S. Thebault

Infliximab-induced acute hepatitis during Crohn's disease therapy: absence of cross-toxicity with adalimumab.

The gold standard treatment of severe Crohn’s disease is a Tumor Necrosis Factor antagonist such as infliximab. Hepatitis is a rare complication of treatment with TNF antagonists [1—5]. We report the case of a patient who developed acute cytolytic hepatitis during infliximab treatment for Crohn’s disease. Once the hepatitis resolved, the patient was treated with adalimumab with no recurrence of hepatitis. A 46-year-old man was referred to our unit in 2008 with a history of mouth and colon ulcers resulting in diagnosis of Crohn’s disease. The patient quickly became steroid-dependent, so treatment was begun with azathioprine. Therapy was stopped one month later due to intestinal intolerance with nausea. The patient’s alanine aminotransferase (ALT, N < 35 IU/L), aspartate aminotransferase (AST, N < 35 IU/L), gamma glutamyltransferase ( GT, N < 60 IU/L), alkaline phosphatase (AP, N < 280 IU/L) and bilirubin (N < 13.2 M/L) values were normal. He suffered of a severe relapse of Crohn’s disease, so treatment with 5 mg/Kg intravenous infusions of infliximab at zero, two and six weeks was started without concomitant treatment. Ten days after the first infusion at a dose of 325 mg, serum levels showed an increase in AST (107 IU/L), ALT (284 IU/L) and GT (108 IU/L). AP (267 IU/L) and bilirubin (13 M/L) values were normal. Laboratory tests on samples taken two weeks after the second infliximab treatment showed a slight decrease in liver enzymes (ALT 172 IU/L and AST 48 IU/L) without normalization (Fig. 1). Infliximab therapy was continued. Liver blood tests after the third infusion showed a relapse with an increase in ALT (528 IU/L), AST (143 IU/L) and GT (128 IU/L) with no significant change in AP (277 IU/L) and bilirubin (14 M/L). Hepatitis was severe with a decrease in prothrombin time to 52%. Liver toxicity due to infliximab was suspected and all t

INFLUENCE OF HCV GENOTYPE 1 SUBTYPES ON THE VIRUS RESPONSE TO PEG INTERFERON ALPHA-2a PLUS RIBAVIRIN THERAPY

New factors that influence the viral response in HCV non‐genotype 2/3 patients must be identified in order to optimize anti‐HCV treatment. This multicenter prospective study evaluates the influence of HCV variability and pharmacological parameters on the virological response of these patients to pegylated interferon α2a (peg‐IFN‐α2a: 180 µg/week) and ribavirin (RBV; 800–1,200 mg/day) for 48 weeks. HCV subtypes were identified by sequencing the NS5B region. Serum RBV and peg‐IFN‐α2a concentrations were measured at weeks 4 and 12. The 115 patients (67 men; median age = 49, range 31–76) included 64 who had never been treated and 27 co‐infected with HIV. The mean baseline HCV RNA was 6.30 ± 0.06 log IU/ml and the HCV genotypes were: G1 (n = 93) with 1a (n = 37) and 1b (n = 50), G4 (n = 20) and G5 (n = 2). Most patients (79/108; 73%) had an early virological response. Independent predictors of an early virological response were interferon naive patients (OR = 2.98, 95% CI: 1.15–7.72) and RBV of >2,200 ng/ml at week 12 (OR = 3.41, 95% CI: 1.31–8.90). Forty of 104 patients (38%) had a sustained virological response. The only independent predictors of a sustained virological response were subtype 1b (OR = 6.82, 95% CI: 1.7–26.8), and HCV RNA <15 IU/ml at week 12 (OR = 25, 95% CI: 6.4–97.6). Thus a serum RBV concentration of >2,200 ng/ml was associated with an early virological response and patients infected with HCV subtype 1b had a better chance of a sustained virological response than did those infected with subtype 1a. J. Med. Virol. 83:437–444, 2011.

Étiologies et évolution des hépatites granulomateuses : étude rétrospective de 21 cas consécutifs

PURPOSE To assess the etiologies and outcome of liver granulomatosis. METHODS We analyzed all consecutive liver granulomatosis diagnosed in our internal medicine department from 2000 to 2008. RESULTS Among 471 liver biopsies, 21 disclosed evidence of liver granulomatosis (4.5%), in sixteen women (76%) and five men, with a median age of 41years. Thirteen were caucasians (62%). At the time of diagnosis, six (28.5%) had isolated abnormal liver function tests, and fifteen (71.4%) presented with clinical manifestations. The underlying cause was identified in 18 cases (85.7%). Eleven (52.3%) were systemic diseases: five (23.8%) primary biliary cirrhosis, two (9.5%) primary sclerosing cholangitis, two (9.5%) common variable immunodeficiency, one (4.7%) Sjögrens syndrome, and one (4.7%) Behçets disease. Two (9.5%) patients had sarcoidosis. Three (14.3%) liver granulomatosis were of infectious origin (tuberculosis, schistosomiasis, and hepatitis C virus), two (9.5%) were neoplastic (Hodgkins lymphoma and liver cell adenoma), and three (14.3%) were idiopathic. With a median of 38 months of follow-up, four patients (19%, two common variable immunodeficiency and two sarcoidosis) developed portal hypertension, independently of cirrhosis. One patient died of cryptococcosis. CONCLUSION In accordance with other European studies, systemic diseases are the main causes of hepatic granulomas. Liver granulomatosis related to common variable immunodeficiency and sarcoidosis are at risk of portal hypertension.

Characterization of overlap syndrome between primary biliary cirrhosis and autoimmune hepatitis according to antimitochondrial antibodies status.

AIMS Codification of variant forms between Primary Biliary Cirrhosis (PBC) and Autoimmune Hepatitis (AIH) has not been definitively standardized. The aim of this study was to compare among 102 consecutive patients, 2 subsets of overlap syndrome (OS, N=21) with and without antimitochondrial antibody (AMA) to two groups of patients with typical PBC (N=43) or AIH (N=38). METHODS OS was defined by the presence in the same patient of at least 2 of 3 accepted criteria of PBC and AIH. Twelve patients with OS were AMA negative and 9 were AMA positive. RESULTS A lower level of alanine transaminase (139+/-48 vs 269+/-154 IU/L, P<0.05) and a trend towards a higher level of alkaline phosphatase or gamma-glutamyl transpeptidase was observed in OS without AMA than in OS with AMA (693+/-200 vs 544+/-124 IU/L; 370+/-66 vs 241+/-77 IU/L, respectively). All AMA-negative patients with OS had antinuclear and/or anti-smooth muscle antibodies. OS without AMA differed from those with AMA in that they had more severe bile duct damage including destructive cholangitis (P<0.05), ductopenia (P<0.05), ductular hyperplasia (P<0.05) and a higher METAVIR fibrosis score (2.5+/-0.3 vs 1.3+/-0.3, P<0.05). The response to therapy was not different between PBC, AIH and OS. CONCLUSIONS According to the presence of AMA, 2 homogeneous subgroups of patients with overlap syndrome between PBC and AIH may be identified. AMA status affects clinical presentation and liver disease severity of OS.

Syphilis revealed by a severe gastric injury.

A 57-year-old man presented with weight loss and severe epigastric pain that had lasted for three weeks and was not relieved by anti-acids. Two months before, he had had maculo-papular lesions on the palms and soles of the feet associated with a macular rash on elbows (Fig. 1). Gastroendoscopy revealed an oedematous and hyperaemic mucosa with multiple muco-purulent erosions and nodular lesions from the mid-body into the antrum (Fig. 2). Endoscopic biopsies were stained with hematoxylin-eosin and revealed chronic inflammation with dense plasma cell infiltrate. Abdominal pain did not improve after one week of hospitalization with intravenous omeprazole therapy associated with antispasmodics and acetaminophen. Cutaneous maculo-papular lesions on the palm and soles of the feet were consistent with secondary syphilis. Serum VDRL and TPHA were positive with a titer of 1/32 and 1/5120 respectively and the clinical diagnosis was confirmed. HIV was negative. Histological diagnosis of gastric syphilis was made using Warthin-Starry stain showing numerous spirochetes in the lamina propria (Fig. 3). Because the patient was allergic to penicillin G, ceftriaxone was used. Antisyphilitic treatment with intravenous ceftriaxone 1 g per day for 14 days resulted in marked clinical, endoscopic and histological improvement.