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H Lobeck

Publications and source records attributed to H Lobeck.

At least 55 records · Page 3Linked to original sources
PubMed1997

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

BACKGROUND/AIMS: The 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. METHODS: Typing 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. RESULTS: Seventy 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. CONCLUSIONS: Our 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.

Adolescent↗
PubMed1997

[Bile duct carcinoma in an adenoma in the anastomotic area after hepaticojejunostomy--a case report].

Cholangiocarcinoma at the choledochoduodenal anastomosis site is a rare complication. Our 71-years-old female patient developed an adenocarcinoma 38 years after cholecystectomy and choledochoduodenal anastomosis. During the previous two years she suffered from recurrent episodes of cholangitis and jaundice. Multiple endoscopically obtained biopsies from a suspicious area at the anastomosis showed a tubular adenoma. With a CA19-9 of 2,429 U/l laparotomy was performed with radical removal of the choledochoduodenostomy and the extrahepatic bile ducts and reconstruction with hepaticojejunostomy. The histological examination revealed a poorly differentiated, partly solid, partly tubular adenocarcinoma of the choledochal duct with metastasis of the lymph nodes in the hepatoduodenal ligament. According to the UICC staging system the tumor was pT2, G3, pN1 classified as stage III. Two months later the patient developed a peritoneal carcinosis with a CA19-9 of 15,050 U/l and died. The development of cholangiocarcinoma may be caused by chronic cholangitis, which may arise from several diseases of the bile ducts like choledochal cysts, primary sclerosing cholangitis or reflux of duodenal contents like in choledochoduodenal anastomoses. Because of the heterogeneity inside the lesions a malignant lesion can only be excluded by histopathological examination of the whole tumor.

Adenoma, Bile Duct↗
PubMed1996

Cytokine pattern during rejection and infection after liver transplantation--improvements in postoperative monitoring?

Despite improvements in immunosuppression, rejection occurs in 50% of liver transplant patients and may cause significant morbidity. The most frequent cause of death after liver transplantation is severe infection. Determination of the cytokine network may lead to earlier detection of patients at risk for severe rejection and infection. For this purpose, 81 patients with 85 liver transplants were monitored for cytokines and neopterin on a daily basis. During the first postoperative month, 28 patients (34.6%) developed acute rejection; 14 patients were successfully treated with methylprednisolone (steroid-sensitive rejection), while 14 patients required additional treatment with FK506 and OKT3 (steroid-resistant rejection). Ten patients developed severe infections, and 11 patients experienced asymptomatic cholangitis. Patients with an uneventful postoperative course (n=37) were the control group. One-year patient survival was 88.9%: 1 patient died because of chronic rejection and Pseudomonas urosepsis; a further 4 patients died of aspergillus pneumonia and bacterial sepsis. Soluble TNF-RII, sIL-2R-, and IL-10 levels were significantly elevated 3 days prior to or at the onset of acute steroid-resistant rejection (P < or = 0.01 versus steroid-sensitive rejection and on uneventful postoperative course). An increase in IL-8, neopterin, and sTNF-RII was indicative of severe infection 3 days prior to onset of infection. In this group of patients, a simultaneous increase in IL-10 indicated a lethal outcome of severe infection. During the second week of acute steroid-resistant rejection and lethal infection, a significant rise in IL-1beta, IFN-gamma, and IL-6 was observed (P < or = 0.01 versus control groups). The different patterns in neopterin- and cytokine-increase could differentiate between severe rejection and severe infection. Furthermore, the increase in these parameters indicated severe rejection--i.e., steroid resistance at the onset of acute rejection--which could prompt us to initiate rescue therapy immediately. The ability to detect patients at risk for severe or lethal infection may result in intensified infectious screening and more aggressive antiinfectious treatment. Therefore, routine monitoring of these parameters may lead to changes in therapeutic management of severe acute rejection and infection after liver transplantation.

Alanine Transaminase↗
PubMed1996

GB virus C infection in patients with chronic hepatitis B and C before and after liver transplantation.

Recently, a novel virus, tentatively designated GB virus (GBV-C) was identified in patients with hepatitis. The frequency of this novel virus infection was therefore investigated in 58 patients with chronic hepatitis B virus (HBV) infection and in 74 patients with chronic hepatitis C virus (HCV) infection who had received orthotopic liver transplantation (OLT) because of decompensated liver cirrhosis. Before OLT, GBV-C sequences were found by reverse transcription nested polymerase chain reaction with primers derived from the helicase-like region in six (10%) of the HBV- and in six (8%) of the HCV-infected patients. Specificity of the polymerase chain reaction products was confirmed in eight of them by direct sequencing. Pretransplant GBV-6 viremia was associated with posttransplant viremia in 75% of patients. The comparison of GBV-C nucleotide and amino acid sequences within the helicase-like region revealed that pre- and posttransplant sequences differed only in 0-7 nucleotide exchanges, and with the exception of one, all of them were silent mutations. After OLT, 29% of the HBV- infected and 12% of the HCV-infected patients became GBV-C positive,indicating a high rate of "de novo" GBV-C infection. By correlating the GBV-C status with the frequency of the occurrence of graft hepatitis in both groups of patients, it became evident that posttransplant GBV-C viremia did not increase the risk for this clinical condition. However, we found a significantly higher percentage of hepatocellular carcinoma in patients with pre-OLT GBV-C/HCV coinfection compared with patients with HCV infection alone (5/6 vs. 16/68;P<0.01).

Adult↗
PubMed1996

Viral dynamics of hepatitis C early after orthotopic liver transplantation: evidence for rapid turnover of serum virions.

The pathogenesis of hepatitis C virus (HCV) infection is likely to be associated with viral replication in vivo, but little is known concerning the dynamics of HCV turnover. We performed serial measurements of serum HCV-RNA levels following orthotopic liver transplantation (OLT) in nine patients with HCV-positive cirrhosis. Serum HCV-RNA levels were determined by quantitative polymerase chain reaction before, immediately after, and for up to 1 month after OLT. There was a rapid decline in HCV-RNA levels from 3.1 +/- 1.3 x 10(5) copies/ mL (mean +/- SEM) preoperatively to 0.15 +/- 0.6 x 10(5) copies/mL on the first and 0.16 +/- 0.6 x 10(5) copies/mL on the second postoperative day (mean viral half-life, 4.0 +/- 0.5 h). Thereafter, HCV-RNA levels increased in all but one patient, and by postoperative day 8 reached 3.6 +/- 1.3 x 10(5) copies/mL, exceeding the preoperative levels irrespective of the use or not of rescue immunosuppressive therapy including steroid bolus administration. In most patients, serum virions continued to increase averaging 11.6 +/- 2.8 x 10(5) copies/mL on the 30th postoperative day. These findings indicate that the half-life of HCV is quite short, and that extrahepatic viral replication contributes little to the total virus pool in serum. Furthermore, the marked HCV replication beginning as early as the third postoperative day strongly suggests that the liver graft is rapidly reinfected by HCV after OLT.

Adult↗
PubMed1996

Clinical significance of recurrent primary biliary cirrhosis after liver transplantation.

Primary biliary cirrhosis (PBC) represents a classic indication for orthotopic liver transplantation (OLT); as an autoimmune disease, however, the existence and incidence of recurrent PBC is a matter of significant controversy. Between September 1988 and September 1994 a total of 544 OLTs was performed at our institution. Forty-nine patients (40 female) with a median age of 50.5 years and previous surgery in 36.4%, received a liver graft for PBC. The mean serum bilirubin level was 8.9 mg/dl (range 0.7-29.7). Immunosuppression was commenced as a cyclosporine A-based quadruple therapy or with FK 506 and prednisolone. Protocol liver biopsies were taken at defined intervals posttransplant. Two patients died due to Legionella pneumonia and hypoxic brain damage 2 and 8 weeks after OLT, resulting in an actuarial 5-year survival rate of 95% with 47/49 patients being alive compared to 83.5% of all other liver recipients. Evidence of recurrence of PBC, as defined by elevated cholestatic parameters and histological features of PBC, was found in four patients, another five patients showed only histological signs. Recurrence of PBC, which might compromise the long-term outcome after OLT, was suspected in 4/47 patients (8.5%). This evidence of recurrent PBC is in conflict with findings of other groups that did not report recurrent PBC. OLT is still the optimal therapy for advanced PBC, with an excellent prognosis.

Female↗
PubMed1996

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%, respectively. 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.

Adult↗
PubMed1996

Management of acute steroid-resistant rejection after liver transplantation.

Prior to the FK506 era, OKT3 was primarily used for treatment of steroid-resistant rejection. Initially FK506 has been used as a last treatment of refractory acute or chronic rejection. We provide strong evidence that the use of FK506 is more successful if rescue therapy is performed early instead of using it as the last resort. Between September 1988 and March 1995 a total of 600 liver transplantations were performed in 550 patients. Of these 550 patients, 426 received primarily cyclosporine A (CsA)-based immunosuppression. Of the 426 CsA patients, 70 (16.4%) required either FK506 (51.4%), or OKT3 rescue therapy (27.1%), or a combination of the two drugs (21.5%). The latter group of patients received first OKT3 and then FK506 rescue when OKT3 therapy failed. Treatment was initiated simultaneously (within 1 week) in 11 patients, and 4 patients received FK506 rescue later during the course of rejection. The highest success rates (88.9%) were observed in patients given FK506 rescue therapy. Retransplantation was necessary more often in patients receiving OKT3 than in those with FK506 rescue therapy (15.8% versus 5.5%, respectively). Retransplantation and death due to chronic rejection increased with the need for additional FK506 rescue therapy after OKT3 failure. This increase was most pronounced in patients receiving FK506 during the late course of rejection, reaching a failure rate of 75.0% (50. 0% of deaths were due to chronic rejection). The lowest incidence of cytomegalovirus infection and of infectious, neurologic, and renal complications was observed in the FK506 rescue group. We conclude that early FK506 rescue therapy may be the treatment of choice for acute steroid-resistant rejection.

Acute Disease↗
PubMed1996

Responsiveness to interferon alpha treatment in patients with chronic hepatitis C coinfected with hepatitis G virus.

BACKGROUND/AIMS: Patients with chronic hepatitis C are often coinfected with the new identified Flaviviridae-like agent, termed hepatitis G virus (HGV). The aim of the study was to investigate the responsiveness of hepatitis G virus to interferon alpha and to evaluate whether a hepatitis G virus coinfection negatively influences the outcome of treatment in chronic hepatitis C. METHODS: One hundred and fifteen patients with histologically proven chronic hepatitis C were treated with interferon alpha and investigated for the presence of hepatitis G virus coinfection by nested polymerase chain reaction with primers from the helicase region of hepatitis G virus. All patients received at least 3 MU (range 3-6) interferon alpha thrice weekly for at least 6 months (mean 8, range 6-12). Polymerase chain reaction products of seven pre- and post-treatment hepatitis G virus positive patients were directly sequenced for identification of sequence variability during the follow-up. RESULTS: Eighteen (16%) patients were coinfected with hepatitis G virus. Although nine (50%) of these patients became HGV RNA negative during interferon alpha therapy, only three patients (17%) remained HGV RNA negative at the end of follow-up (mean 24 months). The rate of sustained response of chronic hepatitis C was not significantly different between patients with hepatitis C virus infection and HCV/HGV coinfection (19% vs 28%). Severity of liver disease as determined by alanine aminotransferase levels, histology and hepatitis C virus viremia was not significantly different in patients with hepatitis C virus or HCV/HGV coinfection. Sequence analysis of the helicase region revealed that our isolates all belonged to the hepatitis G virus and not to the GBV-C like genotype. No amino acid exchanges during the observation period of up to 48 months were observed, indicating that this region is highly conserved. CONCLUSIONS: The responsiveness of hepatitis G virus to interferon alpha in chronic HCV/HGV coinfected patients is similar to that observed in chronic hepatitis C. Hepatitis G virus coinfection seems not to interfere with the efficacy of interferon alpha treatment in patients with chronic hepatitis C.

Adult↗
PubMed1996

[High-resolution magnetic resonance tomography by means of an endorectal coil--the results in rectal tumors].

PURPOSE: To assess the value of high-resolution MRI of the rectum using an endorectal coil. METHODS: 10 volunteers and in 31 patients with suspected rectal tumors were examined. In 17 patients (n = 17) with rectal carcinoma, of which 15 subsequently underwent radical surgery, the preoperatively obtained tumor stage was compared with histology. In 12 patients (n = 12) with rectal adenoma (severe and medium graded epithelial dysplasias according to the WHO) who underwent endoscopy the results of the endorectal surface coil examination were compared with endoscopy and histology. In 4 patients (n = 4) with large rectal adenomas the surface coil was used before and as follow-up after endoscopic electro laser resection and the absence of adenoma after therapy also in the deeper layers of the rectal wall could be confirmed. RESULTS: Visualization of anatomical structures of rectum and adjacent structures is improved by the use of the endorectal surface coil. The diagnosis of carcinoma and adenoma of the rectum and the documentation of the exact extension can be reached with high accuracy (85%). CONCLUSION: MRI with an endorectal surface coil may play an important role in the preoperative diagnosis of rectal carcinoma. This method is useful for primary diagnosis and follow-up of large rectal adenoma after endoscopic electro laser resection.

Adenoma↗
PubMed1996

[Early clinical experiences with MR-guided laser-induced thermotherapy (LITT) of liver metastases in preoperative care].

PURPOSE: To evaluate the LITT-induced changes with the aid of MRT and correlate these with histopathological findings. MATERIAL AND METHODS: Five patients with solitary colorectal liver metastases were treated by means of MR-guided LITT before liver resection. Application time and energy of the Nd:YAG laser (1064 nm) was 10-20 minutes and 4.5-8.8 W. MRT monitoring during the LITT was carried out with temperature-sensitive T1 weighted sequences (FLASH-2-D, turbo FLASH). The extent of the induced necrosis as seen on MR was compared with the unfixed specimen and with the histopathological findings. RESULTS: The extent of necrosis visible by MRT correlated with the histopathological findings with an accuracy of 95.3% +/- 4.2%. Following single treatments (three cases) the metastases suffered a reduction of 24%-55% of their original volume. In two patients a second application produced laser-induced necrosis of 78% and 98% of volume. In these two patients a temperature sound was used for measuring regional heating and showed an exact correlation with MR thermometry. CONCLUSION: The results of pre-operative MR-guided LITT indicates the potential of this form of treatment for obtaining reproducible tumor necrosis of liver metastases.

Aged↗
PubMed1996

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.

Adult↗
PubMed1996

[Orthotopic liver transplantation in therapy of advanced polycystic liver disease].

Polycystic liver disease (PLD) is an autosomal-dominant hereditary disease which usually presents together with polycystic kidney degeneration (ADPKD). The renal problems determine the course of this disease. Due to the development of dialysis an increasing number of patients present with symptoms from their liver cysts: These range from compression caused by hepatomegaly, which can severely limit the quality of life, to chronic liver failure. Ten patients with advanced symptoms of PLD underwent orthotopic liver transplantation, five of them with combined renal transplantation. Postoperative complications occurred in three patients. One patient died postoperatively from multiorgan failure after experiencing coagulopathy of unknown origin. After follow-up of 6-60 months, all patients had better quality of life after transplantation. There was a complete relief of symptoms; liver or renal failure did not occur. Liver transplantation should be considered in patients with highly symptomatic PLD. In the case of severe hepatomegaly or liver and renal failure the combined liver and renal transplantation are able to cure the PLD and ADPKD without rising the disadvantage of immunosuppression incurred with single organ transplantation.

Adult↗
PubMed1996

Treatment of chronic hepatitis C with interferon alpha: long-term follow-up and prognostic relevance of HCV genotypes.

To evaluate the importance of hepatitis C virus (HCV) genotypes for the long-term response to interferon alpha (IFN alpha) therapy, we retrospectively investigated 81 patients with chronic hepatitis C treated within two randomized multicenter studies with comparable inclusion criteria. Forty patients received recombinant IFN alpha 3 MU three times a week for 12 months and 41 patients lymphoblastoid IFN alpha 3 or 5 MU three times a week for 6 or 12 months (total dosage 216-720 MU). The patients were followed up for up to 4 yr (2-4 yr, mean 3.2 yr). A sustained remission defined as normalization of aminotransferases and negative PCR for HCV-RNA was achieved in 23% of patients treated with recombinant IFN alpha and in 25% of the group with lymphoblastoid IFN alpha therapy. All patients with sustained remission showed a normalization of aminotransferases during the first 3 months of therapy. Determination of HCV genotypes revealed a major prevalence of type 1 (77%) versus type 2 (5%) and type 3 (18%). The response rate was significantly higher in patients with type 2 and 3 infections (75 and 73%) than in patients infected with genotype 1 (37%) (p = 0.005). Sustained remission was observed in 13% for genotype 1, in 75% for genotype 2, and in 33% for genotype 3 (differences between type 2/3 versus type 1, p = 0.03). There were no significant differences between responders and non-responders concerning age, level of aminotransferases before therapy or the dosage and type of IFN alpha administered. The data indicate that the determination of HCV genotypes may have prognostic relevance in the responsiveness to IFN alpha therapy.

Adult↗