Liver transplantation for hepatitis B-induced liver disease: long-term outcome and effectiveness of antiviral therapy for prevention of recurrent hepatitis B infection.

OBJECTIVE: The aim of this study was to examine the efficacy of preoperative, perioperative, and long-term treatment in liver transplant (OLT) patients suffering hepatitis B (HBV)-induced liver disease, in terms of graft and survivals as well as disease recurrence. MATERIALS AND METHODS: We reviewed the medical records of 19 HBV-infected patients who underwent OLT between 2000 and 2010 using antiviral treatment with either lamivudine (LAM, n = 14) and/or adefovir/entecavir/tenofovir (n = 8) before OLT. Fifteen subjects showed a HBV DNA-negative status prior to OLT. All patients were administered HBIG (antiHBs immunoglobulin) perioperatively: 10,000 international units (IU) in the anhepatic phase and 2.000 IU/d until day 7 after OLT. The preoperative antiviral regimen was continued as maintenance prophylaxis from day 1 after OLT. In cases of the YMMD mutation the antiviral treatment was switched to combination therapy with entecavir and tenofovir. RESULTS: Patient follow-up as of December 2011 or till time of death ranged from 6 to 129 months (median = 47). All patients were prescribed tacrolimus. None of them experienced HBV-related graft dysfunction or graft loss. All subjects were HBV DNA negative at 6 months after OLT. HBV recurrence in the post-OLT phase was discovered in 3 patients, 2 of whom had undergone OLT because of acute liver failure due to hepatitis B. They showed LAM-resistant mutations at the time of recurrence and underwent entecavir/tenofovir therapy to achieve HBV DNA negative status. CONCLUSIONS: Our study demonstrated excellent long-term outcomes among patients after successful preoperative antiviral treatment for HBV. Patients should be given a high dosage of HBIG during the first week after OLT in combination with the preoperatively established antiviral treatment. In presence of a LAM-resistance mutation, antiviral treatment should be adapted individually to achieve HBV recurrence freedom and graft survival.

Long-term outcome of liver transplantation as treatment modality in patients with hepatocellular carcinoma in cirrhosis: a single-center experience.

BACKGROUND: Hepatocellular carcinoma (HCC) is among the most frequent malignant diseases worldwide. In the vast majority of cases, it is associated with liver cirrhosis. Liver transplantation (OLT) is potentially the gold standard treatment for patients suffering HCC in cirrhosis, because of synchronous eradication of HCC and of the underlying hepatic disease. The aim of this study was to evaluate long-term outcomes of OLT in HCC patients. MATERIAL AND METHODS: Between January 2000 and December 2011, 43 patients who were diagnosed with HCC in liver cirrhosis and underwent OLT in our department, were identified from a prospective database. All patients received their grafts from deceased donors. We analyzed demographic data, laboratory values, number and size of lesions, primary liver disease, diagnostic methods, bridging therapy modalities, and postoperative outcomes, including complications, recurrences, and their treatment. RESULTS: Patient follow-up as of January 2012 or to death ranged from 0 to 138 months (median, 59; mean, 63). None of the patients were lost to follow-up. The gender bias was 85%:15% (male:female) and the median age, 57.8 years (range, 44-69). The most common underlying diseases for cirrhosis and HCC were alcoholic (n = 12) and hepatitis C (n = 16). Thirty-one subjects underwent bridging therapy through transarterial chemoembolization (TACE), and/or radiofrequency ablation. All patients underwent OLT within the Milan criteria according to the preoperative evaluation and histopathologic examination of the explanted liver. Twenty-one of them suffered postoperative complications (48.8%). HCC recurrence, which occurred in 5 (10.4%), was treated by surgery (n = 3), systemic chemotherapy with sorafenib (n = 1), or TACE (n = 1). CONCLUSIONS: OLT for HCC in cirrhosis, displays a relatively high complication rate. It shows good survivals with and low recurrence.

The diagnostic value of systolic acceleration time and resistive index as noninvasive modality for detection of graft rejection after orthotopic liver transplantation.

BACKGROUND: Acute cellular and chronic graft rejection are major disorders in the postoperative setting after orthotopic liver transplantation (OLT). An immediate diagnosis and successful therapy are essential for graft survival. We sought to determine whether quantitative and qualitative analysis of Doppler sonography data was predictive and sensitive as noninvasive diagnostic tools for rejection episodes. MATERIALS AND METHODS: We prospectively recorded and retrospectively analyzed the medical records of patients who underwent OLT between January 2000 and November 2011, identifying patients with acute cellular (ACR) and chronic rejection (CR) and the grade classified the activity index according to BANFF criteria. Analyzed parameters included resistive index (R/I), systolic acceleration time (SAT) in the hepatic artery, laboratory values, histopathologic grade and therapy as well as graft and patient survival. RESULTS: Patient follow-up as of December 2011 or to the time of death ranged from 2 to 132 months (median follow- up: 79 months, mean = 83 months). We registered 29 rejection episodes (ACR n = 20 and CR n = 9) in 20 subjects. The majority of patients received a tacrolimus-based immunsuppressive regimen (n = 14, trough level: 7-12 ng/mL) in addition to high-dose corticosteroids, and sometimes a third drug. One patient displayed a corticosteroid-resistant ACR and 4 CR cases, graft loss followed by retransplantation. R/I was calculated for all patients and SA for those who underwent OLT since 2009. As a control group we used subjects with delayed SAT and high R/I without graft rejection. In all patients with a high R/I (>0.7, range: 0.71-0.91) and in all patients who suffered graft rejection since 2009 (n = 14), we observed a delayed SAT (>0.08, range: 0.08-0.18). The sensitivity and specificity for R/I were 82%, and 54.9%; for SAT 100% and 78%, respectively. CONCLUSION: Delayed SAT (>0.08) and high R/I (>0.7) were sensitive indices of graft rejection episode. The limitation of these diagnostic parameters is their specificity, especially in the immediate postoperative period, where early vascular disorders trigger similar sonographic results. Nevertheless SAT and R/I may be considered to be important diagnostic tools, in combination with elevated laboratory liver values they can provide an early diagnosis of graft rejection.

The value of pre-emptive therapy for cytomegalovirus after liver transplantation.

BACKGROUND: Cytomegalovirus (CMV) infections are among the most common infections following liver transplantation. The main preventive methods for CMV infections are universal prophylaxis and pre-emptive therapy. In our study, we adopted a pre-emptive strategy in a higth-risk group of donor CMV-positive (D+)/recipient CMV-negative (R-) casses. We investigated whether this strategy was safe and effective to prevent CMV disease. METHODS: One hundred fifty-nine liver transplantation recipients who underwent over a 15-year period were retrospectively analyzed after follow-up for at least 6 months (mean, 63 months). Weekly quantitative polymerase chain reaction (PCR) measurements were performed to detect viral DNA. No CMV drug prophylaxis was given: antiviral CMV therapy was initiated when the PCR for CMV-DNA was >400 copies/mL. RESULTS: Fifty-one of 159 liver transplant recipients enrolled in the study received antiviral therapy. High-risk patients (D+/R-) developed CMV infections significantly more often than D-/R- serostatus (P = .005). CMV disease was diagnosed in 12% of CMV-positive patients. Independent of serostatus in 14 cases (27.5%) virological recurrence of CMV infection occurred after primary treatment. Survival analysis showed no significant difference between patients with versus without CMV infection (P = .950). No relationship could be found between transplant rejection and CMV infection (P = .349). CONCLUSION: Our results showed that a pre-emptive strategy to prevent CMV disease was possible, even among the serological high-risk group. Only 12% of cases with CMV infection went on to manifest CMV disease with organ involvement. Survival curves were similar among patients with versus without CMV infections.

Biliary tract complications after orthotopic liver transplantation: still the "Achilles heel"?

Postoperative biliary tract complications after liver transplantation (LT) still lead to early and late morbidity and mortality. Modern interventional endoscopic techniques can replace surgical repair as the first line of treatment. Nevertheless surgical intervention plays an important role in specific situations. We performed a retrospective analysis of patients with biliary complications after LT over a 12-year period. We compared treatment programs based on duration and success rate. The rate of biliary complications was 24.5% (60/245). The side-to-side choledocholedochostomy (CDC) technique showed the significantly lowest rate. The rate of complications after hepaticojejunostomy (HJS) was considerably lower, albeit not significantly. Eighty-one percent of complications after CDC were treated with interventional endoscopy. The duration of treatment of strictures, was 10 times greater than that of leakages. Surgical repair was necessary for 19% of complications occurring after CDC. The treatment options after HJS largely comprised surgical repairs. From a surgical standpoint, choosing the correct method for biliary reconstruction and ensuring normal arterial flow are the best preventive techniques to avoid biliary complications. Over the past 10 years, the primary treatment regimen has moved from surgical repair to interventional endoscopy. Only when endoscopy fails, should one consider surgical repair. The treatment after HJS is still primarily surgical. Percutaneous transhepatic approaches should be avoided. Creation of an inspection stoma to allow endoscopic access is an option.