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Lecture - A Global Challenge: Viral Hepatitis A-E and Therapy of Liver Cancer

FML seminar, December 15, 2012: New Developments in Gastroenterology with Focus on Hepatitis


A Global Challenge: Viral Hepatitis A-E and Therapy of Liver Cancer 

Prof. Dr. Dr. h. c. mult. Hubert E. Blum
University Hospital Freiburg, Germany

Among the five hepatitis virus infections A-E, hepatitis A virus (HAV) and hepatitis E virus (HEV) infection are in most cases acute and self-limiting with seroconversion to anti-HAV and anti-HEV, resp., resulting in immunity against reinfection. With respect to HEV infection, there are novel data regarding its epidemiology and natural clinical course: HEV has 4 genotypes with a distinct geographic distribution. Its transmission is not only waterborne and endemic (genotypes 1 and 2), but also sporadic and zoonotic (genotypes 3 and 4) in Western countries and Asia, causing the so-called ‚autochthonous’ hepatitis E. This is transmitted by among others by the consumption of meat from pigs, wild boar and deer. In transplantation medicine it can be transmitted by the transfusion of blood or blood products and then can take a chronic course in the face of the post-transplant immunosuppression.
Different from HAV and HEV infection, hepatitis B virus (HBV) or hepatitis D virus (HDV) and hepatitis C virus (HCV) infections frequently take a chronic course with a significant potential to progress to liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The natural course depends among others on the age at the time of infection, the gender as well as environmental factors, such as coinfections, alcohol use or smoking.
Apart from the prevention of HBV, HDV and HCV infections, patients with chronic hepatitis B and/ or C should be closely monitored and treated in case of progressive disease with the aim to prevent the development of liver cirrhosis and its complications, including HCCs. In patients with liver cirrhosis and HCC curative therapeutic options are limited to liver transplantation or HCC resection. Considering the age of the patient, co-morbidities, limited functional liver reserve and other aspects, treatment is frequently limited to palliative strategies. These include percutaneous interventions (percutaneous ethanol injection, PEI; radiofrequency thermal ablation, RFA), transarterial interventions (transarterial chemoembolization, TACE; selective intraarterial radiation therapy, SIRT), external radiation therapies (intensity modulated radiotherapy, IMRT; photon beam therapy) as well as so-called ‚targeted therapies’ with inhibitors of receptor tyrosine kinases by monoclonal antibodies (mabs), e.g., bevacizumab or cetuximab and/ or with inhibitors of intracelluar tyrosine kinases (nibs), e.g., sorafenib. The indication for one of these therapeutic strategies depends on the stage of the HCC and is highly individualized. 
In summary, the epidemiology, natural course as well as the diagnosis of hepatitis A-E have been investigated in great detail. Patients with chronic hepatitis B/ D or C have a significant risk for developing liver cirrhosis and/ or a HCC. For patients with HCC there exist different, in part curative, therapeutic strategies, depending on the stage of the HCC as well as the physical state of the patient, incl. age and co-morbidities. In view of the advanced stage of the HCC at the time of diagnosis in the majority of the patients, in clinical practice, successful antiviral treatment of chronic hepatitis B or C is of utmost importance in order to prevent liver cirrhosi and HCC development.


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