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Thomas Berg

Publications and source records attributed to Thomas Berg.

At least 55 records · Page 3Linked to original sources
PubMed2004

Fibrosis progression after liver transplantation in patients with recurrent hepatitis C.

BACKGROUND/AIMS: Aim of our study was to analyze fibrosis progression after liver transplantation (OLT) in hepatitis C virus (HCV)-infected patients based on protocol liver biopsies and to identify risk factors, which may play a role in the development of severe fibrosis stages. METHODS: One hundred and eighty-three liver graft recipients who had a histological follow-up evaluation of 1 year after OLT were analyzed. Overall 1039 protocol liver biopsies were performed after 1-, 3-, 5-, 7- and 10 years and staged according to the Scheuer score. RESULTS: The fibrosis progression rate was not linear. The fibrosis scores were 1.2 after one, 1.7 after three, 1.9 after five, 2.1 after 7 and 2.2 after 10 years. The 39 recipients with fibrosis stages 3 or 4 in the 1-year biopsy had a significantly reduced survival rate, while fibrosis stage 0-2 indicated excellent survival. Independent risk factors for progression of fibrosis at 1 year were HCV genotype 1 and 4 (P=0.01) and donor age>33 years (P=0.01), whereas risk factors for development of cirrhosis (30/183 recipients (16%)) were donor age (P=0.002) and multiple steroid pulses (P=0.05). CONCLUSIONS: These data provide information on the course of recurrent hepatitis C and may be helpful to individualize the treatment of transplanted patients.

Adult↗
PubMed2004

Agreement between the Sunnybrook, House-Brackmann, and Yanagihara facial nerve grading systems in Bell's palsy.

OBJECTIVE: To assess the agreement between the Sunnybrook facial nerve grading system and the House-Brackmann and Yanagihara systems. STUDY DESIGN: Prospective clinical facial nerve grading. SETTING: Tertiary referral center. PATIENTS: One-hundred assessments, 94 in patients with Bell's palsy and 6 with herpes zoster. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Evaluation according to the weighted regional Sunnybrook system, the gross House-Brackmann system, and the unweighted regional Yanagihara system. Weighted kappa statistics was used to measure agreement between the grading systems. RESULTS: The average weighted kappa value between the Sunny-brook, House-Brackmann, and Yanagihara grading systems was 0.65; kappa values increased temporally (but not statistically significantly) up to day 180. The highest agreement value, 0.72, was found between the Sunnybrook and Yanagihara grading systems. The weighted kappa value between the Sunnybrook and House-Brackmann systems was 0.59. In Sunnybrook gradings less than 63, there was an overlap between House-Brackmann scores of III to VI. Reliable conversion tables between the gross House-Brackmann system and the regional Sunnybrook and Yanagihara systems could not be established. CONCLUSION: The Sunnybrook system scores at the same agreement level as the House-Brackmann and Yanagihara grading systems. There is an evaluative difference between the weighted regional Sunnybrook and the gross House-Brackmann systems. Substantial agreement was found between the regional Sunnybrook and Yanagihara scales. Sunnybrook grading is easy and quick. By adding objective measurements and additional secondary defects, the Sunnybrook system can be an alternative to the other predominating grading systems.

Adolescent↗
PubMed2004

Impact of in vivo complement activation and cryoglobulins on graft outcome of HCV-infected renal allograft recipients.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is closely associated with mixed cryoglobulinemia. Cryoglobulins can activate complement leading to vascular damage. We examined whether cryoglobulinemia and complement turnover is associated with HCV infection in renal transplant recipients and whether this has an adverse effect on graft outcome. METHODS: Sera and fresh plasma from 31 HCV-RNA-positive patients after renal transplantation (group I) were studied for cryoglobulins, complement hemolytic activity (CH50), and complement split product C3d. In total, 80 HCV-negative renal transplant recipients (group II) and 72 untreated patients with chronic hepatitis C (group III) without renal transplantation served as controls. RESULTS: Cryoglobulins were detected in 45, 28, and 26% of the patients in group I, II, and III, respectively. A high cryocrit ( > 5%) was present only in patients of group III (p < 0.01%). Mean CH50 values were lower and C3d levels higher in HCV-positive patients (group I and III) compared with HCV-negative patients (p < 0.0001). Cryoglobulins were not associated with extrahepatic manifestations or graft dysfunction, except in five patients of group III demonstrating cryoglobulinemic vasculitis. HCV-positive renal transplant recipients with signs of complement activation showed a significantly greater increase of serum creatinine (0.88 +/- 1.14 mg/dL) when compared with baseline than patients without complement activation (0.34 +/- 0.37 mg/dL; p = 0.035). There was also a tendency toward a higher extent of proteinuria in patients with complement activation (1.38 +/- 2.17 g/d vs. 0.50 +/- 0.77 g/d; p = 0.25, NS). CONCLUSIONS: Cryoglobulins are common in renal allograft recipients, but do not affect graft function. However, complement activation appears to be involved in chronic allograft dysfunction in HCV-infected recipients.

Adult↗
PubMed2003

CC chemokine receptor 5 delta32 polymorphism in two independent cohorts of hepatitis C virus infected patients without hemophilia.

Recently CC chemokine receptor 5 (CCR5) related immune mechanisms and a functional mutation of the CCR5 gene have been implicated in hepatitis C virus (HCV) infection in a cohort of predominantly hemophiliac patients. The present study investigated the frequency and clinical consequences of the CCR5 Delta32 mutation in two genetically homogeneous populations of HCV infected patients with a different risk profile for infection. Genomic DNA samples from 333 German patients with chronic HCV infection were screened by PCR for the presence of the CCR5 Delta32 polymorphism. In-hospital patients admitted for other diseases than viral hepatitis but with a comparable risk for HCV exposure were used as control population ( n=125). Allele frequencies of CCR5 Delta32 polymorphism did not differ significantly between the two groups (7.6% and 9.5%, respectively) and control subjects (10.4%), and did not deviate from Hardy-Weinberg equilibrium in any group. Furthermore, there were no major differences between patients with respect to HCV genotypes, viral loads, liver enzymes, or fibrosis scores in relation to the presence or absence of the heterozygous CCR5 Delta32 mutation. Differences in inflammatory scores in liver biopsy samples and response to antiviral therapy in CCR5 Delta32 heterozygotes in one cohort could neither be reproduced in the other group of patients nor when both cohorts were pooled. These results argue against a strong effect of the CCR5 Delta32 deletion regarding these phenotypes. In conclusion, we found no increased frequency of the CCR5 Delta32 polymorphism in two independent cohorts of patients with HCV infection but without hemophilia as the main risk factor for infection. As the major difference to investigations demonstrating an association between CCR5 Delta32 and HCV infection is the selection of cases and controls, our study emphasizes the importance of epidemiological criteria for association studies of HCV infection.

Adult↗
PubMed2003

Effects of the CCR5-Delta32 mutation on antiviral treatment in chronic hepatitis C.

BACKGROUND/AIMS: The CC-chemokine receptor (CCR) 5-Delta32 mutation may predispose to chronic liver disease and high level viremia in hepatitis C. However, it is unclear whether CCR5-Delta32 also affects the response to antiviral treatment. METHODS: We determined CCR5 genotypes in patients with hepatitis C treated with either interferon-alpha (N=78) or interferon and ribavirin (N=78). In each group, rates of end of treatment responses (ETRs) and sustained virological responses (SVRs) were compared between CCR5-Delta32 carriers and homozygous CCR5 wildtype patients. RESULTS: ETR and SVR were achieved in 25 and 12 patients with interferon-alpha and in 52 and 45 patients with interferon/ribavirin treatment, respectively. CCR5-Delta32 carriers had significantly lower ETR rates than homozygous CCR5 wildtype patients (10.5 vs. 39.0%; P=0.02), whereas SVR rates only showed a non-significant trend (5.3 vs. 18.6%). Multivariate analysis confirmed CCR5-Delta32 carriage as an independent negative predictor for ETR in interferon-alpha monotherapy (odds ratio: 0.16; 95% confidence limits: 0.032-0.82; P=0.03). In interferon/ribavirin treated patients CCR-Delta32 carriers and CCR5 wildtype patients had similar ETR rates [19.2% vs. 23.1%] and SVR rates [20.0% vs. 21.2%]. CONCLUSIONS: Response rates to interferon-alpha monotherapy are reduced in hepatitis C virus (HCV)-infected patients carrying the CCR5-Delta32 mutation. However, interferon/ribavirin combination treatment may overcome this negative effect of CCR5-Delta32.

Adult↗
PubMed2003

Prediction of treatment outcome in patients with chronic hepatitis C: significance of baseline parameters and viral dynamics during therapy.

In patients with chronic hepatitis C virus (HCV) infection scheduled for a 48-week treatment period, premature discontinuation of treatment was previously recommended if HCV-RNA levels remained detectable at week 24 of therapy. Considering the number of side effects and treatment costs, measurement of initial viral decline during therapy may identify virologic nonresponse earlier than 24 weeks. We retrospectively analyzed 260 European patients treated with standard or pegylated interferon alfa (IFN-alpha) and ribavirin for 24 to 48 weeks. Early prediction of virologic response by HCV-RNA decline at weeks 4 and 12 (Versant Quantitative [branched DNA (bDNA) 3.0]; Bayer Diagnostics, Emeryville, CA; and Qualitative [transcription-mediated amplification (TMA)] HCV RNA assay; Bayer Diagnostics) as well as clinical, biochemical, virologic, and histologic baseline parameters were analyzed by logistic regression and receiver operating characteristic (ROC) curves. A viral load at treatment week 4 above 450,000 IU/mL and at week 12 above 30,000 IU/mL was 100% predictive for virologic nonresponse in all patients. From multivariate logistic regression analysis of all patients, independent predictors for sustained virologic response were: genotypes 2 and 3 (P <.0001), a low baseline gamma-glutamyltransferase (GGT) level (P <.0001), a high baseline alanine aminotransferase level (P =.002), and a low baseline viral load (P =.04). None of the latter 3 factors were predictive for sustained virologic response when analysis was restricted to the subgroup of genotypes 2- and 3-infected patients. In conclusion, virologic nonresponse can be predicted early at week 12 of treatment independent from the applied therapeutic regimen based on a cutoff level for HCV RNA of 30,000 IU/mL. This algorithm recognizes 53.7% of nonresponders previously identified at week 24 of treatment.

Adult↗
PubMed2003

Triple therapy with amantadine in treatment-naive patients with chronic hepatitis C: a placebo-controlled trial.

The antiviral efficacy of amantadine in patients with chronic hepatitis C is controversial. In this randomized, prospective, placebo-controlled, multicenter trial, triple therapy with interferon alfa (IFN-alpha)-2a plus ribavirin and amantadine (amantadine group) was compared with combination therapy IFN-alpha plus ribavirin (control group). Four hundred previously untreated patients with histologically proven chronic hepatitis C were randomly allocated to treatment with amantadine sulphate (100 mg twice daily orally) or a matched placebo together with IFN-alpha induction plus ribavirin (1,000-1,200 mg/day orally) for 48 weeks. The primary end point was sustained virologic response (SVR) defined as undetectable serum hepatitis C virus (HCV) RNA (<100 copies/mL) 24 weeks after the end of treatment. SVR was observed in 52% of the amantadine group and in 43.5% of the control group (P =.11). Among patients with HCV genotype 1 infection, the corresponding SVR rates were 39% and 31%, respectively. The virologic on-treatment response rate in week 24 was significantly higher in the amantadine group as compared with the control group (70% vs. 59%, respectively, P =.016). This beneficial effect was mainly related to HCV type 1-infected patients (63% vs. 47%, respectively, P =.012). Independent factors associated with SVR, according to multiple logistic regression analysis, were amantadine treatment, low baseline HCV RNA, platelet counts (>/=250/nL), pretreatment ALT quotient >/=3, and GGT level (<28 U/L) as well as HCV genotypes other than 1. In conclusion, although we could not demonstrate a significant advantage of the triple regimen in univariate analysis, multivariate analysis offers arguments that amantadine should be considered as a potential anti-HCV drug in future studies.

Adult↗
PubMed2002

Increased mortality after liver transplantation for hepatocellular carcinoma in hepatitis B-associated cirrhosis.

Transplant patients suffering from hepatocellular carcinoma in cirrhosis are selected according to tumor nodule number and diameter. Vascular invasion and histopathological grading are predictive of outcome. The prognostic influence of hepatitis B-cirrhosis has been investigated after resection and after local tumor treatment, but not after transplantation. Of the 1,188 transplantations performed between 1989 and 2000, 120 were on patients with hepatocellular carcinoma in cirrhosis (HCC) (follow-up: 57 months; 1-140 months). Within this group, 25 patients (21%) suffered from hepatitis B. Pre-transplant selection criteria were a maximum diameter of 5 degrees cm in uni-nodular tumors, or 3 degrees cm for two to three tumor nodules. The rate of tumors with 2-3 tumor nodules was increased in the hepatitis-B group (52% vs. 29%; P<0.05). Other tumor characteristics did not differ. In the hepatitis-B group, more patients died post-transplantation (44% vs.22%; P<0.05). This difference was due to unspecific causes, not to tumor recurrence or re-infection. These findings may be indicative of a more complicated course in patients suffering from hepatitis B in general.

Carcinoma, Hepatocellular↗
PubMed2002

Distinct enzyme profiles in patients with cryptogenic cirrhosis reflect heterogeneous causes with different outcomes after liver transplantation (OLT): a long-term documentation before and after OLT.

BACKGROUND: Sound information is lacking about the clinical presentation of cryptogenic cirrhosis and its outcome after orthotopic liver transplantation (OLT). METHODS: Among 856 patients who have been transplanted at our center, 40 patients had no evidence of any known etiologies and were therefore defined as suffering from cryptogenic cirrhosis. Their median follow-up period before OLT was 78 months (range, 1-264), and after OLT 97 months (range, 1-132). Laboratory and histological data were evaluated according to features being compatible either with a toxic, hepatitic, or cholestatic condition. RESULTS: The clinical and histological findings differed specifically between these three groups. The toxic-like group (GGT 4-18 x upper limit of normal [ULN]) expressed significantly higher IgA levels, had histologically more often fatty liver changes, and risk factors for non-alcoholic steatohepatitis predominated (56% compared with 3% in the other groups, P=0.01). The hepatitic-like group (ALT 2-18 x ULN) showed histologically features of chronic hepatitis or hepatitic cirrhosis, and only among these patients a median International Autoimmune Hepatitis (IAH) score of 13 was found suggesting autoimmune hepatitis (AiH). In the cholestatic group (AP 2-8 x ULN) histology was compatible with a non-toxic inflammatory process but IAH score excluded AiH in all. After OLT, actuarial graft and patients survival was 90% at 5 years. Mild or moderate graft hepatitis occurred in 9 patients (23%) and was significantly associated with a pre-OLT IAH score >or= 10 (P =0.008). CONCLUSIONS: This study provides arguments that cryptogenic cirrhosis is a heterogeneous disease in which autoimmune mechanisms might be predominately involved and being responsible for recurrence of chronic liver disease observed in some instances after OLT.

Adult↗
PubMed2002

Interferon-alpha, but not the ABL-kinase inhibitor imatinib (STI571), induces expression of myeloblastin and a specific T-cell response in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a clonal disease of hematopoietic stem cells caused by a reciprocal translocation of the long arms of chromosomes 9 and 22. In human leukocyte antigen A*0201(+) (HLA-A*0201(+)) individuals, response after interferon-alpha (IFN-alpha) was shown to be associated with the emergence of CML-specific cytotoxic T cells that recognize PR-1, a myeloblastin (MBN)-derived nonapeptide. In contrast, imatinib potently induces remissions from CML by specific inhibition of the ABL tyrosine kinase. Here, we explored molecular regulations associated with CML responses under different treatment forms using cDNA-array. Expression of MBN was found to be down-regulated in remission under imatinib therapy (0 of 7 MBN(+) patients). In contrast, MBN transcription was readily detectable in the peripheral blood in 8 of 8 tested IFN-alpha patients in complete remission (P =.0002). IFN-alpha-dependent MBN transcription was confirmed in vitro by stimulation of peripheral blood mononuclear cells (PBMCs) with IFN-alpha and by IFN-alpha-mediated activation of the MBN promoter in reporter gene assays. Finally, with the use of HLA-A*0201-restricted, MBN-specific tetrameric complexes, it was demonstrated that all of 4 IFN-alpha-treated patients (100%), but only 2 of 11 imatinib patients (19%), in complete hematological or cytogenetic remission developed MBN-specific cytotoxic T cells (P =.011). Together, the induction of MBN expression by IFN-alpha, but not imatinib, may contribute to the specific ability of IFN-alpha to induce an MBN-specific T-cell response in CML patients. This also implies that the character of remissions achieved with either drug may not be equivalent and therefore a therapy modality combining IFN-alpha and imatinib may be most effective.

Benzamides↗
PubMed2002

alpha-Mannosidosis in the guinea pig: cloning of the lysosomal alpha-mannosidase cDNA and identification of a missense mutation causing alpha-mannosidosis.

alpha-Mannosidosis is a lysosomal storage disorder caused by deficient activity of the lysosomal alpha-mannosidase. We report here the sequencing and expression of the lysosomal alpha-mannosidase cDNA from normal and alpha-mannosidosis guinea pigs. The amino acid sequence of the guinea pig enzyme displayed 82-85% identity to the lysosomal alpha-mannosidase in other mammals. The cDNA of the alpha-mannosidosis guinea pig contained a missense mutation, 679C>T, leading to substitution of arginine by tryptophan at amino acid position 227 (R227W). The R227W allele segregated with the alpha-mannosidosis genotype in the guinea pig colony and introduction of R227W into the wild-type sequence eliminated the production of recombinant alpha-mannosidase activity in heterologous expression studies. Furthermore, the guinea pig mutation has been found in human patients. Our results strongly indicate that the 679C>T mutation causes alpha-mannosidosis and suggest that the guinea pig will be an excellent model for investigation of pathogenesis and evaluation of therapeutic strategies for human alpha-mannosidosis.

Amino Acid Sequence↗
PubMed2002

Mycophenolate mofetil in combination with recombinant interferon alfa-2a in interferon-nonresponder patients with chronic hepatitis C.

BACKGROUND/AIMS: Since ribavirin was able to improve the antiviral efficacy of interferon alfa in patients with chronic hepatitis C, several other adjuncts have been studied. It has been shown that mycophenolate mofetil (MMF) is a more potent inhibitor of the inosine 5'-monophosphate-dehydrogenase (IMPDH) than ribavirin. The present study is a pilot study evaluating the efficacy and safety of combination therapy with interferon alfa-2a and MMF in interferon alfa nonresponder patients. METHODS: Thirty-eight adult patients with chronic hepatitis C who did not respond to a previous interferon alfa monotherapy were enrolled to receive 6 million units of interferon alfa-2a tiw in combination with MMF (1 week 500 mg/day, 1 week 1000 mg/day, 22 weeks 2000 mg/day). RESULTS: An interim analysis of 29 patients after 12 weeks of therapy showed that only one patient had negative hepatitis C virus-RNA at this time point. There was no significant reduction of the viral load during therapy. Due to inefficacy the study was discontinued. CONCLUSIONS: Combination therapy of interferon alfa-2a and MMF is ineffective in improving virological response rates in nonresponder patients with chronic hepatitis C. These data suggest that inhibition of the IMPDH seems not to be the major mechanism of ribavirin in enhancing the antiviral effect of interferon alfa in chronic hepatitis C.

Adult↗
PubMed2002

Increasing applicability of liver transplantation for patients with hepatitis B-related liver disease.

Liver transplantation in patients with hepatitis B has been under discussion for 20 years because of inferior results without reinfection prophylaxis; therefore, we analyzed our overall experience with liver transplantation in hepatitis B patients with immunoprophylaxis, particularly the influence of the available antiviral treatment in different periods. From 1988 to 2000, 228 liver transplants in 206 hepatitis B patients were performed. Indications were acute liver failure (10%), hepatitis B virus (HBV) cirrhosis alone (67%) or with hepatitis D virus (HDV) (13%), or hepatitis C virus (HCV) coinfection (7%). All patients received long-term immunoprophylaxis (anti-HBs > 100 U/L). HBV DNA-positive patients were treated before and after surgery with famciclovir or lamivudine since 1993 and 1996, respectively. Since 1993, antivirals also were used for HBV reinfection. The 1-, 5-, and 10-year patient survival rates were 91%, 81%, and 73%. In patients with hepatocellular carcinoma (HCC) (60% 5-year survival, P <.01) or HBV reinfection (69% 5-year survival, P <.01) survival was significantly impaired. Those with HDV or HCV coinfection had a slightly better survival than with HBV monoinfection (P >.05, not significant). Preoperative positive HBV DNA (hybridization-assay) test results were associated with a slightly impaired patient survival (78% 5-year survival, P >.05, not significant versus DNA-negative). Preoperative positive hepatitis B e antigen (HBeAg) predicted significantly worse survival (P <.05 versus negative HBeAg). Graft loss caused by reinfection was most frequent before the availability of antiviral drugs. Two-year patient survival increased from 85% in era I (1988-1993) to 94% in era III (1997-2000, P <.05). The 2-year recurrence rates in these 2 periods were 42% and 8% (P <.05). In conclusion, excellent long-term results can be achieved in hepatitis B patients after liver transplantation with modern strategies, and survival rates are similar to other indications. Based on our experience, hepatitis B patients, including those with active viral replication, should not be excluded from liver transplantation.

Adult↗