"Hepatic toxicity by methotrexate with weekly single doses associated with folic acid in rheumatoid and psoriatic arthritis. What is its real frequency?"

INTRODUCTION AND OBJECTIVES: Liver injury caused by methotrexate (MTX) has mostly been investigated without applying criteria for the assessment of causality of drug induced liver injury (DILI). Hence, the existence of DILI by MTX in many cases is debatable. This study aimed to describe the frequency and characteristics of liver injury caused by MTX, applying DILI diagnostic criteria. MATERIAL AND METHODS: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients who were treated with MTX in association with folic acid were included. Serial determinations of alanine amino transferase (ALT) and aspartate amino transferase (AST) were performed. The Roussel Uclaf Causality Assessment Method (RUCAM) was applied in cases of increases of ALT/AST over 1.5 upper limit of normal. Liver biopsy was considered when the total cumulative dosage (TCD) of MTX was ≥3.5g. RESULTS: A total of 43 patients were analyzed (median follow up 32 (range: 1-48) months; 3.33 ALT/AST determinations per year). Five subjects presented an increase of ALT/AST. All presented a RUCAM score for MTX≤2 (improbable). Three had a RUCAM score for non-steroidal anti-inflammatory drugs ≥7 (probable) and two patients presented non-alcoholic fatty liver disease. Five patients with no other cause for liver disease consented to liver biopsy (TCD MTX: median 5.1; range: 3.5-7.4g). No significant fibrosis or steatosis was evident on histology. CONCLUSIONS: No biochemical or significant histological liver toxicity for MTX was demonstrated when applying causality criteria for DILI. More studies with this methodology are necessary in order to improve the assessment of its frequency.

[Liver diseases in rheumatoid and psoriatic arthritis]. / Enfermedades hepáticas en artritis reumatoidea y psoriásica.

OBJECTIVE: The aim of this study was to evaluate the prevalence, risk factors and features of liver diseases (LD) in rheumatoid and psoriatic arthritis. PATIENTS AND METHODS: From July 2007 to January 2010, 118 non-selected patients were consecutively examined. The assessment consisted of a medical record, biochemical studies and abdominal ultrasounds. The diagnosis of fatty liver disease was based on the ultrasound drug induced liver injury (DILI) was evaluated by the Maria-Victorino system criteria. Liver biopsy associated with chronic administration of methotrexate was performed using the histological classification of Kleiner et al. For the statistical analysis chi square test with Yates correction, Student's t test or Mann-Whitney test were applied when appropriate. In the multivariate analysis a binary logistic regression was used. The threshold of significance was P < 0.05. RESULTS: LD was diagnosed in 47 patients (39.8%). The most frequent LD was fatty liver disease in 35 patients (29.7%), followed by DILI in 15 (12.7%), associated with non-steroidal anti-inflammatory drugs (NSAID). In the multivariate analysis, obesity was the only independent risk factor associated with fatty liver disease [Odds ratio (OR) 6.4 (confidence interval (CI) 95%: 2.5-16.1; P = 0.000)] and fatty liver disease was the only risk factor associated with DILI [OR 7.7 (CI 95%: 2.0-30.0; P = 0.003)]. CONCLUSIONS: In our series, there was a high prevalence of LD, being fatty liver disease associated with obesity the most frequent finding. The second frequent disease was DILI, being fatty liver disease its main risk factor. The presence of obesity and the use of NSAIDs, especially in patients with steatosis, arise from our results as two conditions that require special care in handling this particular population.

Etiology of hepatocellular carcinoma in Latin America: a prospective, multicenter, international study.

BACKGROUND/AIMS: No prospective study has been published investigating etiology of HCC in Latin America. The primary aim of this prospective study was to analyze the etiology of liver disease in patients with HCC from our area. Secondary aims were to evaluate staging using Okuda and BCLC classifications; and percentage of patients receiving treatment. METHODS: The Governing Board of the Latin American Association for the Study of the Liver designed the protocol. During a 18 month period, all members were invited to load their incident HCC cases on line. RESULTS: 240 cases from 9 countries were uploaded, 174 were male (72.5%), median age was 64 years, interquartile range 57-72. In 85.4% of cases, patients had underlying cirrhosis. Main etiological factors were: HCV in 74 patients (30.8%), alcohol in 49 (20.4%), cryptogenic cirrhosis in 35 (14.6%), HBV in 26 (10.8%), HCV plus alcohol in 14 (5.8%). Considering the combinations, hepatitis C was shown in 91 patients (38%); chronic alcoholism in 68 patients (28%); and hepatitis B in 33 patients (14%). There were no significant differences between the groups in the age at diagnosis. Percentage of male gender was higher in groups of alcohol (94%), HCV plus alcohol (93%) and HBV (85%) than in cryptogenic cirrhosis (60%) and HCV (59%) (p<0.001). CONCLUSIONS: Our prospective study showed that hepatitis C is the more frequent etiology of HCC in Latin America, followed by alcoholic cirrhosis. Demographical results showed a male predominance (male:female ratio 2.6) with an important proportion of patients being diagnosed at their sixties.