Clinical findings in a multi-ethnic adult hepatitis B virus patient population in Denmark with emphasis on genotypic characteristics.

OBJECTIVE: Most knowledge about chronic hepatitis B virus (HBV) infection is based upon studies in high-endemic areas with one or two predominant genotype(s). The aim of the study was to describe clinical characteristics of a heterogeneous genotypic HBV patient population in a low-endemic European country. METHODS: Data from HBV patients currently followed in a Danish university hospital and affiliated regional clinics were reviewed in accordance to genotype status. RESULTS: Of 540 HBV patients, 462 (86%) were of non-Danish ethnicity originating from 43 different countries. HBV genotype was known in 37% of the patients: A (11%), B (25%), C (25%), D (37%) and E (2%). Logistic regression analysis of pre-treatment data among genotype A-D patients receiving nucleos(t)ide analogue (NA) therapy revealed a decreased HBeAg rate by age (OR = 0.93; CI: 0.89-0.97; p < 0.01) and an increased rate in genotype C patients (OR = 20.5; CI: 3.3-129; p < 0.01). Among untreated patients HBeAg rate was also significantly decreased by age (OR = 0.90 (0.85:0.95; p < 0.0001), whereas the rate was increased in both genotype B and C patients (OR = 7.5; CI: 1.8-30.5; p < 0.01 and OR = 12.2; CI: 3.2-46.6; p < 0.001, respectively). No significant variation was found in HBV DNA level in any of the two groups when adjusting for age, gender, genotype and HBeAg. Increased liver pathology prevalence was, irrespectively of treatment status, associated to age and male gender, but not to any genotype. CONCLUSION: In this study population, genotype B and C was found associated with higher HBeAg rate but not with increased liver pathology.

Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial.

BACKGROUND: The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials. METHODS: We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020. Within 48 h of admission, participants were randomly assigned in a 2:1 ratio to receive the TMPRSS2 inhibitor camostat mesilate 200 mg three times daily for 5 days or placebo. The primary outcome was time to discharge or clinical improvement measured as ≥2 points improvement on a 7-point ordinal scale. Other outcomes included 30-day mortality, safety and change in oropharyngeal viral load. FINDINGS: 137 patients were assigned to receive camostat mesilate and 68 to placebo. Median time to clinical improvement was 5 days (interquartile range [IQR], 3 to 7) in the camostat group and 5 days (IQR, 2 to 10) in the placebo group (P = 0·31). The hazard ratio for 30-day mortality in the camostat compared with the placebo group was 0·82 (95% confidence interval [CI], 0·24 to 2·79; P = 0·75). The frequency of adverse events was similar in the two groups. Median change in viral load from baseline to day 5 in the camostat group was -0·22 log10 copies/mL (p <0·05) and -0·82 log10 in the placebo group (P <0·05). INTERPRETATION: Under this protocol, camostat mesilate treatment was not associated with increased adverse events during hospitalization for Covid-19 and did not affect time to clinical improvement, progression to ICU admission or mortality. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001200-42.