High discontinuation rate of azathioprine in autoimmune hepatitis, independent of time of treatment initiation

Contains fulltext : 225262.pdf (Publisher’s version ) (Open Access)BACKGROUND: Guidelines regarding treatment for autoimmune hepatitis (AIH) favour two strategies for azathioprine (AZA) introduction: concurrent with steroids at induction or delayed by 2-4 weeks. The safety and efficacy of both strategies have been unexplored. METHODS: We established a cohort of 900 AIH patients from 12 centres in 7 European countries. There were 631 patients who used AZA as part of the therapeutic regimen. We distinguished two groups: patients with early AZA (<2 weeks) or delayed AZA initiation (≥2 weeks). Primary outcome was discontinuation of AZA in the first year of treatment. Cox regression and propensity score matching was performed to determine difference in outcomes between groups. RESULTS: Patients with early AZA initiation had significantly lower transaminases and bilirubin at baseline. Discontinuation rates of AZA did not differ between early and delayed starters (16.6% vs 14.2%), which did not reach statistical significance (hazard ratio 0.97, 95% confidence interval 0.61-1.55, P = .90). Stratification according to baseline disease activity or propensity score matching did not alter the results. Main reason for AZA discontinuation was intolerance to treatment (14.0% vs 13.2%, P = .78) with nausea and vomiting as main side effects. AIH remission rates were comparable among groups. CONCLUSION: The discontinuation rate of AZA in AIH treatment is ~15% in the first year of treatment. Early or delayed AZA initiation does not differ in remission and discontinuation rates in AIH induction therapy. Our data suggest that either strategy may be used as part of AIH treatment

Rapid Response to Treatment of Autoimmune Hepatitis Associated With Remission at 6 and 12 Months

BACKGROUND & AIMS Changes in serum levels of transaminases immediately after initiation of treatment for autoimmune hepatitis (AIH) might be associated with biochemical markers of remission and liver-related events. We assessed the outcomes of patients with vs without rapid responses to treatment of AIH in a large international cohort. METHODS We performed a retrospective cohort study, collecting data from 2 independent cohorts of adults with AIH from 12 centers in 7 countries in Europe. We collected information on patient demographics; serologic, histologic, and biochemical analyses; and treatment. We used a receiver operating characteristic curve and Youden index to calculate the optimal percentage decrease in level of aspartate aminotransferase (AST) after 8 weeks of treatment that associated with normalization of transaminase levels after 26 weeks of treatment with predniso(lo)ne (primary outcome) in the first (discovery) cohort (n = 370). We evaluated the results in the second (validation) cohort (n = 370). Secondary outcomes were liver-related death or transplantation. We performed univariate and multivariable logistic and Cox regression with correction for confounders. RESULTS A significant decrease in level of AST after 8 weeks of treatment was significantly associated with normalization of transaminase levels at 26 and 52 weeks (P < .001); a decrease of more than 80% in level of AST was associated with optimal normalization. In both cohorts, rapid responders (≥80% decrease in level of AST after 8 weeks) were more likely to achieve normalization of transaminases at 26 and 52 weeks when compared to non-rapid responders. Rapid responders in the discovery cohort had lower risk of liver-related death or transplantation (adjusted hazard ratio 0.18; 95% CI 0.05-0.63; P = .007), although this was not confirmed in the validation cohort. Results from measurement of alanine aminotransferase did not differ significantly from those of AST for the primary outcome. Slow responders (without normalization of transaminases after 1 year) had the highest risk of liver transplantation or liver-related death. CONCLUSIONS In a retrospective study of patients with AIH, we found that a rapid response to treatment, based on level of AST after 8 weeks, associates with normalization of transaminase levels in the following year. Patients with a rapid response also have a lower risk of liver-related death or transplantation than patients without this rapid response

Treatment of Polycystic Liver Disease:Impact on Patient-reported Symptom Severity and Health-related Quality of Life

Polycystic liver disease (PLD) is a genetic disorder in which patients suffer from progressive development of multiple (>10) hepatic cysts. Most patients remain asymptomatic during the course of their disease. However, a minority of PLD patients suffer from symptoms caused by hepatomegaly leading to serious limitations in daily life. Untreated symptomatic PLD patients score significantly worse on health-related quality of life (HRQoL) compared to age and gender-matched populations. Currently, liver transplantation is the only curative treatment for PLD. The main goal of other available therapies is to strive for symptomatic relief and improvement of HRQoL by suppressing disease progression. In this review, we summarize the effect of PLD treatment on patient-reported outcome measures with a distinction between HRQoL and symptom severity. At present there is heterogeneity in application of questionnaires and no questionnaire is available that measures both HRQoL and PLD symptom severity. Therefore, we recommend the combination of a validated PLD-specific symptom severity questionnaire and a general HRQoL questionnaire to evaluate treatment success as a minimal core set. However, the specific choice of questionnaires depends on treatment choice and/or research question. These questionnaires may serve as a biomarker of treatment response, failure, and adverse events

Abdominal wall hernia is a frequent complication of polycystic liver disease and associated with hepatomegaly

BACKGROUND AND AIM: Polycystic liver disease (PLD) is related to hepatomegaly which causes an increased mechanical pressure on the abdominal wall. This may lead to abdominal wall herniation (AWH). We set out to establish the prevalence of AWH in PLD and explore risk factors. METHODS: In this cross-sectional cohort study, we assessed the presence of AWHs from PLD patients with at least 1 abdominal computed tomography or magnetic resonance imaging scan. AWH presence on imaging was independently evaluated by two researchers. Data on potential risk factors were extracted from clinical files. RESULTS: We included 484 patients of which 40.1% (n = 194) had an AWH. We found a clear predominance of umbilical hernias (25.8%, n = 125) while multiple hernias were present in 6.2% (n = 30). Using multivariate analysis, male sex (odds ratio [OR] 2.727 p < .001), abdominal surgery (OR 2.575, p < .001) and disease severity according to the Gigot classification (Type 3 OR 2.853, p < .001) were identified as risk factors. Height-adjusted total liver volume was an independent PLD-specific risk factor in the subgroup of patients with known total liver volume (OR 1.363, p = .001). Patients with multiple hernias were older (62.1 vs. 55.1, p = .001) and more frequently male (22.0% vs. 50.0%, p = .001). CONCLUSION: AWHs occur frequently in PLD with a predominance of umbilical hernias. Hepatomegaly is a clear disease-specific risk factor

Higher need for polycystic liver disease therapy in female patients:sex-specific association between liver volume and need for therapy

BACKGROUND AIM: Prognostic tools or biomarkers are urgently needed in polycystic liver disease (PLD) to monitor disease progression and evaluate treatment outcomes. Total liver volume (TLV) is currently used to assess cross-sectional disease severity and female patients typically have larger livers than males. Therefore, this study explores the sex-specific association between TLV and volume reducing therapy. APPROACH RESULTS: In this prospective cohort study, we included PLD patients from European treatment centers. We explored sex-specific differences in the association between baseline TLV and initiation of volume reducing therapy and determined the cumulative incidence rates of volume reducing therapy in our cohort.We included 358 patients, of whom 157 (43.9%) received treatment. Treated patients had a higher baseline TLV (median TLV 2.16 versus 4.34 liter, p&lt;0.001), were more frequently female (69.7% versus 89.8%, p&lt;0.001) and had a higher risk of liver events (HR 4.381, p&lt;0.001). The cumulative volume reducing therapy rate at 1 year of follow-up was 21.0% for females compared to 9.1% for males. Baseline TLV was associated with volume reducing therapy and there was an interaction with sex (HR females 1.202, p&lt;0.001;HR males 1.790, p&lt;0.001; at 1.5 liters). CONCLUSION: Baseline TLV is strongly associated with volume reducing therapy initiation at follow-up in PLD patients, with sex-specific differences in this association. Disease staging systems should use TLV to predict need for future volume reducing therapy in PLD separately for males and females