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Biomedical subjects

M Sterneck

Publications and source records attributed to M Sterneck.

At least 37 records · Page 2Linked to original sources
PubMed1999

Liver transplantation for acute liver failure.

Under conservative management, the mortality rate of acute liver failure is very high. Liver transplantation is an established life-saving therapy, offering survival rates between 60 and 90%. The decision for liver transplantation should be based on prognostic criteria, including patient's age, aetiology of liver disease, degree and onset of encephalopathy, serum bilirubin, prothrombin time or international normalized ratio (INR), serum creatinine, factor V level and arterial pH. Auxiliary liver transplantation is becoming an attractive treatment modality, allowing temporary bridging of liver function until recovery of the native liver. For children with acute liver failure, living related transplantation represents an additional option. In adult patients, living donation is not yet established since the maximum extent of liver resection safely tolerated and the amount of liver tissue necessary for sufficient graft function is still a matter of debate.

Adolescent↗
PubMed1998

Functional analysis of HBV genomes from patients with fulminant hepatitis.

Two previous case reports suggest that hepatitis B virus (HBV) core promoter variants with a high replication competence contribute to the pathogenesis of fulminant hepatitis B (FHB). We recently found in HBV genomes from patients with FHB an accumulation of mutations within the core promoter region. Therefore, the aim of this study was to investigate the phenotype of these HBV variants. Replication competence and expression of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) of viral genomes from seven patients with FHB and one patient with fulminant recurrent hepatitis after liver transplantation were analyzed by transfection experiments in human hepatoma cells. Compared with wild-type virus, the HBV variants from the seven patients with FHB produced similar or slightly lower levels of intracellular replicative intermediates and extracellular viral particles. In contrast, the HBV genomes from the patient with fulminant recurrent hepatitis synthesized and secreted significantly more HBV DNA. All genomes tested expressed similar or even higher levels of HBeAg compared with wild-type virus, except for those from four patients with a precore stop codon mutation in the respective dominant viral populations. The level of HBsAg produced by all variant genomes was similar or reduced compared with wild-type virus. These data indicate that in some cases HBV variants with enhanced replication competence and/or a defect in HBeAg expression may contribute to the development of FHB. However, neither phenotype is an essential prerequisite; thus, an additional role of other viral or host factors in the pathogenesis of FHB is suggested.

Base Sequence↗
PubMed1998

Vertebral osteomyelitis due to Rhodococcus equi in a liver transplant recipient.

Rhodococcus equi is a rare but well-documented cause of cavitary pneumonia in immunocompromised patients. In this report the first case of R. equi infection manifesting as vertebral osteomyelitis is described. A 39-year-old liver transplant recipient presented with recurrent pneumonia and a pleura-based lung abscess and subsequently developed osteomyelitis of the lower thoracic spine. Surgical debridement and prolonged treatment with rifabutin and clarithromycin resulted in clinical cure. In the literature, 12 other cases of R. equi infection in solid-organ transplant recipients have been reported. Ten of these patients had documented pulmonary disease and seven had extrapulmonary manifestations. Prolonged antibiotic therapy and surgical drainage resulted in clinical improvement in > 90% of the reported cases.

Actinomycetales Infections↗
PubMed1998

Neonatal fulminant hepatitis B: structural and functional analysis of complete hepatitis B virus genomes from mother and infant.

Transmission of hepatitis B virus (HBV) from anti-hepatitis B e (anti-HBe)-positive carrier mothers to their infants may result in neonatal fulminant hepatitis B (FHB). We investigated whether HBV variants with a particular DNA sequence and functional phenotype, responsible for FHB, are selected during transmission. Full-length HBV genomes from a mother-infant pair were completely sequenced and transfected into human hepatoma cells. The dominant neonatal and maternal HBV populations were nearly identical (homology 99.8%) and showed a precore stop codon mutation, T-1762 and A-1764 substitutions in the core promoter region, and pre-S2 start codon mutations. Cells transfected with variants from mother and child, compared with wild-type virus, synthesized and released a similar number or fewer HBV DNA-containing particles. In conclusion, no particular HBV strain emerged during neonatal FHB. In this case, a de novo infection with variants showing a defect in HBe antigen and pre-S2 protein synthesis but not a high replication competence probably contributed to the fulminant disease course.

Adult↗
PubMed1998

Carbohydrate-deficient transferrin: diagnostic efficiency among patients with end-stage liver disease before and after liver transplantation.

We tested the diagnostic validity of carbohydrate-deficient transferrin (CDT) as an indicator for relapse into elevated alcohol consumption among patients who were examined under follow-up treatment before (n = 147) and after (n = 102) orthotopic liver transplantation (OLT) in the outpatient-department of the University Hospital Department of Surgery in Hamburg-Eppendorf. CDT measurements were performed with two commercial kits in parallel (CDTect-RIA and CDT%-RIA). Short-term parameters of alcohol consumption (ethanol, methanol) indicated relapses into elevated alcohol consumption in 11.4% of the evaluated patients with alcoholic liver disease (ALD) before transplantation. Before OLT, median CDT values were determined to be elevated among patients with alcoholic as well as nonalcoholic end-stage liver diseases (NALD). Among patients with ALD, we found elevated CDT medians even in those who were successfully scheduled for OLT after long-term evidence of abstinence proved by biochemical short-term parameters and psychological tests. Both CDTect and CDT% assays had comparable low specificities in selected patient groups before transplantation. CDT% and CDTect were negatively correlated with the albumin level. Before the study ended, CDT was no longer implemented in the evaluation of whether an OLT should be administered. This was due to inconsistent results of CDT in ALD as well as NALD. After OLT, patients with ALD, as well as NALD, had statistically significant lower CDT medians than before OLT, which ranged within reference levels. We determined, according to CDT, elevated alcohol consumption subsequent to OLT in 4 of 13 patients with ALD who underwent transplantation during the study (median observation period: 10 months). CDT does not appear to be useful in evaluating patients before OLT. With regained specificity and high sensitivity in patients after OLT, CDT could be recommended as a standard instrument for quality control in patients with ALD after liver transplantation.

Adult↗
PubMed1998

Amplification of full-length hepatitis B virus genomes from samples from patients with low levels of viremia: frequency and functional consequences of PCR-introduced mutations.

To facilitate the investigation of hepatitis B virus (HBV) sequence variation, we recently established a method for functional analysis of PCR-amplified full-length HBV genomes. This study aimed at estimating the number of mutations introduced during amplification of genomes from samples from patients with low levels of viremia and their influence on replication and antigen expression. Wild-type HBV DNA template molecules in concentrations like those present in samples from patients with very low levels of viremia were amplified, sequenced (30 kb total), and functionally tested. We found that Taq polymerase and a Taq-Pwo polymerase mixture introduced an average of 5.7 and 3.1 mutations per genome, respectively, corresponding to polymerase error rates of 12.1 x 10(-5) and 6.0 x 1(0-5). One of 8 genomes (12%) amplified with Taq polymerase, but 7 of 17 genomes amplified with Taq-Pwo polymerases (41%), remained replication competent. All replication-competent genomes expressed HBs and HBe antigens and had an average of only 0.9 mutations per genome. In contrast, replication-defective genomes had an average of 5.4 mutations, which frequently also disturbed viral antigen expression. From these data we conclude that many of the replication-competent HBV genomes from a clinical specimen will retain their replication and antigen expression phenotypes even after extensive amplification with Taq-Pwo polymerases. Because replication competence is highly sensitive to random mutations, it is the best marker for the identification of HBV genomes with few or no PCR-introduced mutations.

Cloning, Molecular↗
PubMed1997

A new class of defective hepatitis B virus genomes with an internal poly(dA) sequence.

Sequence heterogeneity of hepatitis B virus (HBV) is increasingly recognized to play a role in virus-host interaction. We have used a recently established method for HBV full-length genome amplification to search for novel types of HBV variants and to investigate further the sequence heterogeneity of HBV genome populations. Using this method, a substantial fraction of HBV genomes much shorter than wildtype size was found in some sera and liver biopsies from infected patients. Cloning and sequencing of a number of these HBV genomes as well as hybridization studies revealed a new minor class of HBV genomes with an internal poly(dA) sequence approximately 60 to more than 100 nucleotides long in 4 of 10 patients. The 5'-ends of the internal poly(dA) sequences are located at positions corresponding to the authentic processing/polyadenylation sites of the RNA pregenome, whereas the positions of the 3'-ends are variable due to different sizes of adjacent deletions. These data suggest that the poly(A) tail of the pregenomic RNA is occasionally reverse transcribed by the HBV P-protein and during this process a deletion seems to be introduced into the DNA minus strand. We propose a mechanism by which this could be accomplished during DNA minus strand synthesis.

Base Sequence↗
PubMed1997

Hepatitis B virus sequence changes evolving in liver transplant recipients with fulminant hepatitis.

BACKGROUND/AIMS: Patients undergoing liver transplantation for hepatitis B virus (HBV) related liver cirrhosis are at major risk of developing HBV recurrence, and occasionally fulminant hepatitis. Here we tested in a longitudinal study whether specific viral variants are associated with fulminant HBV infection in the graft. METHODS: The complete HBV genomes isolated from the sera of three patients with HBV and HBV and hepatitis delta virus (HDV) coinfection during chronic infection before and during fulminant reinfection after transplantation were amplified and directly sequenced. RESULTS: Twenty, 25 and 19 mutations, distributed over the entire genome, were identified which differed between the HBV genomes isolated from each patient during chronic and fulminant infection, respectively. This reflects a much higher rate of nucleotide sequence changes than expected from the natural variation of HBV. No common HBV mutation emerged in any of the three cases during fulminant infection. However, precore defective viruses were found to be present in all three patients at the time of fulminant infection and in two of the patients before fulminant infection. Two of the patients had preS2-defective HBVs both before and after transplantation. A point mutation in the 'a'-determinant of the surface protein emerged in one case after transplantation under treatment with polyclonal HBV specific immunoglobulins. CONCLUSIONS: Many new, but no specific common mutations emerged during fulminant HBV reinfection. Although HBeAg defective variants were found in all cases studied, the presence of these variants also during chronic infection in two cases demonstrates that they are not sufficient to cause fulminant hepatitis. Thus, other factors than the emergence of a specific viral strain seem to contribute to the development of fulminant reinfection in a liver graft.

Adult↗
PubMed1997

The Hamburg liver transplant program.

The program of the University of Hamburg is exemplary of the problems faced by programs with rapid growth. Establishing expertise at all levels is essential to shorten the inevitable learning curve. The combination of an adult and a pediatric program was an ideal environment for the development of living donation and cadaveric in-situ split liver transplantation as complimentary solutions to eliminate pediatric mortality on the waiting list without affecting the chances of adult liver transplant candidates.

Adolescent↗
PubMed1996

One year of experience with extended application and modified techniques of split liver transplantation.

As organ donation rates decreased in Europe, the authors started a systematic approach of liver splitting in their center in 1994. During this 1-year experience, 73 cadaveric liver transplantations were performed in 66 patients. Sixteen of these transplantations were the result of split-liver transplantation (21.9% of grafts, 24.2% of patients). Patient and graft survival rates at 3 months were 81.2% and 75%, compared with 89.1% and 76.9 % for whole organs. Two modified techniques were developed, based on the technique of living related liver procurement, and applied in 10 cases. With these new techniques, patient and graft survival rates were 90% and 90%. This systematic approach allowed the total number of transplantations in our program to be maintained, despite the decrease in organ availability.

Graft Survival↗
PubMed1996

[Selection of live donors for segmental liver transplantation in children].

OBJECTIVE: To analyse selection criteria and complications in living related donors of liver segments with a view to introducing standardised guidelines for the selection of such donors. PATIENTS AND METHODS: Forty-two mothers and 31 fathers (median age 31 [19-50] years) were tested between October 1991 and July 1994 for their suitability as donors of a liver segment. RESULTS: 24 of the potential donors (33%) were found not to be suitable. Reasons for this were: poor immunological match of the donor liver as transplant (13), risk factors for thromboembolism (5), and psychological or socioeconomic factors (6). 35 live related donor liver segment transplantations were performed, 34 of the left lateral liver segment, and one of the left liver lobe. The average duration of the operation was 4.5 (3.0-6.0) hours. No foreign blood transfusions were needed. There was one death from pulmonary emboli, and various complications: cerebral seizure (1), gallbladder leak (1), incisional hernia (2) and duodenal ulcer (2). CONCLUSION: Risk of thromboembolism as well as psychological and social factors are the most important exclusion criteria in the selection of donors for live liver segment transplantation.

Adolescent↗
PubMed1996

Hepatitis B virus genomes of patients with fulminant hepatitis do not share a specific mutation.

The pathogenesis of fulminant hepatitis B virus (HBV) infection is not well understood. The aim of this study was to investigate whether there is an association between specific viral variants and a fulminant disease course. The entire HBV genomes from the serum of eight patients with fulminant HBV infection and one patient with fulminant hepatitis during reinfection after liver transplantation were investigated. After isolation and amplification of viral DNA by polymerase chain reaction (PCR), plus and minus strands were directly sequenced. Sequence data were analyzed by comparative sequence alignments with 35 and 2 complete HBV genome sequences from patients without and with fulminant hepatitis, respectively. Several point mutations were present in all regions of the genomes. Many nucleotide changes had never or rarely been found in the reported HBV isolates from patients without fulminant hepatitis. A distinct mutation present in all genomes was not identified. Clusters of rare and unique mutations were observed in the enhancer II core promoter region. Mutations previously suggested to be associated with fulminant HBV infection were not consistently found. A precore stop codon mutation at nucleotide position 1896 or an A-to-T mutation at nucleotide position 1762 and a G-to-A mutation at nucleotide position 1764 in the core promoter region were present in four and three cases, respectively. Fulminant HBV infection does not appear to be caused by a specific genomic mutation. However, various mutations clustering in the enhancer II core promoter region may contribute to a fulminant disease course.

Adult↗
PubMed1996

Distribution of genotypes and response to alpha-interferon in patients with hepatitis C virus infection in Germany.

To determine the distribution of hepatitis C virus (HCV) genotypes in German isolates, nucleotide sequences of the viral nonstructural 5 (NS5) genome domains were analyzed in isolates from 107 chronically HCV-infected patients. Of these 107 patients, 46 (43.0% were infected with subtype 1a and 47 (43.9%) with subtype 1b. Six patients (5.6%) with a history of intravenous drug abuse were infected with subtype 3a. Eight patients (7.5%) who had acquired their HCV infection in Egypt carried subtype 4a. Forty-three of the 107 patients were treated with alpha-interferon. Of these 43 patients, 16 (37.2%) were infected with subtype 1a and 27 patients (62.8%) with subtype 1b. Three patients infected with HCV-subtype 1a (18.7%) and four patients infected with subtype 1b (14.8%) showed a sustained complete response after interferon therapy. The HCV genotype 1 with its subtypes 1a and 1b was the most common source of HCV infection in this group of patients. There was no significant difference in response to alpha-interferon treatment of HCV infection with the subtypes 1a or 1b.

Adolescent↗
PubMed1996

In situ splitting of cadaveric livers. The ultimate expansion of a limited donor pool.

OBJECTIVE: The authors evaluate the safety, applicability, and effectiveness of a new technique for split-liver transplantation. SUMMARY BACKGROUND DATA: Split-liver transplantation offers an attractive way to increase the donor pool for cadaveric liver transplantation. The application of this concept has been hampered by inferior patient and graft survivals and higher complication rates. Without supportive data, the concern about increasing biliary leakage and poor initial graft function persisted. The authors focused on the causes of these complications by presenting a new technique to eliminate these problems. METHODS: Liver splitting was performed in the heart-beating cadaveric organ donor, using the technique described for procurement of the left lateral lobe of a live donor. A detailed description of the technique is presented. A retrospective review of the first 14 transplantations resulting from 7 in situ splitting procedures was collected. The results were compared with 19 conventional split-liver transplants performed during the same period. RESULTS: Six-month patient and graft survivals after in situ split-liver transplantation were 92.8% and 85.7%, respectively. Biliary complications were absent. Postoperative courses were mostly uneventful and characterized by lower peak transaminase levels compared with standard techniques. Early graft function of extrahepatic organs procured simultaneously was excellent. CONCLUSIONS: In situ split-liver transplantation provides superior results, related mainly to reduction of cold ischemic damage of the grafts and avoidance of biliary complications. In situ split-liver transplantation renders graft reduction alone obsolete and opens a donor pool for adults to receive right lobes safely. It allows for long-distance sharing between pediatric and adult liver transplant units because the procedure abolishes ex situ benching and prolonged ischemia time and provides two anatomically perfect grafts with hemostasis accomplished.

Adult↗
PubMed1996

Transplantation of complete and split liver grafts for patients with fulminant hepatic failure.

Fulminant hepatic failure is associated with considerable mortality under conservative management. The aim of this study was to assess applicability and outcome of liver transplantation using cadaveric and living donated grafts in patients with fulminant hepatic failure. 42 patients presenting with fulminant hepatic failure between 1988 and 1995 were retrospectively analyzed. 37 (88%) met the indication criteria for liver transplantation. 22 patients underwent orthotopic liver transplantation, one patient auxiliary orthotopic liver transplantation. Actual survival rate of these patients is 74% alter a mean follow-up of 23 (3-68) months. 38% (14/37) of the patients with an indication for transplantation did not receive a cadaveric graft due to scarcity of cadaveric organs (n = 9), medical contraindications (n = 3) or spontaneous recuperation (n = 2). Only 21% (3/14) of these patients survived. Due to unavailability of a cadaveric organ four patients, six months to 22 years of age, underwent living related liver transplantation as a last possible treatment option. Three of them died from cerebral herniation. It is concluded that transplantation of a cadaveric graft increased survival rate from 21% to 74% in patients with an indication for liver transplantation. Living related liver transplantation as an individual rescue therapy had no favourable outcome.

Adolescent↗