Prevalence Of Hepatotoxicity Research Articles

Twee patiënten met acute toxische hepatitis na recente inname van thee

Two patients with toxic hepatitis after tea ingestion Drug-induced liver injury (DILI) is common and can manifest in various degrees: from asymptomatic increased transaminases to hepatocellular jaundice with an elevated total and direct bilirubin to acute liver failure. When accompanied by jaundice, there is a mortality rate of 10%. In acute liver failure, referral to a tertiary centre is necessary. This article emphasizes the consideration of herbal and dietary supplements (HDS). The use of HDS in Europe and the US is rising. Some studies state that 1 out of 3 to 1 out of 2 Americans take dietary supplements, which raises concerns about HDS-related toxic hepatitis. HDS involve any supplement that could cause liver damage, including herbs, vitamins, minerals, amino acids and proteins. The prevalence of hepatotoxicity is underestimated. DILI is a diagnosis of exclusion. Diseases that should be excluded, are viral hepatitis, non-alcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), hereditary hemochromatosis, autoimmune hepatitis, Wilson’s disease and alpha-1 antitrypsin deficiency. If there is an increased total and direct bilirubin with or without cholestasis, bile duct stones and hepatobiliary malignancies should be excluded. A liver biopsy may be necessary if the diagnosis is unclear or when several diagnoses are plausible. Liver damage usually occurs within 1 to 6 months after starting the product and is usually reversible. It is important to bear in mind HDS when considering DILI as the incidence of HDS is clearly increasing.

Risk factors of severe hepatotoxicity among HIV-1 infected individuals initiated on highly active antiretroviral therapy in the Northwest Region of Cameroon

BackgroundHepatotoxicity due to highly active antiretroviral therapy (HAART) has gained prominent attention since it can be affected by many factors. The aim of this study was to determine the prevalence of hepatotoxicity and related risk factors of severe hepatotoxicity following HAART initiation.MethodsA total of 100 drug-naive patients aged between 18 and 61 years were recruited. They were put on Tenofovir/Lamivudine/Efavirenz [TDF/3TC/EFV] (64), Zidovudine/ Lamivudine/Efavirenz [AZT/3TC/EFV] (22), and Zidovudine/Lamivudine/Nevirapine AZT/3TC/NVP (14) and monitored for 6months and blood samples drawn.Alanine aminotransferases (ALT), aspartate aminotransferases (AST), and alkaline phosphatase (ALP) wereanalyzed by enzymatic methods and used to classify levels of hepatotoxicity.ResultsA total of 37(37%) and 49(49%) patients presented with hepatotoxicity while 15% and 28% had severe hepatotoxicity at 4 and 24 weeks respectively. Serum levels of all enzymes increased significantly (p = 0.001) with increased treatment duration. Univariate analysis revealed that the risk factor of developing severe hepatotoxicity was significantly greater in patients < 30years (p = 0.02), males(p = 0.04), low BMI (p = 0.02), low monthly income (p = 0.01) earners, and patients on AZT + 3TC + NVP regimen (p = 0.01). While multivariate analysis at p < 0.09 showed that age 30–40 years, low BMI, low monthly income, and the use of AZT + 3TC + NVP regimen were independent risk factors.ConclusionsLow BMI, age group of 30–40years, low monthly income, and the use of AZT + 3TC + NVP regimen identified as risk factors for the development of severe hepatotoxicity should be considered as an important strategy by clinicians in preventing the hepatotoxicity.

Combined Use of Febuxostat and Colchicine Does Not Increase Acute Hepatotoxicity in Patients with Gout: A Retrospective Study.

Colchicine has been effectively used to prevent acute flares in patients with gout, but drug-related adverse events have frequently occurred. We investigated whether colchicine therapy with febuxostat is associated with hepatotoxicity in gout patients. Gout patients treated with (n = 121) or without (n = 57) colchicine were enrolled upon initiating febuxostat as a urate-lowering treatment, and clinical and laboratory data at diagnosis were compared. Logistic regression analysis was performed to evaluate the risk factors related to hepatotoxicity. Median age of the with-colchicine and without-colchicine groups was 51.0 (37.0–62.0) and 56.0 (43.5–68.5) years, respectively. During the three months of febuxostat prescription, the prevalence of hepatotoxicity was 13/121 (10.9%) in the with-colchicine group and 4/57 (7.0%) in the without-colchicine group, without statistical significance. The rate of colchicine use was not different between the study subjects with or without hepatotoxicity (76.5% vs. 67.1%, p = 0.587). Pre-existing liver disease was significantly associated with increased risk of hepatotoxicity after febuxostat treatment (odds ratio, 4.083; 95% confidence interval, 1.326–12.577; p = 0.014). Colchicine may be safely used as a prophylactic agent for gout patients with febuxostat. However, upon initiating febuxostat, it is recommended to monitor the development of acute liver injury in gout patients with underlying liver disease.

Proportion and Factors that Associate with Incidence of Hepatotoxicity in Rheumatoid Arthritis Patients Treated with Methotrexate in RSCM Year 2013−2015

Background Rheumatoid arhtirtis (RA) is a chronic autoimmune disease that mainly attacks joints. It may causes joint deformities which leads to lower quality of life of RA patients. RA is treated with metothrexate (MTX) which inhibiting disease progression. MTX is known for its hepatotoxicity side effect, which is described by an elevation of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) beyond the upper normal limit. Factors that may enhance hepatotoxicity are gender, age, cummulative dose of MTX, and duration therapy of MTX. Prevalence of hepatotoxicity caused by MTX therapy in RA patients in Indonesia is still unknown. The objective of this research is to know the proportion of hepatotoxicity and its associations with the factors that may enhance hepatotoxicity caused by MTX therapy in RA patients in RSCM.Method Data about gender, age, cummulative dose and duration therapy of MTX are obtained from 115 RA patients' medical records.Result Proportion of hepatotoxicity in RA patients treated with MTX in RSCM is 42.60%. Gender, age, cummulative dose and duration therapy of MTX do not significantly enhance hepatotoxicity (p&gt;0.05).Conclusion In conclusion gender, age, cummulative dose and duration therapy of MTX do not have association with hepatotoxicity in RA patients treated with MTX. Keywords: Rheumatoid Arthritis, Methotrexate, Hepatotoxicity

Proportion and Factors that Associate with Incidence of Hepatotoxicity in Rheumatoid Arthritis Patients Treated with Methotrexate in RSCM Year 2013−2015

Background Rheumatoid arhtirtis (RA) is a chronic autoimmune disease that mainly attacks joints. It may causes joint deformities which leads to lower quality of life of RA patients. RA is treated with metothrexate (MTX) which inhibiting disease progression. MTX is known for its hepatotoxicity side effect, which is described by an elevation of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) beyond the upper normal limit. Factors that may enhance hepatotoxicity are gender, age, cummulative dose of MTX, and duration therapy of MTX. Prevalence of hepatotoxicity caused by MTX therapy in RA patients in Indonesia is still unknown. The objective of this research is to know the proportion of hepatotoxicity and its associations with the factors that may enhance hepatotoxicity caused by MTX therapy in RA patients in RSCM.Method Data about gender, age, cummulative dose and duration therapy of MTX are obtained from 115 RA patients' medical records.Result Proportion of hepatotoxicity in RA patients treated with MTX in RSCM is 42.60%. Gender, age, cummulative dose and duration therapy of MTX do not significantly enhance hepatotoxicity (p&gt;0.05).Conclusion In conclusion gender, age, cummulative dose and duration therapy of MTX do not have association with hepatotoxicity in RA patients treated with MTX. Keywords: Rheumatoid Arthritis, Methotrexate, Hepatotoxicity

A Review of Azathioprine-Associated Hepatotoxicity and Myelosuppression in Myasthenia Gravis.

Myasthenia gravis (MG) is an autoimmune disorder in which antibodies interfere with neuromuscular transmission. Azathioprine (AZA) is an immunosuppressant frequently used for treatment of various autoimmune conditions, including MG. The literature suggests that the rates of AZA-associated hepatotoxicity and myelosuppression in MG are highly variable. Published studies have not formally analyzed their pattern, severity, timing, and/or recovery. We assessed the prevalence, pattern and timing of AZA associated toxicity in a large group of MG patients. We identified 113 patients with MG with AZA-associated toxicity among 571 managed with this immunosuppressant. The timing of when toxicities occurred as well as pattern of laboratory abnormalities was assessed. The overall prevalence of hepatotoxicity and myelosuppression was 15.2% and 9.1%, respectively. The most common pattern of hepatotoxicity seen was gamma-glutamyl transpeptidase (GGT) enzyme elevation in 67.8% of patients. Of note, 21.2% of patients with myelosuppression had normocytic anemia, 17.3% had pancytopenia, and another 17.3% developed macrocytic anemia. AZA-associated hepatotoxicity and myelosuppression in MG are not uncommon and may be underrecognized depending on the timing, frequency, and specific tests ordered for blood work monitoring.

Risk of hepatotoxicity with concurrent statin and tyrosine kinase inhibitor (TKI) or mTOR inhibitor (mTORi) in patients with metastatic renal cell carcinoma (mRCC).

610 Background: TKIs and statins alone can cause liver injury. When used together, there is additive risk for hepatotoxicity, as seen with pazopanib and simvastatin, and the potential for discontinuing TKI therapy. Liver enzyme abnormalities are also associated with mTORi. Hepatotoxicity from concurrent use of statins as a class with TKI or mTORi as a class in real world practice in mRCC has not been reported. Methods: This observational cohort study included adult patients treated with a TKI or mTORi for mRCC at the Huntsman Cancer Institute from 2004-2014. We performed a treatment line analysis. For each treatment line, CTCAE criteria were used to categorize maximum AST, ALT, and total bilirubin. Highest grade of any liver enzyme was compared between TKI with and without statin and between mTORi with and without statin (Fisher’s Exact test). Results: A total of 162 treatment lines were included. For TKI and statin, the three most common treatment line combinations were sunitinib and simvastatin (7), sunitinib and atorvastatin (4), and pazopanib and simvastatin (3). For mTORi and statin, the three most common treatment line combinations involved simvastatin with temsirolimus (7) and everolimus (3). Prevalence of hepatotoxicity is shown in the table. Conclusions: Our results show a trend toward significance in the prevalence of hepatotoxicity with concomitant mTORi and statin versus mTORi alone, perhaps explained by mTORi-mediated competitive inhibition of simvastatin (sensitive CYP 3A4 substrate). There was no difference in hepatotoxicity for TKI with or without statin, although there were few pazopanib and simvastatin combinations. Study limitations include the small sample size, limited number of TKI or mTORi and statin combinations, and retrospective study design. A larger study is needed to validate these findings. [Table: see text]

Nevirapine-induced Hepatotoxicity in HIV Patients Attending Care and Treatment Clinics in Tanzania

Objective The aim of the study was to determine the prevalence of hepatotoxicity in HIV-infected patients using nevirapinecontaining antiretroviral drugs (ARVs) in comparison with those using efavirenz-based ARVs.

P.2.b.027 Study of antidepressant hepatotoxicity in 122 Tunisian psychiatric outpatients

Introduction: Depression is a common mental disorder, and is according to the World Health Organisation the second leading cause of disability in the world. The discovery of antidepressants and especially Selective Serotonin Recapture Inhibitors (SSRI) has been a major contribution in the treatment of the disease. Despite all the efforts made during the preclinical phase, the drug hepatotoxicity is revealed, most of the time, after their marketing. Hepatotoxicity of antidepressants has played a central role in guiding prescriptions and has been implicated in the decisions of removal from the market of certain molecules. The aim of our study was to estimate the prevalence of hepatotoxicity in patients with major depressive disorder treated with antidepressants and to estimate the most harmful antidepressants for the liver. Patients and Method: We conducted a comparative crosssectional study on patients with recurrent depressive disorder (according to the DSM IV text revised) treated with antidepressants. We included 122 outpatients followed in the psychiatry department of Fattouma Bourguiba Hospital of Monastir (Tunisia) and controls aged from 22 to 59 year old with no history of mental or physical illness. The two groups were paired in age and sex. The hepatotoxicity was assessed by seric assay of Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Direct Bilirubin (DB), Total Bilirubin (TB) Total cholesterol (TC), g-Glutamyltransferase (GGT), Alkaline Phosphatase (PAL) and triglyceride (TG). All chemical analyses were performed on Cobas 600TM (Roche Diagnostics) in the biochemical and toxicological laboratory of the Fattouma Bourguiba Hospital of Monastir. All the statistical analyses were performed with Statistical Package for the Social Sciences (SPSS) 18.0 for windows. Results: The mean age of our patients was 43.79±13.00 year old. The sex ratio was 0.67. Thirty-four per cent of our patients were treated by tricyclic antidepressants (TCA) and 66% were treated by SSRI. Compared with controls, our patients had higher activities of AST (p<10−3) and GGT (p = 0.001) and a higher total bilirubin concentration (p = 0.039). In addition, patients treated longer than one month had an increased activity of AST (p = 0.034) and PAL (p = 0.042). We etablished a significant positive correlation between triglycerides and activities of ALT (r= 0.227; p = 0.012) and PAL (r= 0.293; p = 0.001). The ALT activity was significantly higher in patients treated with TCA compared to those treated with the SSRI (p = 0.011). We observed an increase in ALT and AST activities in 4.7% of patients treated with TCA and 3.7% of patients treated with SSRI. The GGT activity was higher with clomipramine (p = 0.007). Conclusion: Antidepressant treatment is accompanied with higher activities of AST and GGT, higher concentration of TB. Tricyclics seem to be the most hepatoxic antidepressant drugs. All patients should have liver function tests before the initiation of a treatment with an antidepressant and regularly during treatment especially for treatment with TCA and an appropriate education.

Management of and risk factors related to hepatotoxicity during tuberculosis treatment

Hepatotoxicity is one of the most frequent adverse events occurring during tuberculosis treatment that may negatively affect treatment compliance, clinical outcome. This study was designed to evaluate management, risk factors related to hepatotoxicity during tuberculosis treatment. Hospitalized patients for tuberculosis treatment at Sureyyapasa Chest Diseases, and Chest Surgery Training and Research Hospital were included, between January 2004 and December 2007. Prevalence of hepatotoxicity, risk factors were evaluated among tuberculosis patients under anti-tuberculosis treatment according to World Health Organization (WHO) guideline. Hepatotoxicity was defined any elevated liver function tests with accompanying symptoms. Age, gender, past history of anti-tuberculosis treatment, extensity of radiological findings, co-morbid disorders and drug resistance were the risk factors evaluated in terms of development and recurrence of hepatotoxicity. Of 1443 patients (38.37 ± 16.74 years; 64.5% were males), 106 (7.3%) was identified to develop hepatotoxicity on an average of 20 days after beginning treatment and lasting an average of 14 days. Hepatotoxicity for once in 78.3% (n= 83) of patients and more than once in 21.7% (n= 23) patients. All anti-tuberculosis drugs was continued at full dosage after the normalization of liver enzyme in 76.4% (n= 81). In recurrence a step-by-step treatment was re-started by exclusion of responsible drug/s. Treatment was administered without modification of WHO regimes in 79.2%. Pyrazinamide was omitted in 15 cases while rifampicin only in one patient. Triple drug regimen with isoniazid, ethambutol and streptomycin was used in six cases. Quinolon was added to treatment only in one patient. Presence of a co-morbidity was determined to be significant predictor of hepatotoxicity development OR= 3.093 (CI= 1.95-4.89; p= 0.000) past history of anti-tuberculosis treatment was significantly associated with recurrence (p= 0.027). There was no hepatotoxicity dependent mortality. Hepatotoxicity can be successfully management of hepatotoxicity without second line tuberculosis drugs in ongoing treatment regime.

Riesgo de hepatotoxicidad por antirretrovirales en pacientes VIH positivo del Hospital Nacional Guillermo Almenara Irigoyen (HNGAI)

Se revisaron los factores e indicadores de riesgo de hepatotoxicidad en historias clínicas de pacientes VIH positivos que iniciaban un tratamiento antirretroviral de gran actividad (TARGA), entre 1997 a 2003, en el consultorio externo del servicio de Medicina I del Hospital Nacional Guillermo Almenara Irigoyen (HNGAI). La muestra de estudio estuvo conformada por 313 pacientes, de ambos sexos, de 18 a 65 años de edad, con tres a más meses de iniciado el tratamiento antirretroviral. Los factores evaluados fueron: sexo, hepatitis crónica B o C, transaminasas glutámico pirúvica (TGP) y glutámico oxalacética (TGO) basales elevadas e incremento en el conteo de las células CD4 + después del inicio del TARGA. Los resultados del estudio indican que el 54% (169 pacientes) de la muestra estudiada desarrollaron hepatotoxicidad, demostrada a través de TGP y TGO elevadas (14,38% y 15,66%, respectivamente). En nuestro estudio, mediante la evaluación estadística, no se evidenciaron como factores de riesgo el sexo, hepatitis B o hepatitis C ni el incremento en el conteo de las células CD4 + después del inicio del TARGA. La prevalencia de hepatotoxicidad fue de 53,99%.

PTU-053 Is procollagen III aminopeptide a good predictor of liver fibrosis in patients with psoriasis on methotrexate therapy?

<h3>Introduction</h3> The prevalence of hepatotoxicity in long-term methotrexate therapy is around 0–4%. The British Association of Dermatology recommends procollagen III aminopeptide (PIIINP) level monitoring to identify patients at risk of hepatotoxicity with a view to liver biopsy while North American guidelines recommend liver biopsy based on cumulative dose of methotrexate. <h3>Methods</h3> 1. To correlate the accuracy of abnormal PIIINP level to predict liver fibrosis in patients receiving long-term methotrexate for psoriasis. 2. To assess adherence to the British Association of Dermatology guidance for PIIINP monitoring. The histology database (SNOMED) was interrogated for a 5-year period (1 January 2003 to 31 December 2007) to find all patients whose liver biopsies had been reported to show fibrosis, and patients with psoriasis identified. Case notes were reviewed for all psoriasis patients on long-term methotrexate. Levels of PIIINP, cumulative methotrexate dosage, comorbidities, drug history, alcohol intake, liver histology and clinical decision following liver biopsy (continuation or stoppage of methotrexate) were recorded. <h3>Results</h3> 578 liver biopsies during this period yielded 38 patients receiving methotrexate. 7 patients had methotrexate for another condition and were excluded; a further nine were excluded due to lack of case notes or repeat biopsies for follow-up. 22 patients with psoriasis had liver biopsies while on methotrexate treatment, of which 18 had elevated PIIINP levels above recommended threshold for liver biopsy and four patients had clinician decided biopsies. The mean cumulative dose of methotrexate to first biopsy was 3.86 g (range 0.69 g–9.25 g). The mean time to first biopsy was 4.2 years (range 1.1–10.1 years). 2 patients had PIIINP levels above 8 μg/l, one of which had grade 2 fibrosis on biopsy; the remaining 16 had PIIINP between 4.2 and 8 μg/l and two had Grade 2 fibrosis in this group. Liver histology (n=21): 15 patients had steatosis, three patients had grade 2 and one patient had Grade 1 fibrosis and two patients had normal liver histology. Clinical Outcome: four patients with fibrosis had methotrexate stopped as a result of the biopsy findings and the rest were continued (80%). <h3>Conclusion</h3> 19/21 (90%) patients with abnormal PIIINP had abnormal liver histology, but only 19% had fibrosis sufficient to discontinue treatment. PIIINP therefore did not correlate well with liver fibrosis. Newer non-invasive methods such as Fibroscan® may assess fibrosis better in this group of patients and need to be studied.

Comment on “Acute Ethanol Coingestion Confers a Lower Risk of Hepatotoxicity after Deliberate Acetaminophen Overdose”

OBJECTIVES: Little is known about the clinical significance of acute ethanol coingestion around the time of acetaminophen (paracetamol) overdose. This study prospectively examined the effect of acute ethanol coingestion on risk of hepatotoxicity among patients admitted to hospital for N-acetylcysteine (NAC) therapy after deliberate acetaminophen overdose. METHODS: This was a prospective observational study and included sequential patients who presented within 24 hours of acute acetaminophen ingestion and required NAC therapy. Significant hepatotoxicity was defined by alanine transaminase > 1,000 U/L or the international normalized ratio > 1.3 after a standardized intravenous administration of 300 mg/kg NAC. RESULTS: There were 362 patients, including 178 (49.2%) who coingested ethanol acutely. The prevalence of hepatotoxicity was 5.1% (95% CI = 2.6% to 9.5%) in those who ingested ethanol, compared to 15.2% (95% CI = 10.7% to 21.2%) in those who did not (p = 0.0027 by chi-square proportional test). Acute ethanol intake conferred a lower risk of hepatotoxicity in patients who had acetaminophen concentrations above or below the "200-line" and was independent of the interval between ingestion and assessment. CONCLUSIONS: Acute ethanol intake is associated with a lower risk of hepatotoxicity after acetaminophen overdose. This apparent protective effect cannot be explained solely by lower exposure to acetaminophen in this group, nor differences in the interval between ingestion and initiation of treatment. Further work is required to establish mechanisms by which ethanol might confer protection against hepatotoxicity, so as to identify novel strategies for reducing risk after acute acetaminophen ingestion. Language: en

Acute Ethanol Coingestion Confers a Lower Risk of Hepatotoxicity after Deliberate Acetaminophen Overdose

Little is known about the clinical significance of acute ethanol coingestion around the time of acetaminophen (paracetamol) overdose. This study prospectively examined the effect of acute ethanol coingestion on risk of hepatotoxicity among patients admitted to hospital for N-acetylcysteine (NAC) therapy after deliberate acetaminophen overdose. This was a prospective observational study and included sequential patients who presented within 24 hours of acute acetaminophen ingestion and required NAC therapy. Significant hepatotoxicity was defined by alanine transaminase > 1,000 U/L or the international normalized ratio > 1.3 after a standardized intravenous administration of 300 mg/kg NAC. There were 362 patients, including 178 (49.2%) who coingested ethanol acutely. The prevalence of hepatotoxicity was 5.1% (95% CI = 2.6% to 9.5%) in those who ingested ethanol, compared to 15.2% (95% CI = 10.7% to 21.2%) in those who did not (p = 0.0027 by chi-square proportional test). Acute ethanol intake conferred a lower risk of hepatotoxicity in patients who had acetaminophen concentrations above or below the "200-line" and was independent of the interval between ingestion and assessment. Acute ethanol intake is associated with a lower risk of hepatotoxicity after acetaminophen overdose. This apparent protective effect cannot be explained solely by lower exposure to acetaminophen in this group, nor differences in the interval between ingestion and initiation of treatment. Further work is required to establish mechanisms by which ethanol might confer protection against hepatotoxicity, so as to identify novel strategies for reducing risk after acute acetaminophen ingestion.

Prevalence of amiodarone‐related hepatotoxicity in 720 Chinese patients with or without baseline liver dysfunction

The prevalence of hepatotoxicity after longterm oral amiodarone therapy in Chinese patients with or without elevated liver enzymes at baseline is unknown. Amiodarone may still be safely prescribed for Chinese patients who have baseline liver dysfunction. This is a retrospective cross-sectional study. Significant liver dysfunction (SLD) was defined as alanine aminotransferase (ALT) > 2 times upper limit of normal range. Baseline liver function was checked in 628 of the 720 Chinese patients identified. The mean duration of amiodarone use was 615.9 +/- 703.1 days. Ninety patients (14.3%) had elevated baseline ALT. The prevalence of SLD was 3.7% (confidence interval [CI] 2.1-5.3%) and 4.4% (CI 0.2-8.6%) in patients with normal (n = 538) and elevated (n = 90) baseline ALT, respectively (p = 0.765). Therapy was continued in 42 patients with elevated baseline ALT until final follow-up. Eight of these (19.0%) had elevated ALT upon final follow-up, but the derangement was mild (mean ALT 134.8 +/- 145.9 IU/l, median 76 IU/l). During follow up, 24 patients developed SLD and half of these subsequently withdrew from therapy. The ALT levels at final follow-up had improved over time in both groups, but the mean difference was not significant (255.1 +/- 706.4 vs. 131.0 +/- 207.5 IU/l, p = 0.312). The prevalence of SLD in Chinese patients taking oral amiodarone with or without elevated baseline ALT was similar (4.4 vs. 3.7%). It seems that amiodarone may be safely prescribed in patients with elevated baseline ALT.