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Background and Aims Cholestasis is associated with disease severity and worse outcome in COVID‐19. Cases of secondary sclerosing cholangitis (SSC) after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection have been described. Approach and Results Hospitalized patients with COVID‐19 between 03/2020 and 07/2021 were included. Patients were stratified as having (i) no chronic liver disease (CLD), (ii) non‐advanced CLD (non‐ACLD), or (iii) advanced CLD (ACLD). Patients with CLD and non–COVID‐19 pneumonia were matched to patients with CLD and COVID‐19 as a control cohort. Liver chemistries before (Pre) and at first, second, and third blood withdrawal after SARS‐CoV‐2 infection (T1–T3) and at last available time point (last) were recorded. A total of 496 patients were included. In total, 13.1% ( n = 65) had CLD (non‐ACLD: 70.8%; ACLD: 29.2%); the predominant etiology was NAFLD/NASH (60.0%). COVID‐19–related liver injury was more common among patients with CLD (24.6% vs. 10.6%; p = 0.001). After SARS‐CoV‐2 infection, patients with CLD exhibited progressive cholestasis with persistently increasing levels of alkaline phosphatase (Pre: 91.0 vs. T1: 121.0 vs. last: 175.0 U/L; p < 0.001) and gamma‐glutamyl transferase (Pre: 95.0 vs. T1: 135.0 vs. last: 202.0 U/L; p = 0.001). A total of 23.1% of patients with CLD ( n = 15/65) developed cholestatic liver failure (cholestasis plus bilirubin ≥6 mg/dl) during COVID‐19, and 15.4% of patients ( n = 10/65) developed SSC. SSC was significantly more frequent among patients with CLD and COVID‐19 than in patients with CLD and non–COVID‐19 pneumonia ( p = 0.040). COVID‐19–associated SSC occurred predominantly in patients with NAFLD/NASH and metabolic risk factors. A total of 26.3% ( n = 5/19) of patients with ACLD experienced hepatic decompensation after SARS‐CoV‐2 infection. Conclusions About 20% of patients with CLD develop progressive cholestasis after SARS‐CoV‐2 infection. Patients with NAFLD/NASH and metabolic risk factors are at particular risk for developing cholestatic liver failure and/or SSC after COVID‐19.

ObjectiveSystemic inflammation promotes the development of clinical events in patients with advanced chronic liver disease (ACLD). We assessed whether (1) non-selective beta blocker (NSBB) treatment initiation impacts biomarkers of systemic inflammation and (2) whether these changes in systemic inflammation predict complications and mortality.DesignBiomarkers of systemic inflammation, that is, white blood cell count (WBC), C reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin (PCT) were determined at sequential hepatic venous pressure gradient (HVPG) measurements without NSBB and under stable NSBB intake. The influence of NSBB-related changes in systemic inflammation on the risk of decompensation and liver-related death was analysed using competing risk regression.ResultsOur study comprised 307 stable patients with ACLD (Child-A: 77 (25.1%), Child-B: 161 (52.4%), Child-C: 69 (22.5%), median HVPG: 20 (IQR 17–24) mm Hg) including 231 (75.2%) with decompensated disease.WBC significantly decreased upon NSBB therapy initiation (median: −2 (IQR −19;+13)%, p=0.011) in the overall cohort. NSBB-related reductions of WBC (Child-C: −16 (−30;+3)% vs Child-B: −2 (−16;+16)% vs Child-A: +3 (−7;+13)%, p<0.001) and of CRP (Child-C: −26 (−56,+8)% vs Child-B: −16 (−46;+13)% vs Child-A: ±0 (−33;+33)%, p<0.001) were more pronounced in advanced stages of cirrhosis. The NSBB-associated changes in WBC correlated with changes in CRP (Spearman’s ρ=0.228, p<0.001), PCT (ρ=0.470, p=0.002) and IL-6 (ρ=0.501, p=0.001), but not with changes in HVPG (ρ=0.097, p=0.088).An NSBB-related decrease in systemic inflammation (ie, WBC reduction ≥15%) was achieved by n=91 (29.6%) patients and was found to be an independent protective factor of further decompensation (subdistribution HR, sHR: 0.694 (0.49–0.98), p=0.038) in decompensated patients and of liver-related mortality in the overall patient cohort (sHR: 0.561 (0.356–0.883), p=0.013).ConclusionNSBB therapy seems to exert systemic anti-inflammatory activity as evidenced by reductions of WBC and CRP levels. Interestingly, this effect was most pronounced in Child-C and independent of HVPG response. An NSBB-related WBC reduction by ≥15% was associated with a decreased risk of further decompensation and death.

Summary Background and Aim Bulevirtide (BLV) blocks the uptake of the hepatitis D virus (HDV) into hepatocytes via the sodium/bile acid cotransporter NTCP. BLV was conditionally approved by the EMA but real‐life data on BLV efficacy are limited. Methods Patients were treated with BLV monotherapy. Patients who did not achieve further decreases in HDV‐RNA after 24 weeks were offered PEG‐IFN as an add‐on therapy in a response‐guided manner. Results Twenty‐three patients (m: 10, f: 13; mean age: 47.9 years, cirrhosis: 16; median ALT: 71 IU/ml; median HDV‐RNA: 2.1 × 105copies/ml) started BLV monotherapy (2 mg/day: 22; 10 mg/day: 1). Twenty‐two completed ≥24 weeks of treatment (24–137 weeks): Ten (45%) were classified as BLV responders at week 24. BLV was stopped in two patients with >6 months HDV‐RNA undetectability, but both became HDV‐RNA positive again. One patient was transplanted at week 25. One patient terminated treatment because of side effects at week 60. Ten patients are still on BLV monotherapy. Adding PEG‐IFN in eight patients induced an HDV‐RNA decrease in all (1.29 ± 0.19 [SD] log within 12 weeks). HDV‐RNA decreased by >2log or became undetectable in 45%(10/22), 55%(11/20), 65% (13/20) and 69% (9/13); and ALT levels normalised in 64% (14/22), 85% (17/20), 90% (18/20) and in 92% (12/13) patients at weeks 24, 36, 48 and 60, respectively. Portal pressure decreased in 40% (2/5) of patients undergoing repeated measurement under BLV therapy. Conclusion Long‐term BLV monotherapy is safe and effectively decreases HDV‐RNA and ALT—even in patients with cirrhosis. The optimal duration of BLV treatment alone or in combination with PEG‐IFN remains to be established. An algorithm for a response‐guided BLV treatment approach is proposed.

Background&Aims:The COVID-19 pandemic necessitated down-scaling of in-hospital care to prohibit the spread of severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2). We (i)assessed patient perceptions on quality of care by tele-survey(cohort 1) and written questionnaire(cohort 2) and (ii)analyzed trends in elective and non-elective admissions prior to (12/2019- 02/2020) and during (03/2020-05/2020) the COVID-19 pandemic in Austria. Methods:Two-hundred seventy-nine outpatients were recruited into cohort 1 and 138 patients into cohort 2. All admissions from 12/2019 to 05/2020 to the Division of Gastroenterology/Hepatology at the Vienna General Hospital were analyzed. Results:Thirty-two point six percent (n=91/279) of cohort 1 and 72.5%(n=95/131) of cohort 2 had tele-medical contact, while 59.5%(n=166/279)and 68.2%(n=90/132) had face-to-face visits. 24.1%(n=32/133) needed acute medical help during healthcare restrictions, however, 57.3%(n=51/89) reported that contacting their physician during COVID-19 was difficult or impossible. Patient-reported satisfaction with treatment decreased significantly during restrictions in cohort 1 (visual analog scale[VAS] 0-