Traditional Chinese medicine invigorating the spleen and kidney promotes HBsAg seroclearance in the mouse model.

Traditional Chinese medicine (TCM) is often used as an adjuvant or alternative therapy for abnormal liver biochemistry or liver fibrosis associated with chronic hepatitis B (CHB). However, the role of TCM in HBsAg seroclearance remains unclear. We aimed at exploring the role and possible mechanisms of TCM in HBsAg seroclearance. Fifteen widely used TCM granules invigorating the spleen and kidneys were screened. C57BL/6J mice were administered daily with TCM granules by gavage for 1 week. The effect of TCM on the M1 polarization of macrophages was measured using a CD86 assay. According to the principles of formulating prescriptions, three single TCM with the most noticeable effect on M1 polarization, accompanied by two other TCM granules, were used to develop a TCM formula. The hepatitis B virus-expressing mouse model was constructed by hydrodynamic injection of the pAAV/HBV1.2 plasmid. Hepatitis B virus-expressing mice were gavaged daily with phosphate-buffered saline (PBS), TCM formula, or Codonopsis Radix, for 1 week. HBsAg, HBeAg, and hepatitis B virus DNA levels were measured. In addition, gut microbiota was profiled using 16S rDNA sequencing. Several TCM granules showed significant effects on M1 polarization. The TCM formula accelerated HBsAg seroclearance compared with the Codonopsis Radix and PBS groups. Intrahepatic M1 polarization, as indicated by flow cytometry and immunohistochemistry, was induced in the TCM formula and Codonopsis Radix groups. The abundance of Alloprevotella significantly increased in the TCM formula and Codonopsis Radix groups. These results demonstrate that the TCM formula for invigorating the spleen and kidney can accelerate HBsAg seroclearance. This effect can be attributed, at least in part, to M1 polarization of intrahepatic macrophages.

Global burden of acute viral hepatitis and its association with socioeconomic development status, 1990-2019.

BACKGROUND & AIMS: Acute viral hepatitis (AVH) represents an important global health problem; however, the progress in understanding AVH is limited because of the priority of combating persistent HBV and HCV infections. Therefore, an improved understanding of the burden of AVH is required to help design strategies for global intervention. METHODS: Data on 4 major AVH types, including acute hepatitis A, B, C, and E, excluding D, were collected by the Global Burden of Disease (GBD) 2019 database. Age-standardized incidence rates and disability-adjusted life year (DALY) rates for AVH were extracted from GBD 2019 and stratified by sex, level of socio-demographic index (SDI), country, and territory. The association between the burden of AVH and socioeconomic development status, as represented by the SDI, was described. RESULTS: In 2019, there was an age-standardized incidence rate of 3,615.9 (95% CI 3,360.5-3,888.3) and an age-standardized DALY rate of 58.0 (47.3-70.0) per 100,000 person-years for the 4 major types of AVH. Among the major AVH types, acute hepatitis A caused the heaviest burden. There was a significant downward trend in age-standardized DALY rates caused by major incidences of AVH between 1990 and 2019. In 2019, regions or countries located in West and East Africa exhibited the highest age-standardized incidence rates of the 4 major AVH types. These rates were stratified by SDI: high SDI and high-middle SDI locations recorded the lowest incidence and DALY rates of AVH, whereas the low-middle SDI and low SDI locations showed the highest burden of AVH. CONCLUSIONS: The socioeconomic development status and burden of AVH are associated. Therefore, the GBD 2019 data should be used by policymakers to guide cost-effective interventions for AVH. LAY SUMMARY: We identified a negative association between socioeconomic development status and the burden of acute viral hepatitis. The lowest burden of acute viral hepatitis was noted for rich countries, whereas the highest burden of acute viral hepatitis was noted for poor countries.

Liver chemistries in severe or non-severe cases of COVID-19: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease (COVID-19) patients exhibit different patterns of liver impairment, according to growing evidence. AIM: In this study, we sought to provide a comprehensive analysis of liver test parameters in patients with severe and non-severe COVID-19. METHODS: We performed a meta-analysis of published liver manifestations and described the liver damage in COVID-19. We searched PubMed, Google Scholar, Embase, Cochrane Library, medRxiv, bioRxiv, and three Chinese electronic databases through April 18, 2020, in accordance with the Preferred Reporting Items for Meta-Analyses. We analyzed pooled data on liver chemistries stratified by COVID-19 severity using a fixed or random-effects model. RESULTS: A meta-analysis of 56 studies, including 11052 patients, found that the pooled mean alanine aminotransferase (ALT) in severe COVID-19 cases was 35.9 IU/L whereas in non-severe COVID-19 cases was 27.3 IU/L. Average aspartate aminotransferase (AST) levels were 44.3 IU/L in severe cases compared to 27.9 IU/L in non-severe cases. In addition, AST levels are often higher than ALT levels regardless of disease severity. The severe cases tended to have a higher gamma-glutamyltransferase level but a lower albumin level than the non-severe cases. CONCLUSION: Severe COVID-19 was more likely to be associated with abnormal liver test results. Monitoring liver chemistry closely can help detect disease progression early.

Socioeconomics and attributable etiology of primary liver cancer, 1990-2019.

BACKGROUND: Primary liver cancer (PLC) is a major contributor to cancer-related deaths. Data on global and country-specific levels and trends of PLC are essential for understanding the effects of this disease and helping policymakers to allocate resources. AIM: To investigate the association between the burden of PLC and socioeconomic development status. METHODS: Cancer mortality and incidence rates were obtained from the Global Burden of Disease (GBD) 2019, and the data were stratified by country and territory, sex, and the Socio-demographic Index (SDI) level. The association between the attributable etiology of PLC and socioeconomic development status, represented using the SDI, was described. The attributable etiology of PLC included hepatitis B, hepatitis C, alcohol use, and nonalcoholic steatohepatitis. The association between the attributable etiology of PLC and SDI was further stratified by sex and geographical location. A confidence analysis was also performed based on bootstrap draw. RESULTS: The age-standardized incidence rate of PLC was 6.5 [95% confidence intervals (CI): 5.9-7.2] per 100000 person-years, which decreased by -27.5% (-37.0 to -16.6) from 1990 to 2019. Several countries located in East Asia, South Asia, West Africa, and North Africa shouldered the heaviest burden of PLC in 2019. In terms of incidence rates, the first leading underlying cause of PLC identified was hepatitis B, followed by hepatitis C, alcohol use, and nonalcoholic steatohepatitis. Regarding stratification using the SDI, the incidence rate of PLC was the highest for high and middle SDI locations. Further, the leading attributable etiologies of PLC were hepatitis B for the middle and high middle SDI locations while hepatitis C and nonalcoholic steatohepatitis for the high SDI locations. CONCLUSION: The pronounced association between socioeconomic development status and PLC burden indicates socioeconomic development status affects attributable etiologies for PLC. GBD 2019 data are valuable for policymakers implementing PLC cost-effective interventions.

Liver Chemistries in Patients With COVID-19 Who Were Discharged Alive or Died: A Meta-analysis.

Although abnormal liver chemistries are linked to a higher risk of coronavirus disease 2019 (COVID-19)-related death, liver manifestations may be diverse and even confusing. Thus, we performed a meta-analysis of published liver manifestations and described the liver damage in patients with COVID-19 who died or discharged alive. We searched PubMed, Google Scholar, medRxiv, bioRxiv, the Cochrane Library, Embase, and three Chinese electronic databases through April 22, 2020. We analyzed pooled data on liver chemistries stratified by the main clinical outcome of COVID-19, using a fixed or random-effects model. In our meta-analysis of 19 studies, which included a total of 4,103 patients, the pooled mean alanine aminotransferase and aspartate aminotransferase levels were, respectively, 31.7 IU/L and 51.0 IU/L in the patients with COVID-19 who died and 27.7 IU/L and 32.9 IU/L in those discharged alive (both P < 0.0001). Compared with the patients discharged alive, those who died tended to have lower albumin levels but longer prothrombin time and higher international normalized ratio. Conclusion: In this meta-analysis, according to the main clinical outcome of COVID-19, we comprehensively describe three patterns of liver impairment related to COVID-19: hepatocellular injury, cholestasis, and hepatocellular disfunction. The patients who died from COVID-19 tended to have different liver chemistries from those discharged alive. Special caution should be given to the patients with a relatively higher index of liver chemistries.