Epidemiology, clinical features and management of autoimmune hepatitis in Switzerland: a retrospective and prospective cohort study.

BACKGROUND AND AIMS: The Swiss Autoimmune Hepatitis Cohort Study is a nationwide registry, initiated in 2017, that collects retrospective and prospective clinical data and biological samples from patients of all ages with autoimmune hepatitis treated at Swiss hepatology centres. Here, we report the analysis of the first 5 years of registry data. RESULTS: A total of 291 patients with autoimmune hepatitis have been enrolled, 30 of whom were diagnosed before 18 years of age and composed the paediatric cohort. Paediatric cohort: median age at diagnosis 12.5 years (range 1-17, interquartile range (IQR) 8-15), 16 (53%) girls, 6 (32%) with type 2 autoimmune hepatitis, 8 (27%) with autoimmune sclerosing cholangitis, 1 with primary biliary cholangitis variant syndrome, 4 (15%) with inflammatory bowel disease and 10 (41%) with advanced liver fibrosis at diagnosis. Adult cohort: median age at diagnosis 54 years (range 42-64, IQR 18-81), 185 (71%) women, 51 (20%) with primary biliary cholangitis variant syndrome, 22 (8%) with primary sclerosing cholangitis variant syndrome, 9 (4%) with inflammatory bowel disease and 66 (32%) with advanced liver fibrosis at diagnosis. The median follow-up time for the entire cohort was 5.2 years (IQR 3-9.3 years). Treatment in children: 29 (97%) children were initially treated with corticosteroids, 28 of whom received combination treatment with azathioprine. Budesonide was used in four children, all in combination with azathioprine. Mycophenolate mofetil was used in five children, all of whom had previously received corticosteroids and thiopurine. Treatment in adults (data available for 228 patients): 219 (96%) were treated with corticosteroids, mostly in combination with azathioprine. Predniso(lo)ne was the corticosteroid used in three-quarters of patients; the other patients received budesonide. A total of 78 (33%) patients received mycophenolate mofetil, 62 of whom had previously been treated with azathioprine. Complete biochemical response was achieved in 13 of 19 (68%) children and 137 of 182 (75%) adults with available follow-up data. All children were alive at the last follow-up, and none had undergone liver transplantation. Five (2%) adults underwent liver transplantation, two of whom had a fulminant presentation. Four (2%) adults with autoimmune hepatitis died (two from liver-associated causes). CONCLUSION: Patients with autoimmune hepatitis in Switzerland had clinical features similar to those in other cohorts. The proportion of patients diagnosed with primary biliary cholangitis variant syndrome was higher than expected. Autoimmune hepatitis was managed according to guidelines, except for the use of budesonide in a small proportion of paediatric patients. The outcomes were excellent, but the findings must be confirmed over a longer follow-up period.

HCV disease burden and population segments in Switzerland.

BACKGROUND: Switzerland has made strides towards hepatitis C virus elimination, but as of 2019, elimination was not guaranteed. However, political interest in viral hepatitis has been increasing. We sought to develop a better understanding of Switzerland's progress towards HCV elimination and the profile of remaining HCV-RNA-positive patients. METHODS: A previously described Markov model was updated with recent diagnosis and treatment data and run to generate new forecasts for HCV disease burden. Two scenarios were developed to evaluate HCV morbidity and mortality under the status quo and a scenario that achieves the Swiss Hepatitis Strategy Elimination targets. Next, an analysis was conducted to identify population segments bearing a high burden of disease, where future elimination efforts could be directed. RESULTS: At the beginning of 2020, an estimated 32 100 viremic infections remained in Switzerland (0.37% viremic prevalence). Adult (≥18 years of age) permanent residents born abroad represented the largest subpopulation, accounting for 56% of HCV infections. Thirteen countries accounted for ≥60% of viremic infections amongst permanent residents born abroad, with most people currently residing in Zurich, Vaud, Geneva, Bern, Aargau and Ticino. Amongst Swiss-born HCV-RNA-positive persons, two-thirds had a history of IDU, corresponding to 33% of total infections. CONCLUSIONS: In Switzerland, extra efforts for diagnosis and linkage to care are warranted in foreign-born populations and people with a history of drug use. Population-level measures (eg increasing the number of providers, increase screening) can identify patients who may have otherwise fallen through the gaps or avoided care because of stigma.

Assessment of hepatic steatosis by controlled attenuation parameter using the M and XL probes: an individual patient data meta-analysis.

BACKGROUND: Diagnostic tools for liver disease can now include estimation of the grade of hepatic steatosis (S0 to S3). Controlled attenuation parameter (CAP) is a non-invasive method for assessing hepatic steatosis that has become available for patients who are obese (FibroScan XL probe), but a consensus has not yet been reached regarding cutoffs and its diagnostic performance. We aimed to assess diagnostic properties and identify relevant covariates with use of an individual patient data meta-analysis. METHODS: We did an individual patient data meta-analysis, in which we searched PubMed and Web of Science for studies published from database inception until April 30, 2019. Studies reporting original biopsy-controlled data of CAP for non-invasive grading of steatosis were eligible. Probe recommendation was based on automated selection, manual assessment of skin-to-liver-capsule distance, and a body-mass index (BMI) criterion. Receiver operating characteristic methods and mixed models were used to assess diagnostic properties and covariates. Patients with non-alcoholic fatty liver disease (NAFLD) were analysed separately because they are the predominant patient group when using the XL probe. This study is registered with PROSPERO, CRD42018099284. FINDINGS: 16 studies reported histology-controlled CAP including the XL probe, and individual data from 13 papers and 2346 patients were included. Patients with a mean age of 46·5 years (SD 14·5) were recruited from 20 centres in nine countries. 2283 patients had data for BMI; 673 (29%) were normal weight (BMI <25 kg/m2), 530 (23%) were overweight (BMI ≥25 to <30 kg/m2), and 1080 (47%) were obese (BMI ≥30 kg/m2). 1277 (54%) patients had NAFLD, 474 (20%) had viral hepatitis, 285 (12%) had alcohol-associated liver disease, and 310 (13%) had other liver disease aetiologies. The XL probe was recommended in 1050 patients, 930 (89%) of whom had NAFLD; among the patients with NAFLD, the areas under the curve were 0·819 (95% CI 0·769-0·869) for S0 versus S1 to S3 and 0·754 (0·720-0·787) for S0 to S1 versus S2 to S3. CAP values were independently affected by aetiology, diabetes, BMI, aspartate aminotransferase, and sex. Optimal cutoffs differed substantially across aetiologies. Risk of bias according to QUADAS-2 was low. INTERPRETATION: CAP cutoffs varied according to cause, and can effectively recognise significant steatosis in patients with viral hepatitis. CAP cannot grade steatosis in patients with NAFLD adequately, but its value in a NAFLD screening setting needs to be studied, ideally with methods beyond the traditional histological reference standard. FUNDING: The German Federal Ministry of Education and Research and Echosens.

Nonalcoholic fatty liver disease burden - Switzerland 2018-2030.

As a result of epidemic levels of obesity and diabetes mellitus, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) will contribute to increases in the liver-related disease burden in Switzerland. A Markov model was built to quantify fibrosis progression among the NAFLD and NASH populations, and predict disease burden up to 2030. Long-term trending of NAFLD prevalence was based on changes in the prevalence of adult obesity. Published estimates and surveillance data were applied to build and validate the model projections. The prevalence of NAFLD increased up to 2030 in tandem with projected increases in adult obesity. By 2030, there were an estimated 2,234,000 (1,918,000–2,553,000) NAFLD cases, or 24.3% (20.9–27.8%) of the total Swiss population (all ages). Increases in NASH cases were relatively greater than NAFLD cases. Incident cases of advanced liver disease are projected to increase by approximately 40% by 2030, and incident NAFLD liver deaths to increase from 580 deaths in 2018 to 820 deaths in 2030. Continued growth in obesity, in combination with an aging population, will result in increasing number of cases of advanced liver disease and mortality related to NAFLD and NASH. Slowing the growth in obesity and metabolic syndrome, along with future potential therapies, are required to reduce liver disease burden.  .

Controlled attenuation parameter for the assessment of liver steatosis in comparison with liver histology: a single-centre real life experience.

BACKGROUND AND AIMS: Accurate diagnosis and staging of non-alcoholic fatty liver disease are essential for the management of this disorder. Controlled attenuation parameter (CAP) has been suggested as a new noninvasive measurement made during transient elastography to assess liver steatosis. The aim of this study was to evaluate CAP as a diagnostic tool for identifying the presence and degree of hepatic steatosis in consecutive patients in an outpatient liver unit of a tertiary centre. METHODS: Between March 2015 and August 2016, all patients who underwent liver biopsy underwent liver stiffness measurement with simultaneous CAP determination using the FibroScan® M or XL probe. Steatosis, inflammatory activity and fibrosis were assessed using the histological SAF scoring system. In addition, fibrosis was scored according to the METAVIR system, and body mass index (BMI) and the underlying liver disease were also recorded. RESULTS: 224 patients were included in the analysis; 146 (65.2%) were male. Steatosis grades were distributed as follows: S0 n = 85 (37.9%), S1 n = 82 (36.6%), S2 n = 33 (14.7%), S3 n = 24 (10.7%). Mean BMI was 26.8 kg/m2, for the S0 group 24.9 kg/m2, S1 26.5 kg/m2, S2 27.3 kg/m2 and S3 32.5 kg/m2. The CAP differed significantly between steatosis groups S0 to S3. The area under receiver operating characteristics curve for S0 vs S1–S3 was 0.78, for S0/1 vs S2/3 0.83 and for S0–2 vs S3 0.82. Calculated cut-off values were 258.5 dB/m for S0 vs S1–3, 282.5 dB/m for S0/1 vs S2/3 and 307.5 dB/m for S0–2 vs S3. CONCLUSIONS: CAP values are strongly associated with the degree of steatosis irrespective of the underlying liver disease. Integrating CAP measurements in the standard work-up may identify patients with NAFLD.  .

Progress toward implementing the Swiss Hepatitis Strategy: Is HCV elimination possible by 2030?

Catalyzed by the concerns over the growing public health and economic burden of Hepatitis C virus (HCV) in Switzerland, a diverse group of experts and patient representatives came together in 2014 to develop the Swiss Hepatitis Strategy, setting targets for the elimination of viral hepatitis in Switzerland by 2030. Previous studies have reported the estimated number of chronic HCV infections and forecasted burden of disease given different intervention strategies. However, given new prevalence data by the Swiss Federal Office of Public Health, which decreased total infections by about half, an updated analysis is warranted. We aimed to provide an updated viremic prevalence estimate for Switzerland and evaluate the impact on forecasted liver related morbidity and mortality of an 'inaction' scenario and intervention scenarios to achieve the Global Health Sector Strategy for Viral Hepatitis and Swiss Hepatitis Strategy goals by 2030. A Markov disease-progression model was used to calculate the present and future burden of HCV infection by disease stage according to these different strategies. In 2017, there were an estimated 36,800 (95% UI: 26,900-39,200) viremic infections in Switzerland. Given the current standard of care, total viremic infections are expected to decline by 45%, while cases of decompensated cirrhosis, hepatocellular carcinoma, and liver-related deaths will decrease by 20%. If treatment and diagnosis efforts were to cease in 2018, late stage HCV-related morbidity and mortality would increase by 90-100% by 2030. Increasing treatment and diagnosis to achieve the Global Health Sector Strategy or Swiss Hepatitis Strategy goals by 2030, will reduce the number of chronic infections to less than 13,000 and 4,000, respectively. Although the HCV epidemic is declining in Switzerland, efforts to expand diagnosis and treatment are needed to achieve elimination by 2030.

Birth cohort distribution and screening for viraemic hepatitis C virus infections in Switzerland.

OBJECTIVE: In Switzerland, fewer than 40% of hepatitis C virus (HCV) infected individuals have been diagnosed. The aim of this project was to analyse the distribution of HCV cases in order to develop better detection strategies. STUDY DESIGN: Historical data on the HCV-infected population in Switzerland were obtained from published literature, unpublished data and government reports. A disease progression model was used to age the infected population to 2015. The HCV distribution was then used to identify 5-year age cohorts with the highest HCV prevalence. The estimated number of cases needed to screen within an age cohort was calculated using the estimated viraemic prevalence, removing the percent previously diagnosed. RESULTS: In 2015, the median age of the viraemic HCV infected population was 49 years, with 75% of the population born between 1951 and 1985. Random screening of the general population could identify one new viraemic HCV case per 159 persons screened, compared with targeted birth cohort screening, which could identify one new viraemic HCV case per 90-99 persons screened. CONCLUSION: Considering only the direct cost of screening and treatment informing tests, targeted screening by birth cohort is more effective and cost effective than random screening in the general population.

Modeling the Health and Economic Burden of Hepatitis C Virus in Switzerland.

BACKGROUND: Chronic hepatitis C virus infection is a major cause of liver disease in Switzerland and carries a significant cost burden. Currently, only conservative strategies are in place to mitigate the burden of hepatitis C in Switzerland. This study expands on previously described modeling efforts to explore the impact of: no treatment, and treatment to reduce HCC and mortality. Furthermore, the costs associated with untreated HCV were modeled. METHODS: Hepatitis C disease progression and mortality were modeled. Baseline historical assumptions were collected from the literature and expert interviews and strategies were developed to show the impact of different levels of intervention (improved drug cure rates, treatment and diagnosis) until 2030. RESULTS: Under the historical standard of care, the number of advanced stage cases was projected to increase until 2030, at which point the annual economic burden of untreated viremic infections was projected to reach €96.8 (95% Uncertainty Interval: €36 - €232) million. Scenarios to reduce HCV liver-related mortality by 90% by 2030 required treatment of 4,190 ≥F2 or 3,200 ≥F3 patients annually by 2018 using antivirals with a 95% efficacy rate. Delaying the implementation of these scenarios by 2 or 5 years reduced the impact on mortality to 75% and 57%, respectively. CONCLUSIONS: With today's treatment efficacy and uptake rates, hepatitis C disease burden is expected to increase through 2030. A substantial reduction in disease burden can be achieved by means of both higher efficacy drugs and increased treatment uptake. However, these efforts cannot be undertaken without a simultaneous effort to diagnose more infections.