Role of age in presentation, response to therapy and outcome of autoimmune hepatitis

Background: Few studies with diverging results and a small sample size have compared autoimmune hepatitis (AIH) in the elderly to younger patients.Aim: To unbiasedly investigate the role of age in behaviour and treatment outcome of AIH.Methods: 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.Results: 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.Conclusions: 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.</p

Role of age in presentation, response to therapy and outcome of autoimmune hepatitis

Background: Few studies with diverging results and a small sample size have compared autoimmune hepatitis (AIH) in the elderly to younger patients. Aim: To unbiasedly investigate the role of age in behaviour and treatment outcome of AIH. Methods: 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. Results: 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. Conclusions: 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

Nodular Regenerative Hyperplasia of the Liver in Patients with IBD Treated with Allopurinol-Thiopurine Combination Therapy

Background: Thiopurine therapy, particularly thioguanine, has been associated with nodular regenerative hyperplasia (NRH) of the liver. Combination therapy of allopurinol and an adapted low-dose thiopurine leads to a pharmacokinetic profile that has similarities to that of thioguanine. Therefore, allopurinol-Thiopurine combination therapy may also be associated with NRH of the liver. We assessed the prevalence of NRH in patients with inflammatory bowel disease (IBD) treated with allopurinol-Thiopurine combination therapy by liver biopsy specimen examination. Methods: An observational, cross-sectional study was conducted in a Dutch IBD-referral center. Adult patients with IBD, treated for at least 1 year with allopurinol-Thiopurine combination therapy were eligible. All patients underwent a liver biopsy, after standard laboratory and thiopurine metabolite concentration assessments. Histopathology was assessed by an experienced liver pathologist. Results: Twenty-Two patients with IBD were included. The mean duration of combination therapy at the time of the liver biopsy was 24.7 months (SD 5.7). NRH was observed in one of the biopsies (4.8%), any grade of nodularity was observed in 3 biopsy specimens (14%). Other findings included phlebosclerosis (24%), perisinusoidal fibrosis (81%), sinusoidal dilatation (43%), perivenular fibrosis (14%), and periportal fibrosis (29%). Around the time of biopsy, the median 6-Thioguanine nucleotide and 6-methylmercaptopurine ribonucleotide concentrations were 705 pmol × 10 8 red blood cells (RBC) (interquartile range 498-915) and 355 pmol × 10 8 RBC (interquartile range 225-670). Conclusions: The prevalence of histologically assessed NRH in patients with IBD, who were treated with allopurinol-Thiopurine combination therapy, was 5%. This percentage is in line with thiopurine-naive and thioguanine-using patients with IBD. None of the included patients had clinical symptoms or signs suggestive of (noncirrhotic) portal hypertension

Hepatocellular carcinoma in cirrhotic versus noncirrhotic livers : results from a large cohort in the Netherlands

OBJECTIVES: Hepatocellular carcinoma (HCC) usually occurs in patients with cirrhosis, but can also develop in noncirrhotic livers. In the present study we explored associated risk factors for HCC without cirrhosis and compared patient and tumor characteristics and outcomes in HCC patients with and without underlying cirrhosis. METHODS: Patients with HCC diagnosed in the period 2005-2012 in five Dutch academic centers were evaluated. Patients were categorized according to the presence of cirrhosis on the basis of histology or combined radiological and laboratory features. RESULTS: In total, 19% of the 1221 HCC patients had no underlying cirrhosis. Noncirrhotic HCC patients were more likely to be female and to have nonalcoholic fatty liver disease or no risk factors for underlying liver disease, and less likely to have hepatitis C virus or alcohol-related liver disease than did cirrhotic HCC patients. HCCs in noncirrhotic livers were more often unifocal (67 vs. 48%), but tumor size was significantly larger (8 vs. 4 cm). Despite the larger tumors, more patients underwent resection (50 vs. 10%) and overall survival was significantly better than in cirrhotics. In multivariate analyses, absence of cirrhosis [hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.38-0.63] and presence of hepatitis B (HR 0.68, 95% CI 0.51-0.91) were independent predictors for lower mortality, whereas hepatitis C virus was associated with higher mortality (HR 1.32, 95% CI 1.01-1.65). CONCLUSION: HCC without cirrhosis was strongly associated with female sex and presence of nonalcoholic fatty liver disease or no risk factors for underlying liver disease. In absence of cirrhosis, resections were more often performed, with better survival despite larger tumor size

Nodular regenerative hyperplasia rarely leads to liver transplantation: A 20-year cohort study in all Dutch liver transplant units

Background: Nodular regenerative hyperplasia is an uncommon liver condition associated with several autoimmune disorders and drugs. The clinical symptoms of nodular regenerative hyperplasia vary from asymptomatic to severe complications of portal hypertension (nodular regenerative hyperplasia-syndrome). Objective: The purpose of this study was to identify the prognosis and optimal management, as well as the role of liver transplantation, in nodular regenerative hyperplasia. Methods: The pathology databases of all three Dutch liver transplant units were retrospectively scrutinised for explanted livers diagnosed with nodular regenerative hyperplasia or without clear diagnosis. Pre- and post-transplantation clinical, biochemical, radiological and histological information was obtained from electronic and paper records. Results: In total, 1886 patients received a liver transplant. In 255 patients, nodular regenerative hyperplasia could not be excluded. After detailed chart review, the native livers of 11 patients (0.6%) (82% male, median age: 44 years) displayed nodular regenerative hyperplasia. Seven patients (64%) had underlying disorders or drug exposure which possibly caused nodular regenerative hyperplasia. Laboratory and imaging abnormalities were present in all patients but did not contribute to the diagnosis of nodular regenerative hyperplasia. Five-year survival was 73% (median follow-up: four years, range: 2-248 months). Conclusion: Nodular regenerative hyperplasia is a rare finding in patients, predominantly young males, transplanted for end-stage liver disease with unknown aetiology. Nonetheless, liver transplantation may have an important role in end-stage nodular regenerative hyperplasia-syndrome

Increased Mortality Among Patients With vs Without Cirrhosis and Autoimmune Hepatitis

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