Background Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 18 million individuals in Germany. Life-style choices including alcohol, coffee and smoking are frequent but prospective data are rare. Methods The German SLD-Registry aims to describe clinical characteristics and observe outcomes in secondary and tertiary care. Detailed data on life-style choices are prospectively collected. Results Baseline data of 903 patients were analysed. 40% (363/903) reported low grade alcohol consumption (mean 1.4 g/day). The alcohol subgroup had higher ferritin (152 vs. 205 ng/ml) but less frequently high-risk fibrosis scores (FIB-4 >2.67 8.5 vs. 15%; NFS >0.675 9.3 vs. 17%) or LS >= 9.6 kPa (25 vs. 73%; OR 0.546 [0.41-0.73], p<0.001). Smokers (current 83/544, former 136/544) had a trend towards higher CAP (326 and 314 vs. 305dB in never smokers (325/544)). No association of smoking to LS >= 9.6 kPa or cirrhosis stage could be observed (OR 0.94 [0.62-1.43], p=0.78). LS >= 9.6 kPa tended to be less frequent in coffee consumers (1-2 cups/day 229/464, 3-4 cups/day 117/464, >5 cups/day 36/464) than in non-consumers (36, 23 and 28% vs. 45%). CAP was not different between these groups. The OR for coffee consumers was reduced (0.58 [0.97-0.34]; p=0.04) with a significant dose dependency (p<0.003). Conclusion Alcohol and coffee consumption are frequent among MASLD patients. Low grade alcohol and any degree coffee consumption were associated with a decreased risk of advanced liver fibrosis. Our data may confirm the beneficial effects of coffee and indicate that very low alcohol consumption may at least not exert relevant unfavourable effects.

INTRODUCTION AND OBJECTIVES:Treatment response of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) is assessed after 12 months by Paris II criteria. In the German PBC registry, individuals were stratified into adequate and inadequate Paris II responders. We analyzed the concordance between clinical judgement and formal Paris II classification. PATIENTS AND METHODS:Physician-assessed UDCA treatment response was compared to formal Paris II criteria (alkaline phosphatase (ALP) or aspartate-aminotransferase (AST) >1.5 x ULN or bilirubin >1 mg/dL). RESULTS:10/130 (8%) cases were misclassified as inadequate UDCA responders, 44/253 (17%) as adequate responders despite not meeting Paris II criteria. Incorrectly classified responders occurred in 26% versus 13% of individuals at secondary and tertiary centers (p = 0.0141). At secondary centers, 86% of misclassified responders had ALP >1.5 × ULN and 5% had bilirubin >1 mg/dL, compared with 32% and 27% at tertiary centers. ALP levels >1.5 x ULN occurred significantly more often at secondary centers (p = 0.0005). At secondary centers, ALP levels at diagnosis were higher in misclassified versus correctly classified responders (3.6 ± 3.0 x ULN vs. 1.7 ± 0.9 x ULN, p < 0.001) and remained higher after 12 months of therapy (2.3 ± 1.2 vs. 0.9 ± 0.3 × ULN, p < 0.001). CONCLUSIONS:Clinical judgement and Paris II classification differ in 20% of patients. Higher baseline ALP levels and kinetics may lead to misclassification. This may result in withholding of second line treatments in these patients.

Guidelines on primary biliary cholangitis (PBC) recommend therapy with 13–15 mg/kg ursodeoxycholic acid (UDCA) and assessment of treatment response after 12 months. We evaluated to which extent these recommendations are followed in newly diagnosed patients. The German PBC Registry recruited three subgroups: Adequate or inadequate UDCA treatment responders (Paris II criteria) and newly diagnosed patients (<6 months prior to recruitment). We focus on newly diagnosed patients with UDCA monotherapy. 82 patients were recruited (43 at 12 tertiary and 39 at 9 secondary centers) thereof 22% with cirrhosis. Individuals with cirrhosis were older (71 ± 9 vs. 55 ± 14 years, p<0.001) and presented more frequently with diabetes mellitus (44% vs. 13%, p=0.0054) and arterial hypertension (78% vs. 42%, p=0.0076) compared to cases without cirrhosis. 12 months follow-up data were available in 62 patients. UDCA underdosing (<13 mg/kg/d) occurred in 47% and 74% of cases (p=0.013) at tertiary and secondary care at treatment initiation and in 29% and 73% (p=0.002) after 12 months, respectively. Paris II criteria were achieved in 74% and a deep UDCA response (alkaline phosphatase < ULN and bilirubin < 0.6 × ULN) in 32% of cases. Newly diagnosed PBC patients include a substantial proportion of late presenters with cirrhosis. UDCA dosage is suboptimal in many cases. Time point of diagnosis and UDCA dosage should be improved.

INTRODUCTION AND OBJECTIVES:Pruritus is a frequent and burdensome symptom in patients with primary biliary cholangitis (PBC), significantly affecting quality of life. Despite its clinical relevance, data on the prevalence and management, particularly across different levels of healthcare, remain limited. We aimed to assess prevalence, severity, and treatment of pruritus in PBC patients across secondary and tertiary care. PATIENTS AND METHODS:Within the German PBC registry, the intensity and management of pruritus were assessed cross-sectionally by treating physicians using a standardized 4-point verbal rating scale (absent, mild, moderate, severe), as well as by analyzing prescribed antipruritic medications. RESULTS:Pruritus was reported in 23 % (n = 120/515) of patients and classified as mild, moderate, or severe in 59 (49 %), 41 (34 %), and 20 (17 %) cases, respectively. The prevalence of pruritus was 27 % (n = 96/360) for tertiary versus 16 % (n = 24/155) for secondary care (p = 0.006). Moderate or severe pruritus was observed in 13.3 % (n = 48/360) of patients at tertiary centers compared to 8.4 % (n = 13/155) at secondary centers (p = 0.137). Antipruritic therapies were used in only 22.5 % (n = 27/120) patients with pruritus, with bezafibrate being the most frequently prescribed medication (63 %, n = 17/27). Patients with pruritus were more likely to receive antipruritic therapies in tertiary than secondary care: 26 % (n = 25/96) vs. 8 % (n = 2/24) (p = 0.098). CONCLUSIONS:Pruritus in patients with PBC is common and under-treated in the real-world scenario. Assessment and management vary by healthcare level, highlighting the need for standardized care and greater awareness of treatment options across all settings.

The THR-β agonist resmetirom is the first treatment approved for metabolic dysfunction-associated steatohepatitis (MASH) in the US so far. It can be prescribed given MASH and F2/F3-fibrosis (“at-risk MASH”). We analyzed how many patients qualify for resmetirom in a recently recruited Steatotic Liver Disease-cohort involving both tertiary and secondary care centers, the German SLD-Registry. Indication for resmetirom was assessed by three different approaches: (i) biopsy-proven MASH with F2/3 fibrosis and NAS-score ≥ 4; (ii) FibroScan-AST (FAST) score ≥ 0.67 and vibration controlled transient elastography (VCTE) < 15 kPa; (iii) US expert recommendations with VCTE 10–15 kPa and platelets ≥ 140×109/L or VCTE 8–15 kPa. 1113 patients were recruited across 8 tertiary and 12 secondary care centers. NAS grading and staging were available for 180 cases (16%) with 179/180 conducted at tertiary care level. Of these, 61 (34%) qualified for resmetirom. FAST score without histologic assessment was available for 638 cases (57.3%), of which 612 (87%) were from tertiary and 26 (11%) from secondary care centers. Based on approach (ii), 41 (6%) of these individuals qualified for resmetirom compared to 117 (18.3%) using approach (iii). Combining approach (iii) with FAST ≥ 0.67 leads to 191 (30.0%) eligible patients. Using VCTE 8–15 kPa results in 182 (28.5%) eligible patients. Eligibility for resmetirom treatment depends on the available method used to identify “at-risk MASH”. Availability of VCTE was highest among different levels of care.

Real-world data on the management of patients with primary biliary cholangitis (PBC) are so far scarce in Germany. Therefore, we aimed to establish a nationwide registry and describe the clinical characteristics and therapy of PBC patients.Three different cohorts defined as ursodeoxycholic acid (UDCA) responders, as inadequate responders according to Paris II criteria, and as newly diagnosed patients were prospectively recruited.This manuscript includes the baseline data of the project.In total, 33/77 (43%) contacted centres (58% of university hospitals, 38% of non-university hospitals, and 24% of private practices) recruited 515 patients including 204 UDCA responders, 221 inadequate responders to UDCA, and 90 newly diagnosed patients.All patients were treated with UDCA; however, a UDCA dosage below the recommended dosage of 13 mg/kg/d was observed in 38.5% of individuals after 12 months of treatment. UDCA dosages were lower in nonacademic compared to academic centres.Only 75/219 (38.5%) of inadequate responders to UDCA received a second-line therapy with obeticholic acid (OCA) and/or bezafibrate (BZF). OCA (13% vs. 4.5%) and BZF (14% vs. 6.5%) were significantly more often prescribed by academic vs. nonacademic centres.Pruritus (27% vs. 15.5%), fatigue (23% vs. 4.5%), and sicca syndrome (14% vs. 1%) were significantly more often reported by academic centres.The German PBC registry could be established, which indicates suboptimal therapy in a relevant proportion of patients and shows significant differences between academic and nonacademic centres. Results are fundamental to improving clinical management at different levels of care.

Wiegand, Johannes; Franke, Annegret; Stein, Kerstin; Trautwein, Christian; Berg, Thomas Author Information

Einleitung Die nicht-alkoholische Fettleber (NAFL) stellt weltweit die häufigste Form der Fettleber dar. In Deutschland sind etwa 20-30% der Erwachsenen betroffen. Ziel des Deutschen NAFLD-Registers ist es daher, epidemiologische Charakteristika der Fettlebererkrankung und deren natürlichen Verlauf unter Real-World Bedingungen in sekundären und tertiären Versorgungsstrukturen zu dokumentieren.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) affects more than 18 million individuals in Germany. Real-world data help to better characterize the natural history of disease and standard of care. Methods The German NAFLD-Registry is a prospective non-interventional study initiated by the German Liver Foundation and aims to describe clinical characteristics and observe outcomes in patients with NAFLD recruited in secondary and tertiary care. Results From this ongoing study, baseline data of the first 501 patients (mean age 54 years, 48% women) were analysed. 13 % of the study population had a high risk for advanced fibrosis (FIB-4 ≥2.67), approximately one-third had a liver stiffness value ≥9.6kPa measured by transient elastography, and the clinical diagnosis of liver cirrhosis was present in 10%. Typical comorbidities were more prevalent in high risk as compared to low risk patients (FIB-4 <1.3) including arterial hypertension (85 vs. 42%), hypercholesterolemia (39 vs. 16%), and type 2 diabetes mellitus (T2DM) (69 vs. 26%). Patients with T2DM (192/501) had a higher NAFLD disease burden as shown by liver stiffness values ≥9.6 kPa (51%) and clinical diagnosis of cirrhosis (20%). Statins were used in 22% of the main population, while in diabetic patients, metformin, GLP-1 agonists, and SGLT2 inhibitors were used in 65, 17, and 17%, respectively. Uptake of life-style interventions such as physical exercise or nutritional counselling was generally low. Conclusion First data of the German NAFLD registry show that approximately every 10th patient has advanced NAFLD, highlights T2DM patients as a high-risk group and gives insights in the use of comedication and life-style interventions in secondary and tertiary care.

Objectives Grazoprevir/elbasvir and glecaprevir/pibrentasvir (G/P) are the two preferred treatment options for patients with chronic hepatitis C virus (HCV) infection and a glomerular filtration rate (GFR) <30 mL/min. Both therapies have been separately analyzed in different real-life cohorts; however, a direct comparison has not been performed so far. We, therefore, analyzed safety and effectiveness of both regimens in a concerted real-life population. Methods The Germany Hepatitis C-Registry is a prospective national real-world registry. The analysis is based on 2773 patients with documented GFR at baseline treated with grazoprevir/elbasvir (N = 1041), grazoprevir/elbasvir + ribavirin (N = 53) and glecaprevir/pibrentasvir (N = 1679). Results A total of 93 patients with GFR <30 mL/min were treated with grazoprevir/elbasvir (N = 56), grazoprevir/elbasvir + ribavirin (N = 4), and glecaprevir/pibrentasvir (N = 33). They suffered significantly more frequent from diabetes mellitus, hypertension, and coronary heart disease than individuals with GFR >30 mL/min and showed the following baseline characteristics: 20.4, 55.9, 3.2, 12.9, and 5.3% were infected with HCV-genotypes 1a, 1b, 2, 3, and 4; 12.9% suffered from liver cirrhosis; 80.1% were treatment-naïve. Baseline characteristics except distribution of HCV-genotype 1b (n = 43/52 treated with grazoprevir/elbasvir) and sustained virologic response rates (SVR12) did not differ significantly between glecaprevir/pibrentasvir (SVR12: 100%) and grazoprevir/elbasvir (SVR12: 97.9%). Fatigue, headache, abdominal discomfort, and arthralgia were the most frequently reported adverse events without a statistical difference between grazoprevir/elbasvir and glecaprevir/pibrentasvir. Conclusion In patients with chronic hepatitis C and a baseline GFR ≤30 mL/min grazoprevir/elbasvir and glecaprevir/pibrentasvir show an equally favorable safety profile and antiviral efficacy and can both be recommended for real-life use.

Hepatitis C virus infection is causing chronic liver disease, cirrhosis, and hepatocellular carcinoma. By combining direct-acting antivirals (DAAs), high sustained virologic response rates (SVRs) can be achieved. Resistance-associated substitutions (RASs) are commonly observed after DAA failure, and especially nonstructural protein 5A (NS5A) RASs may impact retreatment options.1-3 Data on retreatment of DAA failure patients using first-generation DAAs are limited.4-7 Recently, a second-generation protease- and NS5A-inhibitor plus sofosbuvir (voxilaprevir/velpatasvir/sofosbuvir [VOX/VEL/SOF]) was approved for retreatment after DAA failure.8 However, this and other second-generation regimens are not available in many resource-limited countries or are not reimbursed by regular insurance, and recommendations regarding the selection of retreatment regimens using first-generation DAAs are very important. This study aimed to analyze patients who were re-treated with first-generation DAAs after failure of a DAA combination therapy.

Methods A confirmed PBC diagnosis according to EASL guidelines (at least two of three criteria positive: elevated alkaline phosphatase (AP), AMA-M2 positivity, PBC compatible liver biopsy) is requested and treatment with at least one licensed PBC medication. Subgroups are classified according to their response to therapy with ursodeoxychocholic acid (UDCA) as responders or primary or secondary incomplete responders (Paris II criteria). Newly diagnosed patients were diagnosed within the last six months prior to inclusion.

Background and aims Discontinuation of long-term suppression of HBV replication with nucleos(t)ide analogues (NUCs) can result in durable immune control of hepatitis B virus (HBV) replication in HBeAg negative patients. We have assessed the effect of NUC discontinuation in HBeAg negative patients in a prospective, multicenter, randomized trial (the Stop-NUC study).