Predniso(lo)ne Dosage and Chance of Remission in Patients With Autoimmune Hepatitis

Background & Aims Patients with autoimmune hepatitis (AIH) commonly receive induction therapy with predniso(lo)ne followed by maintenance therapy with azathioprine. European Association for Study of the Liver clinical practice guidelines advise a predniso(lo)ne dose range of 0.50–1 mg/kg/day, which leaves room for practice variation. We performed a multicenter study to determine the efficacy of different dose ranges of predniso(lo)ne induction therapy in a large European cohort of patients with AIH. Methods We performed a retrospective cohort study using a comparative effectiveness design. We collected data from 451 adults with AIH who began treatment from 1978 through 2017 at 9 centers in 5 European countries. We assigned patients to a high-dose group (initial predniso(lo)ne dose ≥0.50 mg/kg/day; n=281) or a low-dose group (<0.50 mg/kg/day; n=170). Logistic regression was performed to determine difference in outcomes between the groups. The primary outcome was normal serum levels of transaminases at 6 months after initiation of therapy. Results There was no significant difference in rates of normalization of transaminases between the high-dose predniso(lo)ne group and the low-dose group (70.5% vs 64.7%; P =.20). After multivariable logistic regression with correction for confounders, there was no difference in the likelihood of normalization of transaminases between the groups (odds ratio, 1.21; 95% CI, 0.78 – 1.87; P =.38). Patients given an initial high dose of predniso(lo)ne received more predniso(lo)ne over time than patients started on a lower dose (median doses over 6 months: 3780 mg vs 2573 mg) ( P <.01). Conclusions In a retrospective study of patients with AIH in Europe, we found that the dose of predniso(lo)ne to induce remission in patients with AIH is less relevant than assumed. An initial predniso(lo)ne dose below 0.50 mg/kg/day substantially decreases unnecessary exposure to predniso(lo)ne in patients with AIH

Hepatic morphopathologic findings of lead poisoning in a drug addict: A case report

We describe the case of a 40-year old Iranian man who was admitted to our hospital with severe abdominal pain, abnormal liver function tests and normocytic anemia. Suffering from multiple sclerosis, he was a regular user of opium for pain relief. Basophilic stippling of erythrocytes pointed towards the diagnosis of lead intoxication, the most likely source being contaminated Iranian opium. Serum lead and zinc protoporphyrin levels were strongly elevated. To assess the hepatotoxic effects of lead poisoning a liver biopsy was performed. Pathomorphologic fi ndings of hepatotoxicity, rarely reported in humans, included active hepatitis together with extensive microvesicular and macrovesicular steatosis, hemosiderosis and cholestasis, and a lymphocytic cholangitis. Whilst treated with chelating therapy, liver enzymes returned to normal, suggesting reversibility of the histological findings

Promising treatment of autoimmune hepatitis with 6-thioguanine after adverse events on azathioprine

The use of corticosteroids in autoimmune hepatitis is an established therapy. To avoid the possible serious side effects of corticosteroids, immunosuppression with azathioprine is often warranted. Azathioprine, a purine analogue, is frequently used to taper or replace corticosteroids. However, approximately 10% of the patients are intolerant to azathioprine. Alternative therapies using mycophenolate, tacrolimus, budesonide, cyclosporine and 6-mercaptopurine have been studied, with variable results. The use of 6-thioguanine, an agent more directly leading to the down-stream active metabolites of azathioprine (6-thioguanine nucleotides) in inflammatory bowel disease patients intolerant to azathioprine or 6-mercaptopurine showed conflicting results. We report three patients with autoimmune hepatitis who could not tolerate azathioprine but tolerated 6-thioguanine 0.3 milligram per kilogram daily well. All three patients improved clinically. Therapeutic drug monitoring was performed. The prospective evaluation of 6-thioguanine as a possible immunosuppressive drug in autoimmune hepatitis patients is warranted

Seroprevalence of Hepatitis E Virus in Autoimmune Hepatitis Patients in the Netherlands

ABSTRACTBackground & Aims: In recent years chronic courses of hepatitis E virus (HEV) infection have been describedin immunosuppressed individuals. This may implicate a potential role for HEV in the development ofautoimmune diseases, including autoimmune hepatitis (AIH). Here we investigated the prevalence of HEVantibodiesin AIH patients in an endemic Central European country.Methods: HEV-specific immunoglobulin G (IgG) and HEV RNA were determined in 354 and 377 AIHpatients, respectively. Clinical characteristics and disease outcome parameters were retrospectively collected.Results: No HEV viraemic patients were identified in this cohort. A total of 106 AIH patients (29.9%) testedpositive for anti-HEV IgG, and this figure was slightly higher compared to the prevalence in a reference cohortincluding 5,329 healthy Dutch blood donors (26.7%; P>0.05).Conclusion: This is the largest study on the association between HEV infection and AIH. Apparently silentHEV infection is present in a significant proportion of AIH patients, yet appears not to have significant clinicalrepercussions in this immune compromised group of patients. Nevertheless, since acute hepatitis E maypresent with histological and biochemical features of AIH, the possibility of a (concomitant) HEV infectionshould be considered in this category of patients

MOESM1 of Epigenetic modifier induced enhancement of fumiquinazoline C production in Aspergillus fumigatus (GA-L7): an endophytic fungus from Grewia asiatica L.

Additional file 1: Figure S1. 1H and 13C NMR spectra of the isolated compounds