The hepatitis B virus (HBV), discovered in 1966, infects more than 350 million people worldwide.1 Hepatitis B is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma, accounting for 1 million deaths annually. Knowledge of the intricacies of viral infection and of the molecular biology of this fascinating virus has led to the successful development of a vaccine and to treatment sometimes capable of eradicating chronic infection. This review addresses many aspects of HBV infection, including the role of the immune system in determining the outcome of clinical infection, recent developments in molecular studies of the virus, and new . . .

Hepatitis B virus infection.

Drug-induced hepatotoxicity.

In vitro transcribed (IVT) mRNA has recently come into focus as a potential new drug class to deliver genetic information. Such synthetic mRNA can be engineered to transiently express proteins by structurally resembling natural mRNA. Advances in addressing the inherent challenges of this drug class, particularly related to controlling the translational efficacy and immunogenicity of the IVTmRNA, provide the basis for a broad range of potential applications. mRNA-based cancer immunotherapies and infectious disease vaccines have entered clinical development. Meanwhile, emerging novel approaches include in vivo delivery of IVT mRNA to replace or supplement proteins, IVT mRNA-based generation of pluripotent stem cells and genome engineering using IVT mRNA-encoded designer nucleases. This Review provides a comprehensive overview of the current state of mRNA-based drug technologies and their applications, and discusses the key challenges and opportunities in developing these into a new class of drugs.

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mRNA-based therapeutics — developing a new class of drugs

Adverse effects of antiretroviral therapy

Chronic viral hepatitis is the principal cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma in the world and now ranks as the chief reason for liver transplantation in adults.1–3 Of the five known hepatitis viruses, three can cause persistent infection and chronic hepatitis: the hepatitis B virus (HBV),4 the hepatitis C virus (HCV),5 and the hepatitis delta (or hepatitis D) virus (HDV).6 The other two viruses, hepatitis A and hepatitis E, cause acute, self-limited disease only. Recent findings suggest that there is an additional form of viral hepatitis to which two recently discovered human viruses — the hepatitis . . .

The treatment of chronic viral hepatitis

Background We describe severe and unexpected multisystem toxicity that occurred during a study of the antiviral nucleoside analogue fialuridine (1-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)-5-iodouracil, or FIAU) as therapy for chronic hepatitis B virus infection. Methods Fifteen patients with chronic hepatitis B were randomly assigned to receive fialuridine at a dose of either 0.10 or 0.25 mg per kilogram of body weight per day for 24 weeks and were monitored every 1 to 2 weeks by means of a physical examination, blood tests, and testing for hepatitis B virus markers. Results During the 13th week lactic acidosis and liver failure suddenly developed in one patient. The study was terminated on an emergency basis, and all treatment with fialuridine was discontinued. Seven patients were found to have severe hepatotoxicity, with progressive lactic acidosis, worsening jaundice, and deteriorating hepatic synthetic function despite the discontinuation of fialuridine. Three other patients had mild hepatotoxicity. Se...

https://www.nejm.org/doi/pdf/10.1056/NEJM199510263331702

Carlos Luciano

Papers

Hepatic failure and lactic acidosis due to fialuridine (fiau), an investigational nucleoside analogue for chronic hepatitis b