Hepatitis Rebound after Infection with Yellow Fever Virus.

In 2018, yellow fever with hepatitis was diagnosed for 2 unvaccinated travelers returning to France from Brazil. Hepatitis persisted for >6 months; liver enzyme levels again increased 2 months after disease onset with no detection of yellow fever virus RNA or other pathogens. Persistent hepatitis with hepatic cytolysis rebound probably resulted from immune response.

Natural course of persistent hepatitis B virus infection in hepatitis B e antigen-positive and hepatitis B e antigen-negative cohorts in Japan based on the Markov model.

This population-based study examined the natural course of hepatitis B e antigen (HBeAg)-positive or HBeAg-negative persistent hepatitis B virus (HBV) infection, adjusted by age and liver disease states using a Markov model. Using 12 417 person-years data (n = 862), annual transition probabilities were estimated, and age-adjusted cumulative incidence and natural history of persistent HBV infection were simulated in both sexes of groups 1 (HBeAg-negative status with HBV DNA level <4.0 log IU/mL at entry) and 2 (persistent HBeAg-positive status throughout the study). In group 1, 15.26% of 30-years old men with chronic hepatitis (CH) were expected to remain in the same state at age 65 years, 28.32% subsided into an hepatitis B surface antigen (HBsAg)-negative state, and 13.20% developed hepatocellular carcinoma (HCC). The expectations for 40-years old men in group 1 were 21.43%, 19.86%, and 15.04%, respectively. The expectations for 30 years women in group 1 were 30.57%, 21.15%, and 4.08%, respectively. These results suggest that HBeAg positivity caused a higher risk of HCC onset in persistent HBV infection after adjustments for age, sex, and liver disease state. HCC was likely to develop, but unlikely to subside into HBsAg clearance, remaining in a CH state with aging, regardless of HBeAg state. Furthermore, both HCC development and HBsAg clearance occurred more frequently in men than in women, irrespective of HBeAg status.

Hepatitis B Virus Envelope Antigen and Hepatitis B Virus Surface Antigen Both Contribute to the Innate Immune Response During Persistent Hepatitis B Virus Infection.

This study aimed to investigate the changes of toll-like receptor 4 (TLR4), proinflammatory cytokine expression, hepatitis B virus surface antigen (HBsAg), and hepatitis B virus envelope antigen (HBeAg) expression as well as innate immune cell percentages in a mouse model of persistent hepatitis B virus (HBV) infection to better understand the innate immune response. Mouse models of persistent HBV infection, HBsAg expression, and HBeAg expression were developed using high-pressure tail-vein injection of recombinant adeno-associated viruses. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum proinflammatory cytokine levels. Immunohistochemistry and western blot assays were used to detect TLR4 expression. Flow cytometric analysis was used to assess the percentage of innate immune cells in the whole blood. Persistent HBV infection, HBsAg expression, and HBeAg expression each significantly decreased the expression of TLR4. Persistent HBV infection significantly increased the percentages of T cells and monocytes, whereas it decreased the percentage of natural killer (NK) cells. Persistent HBeAg expression also decreased the percentage of NK cells, whereas persistent HBsAg expression increased the percentage of NK cells. Both persistent HBsAg and HBeAg expression increased the percentage of monocytes. However, both persistent HBsAg and HBeAg expression decreased the percentage of T cells. HBV as well as HBsAg and HBeAg showed similar effects on the expression of TLR4 and proinflammatory cytokines as well as the percentage of monocytes. Persistent HBV infection increased the percentage of T cells and decreased the percentage of NK cells, whereas only persistent HBeAg expression contributed to a decreased percentage of NK cells.

Tremella polysaccharide: The molecular mechanisms of its drug action.

Tremella fuciformis is an edible medicinal mushroom well known as "Yiner" or "Baimuer" in China and has been used as a Chinese herb for many years. T. fuciformis polysaccharide (TFPS) has been identified as a major bioactive component. Different experimental conditions can obtain different TFPS fractions, which makes TFPS a mixture of different polysaccharides with the molecular weight ranging from 5.82×105Da to 3.74×106Da. The monosaccharides detected in TFPS include mannose, xylose, fucose, glucuronic acid, glucose, and galactose. One characterized TFPS chemical structure consists of a linear (1→3)-linked α-d-mannose backbone with highly branched ß-d-xylose, α-d-fucose and ß-d-glucuronic acid as the side chains. TFPS shows multiple physiological and healthy promoting effects including immunomodulation, antitumor, anti-oxidation, anti-aging, hypoglycemic, hypolipidemic, neuroprotection, and other effects. As a result, "Tremella Polysaccharide Enteric-coated Capsules" was approved by Chinese Food and Drug Administration (SFDA) in 2002 for treating cancer patients with leukopenia induced by chemotherapy and radiotherapy. It is also used as adjuvant drug for treating chronic persistent hepatitis and chronic active hepatitis. In this chapter, 113 independent studies involving in biochemical, pharmacological, and clinical studies of TFPS during the past 46 years (1972-2018) on the base of PubMed, CNKI (China National Knowledge Infrastructure) and Wanfang database search are summarized. TFPS shows efficacy for all types of human diseases in the reported clinical studies. The structure, molecular mechanisms of the immunomodulation, antitumor, anti-oxidation, anti-aging, hypoglycemic, hypolipidemic, preclinical and clinical efficacy are discussed to provide a general picture of TFPS as a clinically used drug.