"Immune activation, aging and gender" and progression of liver disease

Hepatitis C is the predominant cause of liver disease in the HIV-positive population and the most important of the non-AIDS-related causes of death. HCV disease tends to become chronic more frequently in HIV-positive subjects, and to evolve more rapidly into cirrhosis of the liver. The rapidity of the evolution varies considerably from one individual to the next and, if in HIV-negative subjects cirrhosis manifests itself after approx. 40-50 years of disease, in HIV-positive subjects it emerges 10-15 years earlier (1, 2). The severity of the fibrosis is not a gradual event and can be worsened by many factors. Age, sex, duration of the infection and assumption of alcohol are the most well-known variables; obesity, diabetes, steatosis and metabolic disorders are equally important factors that affect the progression of liver disease (3). The severity of the liver disease is very different in men compared to women. Being male is undoubtedly one of the factors most closely related to the gravity of fibrosis (4). In HCV mono-infected women, cirrhosis appears from the age of 60 onwards. With the onset of the menopause, in fact, the progression of liver disease accelerates and the risk of developing cirrhosis or cancer of the liver becomes particularly significant in women over 50. The conditions of menopause or of amenorrhea, irrespective of age, are therefore correlated with the progression of liver disease (5). This evidence led researchers to theorize on the possible anti-fibrogenic role of estrogens. In fact, estrogens in physiological doses in the plasma of women in fertile age contribute to controlling the progression of liver disease through antioxidant mechanisms and lipid peroxidation control mechanisms (6). The reduction of estrogens during the menopause is closely linked to the increase of metabolic disorders. During the menopause, steatosis and cardiovascular diseases increase in parallel with the increase of atherogenic lipoproteins, the accumulation ofintra-abdominal fat and the onset of insulin resistance (3, 7). Recent works have demonstrated how the concentration of HCV viremia in plasma correlates with the degree of insulin resistance and with the concentration of circulating triglycerides, demonstrating how the role of HCV in altering the hepatic lipid and glucide metabolism is functional to its replicative capacity. The correlation between the HCV viral load and the metabolic set-up is still unclear in the mono-infection and has been rarely studied in the HIV/HCV co-infection, where the picture is further altered by the metabolic impact of certain antiretroviral therapies. Over recent years, most of the HIV/HCV co-infected population, belonging - as is common knowledge - to the old intravenous drug user risk categories, have reached the age of 50 and have 20-25 years' history of liver disease. The women are reaching the menopause and are frequently characterized by prolonged states of amenorrhea. This conditions exposes HIV-positive women and the co-infected population, currently in care in our centres, to a sudden and rapid worsening of the liver condition. Over the last few years, we are also witnessing the launching on the market of new anti-HCV molecules which must, of necessity, find an outlet as new drug applications for HIV/HCV co-infected patients, as well as being used to the best advantage in populations with particular complications. (www.actabiomedica.it)