Search

We examined the long-term trend of incident hepatocellular carcinoma (HCC) and hepatic decompensation among chronic hepatitis B (CHB) patients who have achieved hepatitis B surface antigen (HBsAg) seroclearance.All adult CHB monoinfected patients who cleared HBsAg between January 2000 and December 2020 were identified using a territory-wide database in Hong Kong. Patients with liver transplantation and/or HCC before HBsAg seroclearance or follow-up less than 6 months were excluded. The primary and secondary endpoints were HCC and hepatic decompensation respectively.We identified 9,769 CHB patients with HBsAg seroclearance (mean age 57 years, 60.0% male, 13.2% cirrhosis); most had compensated liver function at HBsAg loss. At a median (25HCC risk persists in patients after HBsAg loss, whereas the risk of hepatic decompensation decreases over time.Patients with chronic hepatitis B (CHB) still have a non-negligible risk of hepatocellular carcinoma (HCC) after 12 years of hepatitis B surface antigen (HBsAg) seroclearance, especially among those with cirrhosis. The risk of developing hepatic decompensation decreases over time after HBsAg seroclearance. In clinical practice, although CHB patients who cleared HBsAg have a more favourable clinical outcome than those who remain chronically infected, long-term HCC surveillance would still be necessary for cirrhotic patients and high-risk subgroups of non-cirrhotic patients after HBsAg seroclearance.

Background We examined the effectiveness of molnupiravir and nirmatrelvir/ritonavir in reducing hospitalization and deaths in a real-world cohort of nonhospitalized patients with coronavirus disease 2019 (COVID-19). Methods This was a territory-wide retrospective cohort study in Hong Kong. Nonhospitalized COVID-19 patients who attended designated outpatient clinics between 16 February and 31 March 2022 were identified. Patients hospitalized on the day of the first clinic appointment or used both oral antivirals were excluded. The primary endpoint was hospitalization. The secondary endpoint was a composite of intensive care unit admission, invasive mechanical ventilation use, and/or death. Results Of 93 883 patients, 83 154 (88.6%), 5808 (6.2%), and 4921 (5.2%) were oral antiviral nonusers, molnupiravir users, and nirmatrelvir/ritonavir users, respectively. Compared with nonusers, oral antiviral users were older and had more comorbidities, lower complete vaccination rate, and more hospitalizations in the previous year. Molnupiravir users were older and had more comorbidities, lower complete vaccination rate, and more hospitalizations in the previous year than nirmatrelvir/ritonavir users. At a median follow-up of 30 days, 1931 (2.1%) patients were hospitalized and 225 (0.2%) patients developed the secondary endpoint. After propensity score weighting, nirmatrelvir/ritonavir use (weighted hazard ratio 0.79; 95% confidence interval [CI], 0.65–0.95; P = .011) but not molnupiravir use (weighted hazard ratio 1.17; 95% CI, 0.99–1.39; P = .062) was associated with a reduced risk of hospitalization than nonusers. The use of molnupiravir or nirmatrelvir/ritonavir was not associated with a lower risk of the secondary endpoint as compared with nonusers. Conclusion Use of nirmatrelvir/ritonavir but not molnupiravir was associated with a reduced risk of hospitalization in real-world nonhospitalized patients with COVID-19.

ImportanceOlder patients living in nursing homes are at very high risk of mortality after getting COVID-19.ObjectiveTo evaluate outcomes following oral antiviral treatment for COVID-19 among nonhospitalized older patients living in nursing homes.Design, Setting, and ParticipantsThis is a territory-wide, retrospective cohort study conducted between February 16 and March 31, 2022, with the last follow-up date on April 25, 2022. Participants were patients with COVID-19 living in nursing homes in Hong Kong. Data analysis was performed from May to June 2022.ExposuresMolnupiravir, nirmatrelvir/ritonavir, or no oral antiviral treatment.Main Outcomes and MeasuresThe primary outcome was hospitalization for COVID-19, and the secondary outcome was risk of inpatient disease progression (ie, admission to intensive care unit, use of invasive mechanical ventilation, and/or death).ResultsOf 14 617 patients (mean [SD] age, 84.8 [10.2] years; 8222 women [56.2%]), 8939 (61.2%) did not use oral antivirals, 5195 (35.5%) used molnupiravir, and 483 (3.3%) used nirmatrelvir/ritonavir. Compared with patients who did not use oral antivirals, those who used molnupiravir and nirmatrelvir/ritonavir were more likely to be female and less likely to have comorbid illnesses and hospitalization in the past year. At a median (IQR) follow-up of 30 (30-30) days, 6223 patients (42.6%) were hospitalized and 2307 patients (15.8%) experienced inpatient disease progression. After propensity score weighting, both molnupiravir and nirmatrelvir/ritonavir were associated with a reduced risk of hospitalization (molnupiravir, weighted hazard ratio [wHR], 0.46; 95% CI, 0.37-0.57; P P P P P = .99; inpatient disease progression, wHR, 0.49; 95% CI, 0.20-1.20; P = .12).Conclusions and RelevanceIn this retrospective cohort study, the use of oral antivirals to treat COVID-19 was associated with a reduced risk of hospitalization and inpatient disease progression among patients living in nursing homes. The findings of this study of nursing home residents could be reasonably extrapolated to other frail older patients living in the community.

Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first-line antiviral therapies for patients with chronic hepatitis B (CHB) and reduce the risk of disease progression and liver-related complications, as well as improve survival by effectively suppressing viral replication. Nevertheless, since the first publication in 2019 on a lower risk of hepatocellular carcinoma (HCC) in Korean patients receiving TDF than those receiving ETV, the topic has remained a hot and unsettled debate. Multiple studies and meta-analyses have yielded conflicting results. As HCC takes time to develop, studies are mainly observational to benefit from a larger sample size and longer follow-up that provides a higher statistical power to compare the two treatments. However, TDF was available to CHB patients a few years later than ETV in most countries, thus leading to a difference in follow-up duration. Moreover, despite studying the same topic, the difference in data sources and available parameters, inclusion and exclusion criteria, and use of statistical methods complicated the interpretation and comparison of the findings and contributed to between-study heterogeneity in meta-analyses. This review describes some caveats in interpreting and comparing the results from these observational studies and meta-analyses. Future studies should explore better designed observational studies with high-quality data sources, and aggregation of patient data in meta-analysis to tackle between-study heterogeneity.

ImportanceSome patients treated with nirmatrelvir-ritonavir have experienced rebound of COVID-19 infections and symptoms; however, data are scarce on whether viral rebound also occurs in patients with COVID-19 receiving or not receiving molnupiravir.ObjectiveTo examine the incidence of viral rebound in patients with COVID-19 who were treated with the oral antiviral agents nirmatrelvir-ritonavir and molnupiravir.Design, Setting, and ParticipantsThis cohort study identified 41 255 patients with COVID-19 who were hospitalized from January 1, 2022, to March 31, 2022, in Hong Kong and assessed 12 629 patients with serial cycle threshold (Ct) values measured. Patients were followed up until the occurrence of the clinical end point of interest, death, date of data retrieval (July 31, 2022), or up to 30 days of follow-up, whichever came first.ExposuresMolnupiravir or nirmatrelvir-ritonavir treatment.Main Outcomes and MeasuresViral rebound, defined as a Ct value greater than 40 that decreased to 40 or less.ResultsOf 12 629 patients (mean [SD] age, 65.4 [20.9] years; 6624 [52.5%] male), 11 688 (92.5%) were oral antiviral nonusers, 746 (5.9%) were molnupiravir users, and 195 (1.5%) were nirmatrelvir-ritonavir users. Compared with nonusers, oral antiviral users were older, had more comorbidities, and had lower complete vaccination rates. The mean (SD) baseline Ct value was slightly higher in nirmatrelvir-ritonavir users (22.2 [6.0]) than nonusers (21.0 [5.4]) and molnupiravir users (20.9 [5.4]) (P = .04). Viral rebound occurred in 68 nonusers (0.6%), 2 nirmatrelvir-ritonavir users (1.0%), and 6 molnupiravir users (0.8%). Among 76 patients with viral rebound, 12 of 68 nonusers, 1 of 6 molnupiravir users, and neither of the nirmatrelvir-ritonavir users died of COVID-19.Conclusions and RelevanceIn this cohort study, viral rebound was uncommon in patients taking molnupiravir or nirmatrelvir-ritonavir and was not associated with increased risk of mortality. Given these findings, novel oral antivirals should be considered as a treatment for more patients with COVID-19 in the early phase of the infection.