Background and Aims: Chronic hepatitis delta represents a major global health burden. Clinical features of hepatitis D virus (HDV) infection vary largely between different regions worldwide. Treatment approaches are dependent on the approval status of distinct drugs and financial resources.Methods: The Hepatitis Delta International Network (HDIN) registry involves researchers from all continents (Wranke, Liver International 2018). We here report long‐term follow‐up data of 648 hepatitis D patients recruited by 14 centres in 11 countries. Liver‐related clinical endpoints were defined as hepatic decompensation (ascites, encephalopathy and variceal bleeding), liver transplantation, hepatocellular carcinoma or liver‐related death.Results: Patient data were available from all continents but Africa: 22% from Eastern Mediterranean, 32% from Eastern Europe and Central Asia, 13% from Central and Southern Europe, 14% from South Asia (mainly Pakistan) and 19% from South America (mainly Brazil). The mean follow‐up was 6.4 (.6–28) years. During follow‐up, 195 patients (32%) developed a liver‐related clinical event after 3.5 (±3.3) years. Liver cirrhosis at baseline and a detectable HDV RNA test during follow‐up were associated with a worse clinical outcome in multivariate regression analysis while patients receiving interferon alfa‐based therapies developed clinical endpoints less frequently. Patients from South Asia developed endpoints earlier and had the highest mortality.Conclusions: The HDIN registry confirms the severity of hepatitis D and provides further evidence for HDV viraemia as a main risk factor for disease progression. Hepatitis D seems to take a particularly severe course in patients born in Pakistan. There is an urgent need to extend access to antiviral therapies and to provide appropriate education about HDV infection.

Background: Cirrhosis has been reported as an important risk factor for death in coronavirus disease 2019 (COVID-19) disease. In this study, we aimed to investigate the effects of COVID-19 on the natural course of cirrhosis before and after starting vaccination.Methods: The cirrhosis patients in our cohort (n: 140; median age:56; 71 female) were included in this study. The median MELD (Model For End-stage Liver Disease) score was 11 (6–25) and CCI (Charlson Comorbidity Index) score was 4 (1–11). In total, 85 had CTP (Child-Turcotte-Pugh)-A, 44 had CTP-B and 11 had CTP-C cirrhosis. The course of COVID-19 in this patient group was evaluated before and after COVID-19 vaccination.Results: Between March 2020 and January 2021, 36 of the 140 cirrhosis patients had developed COVID-19. Cirrhosis (+)/COVID-19 (+) and Cirrhosis (+)/COVID-19 (–) groups did not differ in terms of age, CCI and MELD-Na scores, or gender. There were six deaths in the Cirrhosis (+)/COVID-19 (+) group and five in the Cirrhosis (+)/COVID-19 (–) group [6/36 (16.6%) vs. 5/104 (4.8%); p: 0.03]. Patients who died were older, had higher CCI and MELD-Na scores, and lower albumin levels. Having had COVID-19 [6.45 (1.43–29.4); p: 0.015], higher MELD-Na score [1.35 (1.18–1.60); p: 0.001] and higher CCI score [1.65 (1.14–2.39); p: 0.008] were found to be independent predictors of mortality. After effective vaccination started in Turkey, only 11 of the remaining 129 patients developed COVID-19, and only one patient died, who was unvaccinated.Discussion: In our cirrhotic cohort, COVID-19 disease was associated with 16% mortality in the pre-vaccination period. COVID-19 vaccination prevents serious illness and death due to COVID-19 in cirrhotic patients.

Background and Objectives: Fibrosis stage is the key histopathological determinant of liver-related outcomes in metabolic dysfunction-associated steatohepatitis (MASH); however, a reliable noninvasive method for predicting fibrosis stage remains an unmet need. This study aimed to develop an accurate, practical, and noninvasive tool for identifying “at-risk MASH patients”. Materials and Methods: Fifty-six patients with biopsy-confirmed MASH were prospectively enrolled and categorized into fibrosis stages using the NASH-CRN system. In addition to anthropometric and biochemical parameters, seven serum fibrosis biomarkers were evaluated across fibrosis stages. Binary logistic regression analysis was used to construct a scoring model for predicting ≥F2 fibrosis. The diagnostic performance of the proposed model was compared with established noninvasive tests (NITs) and magnetic resonance elastography (MRE) for detecting both ≥F2 and ≥F3 fibrosis. Results: The total metabolic syndrome score was the only variable that significantly distinguished between F1 and F2 stages (p = 0.039). Among the biomarkers, matrix metalloproteinase-1 (MMP-1) showed a significant difference across fibrosis groups (p = 0.009). The AST/ALT ratio was the most robust predictor for differentiating ≥F3 (p < 0.001). A scoring model integrating the total metabolic syndrome score, MMP-1, and AST/ALT ratio demonstrated superior diagnostic accuracy for identifying ≥F2 (AUROC 0.88, 95% CI 0.79–0.97) compared to other NITs and MRE, and strong performance for detecting ≥F3 (AUROC 0.95, 95% CI 0.90–1.00). Conclusions: Total metabolic syndrome score and MMP-1 are promising candidates for future approaches. Combining total metabolic syndrome score, MMP-1, and AST/ALT ratio might detect ≥F2 in MASH with higher diagnostic accuracy than other NITs and MRE.