Orthotopic liver transplantation in human-immunodeficiency-virus-positive patients in Germany.

Objectives. This summary evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-positive patients in Germany. Methods. Retrospective chart analysis of HIV-positive patients, who had been liver-transplanted in Germany between July 1997 and July 2011. Results. 38 transplantations were performed in 32 patients at 9 German transplant centres. The reasons for OLT were end-stage liver disease (ESLD) and/or liver failure due to hepatitis C (HCV) (n = 19), hepatitis B (HBV) (n = 10), multiple viral infections of the liver (n = 2) and Budd-Chiari-Syndrome. In July 2011 19/32 (60%) of the transplanted patients were still alive with a median survival of 61 months (IQR (interquartile range): 41-86 months). 6 patients had died in the early post-transplantation period from septicaemia (n = 4), primary graft dysfunction (n = 1), and intrathoracal hemorrhage (n = 1). Later on 7 patients had died from septicaemia (n = 2), delayed graft failure (n = 2), recurrent HCC (n = 2), and renal failure (n = 1). Recurrent HBV infection was efficiently prevented in 11/12 patients; HCV reinfection occurred in all patients and contributed considerably to the overall mortality. Conclusions. Overall OLT is a feasible approach in HIV-infected patients with acceptable survival rates in Germany. Reinfection with HCV still remains a major clinical challenge in HIV/HCV coinfection after OLT.

[Management of iatrogenic esophageal perforations]. / Management iatrogener Osophagusperforationen.

BACKGROUND: Iatrogenic esophageal perforations are still a life-threatening clinical entity. PATIENTS AND RESULTS: We present the case reports of six patients to demonstrate different treatment options and we focus on new therapeutic strategies which have evolved in the interdisciplinary management of iatrogenic esophageal perforations. Two patients with perforations in the cervical esophagus were operated and in another patient the perforation was closed with fibrin glue. Three patients with perforations in the thoracic esophagus were treated with self-expandable plastic stents. CONCLUSION: The surgical therapy of esophageal perforations still is regarded to be the gold standard and nonadherence should only be considered based on interdisciplinary decisions in individual cases. However, positive results are increasingly being reported for conservative endoscopic treatment, particularly for thoracic perforations.

Successful sealing of benign esophageal leaks after temporary placement of a self-expanding plastic stent without fluoroscopic guidance.

INTRODUCTION: We report on our experience with the temporary use of a self-expanding plastic stent (SEPS) in the treatment of non-malignant esophageal leaks. MATERIAL AND METHODS: Between November 2001 and May 2005 ten patients with iatrogenic esophageal perforations (n = 4), post-surgical leaks (n = 5) and esophago-mediastinal fistulas after caustic injury (n = 1) were treated by temporary SEPS placement. In eight out of ten patients SEPS placement was done without fluoroscopy due to the emergency setting. Stent removal was performed with a rat-toothed forceps. RESULTS: Leaks were located in the proximal (n = 1), middle (n = 6) and distal (n = 3) parts of the esophagus. The mean leakage size was 2 cm. Stent placement without fluoroscopy was always successful. The median duration of stent therapy was 55.5 days (range 15,438). In 7/10 cases the SEPS was readily removed, showing complete healing of the former leak. Four patients died during the follow-up. However, their deaths were not related to the stent therapy. DISCUSSION: The temporary use of the SEPS represents a safe method for sealing benign esophageal leaks. In the emergency-setting SEPS placement without fluoroscopy is feasible and the stent can be easily removed. In contained perforations without severe mediastinitis of the mid esophagus the SEPS should be discussed as a gentle first-line therapy.

[Organ transplantation in human immunodeficiency virus-infected patients. Results of a survey in German transplantation centres]. / Vollorgantransplantation bei Patienten mit HIV-Infektion. Ergebnisse einer Umfrage an deutschen Transplantationszentren.

BACKGROUND: Despite considerable advances following the introduction of highly active antiretroviral therapy, organ transplantation is usually denied categorically for human immunodeficiency virus (HIV) patients, and it is presented in German transplantation law as a contraindication. Today, this should be questioned critically. METHOD: A survey at all 87 German transplant centres was done concerning (1) how many HIV-positive patients were transplanted before and after February 2000, (2) willingness of the centres to transplant HIV-infected patients in the future, and (3) course of transplanted HIV patients so far. RESULTS: With a response rate of 78%, 39% of the questioned centres were accepting HIV patients in the future for transplantation, and 39% rejected this. Twenty percent voted for individual case decision. Three centres had practiced liver transplantation in 11 patients. CONCLUSION: The decision to transplant HIV-positive patients in Germany is mostly based on individual cases and not refused in general. However, prospective studies on this issue are justified and needed.

Sustained suppression of HCV replication and inflammatory activity after interleukin-2 therapy in patients with HIV/hepatitis C virus coinfection.

OBJECTIVE: There is increasing evidence that coinfection of hepatitis C (HCV) with HIV is associated with accelerated progression of liver cirrhosis. The aim of this pilot study was to investigate toxicity and efficacy of interleukin-2 (IL-2) for treatment of affected patients. DESIGN: Because low-dose, daily IL-2 therapy is well tolerated and can elevate CD4 cell counts and improve immune functions, patients were treated with 1-2 million units (MU) IL-2 subcutaneously daily. METHODS: This pilot trial included 7 HIV/HCV-coinfected individuals. During therapy, clinical, virologic, and laboratory parameters were closely monitored. RESULTS: All patients responded to IL-2 therapy with either improvement of either CD4 cell counts or liver function test results. In 2 patients, HCV-RNA in serum became negative 2 and 4 months, respectively, after cessation of therapy. HCV-RNA has remained undetectable in these 2 patients for 18 and 24 months, respectively. Therapy was well tolerated and no grade III or IV toxicities were observed. CONCLUSIONS: Low-dose, daily IL-2 therapy can improve both CD4 cell counts and liver function test results in patients with HIV/HCV coinfection and may in some cases lead to sustained suppression of viremia of HCV.

Selection of hepatitis B virus variants with aminoacid substitutions inside the core antigen during interferon-alpha therapy.

The hepatitis B virus (HBV) core antigen carries many epitopes relevant for B and T cell response that show aminoacid variation during viral infection. In a longitudinal analysis, sequential serum samples of 15 patients that suffered from chronic HBV infection were collected before, during, and after high-dose IFN-alpha treatment. The HBV preCore/Core (preC/C) sequence of the selected samples in each patient was determined and analysed for sequence variations compared to the pretreatment sample. The positions of HBV core aminoacid substitutions were assigned to immunodominant B, CD4(+) and CD8(+) cell epitopes. Seventy-five percent of all aminoacid substitutions were found within immunodominant T and B cell epitopes (12.5% were inside known HBV core mutation cluster regions) that show an increased number of clustered aminoacid substitutions during chronic HBV infection and overlap partially with the immunodominant epitopes. Only 12.5% of the detected core antigen aminoacid substitutions could not be assigned to any epitope or mutation cluster region. Stable HBV core antigen aminoacid substitutions, which were found between pretreatment sequence and the last sequence analysed during therapy, were found most frequently inside T helper cell epitopes. This longitudinal analysis of aminoacid substitutions inside the HBV core antigen in patients with chronic HBV infection shows that core aminoacid variations occur most frequently inside immunodominant HBV core epitopes, possibly due to an immuneselective pressure of the host against the virus. The data also suggest that stable HBV variants with aminoacid substitutions in immunodominant core epitopes can be selected during high-dose IFN-alpha therapy and persist after the end of treatment.