Background: Liver disease causes over two million deaths annually worldwide, comprising approximately 4% of all global fatalities. We aimed to analyze liver disease-related mortality trends from 1990 to 2021 using the World Health Organization (WHO) Mortality Database and forecast global liver disease-related mortality rates up to 2050. Methods: This study examined age-standardized liver disease-related death rates from 1990 to 2021, employing data from the WHO Mortality Database across 112 countries across five continents. The rates over time were calculated using a locally weighted scatter plot smoother curve, with weights assigned based on the population of each country. Furthermore, this study projected liver disease-related mortality rates up to 2050 using a Bayesian age-periodcohort (BAPC) model. Additionally, a decomposition analysis was conducted to discern influencing factors such as population growth, aging, and epidemiological changes. Results: The estimated global age-standardized liver disease-related mortality rates surged significantly from 1990 to 2021 across 112 countries, rising from 103.4 deaths per 1,000,000 people (95% confidence interval [CI], 88.16, 118.74) in 1990 to 173.0 deaths per 1,000,000 people (95% CI, 155.15, 190.95) in 2021. This upward trend was particularly pronounced in low- and middle-income countries, in Africa, and in populations aged 65 years and older.Moreover, age-standardized liver disease-related mortality rates were correlated with a lower Human Development Index (P < 0.001) and sociodemographic index (P = 0.001). According to the BAPC model, the projected trend indicated a sustained and substantial decline in liver disease-related mortality rates, with an estimated decrease from 185.08 deaths per 1,000,000 people (95% CI, 179.79, 190.63) in 2021 to 156.29 (112.32, 214.77) in 2050. From 1990 to 2021, age-standardized liver disease-related deaths surged primarily due to epidemiological changes, whereas from 1990 to 2050, the impact of population aging and growth became the primary contributing factors to the overall increase. Conclusion Global age-standardized liver disease-related mortality has increased significantly and continues to emerge as a crucial global public health issue. Further investigation into liver disease-related mortality rates in Africa is needed, and updating policies is necessary to effectively manage the global burden of liver disease.

Background: Liver disease causes over two million deaths annually worldwide, comprising approximately 4% of all global fatalities. We aimed to analyze liver disease-related mortality trends from 1990 to 2021 using the World Health Organization (WHO) Mortality Database and forecast global liver disease-related mortality rates up to 2050. Methods: This study examined age-standardized liver disease-related death rates from 1990 to 2021, employing data from the WHO Mortality Database across 112 countries across five continents. The rates over time were calculated using a locally weighted scatter plot smoother curve, with weights assigned based on the population of each country. Furthermore, this study projected liver disease-related mortality rates up to 2050 using a Bayesian age-periodcohort (BAPC) model. Additionally, a decomposition analysis was conducted to discern influencing factors such as population growth, aging, and epidemiological changes. Results: The estimated global age-standardized liver disease-related mortality rates surged significantly from 1990 to 2021 across 112 countries, rising from 103.4 deaths per 1,000,000 people (95% confidence interval [CI], 88.16, 118.74) in 1990 to 173.0 deaths per 1,000,000 people (95% CI, 155.15, 190.95) in 2021. This upward trend was particularly pronounced in low- and middle-income countries, in Africa, and in populations aged 65 years and older.Moreover, age-standardized liver disease-related mortality rates were correlated with a lower Human Development Index (P < 0.001) and sociodemographic index (P = 0.001). According to the BAPC model, the projected trend indicated a sustained and substantial decline in liver disease-related mortality rates, with an estimated decrease from 185.08 deaths per 1,000,000 people (95% CI, 179.79, 190.63) in 2021 to 156.29 (112.32, 214.77) in 2050. From 1990 to 2021, age-standardized liver disease-related deaths surged primarily due to epidemiological changes, whereas from 1990 to 2050, the impact of population aging and growth became the primary contributing factors to the overall increase. Conclusion Global age-standardized liver disease-related mortality has increased significantly and continues to emerge as a crucial global public health issue. Further investigation into liver disease-related mortality rates in Africa is needed, and updating policies is necessary to effectively manage the global burden of liver disease.

Background: Liver disease causes over two million deaths annually worldwide, comprising approximately 4% of all global fatalities. We aimed to analyze liver disease-related mortality trends from 1990 to 2021 using the World Health Organization (WHO) Mortality Database and forecast global liver disease-related mortality rates up to 2050. Methods: This study examined age-standardized liver disease-related death rates from 1990 to 2021, employing data from the WHO Mortality Database across 112 countries across five continents. The rates over time were calculated using a locally weighted scatter plot smoother curve, with weights assigned based on the population of each country. Furthermore, this study projected liver disease-related mortality rates up to 2050 using a Bayesian age-periodcohort (BAPC) model. Additionally, a decomposition analysis was conducted to discern influencing factors such as population growth, aging, and epidemiological changes. Results: The estimated global age-standardized liver disease-related mortality rates surged significantly from 1990 to 2021 across 112 countries, rising from 103.4 deaths per 1,000,000 people (95% confidence interval [CI], 88.16, 118.74) in 1990 to 173.0 deaths per 1,000,000 people (95% CI, 155.15, 190.95) in 2021. This upward trend was particularly pronounced in low- and middle-income countries, in Africa, and in populations aged 65 years and older.Moreover, age-standardized liver disease-related mortality rates were correlated with a lower Human Development Index (P < 0.001) and sociodemographic index (P = 0.001). According to the BAPC model, the projected trend indicated a sustained and substantial decline in liver disease-related mortality rates, with an estimated decrease from 185.08 deaths per 1,000,000 people (95% CI, 179.79, 190.63) in 2021 to 156.29 (112.32, 214.77) in 2050. From 1990 to 2021, age-standardized liver disease-related deaths surged primarily due to epidemiological changes, whereas from 1990 to 2050, the impact of population aging and growth became the primary contributing factors to the overall increase. Conclusion Global age-standardized liver disease-related mortality has increased significantly and continues to emerge as a crucial global public health issue. Further investigation into liver disease-related mortality rates in Africa is needed, and updating policies is necessary to effectively manage the global burden of liver disease.

Background: Liver disease causes over two million deaths annually worldwide, comprising approximately 4% of all global fatalities. We aimed to analyze liver disease-related mortality trends from 1990 to 2021 using the World Health Organization (WHO) Mortality Database and forecast global liver disease-related mortality rates up to 2050. Methods: This study examined age-standardized liver disease-related death rates from 1990 to 2021, employing data from the WHO Mortality Database across 112 countries across five continents. The rates over time were calculated using a locally weighted scatter plot smoother curve, with weights assigned based on the population of each country. Furthermore, this study projected liver disease-related mortality rates up to 2050 using a Bayesian age-periodcohort (BAPC) model. Additionally, a decomposition analysis was conducted to discern influencing factors such as population growth, aging, and epidemiological changes. Results: The estimated global age-standardized liver disease-related mortality rates surged significantly from 1990 to 2021 across 112 countries, rising from 103.4 deaths per 1,000,000 people (95% confidence interval [CI], 88.16, 118.74) in 1990 to 173.0 deaths per 1,000,000 people (95% CI, 155.15, 190.95) in 2021. This upward trend was particularly pronounced in low- and middle-income countries, in Africa, and in populations aged 65 years and older.Moreover, age-standardized liver disease-related mortality rates were correlated with a lower Human Development Index (P < 0.001) and sociodemographic index (P = 0.001). According to the BAPC model, the projected trend indicated a sustained and substantial decline in liver disease-related mortality rates, with an estimated decrease from 185.08 deaths per 1,000,000 people (95% CI, 179.79, 190.63) in 2021 to 156.29 (112.32, 214.77) in 2050. From 1990 to 2021, age-standardized liver disease-related deaths surged primarily due to epidemiological changes, whereas from 1990 to 2050, the impact of population aging and growth became the primary contributing factors to the overall increase. Conclusion Global age-standardized liver disease-related mortality has increased significantly and continues to emerge as a crucial global public health issue. Further investigation into liver disease-related mortality rates in Africa is needed, and updating policies is necessary to effectively manage the global burden of liver disease.

Background/Aims: Atezolizumab plus bevacizumab (ATE+BEV) therapy has become the recommended first-line therapy for patients with unresectable hepatocellular carcinoma (HCC) because of favorable treatment responses. However, there is a lack of data on sequential regimens after ATE+BEV treatment failure. We aimed to investigate the clinical outcomes of patients with advanced HCC who received subsequent systemic therapy for disease progression after ATE+BEV. Methods: This multicenter, retrospective study included patients who started second-line systemic treatment with sorafenib or lenvatinib after HCC progressed on ATE+BEV between August 2019 and December 2022. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.). Clinical features of the two groups were balanced through propensity score (PS) matching. Results: This study enrolled 126 patients, 40 (31.7%) in the lenvatinib group, and 86 (68.3%) in the sorafenib group. The median age was 63 years, and males were predominant (88.1%). In PS-matched cohorts (36 patients in each group), the objective response rate was similar between the lenvatinib- and sorafenib-treated groups (5.6% vs. 8.3%; P=0.643), but the disease control rate was superior in the lenvatinib group (66.7% vs. 22.2%; P<0.001). Despite the superior progression- free survival (PFS) in the lenvatinib group (3.5 vs. 1.8 months, P=0.001), the overall survival (OS, 10.3 vs. 7.5 months, P=0.353) did not differ between the two PS-matched treatment groups. Conclusions In second-line therapy for unresectable HCC after ATE+BEV failure, lenvatinib showed better PFS and comparable OS to sorafenib in a real-world setting. Future studies with larger sample sizes and longer follow-ups are needed to optimize second-line treatment.

Background/Aims: Considering emerging evidence on long COVID, comprehensive analyses of the post-acute complications of SARS-CoV-2 infection in the gastrointestinal and hepatobiliary systems are needed. We aimed to investigate the impact of COVID-19 on the long-term risk of gastrointestinal and hepatobiliary diseases and other digestive abnormalities. Methods: We used three large-scale population-based cohorts: the Korean cohort (discovery cohort), the Japanese cohort (validation cohort-A), and the UK Biobank (validation cohort-B). A total of 10,027,506 Korean, 12,218,680 Japanese, and 468,617 UK patients aged ≥20 years who had SARS-CoV-2 infection between 2020 and 2021 were matched to non-infected controls. Seventeen gastrointestinal and eight hepatobiliary outcomes as well as nine other digestive abnormalities following SARS-CoV-2 infection were identified and compared with controls. Results: The discovery cohort revealed heightened risks of gastrointestinal diseases (HR 1.15; 95% CI 1.08–1.22), hepatobiliary diseases (HR 1.30; 95% CI 1.09–1.55), and other digestive abnormalities (HR 1.05; 95% CI 1.01–1.10) beyond the first 30 days of infection, after exposure-driven propensity score-matching. The risk was pronounced according to the COVID-19 severity. The SARS-CoV-2 vaccination was found to lower the risk of gastrointestinal diseases but did not affect hepatobiliary diseases and other digestive disorders. The results derived from validation cohorts were consistent. The risk profile was most pronounced during the initial 3 months; however, it persisted for >6 months in validation cohorts, but not in the discovery cohort. Conclusions The incidence of gastrointestinal disease, hepatobiliary disease, and other digestive abnormalities increased in patients with SARS-CoV-2 infection during the post-acute phase.

Objectives: This study aimed to describe the characteristics and risk factors for severe disease in pregnant women infected with coronavirus disease 2019 (COVID-19) from the early days of the COVID-19 epidemic in Korea to the predominant period of the Delta variant. Methods: A retrospective cohort study was conducted among pregnant women diagnosed with COVID-19 between February 2020 and December 2021. Logistic regression analysis was performed to compare severe and mild cases after adjusting for pregnant women’s age, nationality, infection route, outbreak area, infection period, symptoms, underlying disease, smoking status, trimester, and COVID-19 vaccination status. Results: In total, 2,233 pregnant women were diagnosed with COVID-19 by December 2021. Among these, 96.7% had mild symptoms, 3.3% had severe symptoms, and 0.04% died. The risk factors for severe disease in pregnant women with confirmed COVID-19 were being in the age group of 35 to 45 years, having hyperlipidemia, being in the second or third trimester of pregnancy at the time of COVID-19 diagnosis, being infected during the Delta-predominant period, and having a fever (≥38 °C) at diagnosis. Furthermore, 47.1% of patients in the mild group and 84.9% of patients in the severe group had 3 or more risk factors. Conclusion Pregnant women with COVID-19 mainly experienced mild symptoms, but those with risk factors were at a higher risk of developing severe symptoms. Therefore, treatment and follow-up management should be thoroughly implemented.