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S Zeuzem

Publications and source records attributed to S Zeuzem.

At least 127 records · Page 7Linked to original sources
PubMed1999

Peri-hepatic lymphadenopathy in primary biliary cirrhosis reflects progression of the disease.

OBJECTIVE: We prospectively investigated the peri-hepatic lymph node volume in patients with primary biliary cirrhosis (PBC) and healthy controls to evaluate the correlation with histology, biochemical and immunological features. MATERIALS AND METHODS: The total peri-hepatic lymph node volume in the liver hilus was evaluated by high-resolution ultrasound in 67 consecutive patients with PBC and in 43 healthy controls. Stages I-IV of PBC were biochemically, immunologically and histologically proven in all patients. RESULTS: Adequate visualization of the liver hilus was achieved in 59/67 patients (88%) with PBC and in 39/43 healthy controls (91%). Lymph nodes in the liver hilus were sonographically detected in all 59 patients with PBC and in 26/39 healthy controls (67%) with adequate visualization of the liver hilus. The mean peri-hepatic lymph node volumes were: stage I (n = 9): 0.8 +/- 0.5 ml; stage II (n = 28): 2.4 +/- 1.5 ml; stage III (n = 21): 4.2 +/- 2.3 ml; stage IV (n = 9): 3.2 +/- 1.0 ml. The peri-hepatic lymph node volume did not significantly correlate with cholestasis, liver function tests or the immunological status. CONCLUSIONS: Enlarged lymph nodes in the liver hilus are sonographically detectable in almost all patients with PBC. The total peri-hepatic lymph node volume in patients with PBC reflects histological stage, i.e. larger lymph nodes are observed in more advanced disease.

Adult↗
PubMed1999

Interferon-antibodies and the breakthrough phenomenon during ribavirin/interferon-alpha combination therapy and interferon-alpha monotherapy of patients with chronic hepatitis C.

BACKGROUND/AIMS: The significance of interferon antibodies with respect to response to treatment in patients with chronic hepatitis C treated with interferon-alpha (INF-alpha) remains a matter of debate. The influence of ribavirin on IFN-antibody formation in combination therapy with IFN-alpha has not yet been studied. Therefore we evaluated the relationship between IFN-antibodies and response to ribavirin/IFN-alpha combination therapy and IFN-alpha monotherapy. METHODS: We studied 169 patients with chronic hepatitis C who were treated either with IFN alpha 2a (6 MU, thrice weekly) alone or in combination with ribavirin (14 mg/kg per day) for twelve weeks. Thereafter, patients who achieved a virological response (HCV-RNA-negative) were treated with 3 MU IFN-alpha thrice weekly for another 40 weeks. IFN antibodies were analyzed and quantified by a double-antigen sandwich enzyme immunoassay (EIA). In 86 patients two neutralization assays--an antiviral neutralization assay as well as an antiproliferative neutralization assay--were performed in addition. The relationship of the development of IFN-antibodies with the virologically defined response to treatment was analyzed. RESULTS: Ribavirin did neither influence the prevalence nor the level of IFN-antibodies. The frequencies of IFN-antibody formation did not differ in the response groups. However, patients with breakthrough showed significantly higher IFN-antibody titers as compared to responder at end of treatment (median 1,336 BU/ml vs. 148 BU/ml; p = 0.018). Among the breakthrough patients those with IFN-antibodies showed the reappearance of HCV-RNA during therapy significantly earlier (median week 24) than those without IFN-antibodies (median week 32; p = 0.03). CONCLUSION: The addition of ribavirin to IFN-alpha does not influence the formation of IFN-antibodies. The development of high-titer IFN-antibodies during IFN-alpha or ribavirin/IFN-alpha therapy of patients with chronic hepatitis C may account for the early occurrence of breakthrough in some patients, while other mechanisms seem to be responsible for this phenomenon in the majority of the afflicted patients.

Adult↗
PubMed1998

Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. International Hepatitis Interventional Therapy Group.

BACKGROUND: Interferon alfa is the only effective treatment for patients with chronic hepatitis C. Forty percent of patients have an initial response to this therapy, but most subsequently relapse. We compared the effect of interferon alone with that of interferon plus oral ribavirin for relapses of chronic hepatitis C. METHODS: We studied 345 patients with chronic hepatitis C who relapsed after interferon treatment. A total of 173 patients were randomly assigned to receive standard-dose recombinant interferon alfa-2b concurrently with ribavirin (1000 to 1200 mg orally per day, depending on body weight) for six months, and 172 patients were assigned to receive interferon and placebo. RESULTS: At the completion of treatment, serum levels of hepatitis C virus (HCV) RNA were undetectable in 141 of the 173 patients who were treated with interferon and ribavirin and in 80 of the 172 patients who were treated with interferon alone (82 percent vs. 47 percent, P<0.001). Serum HCV RNA levels remained undetectable 24 weeks after the end of treatment in 84 patients (49 percent) in the combination-therapy group, but in only 8 patients (5 percent) in the interferon group (P<0.001). Sustained normalization of serum alanine aminotransferase concentrations and histologic improvement were highly correlated with virologic response. Base-line serum HCV RNA levels of 2 x 10(6) copies per milliliter or less were associated with higher rates of response in both treatment groups. Viral genotypes other than type 1 were associated with sustained responses only in the combination-therapy group. Combined therapy caused a predictable fall in hemoglobin concentrations but otherwise had a safety profile similar to that of interferon alone. CONCLUSIONS: In patients with chronic hepatitis C who relapse after treatment with interferon, therapy with interferon and oral ribavirin results in higher rates of sustained virologic, biochemical, and histologic response than treatment with interferon alone.

Adult↗
PubMed1998

Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT)

BACKGROUND: Only 15-20% of patients with chronic hepatitis C achieve a sustained virological response with interferon therapy. The aim of this study was to compare the efficacy and safety of interferon alpha2b in combination with oral ribavirin with interferon alone, for treatment of chronic infection with hepatitis C virus (HCV). METHODS: 832 patients aged 18 years or more with chronic HCV who had not been treated with interferon or ribavirin, were enrolled and randomly allocated one of three regimens: 3 mega units (MU) interferon alpha2b three times a week plus 1000-1200 mg ribavirin per day for 48 weeks; 3 MU interferon alpha2b three times a week plus 1000-1200 mg ribavirin per day for 24 weeks; or 3 MU interferon alpha2b three times a week and placebo for 48 weeks. All patients were assessed for safety, tolerance, and efficacy at the end of weeks 1, 2, 4, 6, and 8, and every 4 weeks during treatment. After treatment was completed patients were followed up on weeks 4, 8, 12, and 24. The primary endpoint was loss of detectable HCV-RNA (serum HCV-RNA <100 copies/mL) at week 24 after treatment. FINDINGS: Sustained virological response at 24 weeks after treatment, was found in 119 (43%) of the 277 patients treated for 48 weeks with the combination regimen, 97 (35%) of the 277 patients treated for 24 weeks with the combination regimen (p=O.055), and 53 (19%) of the 278 patients treated for 48 weeks with interferon alone (p<0.001 vs both combination regimens, intention-to-treat analysis). Logistic regression identified five independent factors significantly associated with response: genotype 2 or 3, viral load less than 2 million copies/mL, age 40 years or less, minimal fibrosis stage, and female sex. Among patients with fewer than three of these factors the odds ratio of sustained response was 2.6 (95% Cl 1.4-4.8; p=0.002) for the 48 week combination regimen compared with 24 weeks of the combination regimen. Discontinuation of therapy for adverse events was more frequent with combination (19%) and monotherapy (13%) given for 48 weeks than combination therapy given for 24 weeks (8%). INTERPRETATION: An interferon alpha2b plus ribavirin combination is more effective than 48 weeks of interferon alpha2b monotherapy and has an acceptable safety profile. Patients with few favourable factors benefit more from extending the duration of combination therapy to 48 weeks.

Administration, Oral↗
PubMed1998

Quantification of the initial decline of serum hepatitis C virus RNA and response to interferon alfa.

Although several virus- and host-related predictive factors for the response to interferon alfa (IFN-alpha) have been defined in patients with chronic hepatitis C, no pretreatment parameter can definitely predict the response to antiviral treatment. Assessment of the initial response by quantification of serum hepatitis C virus RNA before and 4 weeks after initiation of therapy may be a clinically applicable and reliable parameter to predict long-term response. Therefore, the aims of the present study were to test the predictive value of a decline in HCV RNA of at least 3 log in the first 4 weeks of treatment (deltaHCV RNA) in patients treated with 3 x 10(6) units of recombinant IFN-alpha2a (rIFN-alpha2a) three times per week subcutaneously and to compare deltaHCV RNA with other established predictive factors, such as HCV genotype and pretreatment viremia. Serum HCV RNA was measured by a validated quantitative reverse transcription-polymerase chain reaction (RT-PCR). Geno/subtyping of HCV was performed by direct sequencing of the nonstructural (NS) 5B region of PCR-amplified isolates and subsequent phylogenetic analysis. Stable HCV RNA levels (deltaHCV RNA < or = 1 log) within the first 4 weeks of IFN-alpha treatment were present in 42 of 70 patients. A decline in HCV RNA levels between 1 to 3 log and more than 3 log was observed in 9 (13%) and 19 patients (27%), respectively. In 21 of 70 patients (30%), HCV RNA was not detectable at the end of 12 months' treatment. Three of 26 patients (11%) with a pretreatment viremia of < or = 10(6) copies/mL (all HCV subtype 3a) and 6 of 44 patients (14%) with a pretreatment viremia of > 10(6) copies/mL (HCV subtypes 1b, 2a, 2c, 3a [two patients], and 4) achieved a virological sustained response to interferon-alpha2a treatment. All patients with a virological sustained response had an initial deltaHCV RNA of more than 3 log. In a stepwise discriminant-function analysis, the initial deltaHCV RNA was confirmed as the strongest predictor of virological sustained response (P < .0001). In conclusion, the data of the present study suggest that IFN-alpha treatment can be terminated after 4 weeks in patients with a decrease in HCV RNA levels of less than 3 log, when apparent HCV eradication is considered the therapeutic target. The predictive value of deltaHCV RNA clearly exceeds the significance of HCV genotype and pretreatment viremia as predictors of successful IFN-alpha treatment.

Adult↗
PubMed1998

Hepatitis C virus dynamics in vivo: effect of ribavirin and interferon alfa on viral turnover.

Treatment of patients with chronic hepatitis C with recombinant interferon alfa (rIFN-alpha) can cause a decrease of serum transaminases and hepatitis C virus (HCV) RNA. Recent trials evaluating combination therapy of IFN-alpha and ribavirin suggested a potential synergistic effect. From serial measurements of serum HCV RNA concentrations following treatment-induced perturbation of the balance between virus production and clearance, we compared the antiviral efficacy of both IFN-alpha alone and IFN-alpha in combination with ribavirin. Chronically HCV-infected patients were treated with either 3 x 3 MU or 3 x 6 MU rIFN-alpha per week or 3 x 6 MU rIFN-alpha plus 14 mg/kg of body weight ribavirin per day. The time-dependent HCV RNA concentrations during antiviral treatment were analyzed by iterative least-squares regression. After initiation of antiviral therapy, HCV RNA declined exponentially below the detection limit of the reverse-transcription polymerase chain reaction assay (1,000 HCV RNA molecules per milliliter) in 10 of 26 (39%), 10 of 19 (53%), and 10 of 18 patients (56%) treated with 3 x 3 MU, 3 x 6 MU rIFN-alpha without and with ribavirin, respectively. Viral clearance from serum was faster in patients treated with 3 x 6 MU rIFN-alpha (t1/2 = 0.23 +/- 0.15) compared with patients treated with 3 x 3 MU rIFN-alpha per week (0.67 +/- 0.36 days) (P < .004). However, half-lives of viral clearance were similar in patients treated with rIFN-alpha or rIFN-alpha plus ribavirin. For virus release from infected hepatocytes, absence and presence of ribavirin yielded half-lives of t1/2 = 2.54 +/- 2.10 and t1/2 = 1.99 +/- 1.70, respectively, indicating that ribavirin does not significantly inhibit HCV production. In conclusion, the data of the present study indicate that higher rIFN-alpha doses accelerate viral clearance from serum. Ribavirin (14 mg/kg/d), however, lacks synergistic antiviral effects in the treatment of chronic hepatitis C with 3 x 6 MU rIFN-alpha per week.

Adult↗
PubMed1998

Effect of ribavirin on virus load and quasispecies distribution in patients infected with hepatitis C virus.

BACKGROUND/AIMS: The combination of ribavirin and interferon alfa has potent synergistic effects in the treatment of chronic hepatitis C. The antiviral mechanism of ribavirin is unknown. We investigated whether a transient initial antiviral effect of ribavirin was sufficient to improve the response to interferon. METHODS: Fifteen HCV-infected patients (ten male, five female; mean age 45.4+/-11.0 years) treated with ribavirin (1000-1200 mg) and 17 untreated patients with chronic hepatitis C (11 male, six female; mean age 45.6+/-9.9 years) were investigated. All patients were either non-responders to (n=19) or relapsed after (n=13) previous interferon treatment. Serum HCV-RNA concentrations and HCV quasispecies distribution were serially measured over 4 weeks by quantitative reverse transcription-polymerase chain reaction and single-strand conformation polymorphism analysis, respectively. RESULTS: In six of the 15 patients treated with ribavirin, but in none of the controls, serum alanine aminotransferase levels declined by at least 30%. Pretreatment HCV-RNA levels ranged from 5.0x10(5)-5.0x10(7) copies/ml. After initiation of ribavirin treatment, minor (0.5-1.0 log) or no changes (<0.5 log) in total hepatitis C viremia were observed in ten and five patients, respectively. In HCV-infected patients without treatment 7/17 patients had minor and 10/17 no changes in viremia. Polymerase chain reaction amplification of the hypervariable region-1 of HCV was successful in 13/15 treated and in 17/17 untreated patients. Changes in HCV quasispecies according to the single-strand conformation polymorphism band pattern occurred in only one patient treated with ribavirin and in three of the untreated patients. CONCLUSIONS: Ribavirin monotherapy has no initial antiviral effect on total hepatitis C viremia nor on HCV quasispecies. Unlike the rapid emergence of antiviral drug-resistant strains in HIV-infected patients, no viral escape phenomena are observed in HCV-infected patients treated with ribavirin.

Adult↗
PubMed1998

Clinical evaluation of autoantibodies to p53 protein in patients with chronic liver disease and hepatocellular carcinoma.

In hepatocellular carcinoma (HCC) of patients from the Western hemisphere, mutations in the p53 tumour suppressor gene are present in up to 37% of cases. Conformational change and cellular accumulation can initiate an immune response with generation of circulating autoantibodies to p53 protein. In the present study, we investigated 711 consecutive patients with chronic liver disease to evaluate the sensitivity and specificity of autoantibodies to p53 protein as a serological marker for HCC. Detection of p53 autoantibodies was performed using an enzyme-linked immunosorbent assay with immobilised recombinant p53 protein. Liver cirrhosis was present in 259 patients (36.4%) and a HCC was diagnosed in 75 patients (10.6%). Autoantibodies to p53 protein were detectable in 15 of 377 patients with chronic liver disease (4.0%) and in 10 of 259 patients presenting with liver cirrhosis (3.9%). All 25 p53 autoantibody-positive/HCC-negative patients were carefully investigated and no underlying malignancy was clinically detected, suggesting that elevated p53 antibody levels may not exclusively be detectable in patients with malignant disease. In patients with clinically manifest HCC, p53 autoantibodies were detected in 17 of 75 cases, thus resulting in a sensitivity of 22.7% and a specificity of 96.1%. In contrast, assessment of serum alpha-fetoprotein (AFP) resulted in a sensitivity and specificity of 69.3 and 91.8% (AFP > 20 ng/ml) and 53.3 and 99.1% (AFP > 100 ng/ml) for the detection of HCC, respectively. The data of the present study reveal that the presence of p53 autoantibodies in patients with chronic liver disease is not completely specific for HCC. Moreover, we obtained no direct evidence that p53 autoantibody formation precedes the clinical diagnosis of HCC. However, serological screening for HCC might be improved by combining AFP and p53 autoantibody assays.

Adolescent↗
PubMed1998

[Ultrasound lymph node imaging in the abdomen and retroperitoneum of healthy probands].

PURPOSE: Transabdominal ultrasonography is able to detect normal sized perihepatic lymph nodes. The role of transabdominal ultrasonography in detecting normal lymph nodes in other abdominal locations has not yet been examined. METHODS: 92 healthy volunteers (57 male, 35 female; age: 33 +/- 9 [19-66] years) were examined by transabdominal ultrasonography. The peripancreatic region, the location between the inferior vena cava and aorta, left paraaortal region, and the right mesenteric region next to the terminal ileum were studied with high resolution ultrasound. All transabdominal ultrasound examinations were performed with a 3.5 and 5 MHz probe using a special magnification mode without substantial loss of resolution (RES-mode, Acuson) and additionally by colour doppler imaging (Acuson XP). RESULTS: In 80/92 (87%) of the healthy subjects, all regions could be adequately visualized. In 72% of patients with adequate visualization, abdominal lymph nodes were detectable. Abdominal lymph nodes could be sonographically detected peripancreatically in 14/80 (18%), in the location between the inferior vena cava and aorta in 44/80 (55%), in the left paraaortal region in 32/80 (40%), and in the right mesenteric region next to the terminal ileum in 31/80 (39%) of the healthy subjects. CONCLUSION: High resolution ultrasonography is able to detect normal lymph nodes in different abdominal locations in 72% of healthy subjects. Sonographic detection of singular normal-sized abdominal lymph nodes is not indicative of abdominal disease.

Abdomen↗
PubMed1998

Rapid microsatellite analysis of paraffin embedded tumour specimens from patients with hereditary non-polyposis colorectal cancer.

In screening for hereditary non-polyposis colorectal cancer (HNPCC)--an autosomal dominant disorder characterised by mutations in mismatch repair genes--detection of microsatellite instability is an important diagnostic criterion. The mono- or dinucleotide repeat DNA sequences are usually amplified from formalin fixed, paraffin embedded tissue by polymerase chain reaction after numerous time consuming steps including deparaffinisation, DNA extraction, and purification. A rapid single step method for direct DNA analysis is described, based on preincubation of paraffin embedded tissue with Triton X-100 followed by DNA amplification with fluorescence labelled primers and electrophoresis in an automated sequencer. This procedure allows precise allele sizing and analysis of genetic instability, is more efficient and time saving, reduces the risk of contamination, and is therefore of particular interest in screening for HNPCC.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed1998

Hepatic and portal vein flow pattern in correlation with intrahepatic fat deposition and liver histology in patients with chronic hepatitis C.

OBJECTIVE: The flow pattern in hepatic veins depends on cardiac physiology and liver histology. The aim of our study was to determine the dependence of the flow pattern of hepatic and portal veins in relation to histologic features in patients with chronic hepatitis C. SUBJECTS AND METHODS: In 135 patients with chronic hepatitis C, the Doppler sonography spectrum of the right hepatic vein was classified as triphasic, biphasic, or monophasic. The flow of the portal vein was characterized according to the undulation (velocity(max,min)). A liver biopsy was performed during sonography, and biopsy specimens were semiquantitatively evaluated on a histologic activity index and a score of the hepatic fat content. Multiple logistic regression analysis was used to identify the histologic features that might contribute to the type of flow pattern. RESULTS: The hepatocyte fat content was the only variable associated with an independent effect on the type of flow pattern (monophasic versus triphasic; odds ratio, 16.26; 95% confidence interval, 6.38-41.45; p < .0001). A pronounced undulation in the portal vein was associated with portal inflammation but not with other parameters of the histologic activity index or the intrahepatic fat deposition. CONCLUSION: On sonography, the normal flow pattern in the right hepatic vein is triphasic. The monophasic flow pattern in the right hepatic vein is mainly caused by intrahepatic fat deposition and occasionally by inflammatory or fibrotic changes. Conversely, the flow pattern of the portal vein is mainly influenced by portal inflammation.

Adult↗
PubMed1998

Quantification of hepatitis C virus RNA by RT-PCR in comparison to the branched DNA method.

INTRODUCTION: Quantification of hepatitis C virus (HCV) serum viremia levels is an important measure to predict and monitor response to interferon-alpha therapy as well as to predict clinical outcome. We were interested to compare the most widely used HCV quantification methods, quantitative RT-PCR (qRT-PCR) and the branched DNA (bDNA) method, with respect to sensitivity and reliability. RESULTS: In the present study, 101 serum samples from patients chronically infected with HCV were simultaneously quantified by an in-house reverse transcriptase (RT)-PCR assay and the branched DNA Quantiplex HCV RNA kit 1.0 and 2.0. The concentration of HCV RNA molecules/ml serum ranged from 1.5 x 10(4) to 1.0 x 10(8) as assessed by our quantitative (q)RT-PCR. Serum concentrations of HCV-genotype 1 were significantly higher when measured with bDNA 1.0 compared to bDNA 2.0 and qRT-PCR, whereas measurements by qRT-PCR and bDNA 2.0 were concordant. Measurements of genotypes 2 and 3 by bDNA 2.0 were significantly higher than by bDNA 1.0. Significantly lower measurements were obtained for genotype 3 by qRT-PCR in comparison to bDNA 2.0. CONCLUSION: Despite subtype-specific differences, there is clinically sufficient agreement in measurements between qRT-PCR and bDNA of HCV RNA concentrations. However, with respect to the therapeutic monitoring of the individual patient, kits and methods should not be exchanged.

DNA, Viral↗