Background
No prognostic score is currently available for long‐term survival in autoimmune hepatitis (AIH) patients.
Objective
The aim of this study was to develop and validate such a prognostic ...score for AIH patients at diagnosis.
Methods
The prognostic score was developed using uni‐ & multivariate Cox regression in a 4‐center Dutch cohort and validated in an independent 6‐center Belgian cohort.
Results
In the derivation cohort of 396 patients 19 liver transplantations (LTs) and 51 deaths occurred (median follow‐up 118 months; interquartile range 60–202 months). In multivariate analysis age (hazard ratio HR 1.045; p < 0.001), non‐caucasian ethnicity (HR 1.897; p = 0.045), cirrhosis (HR 3.266; p < 0.001) and alanine aminotransferase level (HR 0.725; p = 0.003) were significant independent predictors for mortality or LT (C‐statistic 0.827; 95% CI 0.790–0.864). In the validation cohort of 408 patients death or LT occurred in 78 patients during a median follow‐up of 74 months (interquartile range: 25–142 months). Predicted 5‐year event rate did not differ from observed event rate (high risk group 21.5% vs. 15.7% (95% CI: 6.3%–24.2%); moderate risk group 5.8% versus 4.3% (95% CI: 0.0%–9.1%); low risk group 1.9% versus 5.4% (95% CI: 0.0%–11.4%); C‐statistic 0.744 95% CI 0.644–0.844).
Conclusions
A Dutch‐Belgian prognostic score for long‐term transplant‐free survival in AIH patients at diagnosis was developed and validated.
Patients with autoimmune hepatitis (AIH) almost invariably require lifelong immunosuppressive treatment. There is genuine concern about the efficacy and tolerability of the current standard ...combination therapy of prednisolone and azathioprine. Mycophenolate mofetil (MMF) has emerged as an alternative option. The aim of this study was to compare MMF to azathioprine as induction therapy for AIH.
In this 24-week, prospective, randomised, open-label, multicentre superiority trial, 70 patients with treatment-naive AIH received either MMF or azathioprine, both in combination with prednisolone. The primary endpoint was biochemical remission defined as normalisation of serum levels of alanine aminotransferase and IgG after 24 weeks of treatment. Secondary endpoints included safety and tolerability.
Seventy patients (mean 57.9 years SD 14.0; 72.9% female) were randomly assigned to the MMF plus prednisolone (n = 39) or azathioprine plus prednisolone (n = 31) group. The primary endpoint was met in 56.4% and 29.0% of patients assigned to the MMF group and the azathioprine group, respectively (difference, 27.4 percentage points; 95% CI 4.0 to 46.7; p = 0.022). The MMF group exhibited higher complete biochemical response rates at 6 months (72.2% vs. 32.3%; p = 0.004). No serious adverse events occurred in patients who received MMF (0%) but serious adverse events were reported in four patients who received azathioprine (12.9%) (p = 0.034). Two patients in the MMF group (5.1%) and eight patients in the azathioprine group (25.8%) discontinued treatment owing to adverse events or serious adverse events (p = 0.018).
In patients with treatment-naive AIH, MMF with prednisolone led to a significantly higher rate of biochemical remission at 24 weeks compared to azathioprine combined with prednisolone. Azathioprine use was associated with more (serious) adverse events leading to cessation of treatment, suggesting superior tolerability of MMF.
This randomised-controlled trial directly compares azathioprine and mycophenolate mofetil, both in combination with prednisolone, for the induction of biochemical remission in treatment-naive patients with autoimmune hepatitis. Achieving complete remission is desirable to prevent disease progression. Patients assigned to the mycophenolate mofetil group reached biochemical remission more often and experienced fewer adverse events. The findings in this trial may contribute to the re-evaluation of international guidelines for the standard of care in treatment-naive patients with autoimmune hepatitis.
#NCT02900443.
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•Limited efficacy and tolerability of standard prednisolone and azathioprine combination therapy in autoimmune hepatitis.•Mycophenolate mofetil combined with prednisolone is effective as first-line therapy for achieving biochemical remission.•Mycophenolate mofetil has a more favourable tolerability profile than azathioprine.
Few studies with diverging results and a small sample size have compared autoimmune hepatitis (AIH) in the elderly to younger patients.
To unbiasedly investigate the role of age in behaviour and ...treatment outcome of AIH.
All patients with probable or definite AIH type 1 in four tertiary academic centres were included in this retrospective-and since 2006 prospective-cohort study. Influence of age on presentation, remission and outcome of AIH were investigated.
359 patients were included. Presence of cirrhosis at AIH diagnosis around 30% was independent of age. ALAT was higher at age 30-60 years on AIH diagnosis, and above age 60 there were less acute onset, less jaundice and more concurrent autoimmune disease. Remission was reached in 80.2%, incomplete remission in 18.7%, only 1.1% (all aged 50-65) was treatment-refractory. Age was not an independent predictor of remission, while cirrhosis was. Above age 45 there was more diabetes, above age 60 more loss of remission. Rate of progression to cirrhosis was 10% in the 10 years after diagnosis and unrelated to age at AIH diagnosis. With onset below age 30, there was more development of decompensated cirrhosis over time. With higher age at AIH diagnosis there was a lower survival free of liver-related death or liver transplantation.
AIH presents at all ages. Age influences features at diagnosis, but not response to treatment, while survival without liver-related death or liver transplantation decreases with higher age at diagnosis.
Background and AimsA considerable number of autoimmune hepatitis (AIH) patients completely or partially fail on first-line treatment. Several studies on the use of calcineurin inhibitors (CNIs) in ...the treatment of AIH have been published without focusing on indication. The aim was to assess the efficacy of CNIs in the treatment of adult AIH patients, specifically focusing on indication: first-line intolerant and with first-line insufficient response (failure to achieve or maintain remission), and with second versus third-line treatment. MethodsA literature search included studies on the use of CNIs in adult AIH. Patients with past or present use of CNIs from the Dutch AIH group cohort were added. The primary endpoint was biochemical remission while using CNIs. Secondary endpoints were biochemical response, treatment failure, and adverse effects. ResultsTwenty studies from the literature and nine Dutch patients were included describing the use of cyclosporine in 59 and tacrolimus in 219 adult AIH patients. The CNI remission rate was 53% in patients with insufficient response to first-line treatment and 67% in patients intolerant to first-line treatment. CNIs were used as second-line treatment in 73% with a remission rate of 52% and as third-line treatment in 22% with a remission rate of 26%. Cyclosporine was discontinued in 13% and tacrolimus in 11% of patients because of adverse events. ConclusionsCNIs as rescue treatment in adult AIH patients are reasonably effective and safe both with insufficient response or intolerance to previous treatment. Prospective studies are needed.
We aimed to perform geriatric assessment in older patients with inflammatory bowel disease (IBD) to evaluate which IBD characteristics associate with deficits in geriatric assessment and the impact ...of deficits on disease burden (health-related quality of life).
A prospective multicenter cohort study including 405 consecutive outpatient patients with IBD aged ≥65 years. Somatic domain (comorbidity, polypharmacy, malnutrition), impairments in (instrumental) activities of daily living, physical capacity (handgrip strength, gait speed), and mental (depressive symptoms, cognitive impairment) and social domain (life-partner) were assessed. Deficits in geriatric assessment were defined as ≥2 abnormal domains; 2–3 moderate deficits and 4–5 severe deficits. Clinical (Harvey Bradshaw Index >4/partial Mayo Score >2) and biochemical (C-reactive protein ≥10 mg/L and/or fecal calprotectin ≥250 μg/g) disease activity and disease burden (short Inflammatory Bowel Disease Questionnaire) were assessed.
Somatic domain (51.6%) and activities of daily living (43.0%) were most frequently impaired. A total of 160 (39.5%) patients had moderate deficits in their geriatric assessment; 32 (7.9%) severe. Clinical and biochemical disease activity associated with deficits (clinical: adjusted odds ratio, 2.191; 95% confidence interval, 1.284–3.743; P = .004; biochemical: adjusted odds ratio, 3.358; 95% confidence interval, 1.936–5.825; P < .001). Deficits in geriatric assessment independently associate with lower health-related quality of life.
Deficits in geriatric assessment are highly prevalent in older patients with IBD. Patients with active disease are more prone to deficits, and deficits associate with lower health-related quality of life, indicating higher disease burden. Prospective data validating impact of frailty and geriatric assessment on outcomes are warranted to further improve treatment strategies.
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Our goals were to study frailty screening in association with hospitalization and decline in quality of life QoL and functional status in older patients with inflammatory bowel diseases IBD.
This was ...a prospective multicentre cohort study in IBD patients ≥65 years old using frailty screening G8 Questionnaire. Outcomes were all-cause, acute, and IBD-related hospitalization, any infection, any malignancy, QoL EQ5D-3L, and functional decline (Instrumental Activities of Daily Living IADL) during 18 months of follow-up. Confounders were age, IBD type, biochemical disease activity C-reactive protein ≥10 mg/L and/or faecal calprotectin ≥250 µg/g, and comorbidity Charlson Comorbidity Index.
Of 405 patients, with a median age of 70 years, 196 48% were screened as being at risk for frailty. All-cause hospitalizations occurred 136 times in 96 patients 23.7%, and acute hospitalizations 103 times in 74 patients 18.3%. Risk of frailty was not associated with all-cause (adjusted hazard ratio aHR 1.5, 95% confidence interval CI 0.9-2.4), but was associated with acute hospitalizations aHR 2.2, 95% CI 1.3-3.8. Infections occurred in 86 patients 21.2% and these were not associated with frailty. A decline in QoL was experienced by 108 30.6% patients, and a decline in functional status by 46 patients 13.3%. Frailty screening was associated with a decline in QoL (adjusted odds ratio aOR 2.1, 95% CI 1.3-3.6) and functional status aOR 3.7, 95% CI 1.7-8.1.
Frailty screening is associated with worse health outcomes in older patients with IBD. Further studies are needed to assess the feasibility and effectiveness of its implementation in routine care.
Biochemical remission, important treatment goal in autoimmune hepatitis (AIH), has been associated with better long-term survival. The aim of this study was to determine the independent prognostic ...value of aminotransferases and immunoglobulin G (IgG) during treatment on long-term transplant-free survival in AIH.
In a multicenter cohort alanine aminotransferase, aspartate aminotransferase (AST), and IgG were collected at diagnosis and 6, 12, 24, and 36 months after start of therapy and related to long-term outcome using Kaplan-Meier survival and Cox regression analysis with landmark analysis at these time points, excluding patients with follow-up ending before each landmark.
A total of 301 AIH patients with a median follow-up of 99 (range, 7–438) months were included. During follow-up, 15 patients required liver transplantation and 33 patients died. Higher AST at 12 months was associated with worse survival (hazard ratio HR, 1.86; P < .001), while IgG was not associated with survival (HR, 1.30; P = .53). In multivariate analysis AST at 12 months (HR, 2.13; P < .001) was predictive for survival independent of age, AST at diagnosis and cirrhosis. Multivariate analysis for AST yielded similar results at 6 months (HR, 2.61; P = .001), 24 months (HR, 2.93; P = .003), and 36 months (HR, 3.03; P = .010). There was a trend toward a worse survival in patients with mildly elevated aminotransferases (1–1.5× upper limit of normal) compared with patients with normal aminotransferases (P = .097).
Low aminotransferases during treatment are associated with a better long-term survival in autoimmune hepatitis. IgG was not associated with survival in first 12 months of treatment. Normalization of aminotransferases should be the treatment goal for autoimmune hepatitis to improve long-term survival.
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