Mini-laparoscopy is superior in detecting liver cirrhosis and metastases in liver cancer: an over 10-year experience in 1,788 cases.

BACKGROUND/AIMS: Mini-laparoscopy has, since its first description in 1998, proven to be a valuable diagnostic method in liver diseases. We re-evaluated the significance of mini-laparoscopy for diagnosis and staging of liver disease and primary liver and bile duct cancer. PATIENTS AND METHODS: 1,788 consecutive patients who received a diagnostic mini-laparoscopy between 10/1998 and 06/2011 were included in this retrospective cohort study. RESULTS: In chronic liver disease, cirrhosis was detected by mini-laparoscopy in 27% of cases. A comparison of microscopic versus macroscopic diagnosis of cirrhosis revealed a sampling error for histology alone of 21%. Macroscopic inspection of the liver surface contributed to the diagnosis of unknown liver diseases in approximately 38%. In patients with bile duct or liver cancer, mini-laparoscopy led to upstaging of the disease in 33 and 23%, respectively. Major complications (bowel perforation and delayed bleeding) occurred in 0.39% of cases. CONCLUSIONS: Mini-laparoscopy is a valuable procedure with significant diagnostic impact in known and unknown inflammatory and malignant liver diseases. It can be safely performed even in patients with acute liver failure and severe coagulopathy and the diagnostic value does not differ from diagnostic laparoscopy performed with standard instruments.

Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure.

BACKGROUND & AIMS: Fractionated plasma separation and adsorption (FPSA) is an extracorporeal procedure that supports liver function by removing endogenous toxins that cause complications from acute-on-chronic liver failure (AOCLF). We performed a randomized trial to investigate survival of patients with AOCLF treated with FPSA. METHODS: Patients with AOCLF were randomly assigned to groups given a combination of FPSA and standard medical therapy (SMT) (FPSA group, n = 77) or only SMT (SMT group, n = 68). The Prometheus liver support system was used to provide 8 to 11 rounds of FPSA (minimum of 4 hours each) for 3 weeks. Primary end points were survival probabilities at days 28 and 90, irrespective of liver transplantation. RESULTS: Baseline clinical parameters and number of transplant patients were similar between study arms. Serum bilirubin level decreased significantly in the FPSA group but not in the SMT group. In an intention-to-treat analysis, the probabilities of survival on day 28 were 66% in the FPSA group and 63% in the SMT group (P = .70); on day 90, they were 47% and 38%, respectively (P = .35). Baseline factors independently associated with poor prognosis were high SOFA score, bleeding, female sex, spontaneous bacterial peritonitis, intermediate increases in serum creatinine concentration, and combination of alcoholic and viral etiology of liver disease. There were no differences between the 2 groups in the incidence of side effects. CONCLUSIONS: Among all patients with AOCLF, extracorporeal liver support with FPSA does not increase the probability of survival. Further studies are needed to assess whether therapy might be beneficial in specific subsets of patients.

[A 55-year-old woman with thymoma and hypogammaglobulinemia (Good syndrome), ulcerative colitis, and cytomegalovirus infection]. / 55-jährige Patientin mit Thymom und Hypogammaglobulinämie (Good-Syndrom), Colitis ulcerosa sowie CMV-Infektion.

CASE REPORT: The authors report on a 55-year-old female patient after R1 resection of a malignant thymoma with spindle type epithelial cells (WHO type A, Masaoka stage III) referred for further therapy of an ulcerative colitis. At that time, both adjuvant radiation and cytostatic therapy were not applicable due to severe activity of the ulcerative colitis. Under immunosuppressive treatment with azathioprine and steroids, the patient developed cytomegalovirus (CMV) enteritis which was triggered by therapy-induced leukopenia. After a switch from azathioprine to mycophenolatmofetil (MMF) treatment and administration of cidofovir because of nonresponse to ganciclovir and incompatibility of foscarnet sodium (Foscavir), the patient clinically improved. In addition, the patient was treated with immunoglobulins every 3-4 weeks because of antibody deficiency. At present, 3.5 years after R1 resection, the patient still has no clues of a remaining tumor mass under current immunosuppressive therapy. Ulcerative colitis is also in complete remission stage. CONCLUSION: This case indicates the very rare features of a syndrome with thymoma and antibody deficiency which was first described by Robert Good. Furthermore, the impact of immunosuppressive therapy and management of opportunistic infections on the course of this disease is obvious.

Balloon dilatation vs. balloon dilatation plus bile duct endoprostheses for treatment of anastomotic biliary strictures after liver transplantation.

Biliary strictures after liver transplantation are a therapeutic challenge for endoscopy. Anastomotic strictures occur in 10% of patients after liver transplantation, leading untreated to mortality and ultimately to graft failure. Despite of successful reports, to date, there is no defined endoscopic therapy regimen for these cases. Therefore the aim of this study was to determine the most suitable concept for endoscopic treatment of post-liver transplant anastomotic strictures (PTAS). A total of 72 patients post-liver transplantation, who received endoscopic retrograde cholangiography (ERC) as a consequence of suspected biliary complications were retrospectively screened for the presence of PTAS. In all patients graft rejection or bile duct ischemia were excluded prior to ERC by liver biopsy or Doppler ultrasound respectively. We compared either balloon dilatation (BD) alone or dilatation plus placement of an increasing number of bile duct endoprostheses (BD + endoprostheses) in a retrospective analysis. A total of 25 of 75 patients showed PTAS. Overall, endoscopic therapy was successful in 22 of 25 patients (88%). BD was initially successful in 89% but showed recurrence in 62%. BD + endoprostheses was initially successful in 87%, and recurrence was observed only in 31%. All recurrences were successfully retreated by BD + endoprostheses. During 22 of 109 (20%) treatment sessions stone extraction was necessary. Complication rate was low with bacterial cholangitis in 8 of 109 (7.3%) sessions, mild pancreatitis in 10 of 109 (9%) sessions and minor bleeding in 2 of 25 (8%) sphincterotomies. Median follow-up after conclusion of endoscopic therapy is 6 months (range 1-43). In conclusion, our data confirm that endoscopic therapy of PTAS is highly effective and safe. As primarily successful BD shows a high rate of recurrence, we recommend a combination of BD followed by an increasing number and diameter of endoprostheses. Therapy sessions are effective at short intervals of every 2-3 months.

Endoscopic therapy of posttransplant biliary stenoses after right-sided adult living donor liver transplantation.

BACKGROUND & AIMS: Endoscopic treatment of biliary strictures after liver transplantation is a therapeutic challenge. In particular, outcomes of endoscopic therapy of biliary complications in the case of duct-to-duct anastomosis after living related liver transplantation are limited. The aim of this study was to evaluate the feasibility and success of an endoscopic treatment approach to posttransplant biliary strictures (PTBS) after right-sided living donor liver transplantation (RLDLT) with duct-to-duct anastomosis. METHODS: Ninety patients who received adult-to-adult RLDLT in our center were screened retrospectively with respect to endoscopic treatment of PTBS. Therapy was judged as successful when cholestasis parameters returned to normal and bile duct narrowing was reduced significantly after the completion of therapy. RESULTS: Forty of 90 RLDLT patients received duct-to-duct anastomosis, 12 (30%) showed PTBS. Seven of 12 patients were treated successfully by endoscopy; the remaining 5 patients were treated primarily by surgery. Most patients were treated by balloon dilatation followed by insertion of endoprostheses. A median of 2.5 dilatation sessions were necessary and the median treatment duration was 8 months. One patient developed endoscopy-treatable recurrent stenosis, no surgical intervention was necessary. Mild pancreatitis occurred in 7.9% and cholangitis in 5.3% of the procedures. One minor bleeding episode occurred during sphincterotomy. Bleeding was managed endoscopically. CONCLUSIONS: Endoscopic therapy of adult-to-adult right living related liver transplantation with duct-to-duct anastomosis is feasible and frequently is successful. The duct-to-duct anastomosis offers the possibility of endoscopic treatment. Endoscopic treatment of posttransplant biliary strictures is safe, with a low specific complication rate.

Cryoglobulin-associated uptake of hepatitis C virus into human hepatocytes.

AIMS: The mechanisms of binding and uptake of hepatitis C-virus (HCV) are critical determinants of the infection-reinfection cycle but due to ongoing absence of a robust cell culture system, these mechanisms are still largely hypothetical. Cryoglobulins are atypical immunoglobulins, present in 40% of HCV patients. The aim of this study was to determine the role of these HCV-containing cryoglobulins as carrier molecules for viral uptake into primary human hepatocytes. METHODOLOGY: Cryoglobulins were precipitated from serum of chronically HCV-infected patients, labeled with biotin and incubated with freshly prepared hepatocytes from human liver tissue. Binding and endocytosis of HCV-cryoglobulins were studied by specific assays, ligand blot analysis and electron microscopy on hepatocellar plasma membranes. RESULTS: Biotinylated HCV-cryoglobulins specifically bound to hepatocytes and inhibitors of homotypic endosomal fusion reduced their uptake and intracellular trafficking, Ligand-blot and electron microscopy analysis revealed adhesion to hepatocellular plasma membranes. Inoculation of human hepatocytes with HCV-cryoglobulins but not serum from the same patients induced HCV infection in vitro. CONCLUSIONS: HCV may enter hepatocytes in conjunction with cryoglobulins via immunoglobulin or related receptors. We hypothesize, that this mechanism plays a role in chronic hepatitis to support the infection-reinfection cycle of the virus.

Overweight patients are more susceptible for acute liver failure.

BACKGROUND/AIMS: To determine a potential correlation of gender, age, and/or body mass index (BMI) with the development of acute-on-chronic liver failure (AOC). METHODOLOGY: A retrospective 2.5-year study employed 34 patients (65% females and 35% males, aged 37.9 +/- 12.6 years) fulfilling established criteria for acute liver failure (ALF). Patients were subdivided into ALF (n = 18) and AOC (n = 16) groups, according to a history of prior chronic liver disease. Causes of liver failure included drug toxicity (52.9%), viral hepatitis (26.5%), and acute excessive ethanol abuse (11.8%). all anamneses were thoroughly reviewed. Throughout the course of the study, the patients were monitored for established clinical signs and laboratory parameters indicating acute liver injury. Gender, age, and BMI were correlated with the clinical outcome. RESULTS: Twelve patients (35.3%) received an orthotopic liver allograft, with one re-transplantation. Six patients (17.6%), including two transplanted individuals, died in the course of the study. Of all parameters evaluated, BMIs were significantly higher in AOC vs. ALF (p < 0.002), revealing values of > 25 in 62.5% of the AOC patients. When subjected to acute risk factors, elevated BMI clearly coincided with a higher rate of AOC. Importantly, half of all patients initially classified as ALF by employing current criteria thus suffered from AOC coinciding with increased mortality. CONCLUSIONS: Generally, these results call for a reduction of the BMI. Specifically, our findings argue for a closer BMI monitoring of patients at risk of developing chronic liver disease.

Impact of a self-expanding, plastic esophageal stent on various esophageal stenoses, fistulas, and leakages: a single-center experience in 39 patients.

BACKGROUND: In this study, we describe our experience with the use of a self-expanding, covered, plastic esophageal stent (SEPS). The majority of placements were difficult to treat situations, i.e., proximal or extremely proximal stent release or emergency cases in the intensive care unit. METHODS: Thirty-nine patients were treated by insertion of a SEPS by endoscopic or radiologic guidance for the following: malignant stenosis (n = 22), malignant fistula (n = 8), benign stenosis after treatment for malignant disease (n = 6), benign fistula (n = 2), and perforation or leakage after surgery of the esophagus (n = 5). RESULTS: Stent placement was technically feasible in all patients. In patients with a stenosis, esophageal passage was achieved in 92.8%. Fistulas, perforations, and leakages were sealed in 73.3%. In 6 patients (15.4%), the stent was electively removed because of the completion of the therapy. Complications included respiratory insufficiency, mediastinal emphysema, and tracheal impression in one patient each; a new fistula in two patients; bleeding in 3 patients; stent-induced ulcers in two patients; and stent migration in 8 patients. CONCLUSIONS: The therapeutical success and the complication rate after SEPS placement are similar to that reported for self-expanding metal stents. In addition, the SEPS can be readily removed, and the costs are significantly lower.

Detection of circulating autoantibodies directed against the asialoglycoprotein receptor using recombinant receptor subunit H1.

BACKGROUND/AIMS: The asialoglycoprotein-receptor (ASGPR) is a major liver-specific target autoantigen in autoimmune hepatitis. ASGPR heteromers of two subunits H1 and H2 provide clearance of circulating asialoglycoproteins by receptor-mediated endocytosis. The aim of this study was to establish whether a recombinantly expressed subunit H1 presenting conformational epitopes is capable of detecting autoantibodies against ASGPR in patients with inflammatory liver disease. METHODS: The major subunit H1 was expressed in human-embryo-kidney 293-cells and prepared by ligand-affinity-chromatography similar to the complete receptor from normal liver. Reactivities of anti-ASGPR positive sera from 219 patients with both recombinant H1 and natural receptor were compared using enzyme-immunoassay (EIA). RESULTS: 194 of 219 sera (88.6%) showed absorbance values on 293-H1 within a range of +/-15% compared to the natural receptor. 145 of 149 sera (97.3%) positive on ASGPR were also positive on recombinant H1. Titers of 61/62 sera (98.4%) revealed no deviation of more than one dilution step. ASGPR reactivity could be inhibited in 29 sera with up to 50 ng/microl of 293-H1. CONCLUSIONS: These results indicate that the antigenic sites of the human ASGPR are mainly located on the mammalian-expressed subunit H1. Therefore, 293-H1 is a powerful tool for the detection of autoantibodies against ASGPR.

Outcome after orthotopic liver transplantation in five HIV-infected patients with virus hepatitis-induced cirrhosis.

BACKGROUND: We report on our experiences with orthotopic liver transplantation (OLT) in HIV-infected patients. Between July 1998 and October 2001, five HIV-infected patients underwent OLT because of virus-induced liver cirrhosis. One patient suffered from hepatitis B virus (HBV)-, three patients from hepatitis C virus (HCV)- and one patient from HCV/HBV/HDV-related cirrhosis (HDV, hepatitis D virus). The mean duration of HIV infection was 15 years. Patients were prospectively followed up with a mean duration of 25.6 months. RESULTS: Three patients died 3, 10 and 31 months after OLT, respectively, due to graft failure. The causes of graft failure were: recurrent thrombosis of the hepatic artery, HCV-associated cholestatic hepatitis and chemotherapy-induced liver damage due to Hodgkin's disease, which was diagnosed 17 months after OLT, in addition to chronic HCV disease. The two survivors show a stable liver function and non-progredient HIV infection under antiretroviral therapy 61 and 23 months after OLT, respectively. CONCLUSIONS: A medium- or even long-term survival after OLT can be achieved in HIV-infected patients without progression of HIV disease under antiretroviral therapy. However, in our study three out of five patients died due to graft failure. Therefore, prognostic criteria have to be defined for the selection of HIV-infected patients, who may benefit from OLT.

Cyclosporine A, FK-506, 40-0-[2-hydroxyethyl]rapamycin and mycophenolate mofetil inhibit proliferation of human intrahepatic biliary epithelial cells in vitro.

AIM: To investigate the effect of cyclosporine A (CsA), FK-506, and mycophenolate mofetil (MMF) and 40-0-[2-hydroxyethyl]rapamycin (RAD) on proliferation of human intrahepatic biliary epithelial cells (BECs) in vitro. METHODS: BECs were isolated from six human liver tissuespecimens with the immunomagnetic separation method and treated with different concentrations of CsA, FK-506, RAD, and MMF in vitro. Proliferation of the cells was measured by MTT assay at 24 and 48 h after treatment, respectively. One-way analysis of variance was used to analyze the results. Expression of CK 19 in BECs was monitored by flow cytometry and Western blot. RESULTS: Six lines of BECs were established. They survived for 4-18 wk in vitro. Flow cytometry analysis showed that these cells always expressed CK19. CsA, FK-506, RAD, and MMF inhibited proliferation of BECs in a dose-dependent manner. The lowest concentration of CsA, FK-506, RAD, and MMF to inhibit proliferation of BECs (P<0.05) was 500, 100, 0.25, and 100 mug/L, respectively. However, the expression of CK19 by BECs was not changed. CONCLUSION: CsA, FK-506, RAD, and MMF have an antiproliferative effect on human intrahepatic BECs in vitro, while RAD has the strongest growth-inhibitory effect. Their possible effects on liver regeneration and bile duct injury in transplant patients should be further investigated.

Which patients benefit from hemodialysis therapy in hepatorenal syndrome?

BACKGROUND AND AIM: Hepatorenal syndrome (HRS) occurs in patients with advanced liver cirrhosis and has a poor outcome. The aim of the present study was to investigate which patients with HRS are likely to benefit from hemodialysis. METHODS: Data were collected prospectively from 30 patients with Child-Pugh C liver cirrhosis and HRS. Patients were either treated with continuous veno-venous hemodialysis (CVVHD) if they were mechanically ventilated, or with intermittent hemodialysis (HD) if they were not mechanically ventilated. Prognosis was assessed by the Child-Pugh and by the Model for End-Stage Liver Disease (MELD) score. The primary aim of the study was the analysis of overall and 30-day patient survival during hemodialysis therapy. To identify predictive factors of survival, variables obtained before the initiation of dialysis therapy were evaluated. RESULTS: Patients' 30-day survival was 8/30 (median survival time 21 days). Among patients treated with mechanical ventilation, 30-day survival time was 0/15 while 8/15 patients without mechanical ventilation survived more than 30 days (P < 0.001). Using a multivariate model, the relative hazards for serum albumin, international normalized ratio (INR) and catecholamine therapy were not different from one another (P > 0.05), indicating that these parameters were not independent predictors of survival. Mechanical ventilation was an independent risk factor for 30-day (relative hazard 6.6 [1.6-27.7], P < 0.001) and overall survival (relative hazard 6.3 [1.5-26.5], P = 0.01). Child-Pugh (P < 0.01) and the MELD (P < 0.01) score were predictive for overall survival independent of mechanical ventilation. CONCLUSIONS: Patients with HRS without mechanical ventilation may benefit from hemodialysis, whereas hemodialysis seems to be futile in patients with mechanical ventilation.

Presence of markers for liver progenitor cells in human-derived intrahepatic biliary epithelial cells.

AIMS: Rodent intrahepatic bile duct may harbor bipotential liver progenitor cells. In this study, human-derived intrahepatic biliary epithelial cells (BECs) were investigated in terms of whether they have the character of liver progenitor cells. METHODS: Ten liver tissue specimens were obtained after partial hepatectomy or liver explantation. Intrahepatic BECs were isolated by density-gradient centrifugation and immunomagnetic separation using anti-human epithelial antigen and cultured in medium containing epidermal growth factor and hepatocyte growth factor. The isolated and cultured cells were characterized by immunostaining and reverse transcription polymerase chain reaction with a variety of markers for fetal hepatocytes and liver progenitor cells. RESULTS: These cells had proliferated for up to 18 weeks in vitro. They continuously expressed epithelial markers (cytokeratin (CK) 8 and CK 18) as well as biliary markers (CK 7 and CK 19). Remarkably, some isolated and cultured cells also expressed markers for fetal hepatocytes and liver progenitor cells, including albumin, alpha-fetoprotein, alpha1-antitrypsin, c-kit and chromogranin-A. CONCLUSION: Some human-derived intrahepatic BECs coexpressed markers for liver progenitor cells. This finding further supports the hypothesis that the human biliary tree may also consist of liver progenitor cells.

Serum C3 complement concentrations correlate with liver function in patients with liver cirrhosis.

BACKGROUND/AIMS: The aim of this study was to investigate whether C3 and C4 serum complement concentrations have prognostic relevance for patients with liver cirrhosis. METHODOLOGY: Serum complement concentrations of C3 and C4 were measured in 69 patients with liver cirrhosis and correlated with the Child-Pugh score. RESULTS: C3 concentrations were 1.06+/-0.21 g/L in patients with Child-Pugh A liver cirrhosis and significantly lower in Child-Pugh B (0.78+/-0.24 g/L) and even lower Child-Pugh C (0.49+/-0.14 g/L) (p=0.006 B vs. A, p<0.001 C vs. B). Patients with consecutive hepatorenal syndrome (HRS) had the lowest C3 concentrations (0.44+/-0.05 g/L (Child-Pugh C +HRS) vs. 0.54+/-0.06g/dL (Child-Pugh C -HRS); p<0.05). C4 concentrations were 0.21+/-0.08 in Child-Pugh A and significantly lower in Child-Pugh B (0.11+/-0.04) and Child-Pugh C (0.09+/-0.04) patients (p<0.001). There was a negative correlation between C3 (r = -0.81, p<0.001) and C4 (r = -0.51, p<0.05) concentrations and the Child-Pugh score. CONCLUSIONS: Serum complement concentrations of C3 and C4 correlate negatively with the Child-Pugh score in patients with liver cirrhosis. C3 concentrations are lower in those Child-Pugh C cirrhosis patients with consecutive development of HRS.

Asialoglycoprotein receptor facilitates hemolysis in patients with alcoholic liver cirrhosis.

Hemolysis in patients with advanced alcoholic liver disease is a common clinical problem and indicates an unfavorable prognosis. In many cases, the etiology of the hemolysis remains unknown. We observed three patients with alcoholic liver disease, suffering from severe hemolytic anemia, requiring multiple blood transfusions. Steroid therapy was ineffective and two of the patients died. All patients had a soluble variant of the human asialoglycoprotein receptor (s-ASGP-R) in their serum, as well as high titers of autoantibodies against this receptor (anti-ASGP-R). Consecutively, examination of 60 patients with alcoholic liver disease revealed a high incidence for s-ASGP-R (36%) and anti-ASGP-R (27%) in patients with alcoholic liver cirrhosis (ALC) compared to patients with cirrhosis due to viral hepatitis. The potential etiology of hemolysis was studied in vitro on erythrocytes from patients with ALC and from healthy donors. Isolated ASGP-R but not anti-ASGP-R bound to the surface of erythrocytes preferentially of blood group A1 and caused dose-dependent agglutination and hemolysis, while this phenomenon was much lower using erythrocytes of the blood group B and almost absent with blood group O-erythrocytes. Furthermore, agglutination and hemolysis only occurred in erythrocytes from ALC-patients or after the pre-treatment of cells with neuraminidase. ASGP-R induced agglutination and hemolysis was blocked by the competitive ASGP-R inhibitor asialofetuin. In conclusion, our results indicate a new, non-immunological mechanism for hemolysis in patients with alcoholic liver disease, mediated through agglutination by a soluble variant of the human asialoglycoprotein receptor and mechanical shear stress.

Aortoesophageal fistula secondary to stent-graft repair of the thoracic aorta.

PURPOSE: To report the incidence and management of aortoesophageal fistula (AEF) secondary to endovascular stent-graft repair of the descending thoracic aorta. METHODS: A retrospective review was conducted of patients treated at our facility between July 1999 and June 2003. During this interval, 60 patients (46 men; average age 66+/-10 years) underwent thoracic aortic stent-graft placement for a variety of pathologies. RESULTS: AEF occurred in 3 (5%) patients. One 62-year-old man presented with recurrent back pain and fever and died suddenly due to fatal exsanguination; the AEF was revealed at necropsy. The other 2 patients (both women) presented with hematemesis after endovascular repair of thoracic aortic aneurysms. AEF was detected by esophagogastroduodenoscopy. Both patients were treated conservatively, as open surgical repair was refused because of their general condition. Both patients developed severe mediastinitis and died after 5 weeks and 10 months, respectively. CONCLUSIONS: Aortoesophageal fistula is, in our experience, a catastrophic complication of endovascular stent-graft placement. Treatment options are very limited, as these patients are usually not candidates for open surgery. Outcome under conservative management is, however, almost invariably fatal.

Right living donor liver transplantation: an option for adult patients: single institution experience with 74 patients.

OBJECTIVE: To present an institutional experience with the use of right liver grafts in adult patients and to assess the practicability and efficacy of this procedure by analyzing the results. SUMMARY BACKGROUND DATA: Living donor liver transplantation (LDLT) for the pediatric population has gained worldwide acceptance. In the past few years, LDLT has also become feasible for adult patients due to technical evolution in hepatobiliary surgery and increased experience with reduced-size and split-liver transplants. Nevertheless, some graft losses remain unexplained and are possibly due to unrecognized venous outflow problems. METHODS: From April 1998 to September 2002, we performed 74 right LDLTs (segments 5-8). The 74 donors were selected from 474 candidates according to standard protocol. The median age of the donors was 35 years (range 18-58 years) and 51 years (range 18-64 years) in recipients. Standard and extended indications for transplantation were considered. Over the period reported, technical modifications in the bile duct anastomosis (duct-to-duct, end-to-end, or end-to-side) and a new graft implantation technique that provides maximized venous outflow, leading to outcome improvement, were developed. RESULTS: 64.9% of patients had liver cirrhosis and 35.1% had malignancy. While 44 donors (59.5%) presented an uneventful postoperative course, 27% minor (pleural effusion, pneumonia, venous thrombosis, wound infection, incisional hernia) and 13.5% major (biliary leakage, death of a donor due to unrecognized hereditary liver disease, and consecutive liver insufficiency) complications were documented. In recipients, 23% biliary complications and 6.8% hepatic artery thrombosis occurred. The overall patient and graft survival rate after 1 year was 79.4% and 75.3%, respectively. In cases with extended indication, the patient survival rate was 74% and the graft survival rate 68% at 12 months. Using technical modifications in the last 10 recipients, including 2 critically decompensated cirrhotics, the survival rate was 100% at a median follow-up of 3.5 months. CONCLUSIONS: In our transplant program, living donor liver transplantation has become a standard option in the adult patient population. The critical issue of this procedure is donor morbidity. Technical improvements in the harvesting and implantation of right grafts can also offer hope to patients with challenging forms of end-stage liver disease or malignant liver tumors.

Efficacy of combined lamivudine and adefovir dipivoxil treatment for severe HBV graft reinfection after living donor liver transplantation.

Resistance to lamivudine and hyperimmune globulin (HBIG) may cause severe graft reinfection with progression to fulminant hepatic failure in liver transplant recipients. In this report, we describe the clinical course of a patient with perinatally acquired chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma who developed severe fibrosing cholestatic hepatitis after living donor liver transplantation because of the emergence of lamivudine and HBIG-resistant chronic hepatitis B. Immunohistochemistry demonstrated that more than 30% of hepatocytes stained positively for hepatitis B core antigen. Hepatitis B virus sequence analysis revealed several mutations in the polymerase gene (L528M, M552I, M552V) as well as in the surface gene region encoding the immunogenic major hydrophilic loop of the small surface protein (G130N, M133T, D144G). The amino acid exchange at codon 144 has already been described to escape neutralization by HBIG. Combined treatment with lamivudine and adefovir dipivoxil (ADV) was associated with a dramatic biochemical, virological and clinical response with resolution of jaundice, ascites, peripheral edema and pleural effusions. Serum bilirubin normalized, HBV DNA levels significantly decreased and liver biopsy was remarkable for the absence of viral protein. These results indicate that ADV may provide a sustained rescue treatment for aggressive courses of HBV graft reinfection in liver transplant recipients.

Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study.

Patients with liver cirrhosis and a superimposed acute injury with progressive hyperbilirubinemia have a high mortality. A prospective, controlled study was performed to test whether hyperbilirubinemia, 30-day survival, and encephalopathy would be improved by extracorporeal albumin dialysis (ECAD). Twenty-four patients were studied; 23 patients had cirrhosis; 1 had a prolonged cholestatic drug reaction and was excluded from per protocol (PP) analysis. Patients had a plasma bilirubin greater than 20 mg/dL and had not responded to prior standard medical therapy (SMT). Patients were randomized to receive SMT with ECAD or without (control). ECAD was performed with an extracorporeal device that dialyzes blood in a hollow fiber dialyzer (MW cutoff < 60 kd) against 15% albumin. Albumin-bound molecules transfer to dialysate albumin that is regenerated continuously by passage through a charcoal and anion exchange column and a conventional dialyzer. ECAD was associated with improved 30-day survival (PP, 11 of 12 ECAD, 6 of 11 controls; log rank P <.05). Plasma bile acids and bilirubin decreased on average by 43% and 29%, respectively, in the ECAD group after 1 week of treatment, but not in the control group. Renal dysfunction and hepatic encephalopathy improved in the ECAD group, but worsened significantly in the control group. ECAD was safe, with adverse events being rare and identical in both groups. In conclusion, ECAD appears to be effective and safe for the short-term treatment of patients with cirrhosis and superimposed acute injury associated with progressive hyperbilirubinemia and may be useful for increasing survival in such patients awaiting liver transplantation.

Living-related liver transplantation from the view of the donor: a 1-year follow-up survey.

BACKGROUND: In the past, follow-up surveys for living-related liver transplantation (LRLT) mainly focused on the medical outcome of recipients and donors. In this survey the prevalence of personal, familial, or economic problems of the donors and changes of quality of life after donation were studied. METHODS: Questionnaires were sent to 24 donors after right hepatectomy for LRLT (response 92%). The modified EUROTOLD (European Multicenter Study of Transplantation Using Living Donors) questionnaire was used to inquire about the decision-making process, family problems, and economic problems related to the donation. Global quality of life was measured with the SF-36 Health Survey. RESULTS: For most donors the decision to donate was easy or not very difficult (21/22) and was made spontaneously (17/22). The amount of information about the risks of LRLT was limited at the time of decision but increased remarkably immediately before the operation. In 28%, family conflicts occurred (5/22). Retrospectively, all but two donors (91%) would donate again. On average, donors started working after 9 (+/-3.7) weeks and felt fully recovered after 13 (+/-7.3) weeks. Adverse financial affects were experienced by 41% of the donors (9/22) because of the donation, and four of those received a compensation. Importantly, quality of life did not differ between donors and nondonors. CONCLUSION: Donors viewed LRLT positively. Quality of life after donation did not change. However, donors had a prolonged period of physical rehabilitation, and 41% experienced financial disadvantages.