Faculty

Ni Yen Hsuen

Management of childhood Hepatitis B infection: State of the art approach

Though different countries implement different HBV universal vaccination schedules, most programs consist of 3 doses of HBV vaccines and hepatitis B immunoglobulin (HBIG) in high risk groups. The first dose and the HBIG should be administered as early as possible after birth. Almost all the programs resulted in a good control of HBV infection. Taiwan’s world’s first nationwide hepatitis B virus (HBV) universal vaccination program for infants is a good example of the successful vaccination to prevent chronic HBV infection and its subsequent cancer. The prevalence of hepatitis B surface antigen (HBsAg) carriers declined from 9.8% to 0.5% in children in Taipei City after 35 years of universal vaccination. In line with the decrease of chronic HBV infection, the incidence of pediatric hepatocellular carcinoma (HCC), which is related to chronic HBV infection and cirrhosis, also decreased. Up to 2000, the incidence of HCC per 100,000 children declined from 0.54 to 0.20 in Taiwan. We expect the universal vaccination program’s anti-cancer effect certainly will extend to adults. Despite of the success of hepatitis B immunization, childhood chronic HBV infection and HCC have not been eliminated yet. Among those HBsAg carriers born after the vaccination program, nearly all of their mothers were positive for HBsAg. The importance of maternal transmission in the pathogenesis of chronic hepatitis B infection cannot be over-emphasized and should be intervened in the post-vaccination era. In addition to the primary prevention by vaccination, the efficacy of secondary and tertiary prevention of HBV-related complications by antiviral therapies was proven recently. In conclusion, to eliminate HBV infection worldwide, we need to achieve the following three tasks: (1) to eradicate all of the infectious sources, (2) to interrupt every transmission route, (3) to immunize every individual. We need to screen out all the infectious pregnant mothers, minimize the risk of perinatal transmission, administer a universal immunization to the neonates, and adequately give the treatment to all vaccine failure cases.

Genetics of Metabolic Dysfunction-Associated Fatty Liver Disease: A New Perspective

Obesity has already become a very important healthy issue worldwide. Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic disease strongly associated with obesity and insulin resistance. It is not known why not every obese subjects develop NAFLD. Different ethnic/racial groups display differences in NAFLD prevalence, indicating genetic factor plays a role. The genetic approaches to dissect the genetic variations have been shown those genetic loci, including PNPLA3, TM6SF2, GCKR, MBOAT7, HSD17B13 may confer susceptibility to NAFLD in children and adults. PNPLA3 may be the most significant gene. Personalized prediction is required to guide risk stratification and treatment. Genetic variations provide novel insights into the NAFLD pathophysiology and may be incorporated into a predictive model for precision medicine in patients with NAFLD. High-throughput technologies, such as gene array and next generation sequencing, can facilitate the translation of genetic testing in the care of children with NAFLD. To date, genetic studies have successfully advanced our understanding in the pathogenesis of NAFLD, but there are still gaps in translating these genetic studies into clinical applications in the real world. Epigenetic alterations interacting with genetic variations further shape an individual’s susceptibility to NAFLD. A comprehensive analysis of personalized genetic and environmental factors may help assess the risk of children with NAFLD and adopt some early intervention by a precision medicine approach. We have shown the dysbiosisi of Desulfovibrio in NAFLD. Modulation of either genetic or microbiologic products can be the future targets of NAFLD treatment(s). Meanwhile, growing evidence indicates NAFLD could begin at birth or even in utero through a liver-specific programming mechanism. The early life period could be a critical window to prevent metabolic disorders in later life.

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