Long-term Outcome of Autoimmune Hepatitis: Consecutive Patient Cohort and Data on the Second Twenty Years.

BACKGROUND: Mortality rates for autoimmune hepatitis (AIH) vary. Data are lacking beyond 20 years follow-up. AIMS: Analysis of a consecutively recruited large AIH cohort from a single non-transplant tertiary centre in England and an overlapping cohort, already followed for ≥ 20 years. METHODS: We assessed 330 patients presenting 1987-2016 and 65 patients presenting 1971-96 already followed for 20 years. RESULTS: Death/liver transplant rate was 51±4% (all-cause) and 21±4% (liver-related) over 20 years and was independently associated with: decompensation and lower serum ALT at diagnosis; and failure of serum ALT normalisation and higher relapse rate. There was excess mortality over the first year. Patients (n = 65) already followed for twenty years had similar subsequent rates of relapse, disease progression and mortality, to those followed from diagnosis. Azathioprine-intolerant patients (n = 23) switching to Mycophenolate did not have higher mortality over 4(1-17) years, than patients continuing Azathioprine. Following immunosuppression withdrawal (n = 26), six (23% patients) relapsed with no liver-related deaths over 2.3(0-23.1) years. CONCLUSIONS: In this consecutive autoimmune hepatitis cohort, mortality was similar to that in national registry studies, disease progression continued after 20 years, and immunosuppression withdrawal did not compromise survival.

Provision and standards of care for treatment and follow-up of patients with Autoimmune Hepatitis (AIH).

Background: Autoimmune hepatitis (AIH) is a substantial UK health burden, but there is variation in care, facilities and in opinion regarding management. We conducted an audit of service provision and care of patients with AIH in 28 UK hospitals. Methods: Centres provided information about staffing, infrastructure and patient management (measured against predefined guideline-based standards) via a web-based data collection tool. Results: Hospitals (14 university hospitals (UHs), 14 district general hospitals (DGHs)) had median (range) of 8 (3-23) gastroenterologists; including 3 (0-10) hepatologists. Eight hospitals (29%, all DGHs) had no hepatologist. In individual hospital departments, there were 50% (18-100) of all consultants managing AIH: in DGH's 92% (20-100) vs 46% (17-100) in UHs. Specialist nurses managed AIH in only 18%. Seventeen (61%) hospitals had a histopathologist with a liver interest, these were more likely to find rosettes than those without (172/795 vs 50/368; p<0.001).Of 999 steroid-treated patients with ≥12 months follow-up, 25% received steroids for <12 months. After 1 year of treatment, 82% of patients achieved normal serum alanine aminotransaminase (ALT); this was higher in UHs than DGHs. Three-monthly liver blood tests were inadequately recorded in 26%. Of potentially eligible patients with liver decompensation, transplantation was apparently not considered in 5% (n=7). The same standards were attained in different types of hospital. Conclusion: Management of AIH in UK hospitals is often shared between most gastroenterologists. Blood test monitoring and treatment duration are not always in line with recommendations. Some eligible patients with decompensation are not discussed with transplant teams. Care might be improved by expanding specialist input and management by fewer designated consultants.

Treatment and Outcome of Autoimmune Hepatitis (AIH): Audit of 28 UK centres.

BACKGROUND: With few data regarding treatment and outcome of patients with AIH outside of large centres we present such a study of patients with AIH in 28 UK hospitals of varying size and facilities. METHODS: Patients with AIH were identified in 14 University and 14 District General hospitals; incident cases during 2007-2015 and prevalent cases, presenting 2000-2015. Treatment and outcomes were analysed. RESULTS: In 1267 patients with AIH, followed-up for 3.8(0-15) years, 5- and 10-year death/transplant rates were 7.1+0.8% and 10.1+1.3% (all-cause) and 4.0+0.6% and 5.9+1% (liver-related) respectively. Baseline parameters independently associated with death/transplantation for all-causes were: older age, vascular/respiratory co-morbidity, cirrhosis, decompensation, platelet count, attending transplant centre and for liver-related: the last four of these and peak bilirubin All-cause and liver-related death/transplantation was independently associated with: non-treatment with corticosteroids, non-treatment with a steroid-sparing agent (SSA), non-treatment of asymptomatic or non-cirrhotic patients and initial dose of Prednisolone >35mg/0.5mg/kg/day (all-cause only), but not with type of steroid (Prednisolone versus Budesonide) or steroid duration beyond 12-months. Subsequent all-cause and liver-death/transplant rates showed independent associations with smaller percentage fall in serum ALT after 1 and 3-months, but not with failure to normalise levels over 12-months. CONCLUSIONS: We observed higher death/transplant rates in patients with AIH who were untreated with steroids (including asymptomatic or non-cirrhotic sub-groups), those receiving higher Prednisolone doses and those who did not receive an SSA. Similar death/transplant rates were seen in those receiving Prednisolone or Budesonide, those continuing steroids after 12-months and patients attaining normal ALT within 12-months versus not.

Lisinopril-Induced Liver Injury: An Unusual Presentation and Literature Review.

Lisinopril is an angiotensin converting enzyme inhibitor (ACE-I) that has been on market for more than 25 years. ACE-I are usually well tolerated and rarely have serious or life-threatening side effects. We describe an unusual presentation of fulminant hepatic cholestasis probably secondary to lisinopril. To our knowledge, this is the second case report which shows lisinopril-induced liver injury though a cholestatic mechanism. The patient was a 59-year-old woman with type 2 diabetes, a high body mass index and hypertension, who presented with a 5-week history of jaundice and itching. She had been started on lisinopril for diabetic nephropathy 8 weeks before admission. Other causes for cholestasis had been excluded through non-invasive immunology and virology screening, an ultrasound of the liver, magnetic resonance cholangiopancreatography and a liver biopsy. The biopsy was consistent with drug-induced liver injury. Lisinopril was stopped 2 weeks before admission. The patient's hospital stay was complicated by contrast nephropathy and influenza A which were both treated appropriately. Unfortunately, the liver cholestasis did not completely resolve following withdrawal of lisinopril and the patient died after 4 months. A literature search yielded only six other reported cases of lisinopril-induced liver injury. Five cases described hepatocellular damage and one showed cholestatic injury. LEARNING POINTS: Angiotensin converting enzyme inhibitors (ACE-I) rarely have serious or life-threatening side effects.Lisinopril-induced liver injury can present as hepatocellular or cholestatic injury.Severe hepatotoxicity secondary to lisinopril can be life threatening irrespective of the liver injury pattern.

Diagnosis, presentation and initial severity of Autoimmune Hepatitis (AIH) in patients attending 28 hospitals in the UK.

BACKGROUND & AIMS: There is limited information regarding patients with AIH outside relatively few large centres. We describe here the presenting features of patients with AIH, collected as part of an audit involving 28 UK hospitals. METHODS: Patients (incident since 1/1/2007 or prevalent since 1/1/2000) were ≥18 years and either met 1999 International AIH Group (IAIHG) diagnostic criteria (n = 1164), or received immunosuppressive therapy for clinically diagnosed AIH (n = 103). RESULTS: Of 1267 patients (80% women, 91% Caucasian, age (median(range)) 55(8-86) years, 0.5% had acute viral hepatitis (CMV/EBV/HEV); 2% were taking Nitrofurantoin and 0.7% Khat. Twenty-one percent had clinical decompensation and/or a MELD score of >15. Time from first abnormal liver tests to diagnosis was ≥1 year in 19% and was longer in jaundiced vs non-jaundiced patients. HBV and HCV serology were undocumented in 4%, serum immunoglobulins in 31% and autoantibodies in 11%-27%. When documented, ≥1 antibody was present in 83%. LKM-1-positive and autoantibody-negative patients had more severe disease. Histological cirrhosis was reported in 23%, interface hepatitis 88%, predominant lymphocytes/plasma cells 75%, rosettes 19% and emperipolesis 0.4%. Only 65% of those meeting 1999 IAIHG criteria also met simplified IAIHG criteria. University Hospitals compared to District General Hospitals, were more likely to report histological features of AIH. CONCLUSIONS: This cohort from across the UK is older than other multicentre AIH cohorts. One-fifth had decompensation or MELD >15. Diagnosis was delayed in 19%, diagnostic testing was incomplete in one-third and rosettes and emperipolesis were infrequently reported.

Gastrostomies Preserve But Do Not Increase Quality of Life for Patients and Caregivers.

BACKGROUND & AIMS: Gastrostomies are widely used to provide long-term enteral nutrition to patients with neurologic conditions that affect swallowing (eg, following a cerebrovascular accident or for patients with motor neuron disease) or with oropharyngeal malignancies. The benefits derived from this intervention are uncertain for patients and caregivers. We conducted a prospective, multicenter cohort study to determine how gastrostomies affect health-related quality of life (HRQoL) in recipients and caregivers. METHODS: We performed a study of 100 patients who received gastrostomies (55% percutaneous endoscopic gastrostomy, 45% radiologically inserted) at 5 centers in the United Kingdom, 100 caregivers, and 200 population control subjects. We used the EuroQol-5D (comprising a questionnaire, index, visual analogue scale) to assess HRQoL for patients and caregivers before the gastrostomy insertion and then 3 months afterward; findings were compared with those from control subjects. Ten patients and 10 caregivers were also interviewed after the procedure to explore quantitative findings. Findings from the EuroQol-5D and semi-structured interviews were integrated using a mixed-methods matrix. RESULTS: Six patients died before the 3-month HRQoL reassessments. We observed no significant longitudinal changes in mean EuroQol-5D index scores for patients (0.70 before vs 0.710 after; P = .83) or caregivers (0.95 before vs 0.95 after; P = .32) following gastrostomy insertion. The semi-structured interviews revealed problems in managing gastrostomy tubes, social isolation, and psychological and emotional consequences that reduced HRQoL. CONCLUSIONS: We performed a mixed-methods prospective study of the effects of gastrostomy feeding on HRQoL. HRQoL did not significantly improve after gastrostomy insertion for patients or caregivers. The lack of significant decrease in HRQoL after the procedure indicates that gastrostomies may help maintain HRQoL. Findings have relevance to those involved in gastrostomy insertion decisions and indicate the importance of carefully selecting patients for this intervention, despite the relative ease of insertion.

Long-Term Prognostic Significance of Persisting Histological Activity Despite Biochemical Remission in Autoimmune Hepatitis.

OBJECTIVES: Biochemical remission is widely considered a satisfactory treatment end point in autoimmune hepatitis (AIH). The significance of persisting histological activity despite biochemical remission is unknown. We aimed to assess the frequency and prognostic significance of persisting histological inflammation in patients with AIH who had achieved biochemical remission with treatment. METHODS: We studied 120 patients (median age at diagnosis 57 years; 81% female) with AIH by International Criteria (59% definite), who received immunosuppressive treatment and underwent a follow-up liver biopsy after at least 6 months of sustained biochemical remission (defined as normal serum ALT and globulin). RESULTS: Fifty-five patients (46%) had persisting histological activity (Ishak histological activity index (HAI) ≥4). These patients had higher serum ALT (24 vs. 18 IU/l, P=0.003) and AST (27 vs. 23 IU/l, P=0.03) at the time of follow-up biopsy, compared with patients who achieved histological remission (HAI ≤3). They had less frequent regression of fibrosis on follow-up biopsy compared with those achieving histological remission (32 vs. 60%, P=0.004) and had excess mortality (standardized mortality ratio 1.4 vs. 0.7, P<0.05). The excess mortality was due to liver disease. On multivariate analysis, persisting histological activity was independently associated with all-cause death/transplantation (HR 3.1 (95% CI 1.2-8.1); P=0.02); an association with liver-related death/transplantation fell short of significance (HR 9.7 (95% CI 0.84-111.6; P=0.07). CONCLUSIONS: Persisting histological activity, despite biochemical remission, is frequent in patients with treated AIH and is associated with lower rates of fibrosis regression and reduced long-term survival.

Albumin level and patient age predict outcomes in patients referred for gastrostomy insertion: internal and external validation of a gastrostomy score and comparison with artificial neural networks.

BACKGROUND: Significant mortality after gastrostomy insertion remains and some risk factors have been identified, but no predictive scoring system exists. OBJECTIVE: To identify risk factors for mortality, formulate a predictive scoring system, and validate the score. Comparison to an artificial neural network (ANN). DESIGN: Endoscopic database analysis. SETTING: Six hospitals (2 teaching hospitals) in the South Yorkshire region, United Kingdom. PATIENTS: This study involved all patients referred for gastrostomy insertion. INTERVENTION: Generation of clinical scores to predict 30-day mortality in patients undergoing gastrostomy insertion. MAIN OUTCOME MEASUREMENTS: Risk factors for 30-day mortality. Internal and external validation of the score. Comparison with an ANN. RESULTS: Univariate analysis showed that 30-day mortality was associated with age, albumin levels, and cardiac and neurological comorbidities. Multivariate analysis showed that only age and albumin levels were independent. Modeling provided scores of 0, 1, 2, and 3 corresponding to 30-day mortalities of 0% (0-2.1), 7% (2.9-13.9), 21.3% (13.5-30.9), and 37.3% (24.1-51.9), respectively. Application of the scoring system at the other teaching hospital and the 4 district general hospitals gave 30-day mortality rates that were not significantly different from those predicted. Receiver operating characteristic curves for the score and the ANN were comparable. LIMITATIONS: Nonrandomized study. Score not used as a decision-making tool. CONCLUSION: The gastrostomy score provides an estimate of 30-day mortality for patients (and their relatives) when gastrostomy insertion is being discussed. This score requires evaluation as a decision-making tool in clinical practice. ANN analysis results were similar to the outcomes from the clinical score.

Long-term outcomes of patients with autoimmune hepatitis managed at a nontransplant center.

BACKGROUND & AIMS: The long-term outcomes of patients treated for autoimmune hepatitis (AIH) are considered to be good. However, follow-up data beyond 10 years are limited and confined to tertiary referral centers. We assessed long-term outcomes and determinants of outcome in patients with AIH from a nontransplant center. METHODS: We studied 245 patients (204 women; median age, 56 years; range, 2.5-87 years) with AIH (167 definite by International AIH Group criteria) managed at a single nontransplant center from 1971 to 2007. RESULTS: 229 patients (93%) achieved normal serum levels of alanine aminotransferase within 12 months after treatment. After a median follow-up period of 9.4 years (range, 0.01-36 years), 11 patients received liver transplants (2 subsequently died). Seventy other patients died (30 from liver disease), 15 were censored (moved away, defaulted, or developed primary biliary cirrhosis), and 149 were still being followed up on December 31, 2007. Survival rates from all-cause death or transplantation were 82%±3% and 48%±5% after 10 and 20 years, respectively, and from liver-related death or transplantation were 91%±2% and 70%±5%, respectively. The standardized mortality ratio was 1.63 for all-cause death (95% confidence interval [CI], 1.25-2.02), 1.86 also considering liver transplant as "death" (95% CI, 1.49-2.26), and 0.91 for non-liver-related death (95% CI, 0.62-1.19). By Cox regression analysis, liver decompensation, cirrhosis at any time, failure to normalize levels of alanine aminotransferase within 12 months, and >4 relapses per decade were significantly associated with liver-related death or transplant. CONCLUSIONS: Despite a good initial response to immunosuppression, long-term mortality of patients with AIH is greater than that of the general population.