Hartmut Lobeck

Distribution of hepatitis C virus genotypes in German patients with chronic hepatitis C: correlation with clinical and virological parameters

BACKGROUND/AIMSnThe hepatitis C virus genotypes have been shown to be differently distributed between distinct geographical areas and to be associated with different clinical presentations. In the present study we investigated the distribution of HCV genotypes in 379 German patients with chronic hepatitis C in relation to age, sex, route of infection, liver histology and viremia.nnnMETHODSnTyping of HCV was done using restriction fragment length polymorphism analysis as well as a DNA enzyme immunoassay. HCV RNA concentrations were determined by quantitative polymerase chain reaction. Liver biopsies were performed in 187 patients and the histological activity was graded by the Knodell score.nnnRESULTSnSeventy percent were infected with genotype 1 (20% subtype 1a, 80% subtype 1b), 4% with genotype 2 and 26% with genotype 3 (all subtype 3a). Genotype 3a and 1a infection was significantly associated with intravenous drug abuse. In contrast, genotype 1 predominated in patients with post-transfusion hepatitis and infection of unknown origin. A changing relative prevalence of HCV genotypes in relation to age was also observed. Patients with genotype 3 infection showed significantly lower HCV RNA levels and a lower mean histological activity score as compared to patients with genotype 1 and genotype 2. However, using multivariate analysis, only age and mode of transmission but not histological activitiy score were shown to be independent variables.nnnCONCLUSIONSnOur study confirms previous reports from other countries that HCV variants can be classified into a relatively small number of discrete genotypes, and that the subtype 1b clearly predominates. However, we found evidence that there is a changing relative prevalence of HCV genotypes in relation to age, and that the mode of transmission is reflected in the predominance of certain genotypes.

Liver transplantation for PNH with Budd-Chiari syndrome. A case report

A 54-year-old male patient with end-stage liver failure from Budd-Chiari syndrome due to paroxysmal nocturnal hemoglobinuria (PNH) underwent liver transplantation (OLT) in 1989. Retransplantation became necessary 1 year later when thrombotic occlusion of the portal vein and common hepatic artery led to graft loss after withdrawal of anticoagulation therapy because of several gastrointestinal bleeding episodes. The patient is now alive 3 years after the first OLT. To the best of our knowledge and according to the literature, this is, to date, the longest that any PNH patient has survived after liver transplantation. Although the course of this patient was complicated in a way similar to that reported for other cases in the literature, patients with PNH should not, in principle, be excluded from liver transplantation. Lifelong anticoagulation with coumarin and the use of steroids together with cyclosporin reduce the risk of recurrent thrombosis and PNH crises.

Selection of small hepatocellular carcinoma improves long‐term results of hepatic transplantation for malignancy

Abstract Liver transplantation for advanced hepatocellular carcinoma is often followed by early tumour recurrence and death. At the beginning of the liver transplantation programme at Berlin Virchow we decided to offer liver transplantation only to patients with solitary tumours not exceeding a maximum diameter of 5 cm or to patients with two or three tumour nodes with a maximum diameter of 4 cm. From September 1988 to October 1993 435 liver transplants were performed in 403 patients. Of these, 32 patients (8 %) had a histologically confirmed hepatocellular carcinoma (29 males, 3 females, median age 56 years). The overall actuarial survival according to Kaplan‐Meier for the whole series of 32 patients with hepatocellular carcinoma was 82%, 78%, and 78% at 1, 2 and 3 years, respectively. Tumour size alone did not seem to be a relevant factor when comparing patients with tumours up to or larger than 3 cm in diameter. Patients with solitary tumours had a better prognosis than patients with multiple tumours. The largest difference was found between patients with stage I‐III (UICC) tumours and those with stage IVA tumours: 1‐, 2‐ and 3‐year survival rates were 89% throughout in the former group, while the corresponding figures for patients with stage IVA tumours were 63%, 47% and 47%. Efforts should be made to identify stage IVA tumours preoperatively in order to use the precious resource of scarce donor livers in an optimal way.

Conversion to tacrolimus after liver transplantation

We have reviewed our experience with conversion to tacrolimus after 435 liver transplantations. Tacrolimus was administered as a rescue agent in 33 patients until October 1993. Indications for rescue therapy were: cholestatic forms of severe, steroid-resistant cellular rejection (n=8), OKT3-resistant cellular rejections (n=6), cellular rejections in patients suffering from cyclosporin malabsorption (n=4), late onset cellular rejections (n=4), early chronic rejections (n=3), and chronic vascular or ductopenic rejections (n=8). Response was evident in 29 of the 33 patients (88%), whereas 4 patients (12%) were nonresponsive. Patient and graft survival were 76% and 70%, respecitively. Graft loss with or without patient death occurred in three of eight patients suffering from severe, steroid-resistant cellular rejection, in two of six patients with OKT3-resistant cellular rejections, and in five of eight patients undergoing chronic rejection. In severe steroid-resistant cellular rejection, successful tacrolimus rescue therapy corresponded to a significantly lower total serum bilirubin than unsuccessful therapy (12.0±5.6 mg% vs 29.7±5.9 mg%, P(0.05). We conclude that tacrolimus rescue therapy is a safe and efficient alternative for high-risk cases that do not respond to conservative treatment. In severe, steroid-resistant cellular rejection and in chronic ductopenic rejection, conversion to tacrolimus is beneficial only in a limited number of cases. A predictive parameter, which total serum bilirubin may prove to be in severe, steroid-resistant cellular rejection, is needed to select those cases that might benefit more from retransplantation than from conversion to tacrolimus.

HIV-assoziierte Speicheldrüsenerkrankungen

HIV-associated salivary gland disease (HIV-SGD) includes lymphoepithelial lesions and cysts involving the salivary gland tissue and/or intraglandular lymph nodes, and Sjögren-like conditions. Three cases of salivary gland disease occurring in HIV-infected patients are reported. Histopathological examination showed squamous epithelium-lined cysts. In the walls of the cysts lymphoid tissue, epitheloid granulomas and giant cells were found. The clinical and histopathological criteria as well as magnetic resonance imaging and therapy are discussed.HIV-assoziierte Speicheldrüsenerkrankungen (HIV salivary gland disease, HIV-SGD) sind histologisch durch eine Hyperplasie der Parotislymphknoten, eine lymphozytäre Sialadenitis undloder benigne lymphoepitheliale Zysten charakterisiert, In dieser Untersuchung werden 3 Fälle der HIV-assoziierten Speicheldrüsenerkrankungen bei 2 Patienten mit Voll-bild AIDS und 1 Patienten mit einer primären HIV-Infektion vorgestellt. Klinische und histopathologische Aspekte sowie die Darstellung mittels Magnetresonanztomographie werden diskutiert. HIV-associated salivary gland disease (HIV-SGD) includes lymphoepithelial lesions and cysts involving the salivary gland tissue and/or intraglandular lymph nodes, and Sjögren-like conditions. Three cases of salivary gland disease occurring in HIV-infected patients are reported. Histopathological examination showed squamous epithelium-lined cysts. In the walls of the cysts lymphoid tissue, epitheloid granulomas and giant cells were found. The clinical and histopathological criteria as well as magnetic resonance imaging and therapy are discussed.

Use of Endorectal Surface Coil Magnetic Resonance Imaging for Diagnosis of a Multicystic Seminal Vesicle with Ipsilateral Renal Agenesis

We report a symptomatic multicystic seminal vesicle with ipsilateral renal agenesis in a 37-year-old man. Preoperatively the diagnosis could be suggested by different imaging modalities, including endorectal surface coil magnetic resonance imaging. To our knowledge, we present the 1st case of seminal vesicle cyst to be evaluated by magnetic resonance imaging using a rectal coil. The value of different imaging modalities is discussed.

QUADRUPEL-INDUKTIONSTHERAPIE NACH LEBERTRANSPLANTATION MIT ATG ODER INTERLEUKIN-2 REZEPTOR ANTIKORPER BT563. EINE PROSPEKTIV RANDOMISIERTE STUDIE

Obwohl durch die zunehmende Erfahrung der letzten Jahrzehnte die orthotope Lebertransplantation heute eine anerkannte Standardmethode zur Behandlung terminaler Lebererkrankungen darstellt und in erfahrenen Zentren 1-Jahres-Uberlebensraten von 90% erreicht werden, wird die Wahl der immunsuppressiven Induktionstherapie noch kontrovers diskutiert [1]. Durch die Addition einer poliklonalen anti-Thymozytenpraparation (ATG) konnten Kalayoglu und Mitarbeiter die Inzidenz von Abstosungsreaktionen mindern ohne die Anzahl von Infektionen zu erhohen [2]. Unsere eigenen Erfahrungen mit dieser Vierfach-Induktionstherapie bestatigten die guten Ergebnisse, allerdings werden beim Einsatz von ATG Nebenwirkungen, wie Tachykardie, Hypertension, Fieber, Ubelkeit und Erbrechen beobachtet [3, 4].