proformas. Rate data were meta-analysed to generate summary rates with 95%CI within age-related subgroups using a random effects model.

RESULTS:

Seven relevant studies (18,610 participants, including 115 cases of hepatotoxicity) met the selection criteria. The median rate of hepatotoxicity was 1.8% (range 0.07-11.9). On average, rates were higher among those aged ≥ 35 years (1.7%, 95%CI 1.4-2.2) than those aged <35 years (0.2%, 95%CI 0.1-0.3).

CONCLUSION:

The rates of hepatotoxicity were low. Summary estimates of risks generated in this review can be used for counselling individuals for whom chemoprophylaxis is recommended. The use of INH for the treatment of LTBI is safe in older patients with clinical or biochemical monitoring.

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