EVALUATION OF VIRAL HEPATITIS IN SOLID ORGAN TRANSPLANTATION

Uspješna transplantacija bubrega je optimalna metoda liječenja bolesnika koji se nalaze u završnom stadiju kronične bubrežne bolesti. Za uspjeh same transplantacije, kao i dugoročnog preživljenja bolesnika i njegovog transplantata, nužna je detaljna evaluacija primatelja i potencijalnog darivatelja organa, bilo da se radi o kadaveričnom ili živom darivatelju. Poseban problem u sklopu infektivnih bolesti su virusi hepatitisa, osobito virus hepatitisa B (HBV) i C (HCV), a u novije vrijeme sve se više spominje i virus hepatitisa E (HEV) kao značajan uzrok kroničnog hepatitisa u populaciji bolesnika s transplantatom. Unatoč poboljšanju preventivnih mjera posljednjeg desetljeća incidencija virusnih hepatitisa je u bolesnika koji se liječe postupcima hemodijalize značajno smanjena. Međutim, njihova incidencija i dalje je veća u toj skupini bolesnika kao i u bolesnika kojima je transplantiran bubreg u odnosu na opću populaciju. Virusni hepatitisi su značajan čimbenik povećanog morbiditeta i mortaliteta u tim populacijama bolesnika, ali i prema većini studija značajan čimbenik disfunkcije bubrežnog transplantata. Naime, u bolesnika koji su podvrgnuti transplantaciji bubrega primarni cilj je očuvanje dobre funkcije transplantata, uz primjenu učinkovite, a što manje toksične imunosupresivne terapije. Osim toga, nužno je praćenje i adekvatna terapija virusnih hepatitisa, s obzirom na dobro poznatu činjenicu da te infekcije vode prema kroničnom hepatitisu, cirozi jetre i hepatocelularnom karcinomu. Nadalje, HBV i HCV mogu inducirati nastanak de novo membranskog glomerulonefritisa u bubrežnom transplantatu.Renal transplantation has significantly improved survival of patients with end-stage renal disease (ESRD). Transplantation is the best treatment in this population of patients. Despite the introduction of various preventive measures, viral hepatitis, i.e. hepa¬titis B virus (HBV) and hepatitis C virus (HCV) infections, are still a major problem because they are common in patients on re¬nal replacement therapy as well as in allograft recipients. They are a significant cause of morbidity and mortality in this patient population. In recent years, hepatitis E virus (HEV) infection has been added as an emergent cause of chronic hepatitis in solid organ transplantation, mainly in renal and liver allograft recipients. Most studies show higher mortality in renal transplant recipi¬ents (RTRs) infected with HBV, compared with RTRs without HBV infection, although this topic is still under debate. Furthermore, HCV infection in RTRs is associated with a significant reduction in patient and graft survival due to liver disease and septic com¬plications related to cirrhosis and immunosuppressive therapy. The immunosuppressive therapy prescribed after transplantation modifies the natural history of chronic HCV infection. Given the high prevalence of HCV and HBV infections in RTRs, a growing incidence of hepatocellular carcinoma and the possible contribution of immunosuppression might be expected in these patients. Therefore, after renal transplantation, early screening with abdominal ultrasound (every 3 months in cirrhotic patients and every 6-12 months in non-cirrhotic RTRs) is necessary when the risk factors such as HBV and HCV are present. The European Asso¬ciation for the Study of the Liver (EASL) recommends that all HbsAg-positive patients who are candidates for solid organ trans¬plantation should be treated with nucleoside analogs. The KDIGO guidelines recommend that all HbsAg-positive RTRs receive prophylaxis with tenofovir, entecavir or lamivudine; however, tenofovir and entecavir are preferable to lamivudin. Viral suppres¬sion by inhibiting necro-inflammation may result in reduced fibrosis, thereby improving transplant survival. Active HCV infection in a dialysis patient requires evaluation of liver fibrosis. Antiviral therapy should be given to all HCV-infected dialysis patients in order to achieve a sustained virologic response (SVR) not only to avoid subsequent hepatic deterioration but also to limit the risks of HCV-related posttransplant de novo glomerulonephritis. Systematic vaccination of all HbsAg-negative patients is the best preventive treatment of HBV infection. HbsAg positive donors are only used occasionally, whereas the use of hepatitis B core antibody (HbcAb)+, HbsAg negative donors is more common but remains somewhat controversial. The presence of antibody to HCV is indicative of HCV infection because antibody to HCV appears in peripheral blood within two months of HCV exposure. However, it is important to emphasize that detection of antibody to HCV by serologic screening of the donor is not predictive of HCV transmission. Approximately 50% of patients positive for antibody to HCV have detectable hepatitis C viremia by PCR analysis of peripheral blood. Therefore, all organ donors with PCR analysis positive for HCV will transmit HCV to RTRs. On the other hand, the risk of transmission from an organ donor with negative PCR analysis is unclear. Another problem in the evalua¬tion of the potential donors of solid organs is the fact that antibody testing by enzyme-linked immunosorbent assays (ELISAs) will not detect recent infections. The use of nucleid acid testing (NAT) could be useful because it involves amplification of viral gene products and thus is not dependent on antibody formation. Therefore, by using this method the period between the infection and detectability, which is known as the window period, could be reduced. However, this method is expensive and time consuming