Hereditary cholestasis in childhood and infancy with normal serum gamma‐glutamyltransferase (GGT) activity is linked to several genes. Many patients, however, remain genetically undiagnosed. Defects in myosin VB (MYO5B; encoded by MYO5B) cause microvillus inclusion disease (MVID; MIM251850) with recurrent watery diarrhea. Cholestasis, reported as an atypical presentation in MVID, has been considered a side effect of parenteral alimentation. Here, however, we report on 10 patients who experienced cholestasis associated with biallelic, or suspected biallelic, mutations in MYO5B and who had neither recurrent diarrhea nor received parenteral alimentation. Seven of them are from two study cohorts, together comprising 31 undiagnosed low‐GGT cholestasis patients; 3 are sporadic. Cholestasis in 2 patients was progressive, in 3 recurrent, in 2 transient, and in 3 uncategorized because of insufficient follow‐up. Liver biopsy specimens revealed giant‐cell change of hepatocytes and intralobular cholestasis with abnormal distribution of bile salt export pump (BSEP) at canaliculi, as well as coarse granular dislocation of MYO5B. Mass spectrometry of plasma demonstrated increased total bile acids, primary bile acids, and conjugated bile acids, with decreased free bile acids, similar to changes in BSEP‐deficient patients. Literature review revealed that patients with biallelic mutations predicted to eliminate MYO5B expression were more frequent in typical MVID than in isolated‐cholestasis patients (11 of 38 vs. 0 of 13). Conclusion: MYO5B deficiency may underlie 20% of previously undiagnosed low‐GGT cholestasis. MYO5B deficiency appears to impair targeting of BSEP to the canalicular membrane with hampered bile acid excretion, resulting in a spectrum of cholestasis without diarrhea. (Hepatology 2017;65:1655‐1669).

Transformation of hepatitis B serologic markers in babies born to hepatitis B surface antigen positive mothers

Inactive chronic hepatitis B (CHB) carriers make up the largest group of hepatitis B virus-infected patients, and China bears the largest total CHB burden of any country. We therefore assessed the population health impact and cost-effectiveness of a strategy of lifelong monitoring for inactive CHB and treatment of eligible patients in Shanghai, China. We used a computer simulation model to project health outcomes among a population cohort of CHB based on age-specific prevalence of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and cirrhosis. Using a Markov model we simulated patients' progression through a discrete series of health states, and compared current practice to a monitor and treat (M&T) strategy. We measured lifetime costs and quality-adjusted life years (QALYs) (both discounted at 3% per year), incremental cost-effectiveness ratios (ICERs), and clinical outcomes such as development of hepatocellular carcinoma (HCC). We estimated that there are 1.5 million CHB-infected persons in Shanghai. The M&T strategy costs US$20,730 per patient and yields a discounted QALY of 15.45, which represents incremental costs and health benefits of US$275 and 0.10 QALYs compared to current practice, and an ICER of US$2,996 per QALY gained. In the base case, we estimated that the M&T strategy will reduce HCC and CHB-related mortality by only around 1%. If variables such as adherence to monitoring and treatment could be substantially improved the M&T strategy could reduce HCC by 70% and CHB-related mortality by 83%. Conclusion : Lifelong monitoring of inactive CHB carriers is cost-effective in Shanghai according to typical benchmarks for value for money, but achieving substantial population-level health gains depends on identifying more CHB-infected cases in the population, and increasing rates of treatment, monitoring, and treatment adherence. (Hepatology 2014;60:46–55)