Ulrich Treichel

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.

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.

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.

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. Liver Transpl 12:88–94, 2006.

Interaction of Hypericum perforatum (St. John's wort) with cyclosporin A metabolism in a patient after liver transplantation

Immunosuppressive therapy in patients after liver transplantation requires careful monitoring of blood levels for immunosuppressive agents such as cyclosporin A. A variety of drugs are capable of interfering with the metabolism of cyclosporin A. We observed a 63-year-old patient who received a liver allograft for cryptogenic liver cirrhosis in 1998. This patient developed severe acute rejection 14 months after transplantation which was associated with a sudden drop in cyclosporin A levels. Two weeks previously, he had started taking the herbal drug Hypericum perforatum (2 x 900 mg/day) for increasing episodes of depression. The cyclosporin A dosage later had to be doubled, which caused some side effects. Finally, an assessment of oral cyclosporin A resorption suggested an enhanced cyclosporin A metabolism. Hypericum perforatum was stopped. Both cyclosporin A dosage and blood levels immediately returned to normal. The liver function recovered completely. In conclusion, this observation is a previously undescribed drug interaction of a widely used herbal drug (Hypericum perforatum, i.e. St. Johns wort) in a patient after 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.

Demographics of anti-asialoglycoprotein receptor autoantibodies in autoimmune hepatitis

BACKGROUND/AIMS The asialoglycoprotein receptor (ASGPR) is an established, liver-specific autoantigen. This multicenter study investigated the specificity of anti-ASGPR autoantibodies for autoimmune hepatitis (AIH) in different ethnic groups. METHODS Nine hundred fourteen sera from European, Japanese, and North American (U.S.) patients with chronic inflammatory liver disorders were tested. An enzyme-immunoassay using human ASGPR and a radioimmunoassay against rabbit ASGPR, performed independently on coded sera, were compared. RESULTS The highest frequency (76%) of anti-human ASGPR was found in AIH patients (11/24 U.S.; 21/25 European; 28/30 Japanese), particularly in those with active disease before treatment (53/62, 85%), and decreased in titer with response to immunosuppressive therapy. These antibodies were found at low titers in 43 (11%) of 385 patients with viral hepatitis and in 25 (7.6%) of 328 patients with other chronic inflammatory liver disorders (P < 0.0005 compared with all AIH patients). Twenty of 37 sera tested by enzyme-immunoassay and radioimmunoassay were positive, and nine were negative for anti-ASGPR by both assays (78% concordance); six sera were exclusively positive on human substrate. CONCLUSIONS Circulating anti-ASGPR autoantibodies are closely associated with autoimmune hepatitis independent of geographic or ethnic criteria. Two anti-ASGPR assays currently in use show high reliability.

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.

Receptor-mediated entry of hepatitis B virus particles into liver cells

SummaryIn previous reports several receptors for either natural hepatitis B virus (HBV) particles or genetically engineered virus have been described, whereby endocytosis represents a putative uptake mechanism for HBV particles. We have found that HBV-particles from viremic carriers could bind to the human asialoglycoprotein receptor (ASGPR), which mediates glycoprotein uptake into liver cells. The HBV-ASGPR interaction was studied in a cell culture system using hepatoma HepG2 and HuH7 cells compared to COS cells as controls. About 50% of HBsAg-secretion into the cell culture supernatant after HBV-inoculation as a function of HBV-uptake could be inhibited by the specific ASGPR-ligand asialofetuin. COS-cells did not show HBsAg-secretion. If the cells were grown as clones, 15% of HepG2-cells demonstrated HBsAg-secretion but only 5% in the presence of asialofetuin. HBV-particle uptake was further confirmed by HBV-DNA analysis using PCR. HBV-ASGPR interaction was studied with purified, biotin-conjugated human ASGPR. Quantitative inhibition with asialofetuin indicated a high-affinity binding of HBV-particles to purified ASGPR. After denaturing polyacrylamid gel electrophoresis and transblotting of isolated HBV-particles a receptor-blotting system was established which identified distinct binding sites for biotinylated receptors.These results suggest that the ASGPR is capable of specifically binding HBV-particles and, moreover, to mediate their hepatic endocytosis which ultimately could be responsible for the HBV-infection of liver cells.

Autoantibodies against the human asialoglycoprotein receptor: Effects of therapy in autoimmune and virus-induced chronic active hepatitis

The hepatic asialoglycoprotein receptor (ASGPR) was recently identified as a target antigen for both humoral and cellular immune response in inflammatory liver diseases. Thereby anti-ASGPR autoantibodies directed against human substrate were closely associated with autoimmune chronic active hepatitis. The present study compares the occurrence, titer and immunoglobulin classification of anti-human(h-)-ASGPR antibodies in 23 patients with newly diagnosed autoimmune chronic hepatitis before and after initiation of immunosuppressive therapy to 22 patients with autoimmune hepatitis in remission. Additionally, 1-year follow-up examinations of 42 patients with HBsAg-positive chronic hepatitis and of 32 patients with chronic hepatitis C receiving recombinant interferon-alpha were included. Nineteen of 23 patients with newly diagnosed and 9/22 with autoimmune hepatitis in remission, 5/42 with untreated chronic hepatitis B and 5/32 patients with chronic hepatitis C exhibited anti-h-ASGPR at the beginning of the study. In autoimmune hepatitis anti-h-ASGPR were found in higher titers (median > 1:1000) than in viral hepatitis (maximum 1:400). After initiation of immunosuppressive therapy in autoimmune hepatitis anti-h-ASGPR decreased sharply. Eight of 19 patients eliminated anti-h-ASGPR within 18 months in contrast to 11 patients with persistent anti-h-ASGPR titer over 18 months and longer. Anti-h-ASGPR with maximum titer of 1:600 were detected in 5 patients with chronic hepatitis B (transiently in 4/5 patients) and in 2 patients with chronic hepatitis C during interferon-alpha. Anti-h-ASGPR were from immunoglobulin classes IgG and IgM in cases with untreated autoimmune hepatitis and chronic hepatitis B and C exhibiting mainly IgG2-subclass in autoimmune and IgG4 in viral hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)