Incidence trends of acute viral hepatitis caused by four viral etiologies between 1990 and 2019 at the global, regional and national levels.

BACKGROUND: Hepatitis is a major public health challenge and a leading cause of death worldwide. We aimed to study the cause-specific incidence and temporal trends of acute viral hepatitis (AVH). METHODS: Data on AVH etiologies were available from the Global Burden of Disease study 2019. Estimated annual percentage change (EAPC) was used to quantify temporal trend in AVH age-standardized incidence rates (ASIRs) by region, sex and aetiology. RESULTS: From 1990 to 2019, the global incidence of AVH increased by 8.02%, from 244 350 063 in 1990 to 263 951 645 in 2019, with an average decreasing ASIR of 0.52% (95% CI -0.58% to -0.45%) annually. The ASIR of AVH due to hepatitis B virus (HBV) decreased, while those of hepatitis A (HAV), hepatitis C (HCV) and hepatitis E (HEV) remained stable, with EAPCs (95% CI) of -1.47 (-1.58 to -1.36), 0 (-0.09 to 0.09), -0.35 (-0.83 to -0.13), and -0.16 (-0.41 to 0.09) respectively. Although the number of new AVH cases increased in the low sociodemographic index (SDI), low-middle SDI regions, the ASIRs decreased in all five SDI regions. Globally, HAV and HBV are the leading causes of acute hepatitis. The EAPC is significantly associated with a baseline ASIR of less than 5500 per 100 000 population (ρ = -0.44), and with the 2019 human development index (HDI) (ρ = 0.16) for AVH. CONCLUSIONS: Although the ASIR of AVH showed a generally decreasing trend, the burden of AVH remains a major public health challenge globally. The findings may be helpful for policymakers in establishing appropriate policies to reduce the viral hepatitis burden.

The burden of primary liver cancer caused by specific etiologies from 1990 to 2019 at the global, regional, and national levels.

BACKGROUND: Liver cancer is one of the most common cancers worldwide. We aimed to report the burden of liver cancer at the global, regional, and national levels in 204 countries from 1990 to 2019, stratified by etiology, sex, age, and sociodemographic index (SDI). METHODS: Data of mortality, incidence, and disability-adjusted life years (DALYs) of liver cancer and its etiology were available from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2019. The trends in the liver cancer burden were assessed by the annual percentage change. All estimates are presented as numbers and age-standardized rates (ASRs) per 100,000 population, with uncertainty intervals (UIs). RESULTS: Globally, 484,577 (95% UI 444,091-525,798) mortalities, 534,364 (486,550-588,639) incident cases, and 12,528,422 (11,400,671-13,687,675) disability-adjusted life years (DALYs) due to liver cancer occurred in 2019. The ASRs were 5.95 (5.44-6.44), 6.51 (5.95-7.16), and 151.08 (137.53-164.8) per 100,000 population for the mortalities, incidences, and DALYs, respectively. From 1990 to 2019, the numbers increased, whereas the ASRs decreased. Hepatitis B and Hepatitis C are the major causes of liver cancer mortality. The liver cancer mortality in 2019 increased with age, peaking at 65-69 and 70-74 age group in males and females, respectively, and the number was higher in males than in females. Generally, there were nonlinear associations between the ASR and SDIs values at the regional and national levels. China had the highest numbers of mortalities, incident cases, and DALYs, whereas Mongolia has the highest ASR in 2019. CONCLUSION: Liver cancer remains a major public health issue worldwide, but etiological and geographical variations exist. It is necessary to increase awareness of the population regarding liver cancer, its etiologies and the importance of early detection, and diagnosis and treatment.

Long non-coding RNA HOTAIR promotes hepatocellular carcinoma progression by regulating miR-526b-3p/DHX33 axis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common human cancers. Long non-coding RNAs (lncRNAs) play pivotal roles in progression of various cancers, including HCC. OBJECTIVE: We aimed to explore the exact role and underlying mechanism of lncRNA HOX transcript antisense intergenic RNA (HOTAIR) in HCC. METHODS: Quantitative real time polymerase chain reaction (qRT-PCR) was carried out to determine the levels of HOTAIR, DEAH-box helicase 33 (DHX33) and miR-526b-3p. Western blot assay was used to detect the protein level of DHX33. Besides, cell proliferation and apoptosis were assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and flow cytometry analysis, respectively. Cell migration and invasion were detected by transwell assay. The interaction between miR-526b-3p and HOTAIR or DHX33 was predicted by starbase and confirmed by the dual-luciferase reporter assay. Murine xenograft model was established through injecting Huh7 cells transfected with sh-NC or sh-HOTAIR. RESULTS: The levels of HOTAIR and DHX33 were increased in HCC tissues and cells. Knockdown of either HOTAIR or DHX33 suppressed proliferation, migration and invasion but increased apoptosis in HCC cells. Moreover, DHX33 overexpression reversed the suppressive effect of HOTAIR knockdown on progression of HCC cells. Interestingly, miR-526b-3p could directly bind to HOTAIR, and DHX33 was a direct target of miR-526b-3p. Additionally, interference of HOTAIR restrained the tumor growth by upregulating miR-526b-3p and downregulating DHX33 in vivo. CONCLUSIONS: HOTAIR knockdown suppressed cell proliferation, migration and invasion, and promoted apoptosis via regulating miR-526b-3p/DHX33 axis in HCC cells, providing a potential avenue for treatment of HCC.

The global, regional, and national burden of gallbladder and biliary tract cancer and its attributable risk factors in 195 countries and territories, 1990 to 2017: A systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: The global burden of gallbladder and biliary tract cancer (GBTC) is increasing. A comprehensive evaluation of the burden is crucial to improve strategies for GBTC prevention and treatment. METHODS: The incidence rates, mortality, and disability-adjusted life years (DALYs) of GBTC from 1990 to 2017 were extracted from the Global Burden of Diseases Study (GBD) 2017. Estimated annual percent changes (EAPCs) were calculated to quantify GBTC trends during the study period. RESULTS: Globally, there were 210,878 new cases, 173,974 deaths, and 3,483,046 DALYs because of GBTC in 2017. GBTC incidence increased by 76%, mortality increased by 65%, and DALYs increased by 52% from 1990 to 2017. In addition, relatively higher Socio-Demographic Index regions had greater incidence and death rates but greatly decreased age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR). At the national level, Chile had the highest ASIR (10.38 per 100,000 population) and the highest ASDR (10.43 per 100,000 population) in 2017. The largest increases in ASIR (EAPC, 3.38) and ASDR (EAPC, 3.39) were observed in Georgia. Nonlinear associations were observed between the ASDR, the Socio-Demographic Index, and DALYs at the 21 GBD regional levels and at the national level. The proportions of GBTC age-standardized deaths and DALYs attributable to high body mass index were 15.4% and 16%, respectively. CONCLUSIONS: GBTC remains a major health burden worldwide. These findings are expected to prompt policymakers to establish a cost-effective method for the early diagnosis, prevention, and treatment of GBTC, reducing its modifiable risk factors and reversing its increasing trends. LAY SUMMARY: Although the rates of age-standardized incidence, death, and disability-adjusted life-years for gallbladder and biliary tract cancer decreased from 1990 to 2017, the numbers of these measures increased. Nonlinear associations existed between the age-standardized death rate, the Socio-Demographic Index, and disability-adjusted life-years at the 21 regional and national levels in the Global Burden of Disease Study.

Efficacy and safety of gemcitabine-capecitabine combination therapy for pancreatic cancer: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Recent randomized controlled trials revealed the combination of gemcitabine and capecitabine (GemCap) regime shows promising efficacy in pancreatic cancer patients. Here, we conducted a meta-analysis to compare the efficacy and safety of gemcitabine (Gem) with GemCap for pancreatic cancer. METHODS: The database of MEDLINE (PubMed), EMBASE, Cochrane Central Controster of Controlled Trials, Web of Science was searched for relevant randomized controlled trials before 8 April, 2020. The outcomes were overall survival (OS), 12-month survival rate, progress free survival (PFS), partial response rate (PRR), objective response rate (ORR), and Grade 3/4 toxicities. RESULTS: Five randomized controlled trials involving 1879 patients were included in this study. The results showed that GemCap significantly improves the OS (hazard ratio = 1.15, 95% CI: 1.037-1.276, P = .008), PFS (hazard ratio = 1.211, 95% CI 1.09-1.344, P = 0), PRR (relative risk (RR) = 0.649, 95% CI 0.488-0.862, P = .003), ORR (RR = 0.605, 95% CI 0.458-0.799, P = 0), and the overall toxicity (RR = 0.708, 95% CI 0.620-0.808, P = .000) compared to Gem alone. However, no significant difference was found in 12-month survival. CONCLUSIONS: Despite a higher incidence of Grade 3/4 toxicity, GemCap was associated with better outcomes of OS, PFS, PRR, ORR, as compared with Gem, which is likely to become a promising therapy for pancreatic cancer.

The global, regional, and national burden of pancreatitis in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Pancreatitis is a critical public health problem, and the burden of pancreatitis is increasing. We report the rates and trends of the prevalence, incidence, and years lived with disability (YLDs) for pancreatitis at the global, regional, and national levels in 195 countries and territories from 1990 to 2017, stratified by sex, age, and sociodemographic index (SDI). METHODS: Data on pancreatitis were available from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Numbers and age-standardized prevalence, incidence, and YLDs' rates per 100,000 population were estimated through a systematic analysis of modeled data from the 2017 GBD study. Both acute and chronic pancreatitis are being modeled separately in the GBD 2017; however, our data show acute and chronic pancreatitis together. Estimates were reported with uncertainty intervals (UIs). RESULTS: Globally, in 2017, the age-standardized rates were 76.2 (95% UIs 68.9 to 83.4), 20.6 (19.2 to 22.1), and 4.5 (2.3 to 7.6) per 100,000 population for the point prevalence, incidence, and YLDs, respectively. From 1990 to 2017, the percent changes in the age-standardized prevalence and YLDs rates increased, whereas the age-standardized incidence rate decreased. The global prevalence increased with age up to 60-64 years and 44-49 years in females and males, respectively, and then decreased, with no significant difference between females and males. The global prevalence rate increased with age, peaking in the 95+ age group, with no difference between sexes. Generally, positive correlation between age-standardized YLDs and SDIs at the regional and national levels was observed. Slovakia (297.7 [273.4 to 325.3]), Belgium (274.3 [242.6 to 306.5]), and Poland (266.7 [248.2 to 284.4]) had the highest age-standardized prevalence rates in 2017. Taiwan (Province of China) (104.2% [94.8 to 115.2%]), Maldives (72.4% [66.5 to 79.2%]), and Iceland (64.8% [57.2 to 72.9%]) had the largest increases in age-standardized prevalence rates from 1990 to 2017. CONCLUSIONS: Pancreatitis is a major public health issue worldwide. The age-standardized prevalence and YLDs rates increased, but the age-standardized incidence rate decreased from 1990 to 2017. Improving the quality of pancreatitis health data in all regions and countries is strongly recommended for better monitoring the burden of pancreatitis.

Prognostic Significance of Preoperative Gamma-Glutamyltransferase to Alkaline Phosphatase Ratio in Hepatocellular Carcinoma Patients with Curative Liver Resection: A Retrospective Cohort Study.

PURPOSE: Gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) were involved in the development and progression of cancers. This study aimed to evaluate the prognostic value of a preoperative GGT:ALP ratio (GAR) in hepatocellular carcinoma (HCC) patients with curative liver resection. PATIENTS AND METHODS: A total of 380 HCC patients underwent curative liver resection before December 2017 and from January to December 2018 were included and stratified into training set and validation set, respectively. Prediction accuracy was evaluated by the area under the receiver operating characteristic curve (AUC). Factors determined to be significant for overall survival (OS) and tumor-free survival (TFS) by using Cox regression analysis. The Kaplan-Meier method and Log rank test were utilized for survival analysis. RESULTS: The AUC of GAR was 0.70 (P < 0.001). An optimal cut-off value of 0.91 yielded a sensitivity of 78.1% and a specificity of 60.4% for GAR (P < 0.001), which stratified the HCC patients into high-risk (>0.91) and low-risk (≤ 0.91) groups. Time-dependent ROC revealed that the AUCs for 1-, 3-, and 5-year OS predictions for GAR were 0.60, 0.69 and 0.62, respectively. In addition, GAR was identified as an independent risk factor for OS and TFS both in training and validation cohort by univariate and multivariate Cox regression analysis, as well as a good prognostic indicator for patients with Barcelona Clinic Liver Cancer stage C or without vascular invasion. Notably, the AUC of the GAR for survival was better than several potential prognostic indices (P < 0.05). CONCLUSION: We identified the GAR as a prognostic indicator in two independent cohorts of HCC patients with curative liver resection. The patients with decreased GAR score were significantly associated with better OS and TFS.