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Immigration, cheap air travel, and globalization are all factors contributing to a worldwide spread of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. End-stage chronic liver disease (ESLD) as a result of co-infection with HBV/HCV is now the major cause of death for individuals who have been infected with the HIV virus. The high incidence of HCV infection in Egypt—the legacy left from the mass use of tartar emetic to eradicate schistosomiasis, as in other high prevalence areas—will take years to reduce. Steatohepatitis due to non-alcoholic fatty liver disease is developing into a new and major health problem as a result of rising levels of obesity in populations worldwide. Hepatic steatosis also has an adverse influence on the progression of other liver diseases including chronic HCV infection and alcoholic liver disease. In many countries, considerable public concern is on the rise due to increased levels of alcohol consumption adversely affecting younger and affluent age groups. With the rising prevalence of cirrhosis, primary hepatocellular carcinoma (HCC) is increasing in frequency as is that of primary intrahepatic cholangiocarcinoma. Finally, despite the successes of liver transplantation, many deserving patients are not getting transplants due to low levels of cadaver organ donation in many countries, thereby increasing pressures on the use of living donor liver transplantation. Only through a concerted effort from governments, health agencies, healthcare professionals at all levels, and the pharmaceutical industry can this grim outlook for liver disease worldwide be reversed.