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End Stage Liver Disease (end + stage_liver_disease)
Selected AbstractsHyperbaric oxygen therapy and liver transplantationHPB, Issue 3 2007VIJAYARAGAVAN MURALIDHARAN Abstract Liver transplantation is the treatment of choice for end stage liver disease and is often used for primary liver malignancies. The main limitation of its wider application is the availability of suitable donor organs. The use of marginal donor organs, split-liver transplantation and living-related liver transplantation techniques contribute to increase the donor pool. However, the use of these techniques is associated with a higher risk of post transplantation organ dysfunction, predominantly due to ischaemia, preservation and reperfusion injury (IPRI). A number of studies have demonstrated that hyperbaric oxygen (HBO) therapy influences IPRI and consequential acute cellular rejection. This article reviews the rationale of HBO therapy in the field of transplantation with particular emphasis on liver transplantation. [source] NeoHepatocytes From Alcoholics and Controls Express Hepatocyte Markers and Display Reduced Fibrogenic TGF-,/Smad3 Signaling: Advantage for Cell Transplantation?ALCOHOLISM, Issue 4 2010Sabrina Ehnert Background:, Liver transplantation is the only definitive treatment for end stage liver disease. Donor organ scarcity raises a growing interest in new therapeutic options. Recently, we have shown that injection of monocyte-derived NeoHepatocytes can increase survival in rats with extended liver resection. In order to apply this technology in humans with chronic liver diseases in an autologous setting, we generated NeoHepatocytes from patients with alcoholic liver disease and healthy controls and compared those to human hepatocytes. Methods:, We generated NeoHepatocytes from alcoholics with Child A and B cirrhosis and healthy controls. Hepatocytes marker expression and transforming growth factor (TGF)-, signaling was investigated by RT-PCR, Western blot, immunofluorescent staining, and adenoviral reporter assays. Glucose and urea was measured photometrically. Phase I and II enzyme activities were measured using fluorogenic substrates. Neutral lipids were visualized by Oil Red O staining. Results:, There was no significant difference in generation and yield of NeoHepatocytes from alcoholics and controls. Hepatocyte markers, e.g., cytokeratin18 and alcohol dehydrogenase 1, increased significantly throughout differentiation. Glucose and urea production did not differ between alcoholics and controls and was comparable to human hepatocytes. During differentiation, phase I and II enzyme activities increased, however remained significantly lower than in human hepatocytes. Fat accumulation was induced by treatment with insulin, TGF-, and ethanol only in differentiated cells and hepatocytes. TGF-, signaling, via Smad transcription factors, critically required for progression of chronic liver disease, was comparable among the investigated cell types, merely expression of Smad1 and -3 was reduced (,30 and ,60%) in monocytes, programmable cells of monocytic origin, and NeoHepatocytes. Subsequently, expression of TGF-, regulated pro-fibrogenic genes, e.g., connective tissue growth factor and fibronectin was reduced. Conclusions:, Generation of NeoHepatocytes from alcoholics, displaying several features of human hepatocytes, offers new perspectives for cell therapeutic approaches, as cells can be obtained repeatedly in a noninvasive manner. Furthermore, the autologous setting reduces the need for immunosuppressants, which may support recovery of patients which are declined for liver transplantation. [source] MTHFR C677T Polymorphism and Risk of HCC in Patients With Liver Cirrhosis: Role of Male Gender and Alcohol ConsumptionALCOHOLISM, Issue 1 2009Carlo Fabris Background:, A single nucleotide polymorphism (SNP) C677T in the methylenetetrahydrofolate reductase (MTHFR) gene has been identified. The TT or CT genotypes show a marked reduction of the enzyme activity; this causes higher homocysteine levels and alterations of folate metabolism. Folate metabolism is essential for DNA synthesis and methylation, crucial steps in carcinogenesis. In this paper, we investigated whether the MTHFR C677T SNP could influence the occurrence of hepatocellular carcinoma (HCC) in a cohort of patients transplanted for end stage liver disease of different etiologies. Methods:, Two hundred and twelve consecutive patients who underwent liver transplantation for end stage liver disease due to hepatitis B or C, alcoholic liver disease, and other causes were studied. Two hundred and thirty-six blood donors served as controls. Focal hepatic lesions were searched in the sectioned explanted livers. The presence of the MTHFR C677T SNP was determined via polymerase chain reaction amplification. Results:, Among the 65 patients with HCC, 22 had the CC genotype, 30 the CT, and 13 the TT genotype. Only in patients with alcoholic liver disease was a significant association detected between the TT genotype and the presence of liver cancer (6/17 vs. 5/46, p < 0.05). At stepwise logistic regression analysis the independent selected predictors of HCC were found: age at transplantation >55 years (p < 0.001) and the association among male gender, alcoholic liver disease, and MTHFR TT genotype (p = 0.002). Conclusions:, The present study suggests that male TT carriers with alcoholic cirrhosis bear an increased risk of developing HCC. [source] Liver transplantation for primary sclerosing cholangitisLIVER INTERNATIONAL, Issue 2 2000Paul J. Gow Abstract: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology that is progressive in most symptomatic patients, advancing toward cirrhosis and liver failure. Liver transplantation is the only therapeutic option for patients with end stage liver disease resulting from this disorder. The results of transplantation for PSC are excellent with one-year survival rates of 90,97% and five-year survival rates of 80,85%, but are closely related to pre-transplant Child-Pugh stage. Recurrence of PSC after liver transplantation is common, occurring in up to 20% of patients, but it appears to have little effect on patient survival, as survival of patients with recurrent PSC is similar to that of those without evidence of recurrence. Cholangiocarcinoma is a catastrophic complication of PSC and as yet no reliable screening method exists. The results of liver transplantation for patients with clinically apparent cholangiocarcinoma are extremely poor, however in patients in whom a microscopic tumour is detected in the explanted liver, survival is similar to those transplanted with PSC without cholangiocarcinoma. Activity of inflammatory bowel disease (IBD) appears to be more severe after transplantation, especially in units where steroid immunosuppression is withdrawn early. Colon cancer appears within the first few years after transplantation in approximately 7% of patients with IBD who are transplanted for PSC. Annual colonoscopy in this population seems prudent. [source] Use of yttrium-90 microspheres (TheraSphere®) in a patient with unresectable hepatocellular carcinoma leading to liver transplantation: A case reportLIVER TRANSPLANTATION, Issue 9 2005Laura M. Kulik Prior to therapy, model for end stage liver disease (MELD) scoring, diagnostic imaging and tumor staging were performed in a patient with T3 HCC. The patient received an orthotopic liver transplant (OLT) 42 days after treatment. The explant specimen showed complete necrosis of the target tumor. Follow-up of this patient has demonstrated no evidence of recurrence. There was no life threatening or fatal adverse experiences related to treatment. This case report documents the natural course, history and outcome of a patient treated with yttrium-90 for unresectable HCC. The patient was downstaged from T3 to T2 and was subsequently transplanted. (Liver Transpl 2005;11:1127,1131.) [source] Around the world with the model for end-stage liver diseaseLIVER TRANSPLANTATION, Issue 10 2003Richard B. Freeman Jr MD Background: Indices for predicting survival are essential for assessing prognosis and assigning priority for liver transplantation in patients with liver cirrhosis. The model for end stage liver disease (MELD) has been proposed as a tool to predict mortality risk in cirrhotic patients. However, this model has not been validated beyond its original setting. Aim: To evaluate the short and medium term survival prognosis of a European series of cirrhotic patients by means of MELD compared with the Child-Pugh score. We also assessed correlations between the MELD scoring system and the degree of impairment of liver function, as evaluated by the monoethylglycinexylidide (MEGX) test. Patients and methods: We retrospectively evaluated survival of a cohort of 129 cirrhotic patients with a follow up period of at least one year. The Child-Pugh score was calculated and the MELD score was computed according to the original formula for each patient. All patients had undergone a MEGX test. Multivariate analysis was performed on all variables to identify the parameters independently associated with one year and six month survival. MELD values were correlated with both Child-Pugh scores and MEGX test results. Results: Thirty one patients died within the first year of follow up. Child-Pugh and MELD scores, and MEGX serum levels were significantly different among patients who survived and those who died. Serum creatinine, international normalized ratio, and MEGX60 were independently associated with six month mortality while the same variables and the presence of ascites were associated with one year mortality. MELD scores showed significant correlations with both MEGX values and Child-Pugh scores. Conclusions: In a European series of cirrhotic patients the MELD score is an excellent predictor of both short and medium term survival, and performs at least as well as the Child-Pugh score. An increase in MELD score is associated with a decrease in residual liver function. [source] Rapid assessment and safe management of severe pulmonary hypertension with milrinone during orthotopic liver transplantationCLINICAL TRANSPLANTATION, Issue 4 2010Kyota Fukazawa Fukazawa K, Poliac LC, Pretto EA. Rapid assessment and safe management of severe pulmonary hypertension with milrinone during orthotopic liver transplantation. Clin Transplant 2010: 24: 515,519. © 2009 John Wiley & Sons A/S. Abstract:, The incidence of porto-pulmonary hypertension (PPHN) in patients with end stage liver disease is 8.5%. Evidence indicates that proceeding with orthotopic liver transplantation (OLT) in patients diagnosed with severe PPHN (mean pulmonary artery pressure [mPAP] > 45 mmHg) at the time of OLT surgery is associated with high perioperative mortality. We describe a case of severe PPHN that was diagnosed by right heart catheterization at the time of surgery. We quickly determined the reversibility of PPHN with a bolus of milrinone and proceeded with OLT. Further episodes of pulmonary hypertension were successfully managed with continuous milrinone infusion and transesophageal echocardiography monitoring. Reversibility via vasodilator trial after identification of high pulmonary artery pressures (PAP) may be an important indication of the feasibility of OLT. Milrinone may be useful for the rapid identification of the reversibility of high PAP and may be an effective agent to control abrupt increases in PAP during OLT. [source] Four-year follow-up of a prospective randomized trial of mycophenolate mofetil with cyclosporine microemulsion or tacrolimus following liver transplantationCLINICAL TRANSPLANTATION, Issue 4 2004Robert A Fisher Abstract:, Background:, This is a 4-yr follow-up of a trial using mycophenolate mofetil (MMF) induction in orthotopic liver transplantation (OLT). The goal of this study was to evaluate a multidrug approach that would reduce both early and long-term morbidity related to immunosuppression while maintaining an acceptable freedom from rejection. Methods:, This was a prospective, randomized, intent to treat study designed to compare the primary endpoints of rejection and infection, and secondary endpoints of liver function, renal function, bone marrow function, cardiovascular risk factors, and the recurrence of hepatitis C. Ninety-nine consecutive patients with end stage liver disease who underwent OLT were randomized to receive either cyclosporine microemulsion (N) (50 patients) or tacrolimus (FK) (49 patients) starting on postoperative day 2, with MMF and an identical steroid taper begun preoperatively. Results:, Ninety of 99 patients (N 46, FK 44) completed the 4-yr follow-up. The overall 4-yr patient and graft survivals were 93 and 89%, respectively. There was no significant difference in 4-yr patient (N 96% vs. FK 90%, p = ns) or graft (N, 90% vs. FK, 88%, p = ns) survival between groups. The 4-yr rejection rate was not significantly different in either arm (N = 34%, FK = 24%; p = 0.28). There were no differences in infection rates in either arm. The patients with hepatitis C had no differences in the viral titers or Knodell biopsy scores between groups. However, in the hepatitis C subgroup (37 patients), the FK patients had a significantly lower rejection rate (p = 0.0097) and a significantly lower clinically recurrent hepatitis C rate (p = 0.05) than the N patients. No difference was seen in the percent of patients weaned off of steroids after 4 yr (N 51%, FK 49%). There were no differences in the incidences of diabetes mellitus and hypertension. When renal dysfunction was analyzed, a significant difference in the number of patients whose creatinine had increased twofold since transplant was seen (N 63%, FK 38%, p = 0.04). Conclusions:, Use of MMF induction and maintenance following OLT in conjunction with either N or FK and an identical steroid taper, resulted in an acceptable long-term incidence of rejection and infection, without an increase in long-term graft or patient morbidity. [source] | ||||||||||