W J Hofmann

Publications (75)335.69 Total impact

• Article: [Primary sarcomas and sarcoma metastases in the liver: morphological and molecular aspects].

  G Mechtersheimer, R Penzel, W J Hofmann, P Schirmacher
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  ABSTRACT: The considerable progress made in radiology, in surgical management with curative intent, and in the identification of molecularly targeted small molecules, such as the tyrosine kinase inhibitor imatinib mesylate, in the treatment of gastrointestinal stromal tumors has greatly influenced the treatment of sarcoma manifestations within the liver. This requires not only the unequivocal pathomorphological differentiation of sarcomas from other tumor entities, e. g. spindle cell dedifferentiated/pleomorphic carcinomas, aggressive non-Hodgkin lymphomas or amelanotic malignant melanomas, but also an accurate subtyping of this complex group of tumors. Additionally to macroscopic and histological findings, the recognition of characteristic immunophenotypic constellations and, at least in some types of sarcoma, the identification of molecular signatures, have greatly expanded the diagnostic tools in pathology.
  Der Pathologe 08/2006; 27(4):251-62. · 0.67 Impact Factor
• Article: Primäre Sarkome und Sarkommetastasen in der Leber

  G. Mechtersheimer, R. Penzel, W. J. Hofmann, P. Schirmacher
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  ABSTRACT: Die Fortschritte in der Bildgebung, im operativen Management mit kurativer Zielsetzung und in der Identifizierung neuartiger, gegen molekulare Zielstrukturen gerichteter Therapiesubstanzen, wie beispielsweise der Tyrosinkinaseinhibitor Imatinib bei gastrointestinalen Stromatumoren (GIST), haben die Behandlung von hepatischen Sarkommanifestationen in den letzten Jahren entscheidend beeinflusst. Voraussetzung fr ein adquates therapeutisches Procedere ist nicht nur die klare pathomorphologische Abgrenzung von Sarkomen gegenber anderen Tumorentitten, wie spindelzellig dedifferenzierten/pleomorphen Karzinomen, aggressiven Non-Hodgkin-Lymphomen oder amelanotischen malignen Melanomen, sondern auch ihre genaue Subtypisierung. Neben der Makro- und Histomorphologie haben charakteristische immunphnotypische Konstellationen und bei einzelnen Sarkomentitten auch molekulare Signaturen das diagnostische Werkzeug der Pathologie deutlich erweitert.The considerable progress made in radiology, in surgical management with curative intent, and in the identification of molecularly targeted small molecules, such as the tyrosine kinase inhibitor imatinib mesylate, in the treatment of gastrointestinal stromal tumors has greatly influenced the treatment of sarcoma manifestations within the liver. This requires not only the unequivocal pathomorphological differentiation of sarcomas from other tumor entities, e. g. spindle cell dedifferentiated/pleomorphic carcinomas, aggressive non-Hodgkin lymphomas or amelanotic malignant melanomas, but also an accurate subtyping of this complex group of tumors. Additionally to macroscopic and histological findings, the recognition of characteristic immunophenotypic constellations and, at least in some types of sarcoma, the identification of molecular signatures, have greatly expanded the diagnostic tools in pathology.
  Der Pathologe 06/2006; 27(4):251-262. · 0.67 Impact Factor
• Article: [Clinical usefulness and diagnostic value of percutaneous liver biopsy in patients with chronically elevated liver enzymes of non-viral origin].

  L Schwake, U Müller, L Theilmann, A von Herbay, W J Hofmann, W Stremmel, B Kallinowski
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  ABSTRACT: In the context of increasing non-invasive diagnostic techniques the purpose of the present study was to determine the clinical usefulness and the diagnostic value of percutaneous liver biopsy in patients with chronically elevated liver enzymes of non-viral origin. 100 patients from the outpatient clinic of the department of gastroenterology and hepatology who had a liver biopsy in the years 1996 to 1998 because of chronically elevated alanine-aminotransferase (ALT) and/or gamma-glutamyltransferase (gamma-GT) levels were included. Exclusion criteria were as follows: chronic hepatitis B or C infection, focal liver disease and clinical signs of hepatic decompensation. Retrospectively gained clinical data were independently evaluated by two experienced hepatologists. Initially, both examiners made a preliminary clinical diagnosis prior to knowing results from liver histology. With the results from liver histology both examiners were asked to make a final diagnosis. For each patient, the preliminary clinical diagnoses of both examiners were then correlated with the corresponding final diagnoses. Liver histology led in 71 % respectively 74 % of the patients to confirmation or specification of the clinical diagnosis. Liver biopsy was particularly helpful in differentiating non-decompensated liver cirrhosis, cryptogenic hepatitis, auto-immune hepatitis and biliary diseases. Despite improved non-invasive diagnostic tools including a broad spectrum of serologic tests liver biopsy is often indispensable for differentiating primary liver from biliary diseases and for the early detection of patients with liver cirrhosis.
  Zeitschrift für Gastroenterologie 05/2003; 41(4):303-9. · 0.90 Impact Factor
• Article: Expression of the multidrug resistance proteins MRP2 and MRP3 in human hepatocellular carcinoma.

  A T Nies, J König, M Pfannschmidt, E Klar, W J Hofmann, D Keppler
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  ABSTRACT: Treatment of hepatocellular carcinoma (HCC) by chemotherapy is often impeded by the intrinsic multidrug resistance (MDR) of this frequent primary cancer of the liver. The MDR phenotype can be caused by ATP-dependent export of chemotherapeutic drugs across the plasma membrane being mediated by transporters of the MDR P-glycoprotein family or of the multidrug resistance protein (MRP) family. To elucidate the role of MRP family members in HCC, we analyzed the expression and subcellular localization of MRP1 (ABCC1), MRP2 (ABCC2) and MRP3 (ABCC3); all 3 isoforms have been shown to confer resistance to chemotherapeutic drugs. Semiquantitative RT-PCR demonstrated that MRP2 and MRP3 mRNA expression in HCC was at least 10-fold higher than MRP1 mRNA expression. MRP2 immunostaining was observed in 87% (33/38) of HCC samples. MRP2 was localized in the plasma membrane in a polarized fashion, either in trabecular structures resembling the canalicular membrane or in the luminal membrane when cells had a pseudoglandular arrangement. MRP3 was detected in all samples examined (9/9) by RT-PCR and by immunofluorescence microscopy. MRP3 was localized to the basolateral membrane of carcinoma cells. Double-label immunofluorescence microscopy with antibodies specific for MRP2 or MRP3 indicated that carcinoma cells expressed both MRP isoforms simultaneously. When MRP1 was detected by immunofluorescence microscopy, it was localized on the intracellular membranes of carcinoma cells. Thus, plasma membrane expression of MRP2 and MRP3, but not of MRP1, can contribute to the MDR phenotype of HCC.
  International Journal of Cancer 12/2001; 94(4):492-9. · 5.44 Impact Factor
• Article: Loss of CD95 expression is linked to most but not all p53 mutants in European hepatocellular carcinoma.

  M Volkmann, J H Schiff, Y Hajjar, G Otto, F Stilgenbauer, W Fiehn, P R Galle, W J Hofmann
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  ABSTRACT: Experimental data have shown p53-dependent CD95 induction to be associated with increased levels of apoptosis after cytostatic treatment in hepatoma cells. A study of Japanese hepatocellular carcinoma (HCC) has reported an inverse correlation between CD95 and p53 expression. To examine the interaction of p53 and CD95 in tumors we investigated which alterations in p53 can be linked to loss of CD95 expression in European HCC. In 39 tumors we analyzed CD95 by immunohistochemistry and assessed the correlation between the findings of the p53 status as determined by immunohistochemistry and single-strand conformation polymorphism with polymerase chain reaction sequencing. In 10 of 14 tumors with evidence of p53 aberration there was also loss of CD95 expression, compared to 6 of 25 samples with apparent wild-type p53 (P<0.01). Three tumors with p53 mutations but sustained CD95 expression showed single base substitutions mapping to a narrow region of 20 codons in p53. A significant correlation with differentiation status of the tumor was found for the p53 aberration but not for CD95 expression. This is the first study to link loss of CD95 expression to specific p53 alterations in HCC. Functional p53 appears to be a major factor for CD95 expression in hepatocytes, the loss of which could contribute to chemoresistance and possibly immune evasion in hepatocellular carcinoma. Sustained CD95 expression in tumors with certain p53 aberrations may indicate functional heterogeneity of p53 mutants.
  Journal of Molecular Medicine 10/2001; 79(10):594-600. · 4.67 Impact Factor
• Article: [Puzzling liver findings. Peliosis hepatis].

  K Wasser, W J Hofmann, R Singer, M Essig, S Delorme
  Der Radiologe 02/2001; 41(1):95-8. · 0.61 Impact Factor
• Article: [Pathohistological findings in liver metastases].

  H Bläker, W J Hofmann, D Theuer, H F Otto
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  ABSTRACT: Metastatic tumors are the most common malignancies of the liver. The frequency distribution of the primary tumor location site closely resembles the frequency distribution of primary cancers in general. Yet, due to the liver's filter function of the portal blood-stream, metastatic tumors of the gastrointestinal tract are overrepresented. Most metastatic tumors show a nodular growth pattern with a demarcation of the tumor by inflammatory or fibrous reactive tissue; a diffuse metastatic tumor spread within the sinusoids is uncommon. Metastatic liver tumors may be the first clinically detectable manifestation of an unknown primary tumor. In these cases, the histological and immunohistochemical pattern of the metastatic tumor cells may give a clue of the location of the corresponding primary tumor.
  Der Radiologe 02/2001; 41(1):1-7. · 0.61 Impact Factor
• Article: Hepatic failure with neonatal tissue siderosis of hemochromatotic type in an infant presenting with meconium ileus. Case report and differential diagnosis of the perinatal iron storage disorders.

  C Sergi, U Himbert, F Weinhardt, W Heilmann, P Meyer, B Beedgen, E Zilow, W J Hofmann, O Linderkamp, H F Otto
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  ABSTRACT: We report on a female preterm infant with hepatic failure and neonatal tissue siderosis of hemochromatotic type diagnosed by using both histochemistry and atomic absorption spectroscopy. The infant presented with meconium ileus, signs of rapidly progressive hepatic failure, and hyperferritinemia (7132 ng/ml). Despite surgery and intensive care the infant died 32 days after birth. Postmortem examination showed a wrinkled liver with extensive collapse of the hepatic architecture and regenerating nodules as well as hepatic and extrahepatic iron accumulation of hemochromatotic type, sparing the reticuloendothelial system. Atomic absorption spectroscopy confirmed an increase in the iron content of various organs: liver, heart, pancreas, oral salivary gland, kidney, and adrenal gland. The increase in the iron content of various organs was determined by comparing the analysis of the propositus with those of 5 gestationally age-related preterm infants who had died in the intensive care unit: 2 died of meconium aspiration syndrome, the other 3 of hyaline membrane disease, bronchopulmonary dysplasia, and immaturity, respectively. We also compared the analysis of 15 fetuses having a a condition predisposing to iron accumulation (trisomy 21, trisomy 18, cytomegalovirus, amnion infection syndrome, Rhesus- and ABO-incompatibility, congenital hemolysis, anti-phospholipid syndrome, congenital heart disease). Delta F508, the most frequent mutation seen in cystic fibrosis patients, was excluded by gene sequencing. Different noxae causing iron accumulation in the neonatal period have led to the statement that neonatal hemochromatosis may collect different etiologies, such as metabolic disorders, infections, chromosomal aberrations, and immunological disorders. In this study, we report the singular evidence of neonatal iron accumulation of hemochromatotic type in an infant presenting with meconium ileus and propose a classification of the neonatal disorders associated with iron accumulation.
  Pathology - Research and Practice 02/2001; 197(10):699-709; discussion 711-3. · 1.21 Impact Factor
• Article: [Ulcers of the colon in association with nonsteroidal anti-inflammatory drugs (NSAID)--a rare cause of gastrointestinal bleeding? Report of 3 cases].

  L Schwake, T Schlenker, S Schwake, W J Hofmann, W Stremmel
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  ABSTRACT: Although adverse side effects of nonsteroidal anti-inflammatory drugs (NSAID) can affect the whole gastrointestinal tract, most reports refer to upper gastrointestinal tract complications. We report on 3 patients with lower gastrointestinal bleeding (patient 1 and 2) respectively detectable fecal blood loss (patient 3) after the use of NSAID. Patient 1 and 3 were taking NSAID over at least 6 months for the treatment of rheumatic diseases while patient 2 reported a single use of 2 g acetylsalicylic acid. Colonoscopy showed a single ulcer of the colon in patients 1 and 2. Due to acute bleeding patient 1 required interventional endoscopic treatment. Colonoscopy of patient 3 revealed multiple colonic ulcerations. Gastroduodenoscopy also detected adverse NSAID-effects on the upper gastrointestinal tract in patient 1 and 3 (ulcers of the stomach, erosive duodenitis). NSAID-medication was discontinued in all patients and, additionally, mesalazine was administered to patient 3. Consecutively, symptoms and lesions disappeared. Our cases stress the clinical importance of NSAID-toxicity distal to the small intestine which may exist concomitantly to lesions of the upper gastrointestinal tract and is not obligatory dose-dependent.
  Zeitschrift für Gastroenterologie 01/2001; 38(12):957-61. · 0.90 Impact Factor
• Article: Rätselhafter Leberbefund: Peliosis Hepatis

  K. Wasser, W.J. Hofmann, R. Singer, M. Essig, S. Delorme
  Radiologe. 01/2001; 41:95-98.
• Article: Pathohistologische Befunde bei Lebermetastasen

  H. Bläker, W.J. Hofmann, D. Theuer, H.F. Otto
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  ABSTRACT: Die überwiegende Zahl der malignen Geschwülste der Leber sind Metastasen. Die Häufigkeitsverteilung bzgl. ihrer Herkunft ähnelt der allgemeinen Krebsstatistik von Primärtumoren, aufgrund der funktionell anatomischen Besonderheit der Leber als “Filter” des Portalkreislaufs sind jedoch gastrointestinale Karzinommetastasen überrepräsentiert. Metastasen wachsen selten diffus, überwiegend nodulär, wobei eine peritumoröse Reaktion zu beobachten ist, die sich in einer kapselartigen oder entzündlichen Demarkation der Metastase äußert. Die Art der Demarkation scheint einen Einfluss auf die Prognose des Tumorleidens zu haben. Nicht selten sind Metastasen die erste, klinisch fassbare Manifestation eines unbekannten Primärtumors. Aufgabe des Pathologen ist somit neben der histologischen Sicherung einer Metastase bei bekanntem Primärtumor eine Eingrenzung der Herkunftsmöglichkeiten bei Metastasen eines Primärtumors unbekannter Lokalisation. Metastatic tumors are the most common malignancies of the liver. The frequency distribution of the primary tumor location site closely resembles the frequency distribution of primary cancers in general. Yet, due to the liver's filter function of the portal bloodstream, metastatic tumors of the gastrointestinal tract are overrepresented. Most metastatic tumors show a nodular growth pattern with a demarcation of the tumor by inflammatory or fibrous reactive tissue; a diffuse metastatic tumor spread within the sinusoids is uncommon. Metastatic liver tumors may be the first clinically detectable manifestation of an unknown primary tumor. In these cases, the histological and immunohistochemical pattern of the metastatic tumor cells may give a clue of the location of the corresponding primary tumor.
  Der Radiologe 12/2000; 41(1):1-7. · 0.61 Impact Factor
• Article: Extrapulmonary sarcoidosis primarily diagnosed in the liver.

  S Mueller, M W Boehme, W J Hofmann, W Stremmel
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  ABSTRACT: Sarcoidosis is a relatively common, chronic, multisystem disease of unknown origin characterized by the presence of noncaseating epithelioid granulomas. Although an array of organs may be affected by the disease, the commonest site of affection is the lung. We describe a 73-year-old patient admitted to our hospital because of fatigue, weight loss, and an increased alkaline phosphatase level. In conjunction with clinical presentation, laboratory variables, and imaging analysis, a liver biopsy finally confirmed the diagnosis of a systemic sarcoidosis without affection of the lung or mediastinal lymph nodes. Treatment with ursodeoxycholic acid before diagnosis did not improve clinical symptoms and cholestasis indicators. After prednisone treatment, liver enzyme values normalized and remained normal during follow-up for 2 years after diagnosis. The literature on hepatic manifestation of sarcoidosis, its diagnosis, treatment, and prognosis is reviewed. This single case of sarcoidosis presented to the clinician almost exclusively with liver enzyme abnormalities. The consideration of sarcoidosis in such cases is of utmost importance, since the differential diagnosis of hepatic granulomas includes infectious diseases in which treatment with corticosteroids could be fatal.
  Scandinavian Journal of Gastroenterology 10/2000; 35(9):1003-8. · 2.02 Impact Factor
• Article: CDKN2 mutation is infrequent in german hepatocellular carcinoma.

  M Volkmann, F Stilgenbauer, W J Hofmann, G Otto, J H Schiff, W Fiehn
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  ABSTRACT: For hepatocellular carcinoma, only scarce and controversial data on CDKN2 alterations are available. A high rate of mutations in a Chinese study contrasts with a low rate found in Japanese tumors and a CDKN2 germline mutation in 4/26 Swiss tumors examined. We analyzed 23 hepatocellular carcinomas from German patients for homozygous deletions of CDKN2 by coamplification with the human tyrosine hydroxylase (TH) gene and for CDKN2 mutations by PCR-single strand conformation polymorphism analysis and direct DNA sequencing. Our results indicate the lack of homozygous deletions. In one tumor, DNA sequencing showed a GCG-ACG (alanine-threonine) substitution at codon 148, a polymorphism in exon 2 of CDKN2. We conclude that the alteration of CDKN2 by deletion or mutation appears not to be a frequent event in hepatocarcinogenesis in German patients.
  Oncology 12/1999; 57(4):306-10. · 2.27 Impact Factor
• Article: Thermodiffusion for continuous quantification of hepatic microcirculation--validation and potential in liver transplantation.

  E Klar, T Kraus, J Bleyl, W H Newman, H F Bowman, W J Hofmann, R Kummer, M Bredt, C Herfarth
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  ABSTRACT: Hepatic microcirculation is a main determinant of reperfusion injury and graft quality in liver transplantation. Methods available for the quantification of hepatic microcirculation are indirect, are invasive, or preclude postoperative application. The aim of this study was the validation of thermodiffusion in a new modification allowing long-term use in the clinical setting. In six pigs Doppler flowmeters were positioned around the hepatic artery and portal vein for the measurement of total liver blood flow. Liver perfusion was quantified by thermodiffusion and compared to H(2) clearance as an established technique under baseline conditions, during different degrees of portal venous obstruction and during occlusion of the hepatic artery. Thermodiffusion measurements were recorded for five days postoperatively followed by histological evaluation of the hepatic puncture site. Perfusion data obtained by thermodiffusion were significantly correlated to H(2) clearance (r = 0.94, P < 0. 001) and to liver blood flow (r = 0.9, P < 0.05). The agreement between thermodiffusion and H(2) clearance was excellent (mean difference -2.1 ml/100 g/min; limits of agreement -12.5 and 8.3 ml/100 g/min). Occlusion of the portal vein or hepatic artery was immediately detected by thermodiffusion, indicating a decrease of perfusion by 64 +/- 7% or 27 +/- 5% of baseline, respectively. Perfusion values at baseline and during vascular occlusion were reproducible during the entire observation period. Histological changes of the liver tissue adjacent to the thermodiffusion probes were minute and did not influence long-term measurements. In vivo validation proved that enhanced thermodiffusion is a minimally invasive technique for the continuous, real-time quantification of hepatic microcirculation. Changes in liver perfusion can be safely detected over several days postoperatively. The implication for liver transplantation has led to the clinical application of thermodiffusion.
  Microvascular Research 09/1999; 58(2):156-66. · 2.83 Impact Factor
• Article: Beta-catenin accumulation and mutation of the CTNNB1 gene in hepatoblastoma.

  H Bläker, W J Hofmann, R J Rieker, R Penzel, M Graf, H F Otto
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  ABSTRACT: Hepatoblastoma is a rare malignant tumor of the liver that occurs in children at an average age of 2 to 3 years. Epidemiologic studies have shown an increased frequency of this tumor type in families affected by adenomatous polyposis coli. In addition to the epidemiologic data, molecular genetic studies suggest that inactivation of the APC tumor suppressor may be involved in hepatoblastoma tumorigenesis. A major function of APC is the downregulation of beta-catenin, a transcription-activating protein with oncogenic potential. In an ongoing immunohistochemical study of beta-catenin expression in sporadic cases of tumor types that are associated with adenomatous polyposis coli, we observed increased beta-catenin levels in the cytoplasm and in the nuclei of three investigated hepatoblastomas. Sequencing of exon 3 of the beta-catenin gene (CTNNB1) revealed an activating mutation in one of the tumor samples. Our data indicate for the first time that beta-catenin accumulation may play a role in the development of hepatoblastoma and that activating mutations of the beta-catenin gene may substitute biallelic APC inactivation in this tumor type. Genes Chromosomes Cancer 25:399-402, 1999.
  Genes Chromosomes and Cancer 09/1999; 25(4):399-402. · 3.31 Impact Factor
• Article: Hepatotropism of GB virus C (GBV-C): GBV-C replication in human hepatocytes and cells of human hepatoma cell lines.

  S Seipp, M Scheidel, W J Hofmann, U Töx, L Theilmann, T Goeser, B Kallinowski
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  ABSTRACT: Recently, GB virus C (GBV-C) has been identified as another virus potentially causing viral hepatitis. However, its hepatotropism and pattern of infection in humans is still unknown. To elucidate the presence and replication of GBV-C in the human liver, we investigated tissue samples of six explanted livers from five GBV-C mono- or GBV-C/HCV co-infected patients for GBV-C RNA plus- and minus-strand RNA. These tissues were examined using nested RT-PCR followed by Southern blot hybridization as well as fluorescence in situ hybridization on liver cryosections. To further substantiate susceptibility of liver cells for GBV-C, in vitro infection of human hepatoma cells (HuH7, HepG2) with GBV-C mono-infected serum was performed. By reverse transcription followed by nested PCR (RT-PCR), 5 of 6 liver specimens (4/5 patients) were positive for GBV-C plus-strand RNA, and viral minus-strand RNA could be detected in 4 of 6 liver specimens (4/5 patients). One liver sample was negative for GBV-C RNA. In two specimens we could identify GBV-C infection by in situ hybridization. Virus infection appeared to be restricted to hepatocytes and detection of minus-strand RNA showed viral replication in a few highly infected liver cells. In vitro infection of HepG2 or HuH7 cells confirmed these findings by a release of virions into supernatant. In conclusion, our results establish GBV-C as a hepatotropic virus infecting human cells of hepatic origin in vivo and in vitro.
  Journal of Hepatology 05/1999; 30(4):570-9. · 9.26 Impact Factor
• Article: Fatal course of veno-occlusive disease of the liver (endophlebitis hepatica obliterans) in a preterm infant.

  C Sergi, B Beedgen, O Linderkamp, W J Hofmann
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  ABSTRACT: We describe the fatal course of a preterm infant of 34 weeks' gestation with veno-occlusive disease of the liver and refractory ascites. Despite aggressive medical management, the baby died twenty-two hours post partum because of cerebral haemorrhage before potentially life-saving organ transplantation could take place. At autopsy, paucity of lymphoid tissue in lymph nodes, thymus, spleen, and gastrointestinal tract were also seen. To our knowledge, this is the youngest infant with veno-occlusive disease of the liver reported in the literature.
  Pathology - Research and Practice 02/1999; 195(12):847-51. · 1.21 Impact Factor
• Article: The distribution of HBV, HCV and HGV among livers with fulminant hepatic failure of different aetiology.

  C Sergi, K Jundt, S Seipp, T Goeser, L Theilmann, G Otto, H F Otto, W J Hofmann
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  ABSTRACT: The aim of the study was to assess the impact factor of HCV and HGV in fulminant hepatic failure. The 5'-untranslated regions of HCV RNA and HGV RNA and a segment of the core antigen sequence of HBV were amplified after extracting the nucleic acids from snap-frozen tissue aliquots from explanted livers of 26 consecutive patients undergoing orthotopic liver transplantation for fulminant hepatic failure preoperatively diagnosed as either autoimmune (n=2), HAV/HBV (n=8), toxic (n=4) or aetiologically unknown (n=12). HCV RNA was detected in five of 26 (19.2%) livers with fulminant hepatic failure. All five HCV RNA-positive livers belonged to the group of non-toxic, non-autoimmune liver failure (n=20), three of them were found in the group of liver failure with unknown aetiology (n=12) and two in the group of HBV-associated liver failure (n=7), making an HCV incidence of 25%, 25% and 28.6%, in the different groups, respectively. HGV RNA was detected in 10 of 17 (58.8%) explants and in all four groups of fulminant hepatic failure as defined preoperatively. HBV DNA was identified in six livers of 26 patients (23.1%) with fulminant hepatic failure. Neither HCV RNA nor HBV DNA was detected in the livers of patients with toxic or autoimmune fulminant hepatic failure. These results indicate that HBV and HCV, but not HGV, play an aetiologic role in fulminant hepatic failure. HCV-positive cases were concentrated either in the group of otherwise unexplained fulminant hepatic failure or in the group of HBV fulminant hepatic failure. HGV-positive cases, on the other hand, were found within all four preoperatively defined groups, indicating a role as cofactor rather than as single aetiologic agent.
  Journal of Hepatology 01/1999; 29(6):861-71. · 9.26 Impact Factor
• Article: Hepatocellular injury early after reperfusion is correlated with liver microcirculation and predicts outcome after transplantation.

  S M Maksan, T Kraus, W J Hofmann, A Mehrabi, M M Gebhard, C Herfarth, E Klar
  Transplantation Proceedings 12/1998; 30(7):3716-7. · 1.00 Impact Factor
• Article: Hepatic failure and liver cell damage in acute Wilson's disease involve CD95 (APO-1/Fas) mediated apoptosis.

  S Strand, W J Hofmann, A Grambihler, H Hug, M Volkmann, G Otto, H Wesch, S M Mariani, V Hack, W Stremmel, P H Krammer, P R Galle
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  ABSTRACT: Wilson's disease can result in fulminant liver failure due to hepatic copper overload. The CD95 system mediates apoptosis and has been demonstrated to be involved in liver disease. In this study CD95 mediated apoptosis was investigated in patients with fulminant hepatic failure in the course of Wilson's disease and in an in vitro model of copper treated human hepatoma cells. In patients, hepatic expression of CD95 and CD95L mRNA and apoptosis were detected. Copper overload in vitro resulted in hepatocytic apoptosis which could be reduced with a neutralizing anti-CD95L antibody. Copper treatment of hepatocytes results in activation of the CD95 system and induction of apoptosis which is operative during the course of hepatic failure in acute Wilson's disease.
  Nature Medicine 06/1998; 4(5):588-93. · 22.46 Impact Factor