A challenging alfa-fetoprotein in a cirrhotic patient.

A 57-year-old Italian man was admitted to our Hospital for investigation of a progressively raising alfa-fetoprotein (AFP) on the background of chronic hepatitis B infection. At abdominal imaging,liver morphology was suspected for advanced fibrosis but without any focal lesion. Clinical and ultrasonographic examinations were negative for testicular masses. When the patient was screened for gastroesophageal varices, upper intestinal endoscopy did not show signs of portal hypertension, while it revealed a gastric lesion which was histologically characterized as hepatoid adenocarcinoma of the stomach (HAS), with strong immunohistochemical positivity for AFP. The patient underwent subtotal gastrectomy and AFP fell within the normal range. This is a very rare case in which AFP-producing gastric cancer (AFPPGC), in the form of HAS, presented in a patient with chronic liver disease. Physicians should be particularly aware of AFPPGC when following patients with liver disorders due to the common use of AFP in this setting.

The role of ribavirin in the combination therapy of hepatitis C virus infection.

Ribavirin is a very broad-spectrum anti-viral agent used clinically to treat infections by Lassa fever virus, respiratory syncytial virus (RSV) and, in combination with Interferon-alpha (IFN-alpha), hepatitis C virus (HCV). Although it was originally synthesized over 30 years ago, the precise mechanisms of its therapeutic activities are still not fully understood. Ribavirin was shown to possess both direct and indirect action mechanisms against several DNA and RNA viruses. These include direct inhibition of viral RNA-dependent RNA polymerases, inhibition of the host inosine monophosphate dehydrogenase, modulation of the host immune response and inhibition of viral capping enzymes. More recently, ribavirin was demonstrated to be able to act as an RNA virus mutagen, increasing mutations in the RNA virus genome and reducing their infectivity. Still the real challenge is to identify which of its biological properties is responsible for the observed clinical efficacy on specific infections. Under this aspect, renewed interest results from its synergistic enhancement of interferon-alpha (IFN-alpha) therapy, which could open the way to develop more powerful anti-HCV compounds. This work purpose is to provide a broad overview of all the recognized ribavirin action mechanisms against HCV, which can possibly also explain its synergistic behavior with IFN-alpha. An overview on the corresponding HCV treatment clinical observations is also provided in the second part of this work.