Its diagnosis requires a liver biopsy and it usually responds to increased immunosuppression. Immunosuppression predisposes to infections, cytomegalovirus infection/disease being one of the most important ones, and to malignancies, in particular Epstein–Barr virus associated post-transplant lymphoproliferative disorder. The individual immunosuppressive agents used have their individual side effect profile. Calcineurin inhibitors (cyclosporine A, tacrolimus), which
formthe backbone of maintenance immunosuppression, are, among others, associated with nephrotoxicity. Steroids and calcineurin inhibitors predispose to weight gain, hypertension, dyslipidemia, and insulin resistance/diabetes, which develop in 30–60% of patients. Thus, liver transplant recipients are at a threefold higher risk for fatal and non-fatal cardiovascular GSK-3 phosphorylation events than the normal population. Finally, some underlying liver disease may Proteases inhibitor recur with varying frequency and may impact, such as hepatitis C recurrence, on survival outcome. The internist/family physician and transplant hepatologist share
the long-term care for the liver transplant recipient, the former bringing his or her expertise with managing cardiovascular risk factors and many conditions common in the non-transplant population that may occur also in the liver transplant recipient, the latter his or her experience with managing immunosuppression and graft related issues. “
“Telomere shortening impairs liver regeneration in mice and is associated with cirrhosis formation in humans with chronic liver disease. In humans, telomerase mutations have been associated with familial diseases leading to bone marrow failure or lung fibrosis. It is currently unknown whether telomerase mutations associate with cirrhosis induced by chronic liver disease. The telomerase Pregnenolone RNA component (TERC) and the telomerase reverse transcriptase (TERT) were sequenced in 1,121 individuals (521 patients with cirrhosis induced by chronic liver disease and 600 noncirrhosis controls).
Telomere length was analyzed in patients carrying telomerase gene mutations. Functional defects of telomerase gene mutations were investigated in primary human fibroblasts and patient-derived lymphocytes. An increased incidence of telomerase mutations was detected in cirrhosis patients (allele frequency 0.017) compared to noncirrhosis controls (0.003, P value 0.0007; relative risk [RR] 1.859; 95% confidence interval [CI] 1.552-2.227). Cirrhosis patients with TERT mutations showed shortened telomeres in white blood cells compared to control patients. Cirrhosis-associated telomerase mutations led to reduced telomerase activity and defects in maintaining telomere length and the replicative potential of primary cells in culture. Conclusion: This study provides the first experimental evidence that telomerase gene mutations are present in patients developing cirrhosis as a consequence of chronic liver disease.