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      Recurrence of diseases following orthotopic liver transplantation.

      The American Journal of Gastroenterology
      Carcinoma, Hepatocellular, pathology, surgery, Cholangitis, Sclerosing, Graft Survival, Hepatitis B, Hepatitis C, Hepatitis, Autoimmune, Humans, Liver Cirrhosis, Liver Diseases, Liver Diseases, Alcoholic, Liver Neoplasms, Liver Transplantation

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          Abstract

          Long-term graft survival and mortality after liver transplantation continue to improve. However, disease recurrence remains a major stumbling block, especially among patients with hepatitis C. Chronic hepatitis C recurs to varying degrees in nearly all patients who undergo transplantation. Transplantation for hepatitis C is associated with higher rates of graft failure and death compared with transplantation for other indications, and retransplantation for hepatitis C related liver failure remains controversial. Recurrence of hepatitis B has been markedly reduced with improved prophylactic regimens. Further, rates of hepatocellular carcinoma recurrence have also decreased, as improved patient selection criteria have prioritized transplantation for those with a low risk of recurrence. Primary biliary cirrhosis recurs in some patients, but it is often relatively mild. Autoimmune liver disease has also been shown to have a relatively benign post-transplantation course, but some studies have indicated that it slowly progresses in most recipients. It has been recently reported that alcoholic liver disease liver transplant recipients who return to drinking have worsened mortality. In such patients worse outcomes are not due to graft failure, but instead to other comorbidities. Recurrences of other diseases, including nonalcoholic steatohepatitis and primary sclerosing cholangitis, are now being recognized as having potentially detrimental effects on graft survival and mortality. Expert clinical management may help prevent and treat complications associated with disease recurrence.

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          Most cited references69

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          Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival.

          The precise staging of hepatocellular carcinoma (HCC) based on the size and number of lesions that predict recurrence after orthotopic liver transplantation (OLT) has not been clearly established. We therefore analyzed the outcome of 70 consecutive patients with cirrhosis and HCC who underwent OLT over a 12-year period at our institution. Pathologic tumor staging of the explanted liver was based on the American Tumor Study Group modified Tumor-Node-Metastases (TNM) Staging Classification. Tumor recurrence occurred in 11.4% of patients after OLT. The Kaplan-Meier survival rates at 1 and 5 years were 91.3% and 72.4%, respectively, for patients with pT1 or pT2 HCC; and 82.4% and 74.1%, respectively, for pT3 tumors (P =.87). Patients with pT4 tumors, however, had a significantly worse 1-year survival of 33.3% (P =.0001). An alpha-fetoprotein (AFP) level > 1,000 ng/mL, total tumor diameter > 8 cm, age > or = 55 years and poorly differentiated histologic grade were also significant predictors for reduced survival in univariate analysis. Only pT4 stage and total tumor diameter remained statistically significant in multivariate analysis. Patients with HCC meeting the following criteria: solitary tumor < or = 6.5 cm, or < or = 3 nodules with the largest lesion < or = 4.5 cm and total tumor diameter < or = 8 cm, had survival rates of 90% and 75.2%, at 1 and 5 years, respectively, after OLT versus a 50% 1-year survival for patients with tumors exceeding these limits (P =.0005). We conclude that the current criteria for OLT based on tumor size may be modestly expanded while still preserving excellent survival after OLT.
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            Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C.

            Patient adherence to prescribed antiviral therapy in human immunodeficiency virus infection enhances response. We evaluated the impact of adherence to combination therapy with interferon or peginterferon plus ribavirin in chronic hepatitis C patients. We assessed the effect of dose reduction on sustained virologic response (SVR) from prior trials with interferon alpha-2b plus ribavirin (n = 1010) or peginterferon alpha-2b 1.5 microg/kg/week plus ribavirin (n = 511). The actual treatment administered was verified from drug dispensing/return records and patient diaries. Two groups were defined: (1) patients who received >or=80% of both their total interferon and ribavirin doses for >or=80% of the expected duration of therapy and (2) patients who received reduced doses ( or=80% of the expected duration of therapy). A statistical model provided comparative estimates of the response rates in compliant patients. Most patients were at least 80% compliant with interferon alpha-2b/ribavirin or peginterferon alpha-2b/ribavirin therapy and had SVR rates of 52% and 63%, respectively, for the 2 regimens. This was most apparent for HCV-1-infected patients. The impacts of adherence on efficacy from subgroup analysis and the statistical modeling approach were similar. HCV-1-infected patients who can be maintained on >80% of their interferon or peginterferon alpha-2b and ribavirin dosage for the duration of treatment in the setting of a clinical trial exhibit enhanced sustained response rates. Our results suggest that adherence will enhance the likelihood of achieving an initial virologic response. Adherence beyond 12-24 weeks will be advantageous only for those patients who have achieved such an early virologic response.
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              Liver transplantation in European patients with the hepatitis B surface antigen.

              The role of liver transplantation in patients positive for the hepatitis B surface antigen (HBsAg) is controversial because of the high rate of recurrent hepatitis B virus (HBV) infection. It has not been determined whether this risk is greater for certain patients and whether the administration of anti-hepatitis B surface antigen (anti-HBs) immune globulin is beneficial. We conducted a retrospective study at 17 European centers of 372 consecutive HBsAg-positive patients who underwent liver transplantation between 1977 and 1990. Recurrence of HBV infection was defined as the reappearance of HBsAg in serum. For all 334 patients with follow-up data, the mean (+/- SE) three-year actuarial risk of recurrence of HBV was 50 +/- 3 percent. The risk was 67 +/- 4 percent among 163 patients with HBV-related cirrhosis, 32 +/- 5 percent among 110 patients with cirrhosis related to hepatitis delta virus, 40 +/- 16 percent among 14 patients with fulminant hepatitis delta infection, and 17 +/- 7 percent among 39 patients with fulminant HBV infection (P < 0.001). Among the patients with HBV-related cirrhosis, the risk of HBV recurrence was greatest (83 +/- 6 percent) in those who were seropositive for HBV DNA at the transplantation and lowest (58 +/- 7 percent) in those with neither HBV DNA nor hepatitis B e antigen detectable in serum. With respect to the use of passive prophylaxis with anti-HBs immune globulin, the risk of HBV recurrence was 75 +/- 6 percent among the 67 patients given no immunoprophylaxis, 74 +/- 5 percent among the 83 treated for two months, and 36 +/- 4 percent among the 209 treated for six months or longer (P < 0.001). In a multivariate analysis the predictors of a lower risk of HBV recurrence were the long-term administration of the immune globulin, hepatitis delta virus superinfection, and acute liver disease. For the entire study cohort, survival was 75 percent at one year and 63 percent at three years, but for those in whom HBV infection recurred, survival was 68 percent at one year and 44 percent at three years. In this retrospective study of HBsAg-positive patients, liver transplantation had better results in those who had fulminant hepatitis or delta virus superinfection. An absence of viral replication at the time of transplantation and long-term immunoprophylaxis were associated with a reduced risk of recurrent HBV infection and reduced mortality.
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