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J T Brouwer

Publications and source records attributed to J T Brouwer.

At least 37 records · Page 2Linked to original sources
PubMed1998

Hepatitis C virus genotypes: epidemiological and clinical associations. Benelux Study Group on Treatment of Chronic Hepatitis C.

In a cohort of 292 chronic hepatitis C patients living in the Benelux countries the relationship between viral genotype and geographical origin, route of transmission, clinical characteristics and severity of liver disease was analyzed. HCV-RNA isolates could be classified by the Line Probe Assay (LiPA) as 1a, 1b, 2, 3, 4 or 5 in 286 (98%) cases. Patients of European origin were predominantly infected with HCV subtype 1b (164/254, 65%, CI 58-70%), as were patients of Asian origin (7/13, 54%). Patients originating from Surinam (South America) had predominantly type 2 (9/10, 90%), whereas Africans were mainly infected with type 4 (7/9, 77%). Blood transfusion was the mode of transmission in 142 (50%) patients, intravenous drug abuse (IVDA) in 40 (14%), occupational needle accident or tattoo in 11 (4%); no obvious source of infection was found in 93 (33%). In patients infected by blood transfusion, subtype 1b was predominant (70%, CI 61-77%), whereas subtypes la and 3 were predominant in those infected by IVDA (25% and 45%, respectively, p<0.001). Cirrhosis was observed in 68 (24%) patients; in multivariate analysis, factors independently related to cirrhosis were: the duration of infection, age and prior hepatitis B. No significant relationship was found between the severity of fibrosis or liver inflammation and the HCV (sub)types. In summary, in this large cohort of patients in the Benelux countries the hepatitis C virus (sub)type present was clearly related to the country of origin and the route of transmission, but not to the severity of liver disease.

Adult↗
PubMed1997

Therapy of hepatitis C: patients with cirrhosis.

The management of both compensated and decompensated cirrhosis caused by hepatitis C must be viewed in the context of the natural history of the disease. The prognosis of compensated cirrhosis caused by hepatitis C is relatively good. In a recent retrospective study, after 5 years of follow-up evaluation, 18% of patients had developed hepatic decompensation and 7% hepatocellular carcinoma. Overall 5-year survival rate was 91%. Treatment with alpha interferon appears to decrease the incidence of hepatocellular carcinoma in patients who achieve a sustained remission. However, on an intention-to-treat basis and after adjustment for differences in clinical and serological features at entry, interferon therapy does not correlate with a reduced incidence of liver cancer or improved survival. Combined analysis of multiple large studies on patients with cirrhosis caused by hepatitis C indicates that current regimens of alpha interferon (3 to 6 million units three times weekly for 6 to 12 months) result in a sustained biochemical response in 9% of patients. The rates of sustained virological responses are less well documented. Virological measurements during therapy show that only 22% of patients become hepatitis C virus (HCV) RNA negative by 4 weeks and, thereafter, there is a high rate of breakthrough. In small studies, the combination of interferon and ribavirin leads to sustained biochemical and virological response rates of 21%, more than twice the rates achieved with interferon alone. The prognosis of decompensated cirrhosis caused by hepatitis C is poor, with a 5-year survival rate of only 50%. The efficacy of interferon in patients with decompensated cirrhosis is not well documented and its use cannot be recommended. In contrast, 5-year survival rates after liver transplantation for cirrhosis caused by hepatitis C is excellent, in the range of 70% to 80%. Recurrence of HCV infection occurs in more than 95% of patients, but in short-term follow-up studies, recurrence of cirrhosis and graft failure occurs in only 10% of patients.

Antiviral Agents↗
PubMed1997

Ribavirin enhances the efficacy but not the adverse effects of interferon in chronic hepatitis C. Meta-analysis of individual patient data from European centers.

BACKGROUND/AIMS: This study aimed to obtain a more precise estimation of the efficacy and tolerability of interferon-ribavirin combination therapy for chronic hepatitis C. METHODS: A meta-analysis was carried out of individual patient data comprising about 90% of the published experience with combination therapy. The study was set in four European university-affiliated liver referral centers. A total of 186 individuals with chronic hepatitis C who had participated in three randomized controlled trials and one open study were selected for the study. Fifty-one had received ribavirin monotherapy (1000-1200 mg/day), 37 interferon monotherapy (3 MU 3x/week) and 78 interferon-ribavirin combination therapy (dosage as for monotherapy) for 6 months. Twenty patients served as controls. Follow-up after therapy was 6 months. Data analysis was by the multivariate logistical regression method. RESULTS: The primary outcome measure for efficacy was the percentage with a sustained response (ALT normalization and HCV RNA negativity 6 months after therapy). The sustained response rate was significantly higher for interferon-ribavirin combination therapy than for interferon or ribavirin monotherapy (odds ratio IFN-Riba vs IFN = 9.8, 95% CI 1.9-50). The estimated probability of sustained response following interferon-ribavirin combination therapy was 51% for patients without previous IFN therapy, 52% for patients with previous IFN therapy and response-relapse, and 16% for previous IFN non-responders. No serious adverse events were observed and less than 10% withdrew. CONCLUSIONS: The efficacy of interferon-ribavirin therapy appears to be enhanced two- to threefold over interferon monotherapy in all major subgroups of chronic hepatitis C patients tested. In view of its acceptable toxicity profile, interferon-ribavirin combination therapy is a candidate for the new standard therapy for chronic hepatitis C.

Adult↗
PubMed1997

Effectiveness of interferon alfa on incidence of hepatocellular carcinoma and decompensation in cirrhosis type C. European Concerted Action on Viral Hepatitis (EUROHEP).

BACKGROUND/AIMS: The role of interferon alfa treatment in improving morbidity endpoints in patients with chronic hepatitis C infection is currently under debate. The aim of this study was to evaluate the effectiveness of interferon in preventing hepatocellular carcinoma and decompensation in cirrhosis type C. METHODS: A retrospective cohort study was carried out on 329 consecutive Caucasian patients with cirrhosis followed for a mean period of 5 years at seven tertiary care university hospitals. Inclusion criteria were biopsy-proven cirrhosis, anti-HCV positivity, abnormal serum aminotransferase levels and absence of complications of cirrhosis. RESULTS: The yearly incidence of hepatocellular carcinoma was 2.3% for 136 untreated patients and 1.0% for 193 patients treated with interferon alfa. The yearly incidence of hepatic decompensation was 5.7 for untreated and 1.5 for the treated patients. Fourteen (7%) of 193 treated patients showed sustained aminotransferase normalization and none of them developed complications of cirrhosis. At enrollment, untreated patients were older and had more severe liver disease than patients treated with interferon. After adjustment for clinical and serologic differences at entry between treated and untreated patients, the 5-year estimated probability of the occurrence of hepatocellular carcinoma was 2.1% and 2.7% and of decompensation was 7% and 11% for treated and untreated cases, respectively. CONCLUSIONS: This analysis did not detect any significant benefit of interferon alfa on morbidity in patients with compensated cirrhosis type C, although it suggests a reduction in complications of cirrhosis for those with a sustained response to therapy, and it indicates the need for better therapies.

Antiviral Agents↗
PubMed1997

Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients.

BACKGROUND & AIMS: Few data are available concerning the long-term prognosis of chronic liver disease associated with hepatitis C virus infection. This study examined the morbidity and survival of patients with compensated cirrhosis type C. METHODS: A cohort of 384 European cirrhotic patients was enrolled at seven tertiary referral hospitals and followed up for a mean period of 5 years. Inclusion criteria were biopsy-proven cirrhosis, abnormal serum aminotransferase levels, absence of complications of cirrhosis, and exclusion of hepatitis A and B viruses and of metabolic, toxic, or autoimmune liver diseases. RESULTS: Antibodies against hepatitis C virus were positive in 98% of 361 patients tested. The 5-year risk of hepatocellular carcinoma was 7% and that of decompensation was 18%. Death occurred in 51 patients (13%), with 70% dying of liver disease. Survival probability was 91% and 79% at 5 and 10 years, respectively. Two hundred five patients (53%) were treated with interferon alfa. After adjustment for clinical and serological differences at baseline between patients treated or not treated with interferon, the 5-year estimated survival probability was 96% and 95% for treated and untreated patients, respectively. CONCLUSIONS: In this cohort of patients, life expectancy is relatively long, in agreement with the morbidity data showing a slowly progressive disease.

Carcinoma, Hepatocellular↗
PubMed1997

Antiviral therapy of hepatitis C.

BACKGROUND: Chronic hepatitis C can be treated with interferon therapy, but persistent viral clearance is only achieved in 20% of patients. Which patients have a high chance of viral clearance and what other treatment might enhance the effectivity of interferon therapy are reviewed. METHODS: Data from published randomized trials on interferon mono-therapy, ribavirin mono-therapy and combination therapy of interferon-ribavirin and interferon-ursodeoxycholic acid are analysed separately and in a meta-analysis of individual data. RESULTS: Interferon mono-therapy leads to viral clearance in only 10% of patients with genotype 1 and in less than 10% in cirrhosis; patients with plasma HCV RNA detectable at 4 weeks of therapy have only 2% chance of viral clearance. Prolongation of therapy reduces relapse in treatment responders. Interferon-ribavirin combination therapy appears to enhance the efficacy 2-3 fold without increasing toxicity. CONCLUSIONS: The benefit-risk/cost ratio of interferon mono-therapy can be improved by selection of patients, monitoring plasma HCV RNA at 4 weeks, and prolonging therapy to 12 months in responders with genotype 1. Interferon-ribavirin combination is promising for its enhanced efficacy.

Antiviral Agents↗
PubMed1996

Interferon-ribavirin combination therapy for chronic hepatitis C.

Following preliminary reports of small studies that suggested a clinically important enhanced benefit from combination therapy with interferon-alpha (IFN) and ribavirin over IFN monotherapy in chronic hepatitis C, a meta-analysis of data from these studies was performed to estimate the efficacy and tolerability of combination therapy in chronic hepatitis C. Records were obtained from 59 patients who had received combination therapy with IFN 3 MU three times weekly and ribavirin 1000-1200 mg daily for six months and were followed for six months after stopping combination therapy. Outcome measures included the percentage of patients showing ALT normalization and HCV-RNA negativity six months after therapy (sustained response) and the percentage of patients stopping therapy because of side effects. Sustained response was observed in 21% of IFN nonresponders and in 60% of patients who had relapsed after IFN. For naive patients, the estimated sustained response rate was 52%; the observed response rate was 46%. No serious adverse effects were noted; less than 10% of patients discontinued study medication. This meta-analysis of IFN-ribavirin combination therapy for chronic hepatitis C suggests that combination therapy results in a two- to threefold greater efficacy than IFN monotherapy, whereas side effects are similar to IFN monotherapy, with the exception of ribavirin-induced anemia. Interferon-ribavirin combination therapy might become the next step in antiviral therapy for chronic hepatitis C.

Antiviral Agents↗
PubMed1996

Haptoglobin polymorphism and chronic hepatitis C.

BACKGROUND/AIMS: Haptoglobin (Hp) is a hemoglobin-binding acute phase protein characterized by a genetic polymorphism due to the existence of two different alleles encoding for the alpha chain of the protein. Three phenotypes have been described: Hp 1-1, Hp 2-1 and Hp 2-2. The latter two forms are known to possess immunoglobulin-like properties and play a role in the immune response. Recently, it has been shown that in subjects suffering from hepatitis C, serum Hp concentrations were lower than in the reference population. In the present study we examined whether the haptoglobin phenotype distribution in chronic HCV patients was different from the reference population. We also looked for possible relationships between Hp phenotypes and hepatitis C virus types and response to interferon alpha therapy. Moreover, Hp concentrations were determined. METHODS: The study population consisted of 239 Caucasian patients with proven hepatitis C. Hp phenotypes were determined using starch gel electrophoresis of hemoglobin-supplemented serum, followed by peroxidase staining. Serum Hp concentrations were assayed with an immunonephelometric method. Hepatitis C virus was genotyped and classified according to an internationally accepted system. Two hundred and twenty healthy Caucasian blood-donors served as the reference population. RESULTS: In the reference population, 35 individuals (15.9%) had Hp 1-1, 106 persons (48.2%) had Hp 2-1 and 79 had Hp 2-2 (35.9%), resulting in an Hp 1 allele frequency of 0.400, which is in agreement with the Hardy-Weinberg equilibrium. Hp phenotype distributions and Hp allele frequencies in the chronic hepatitis C virus patient group differed significantly from those obtained in the reference population. In the patient population, 59 individuals (24.7%) had Hp 1-1, 112 persons (46.9%) had Hp 2-1 and 68 had Hp 2-2 (28.5%). This resulted in an Hp 1 allele frequency of 0.481, which is in agreement with the Hardy-Weinberg equilibrium. No statistically significant differences were found between Hp phenotype distribution and hepatitis C virus types or response to interferon alpha therapy. CONCLUSIONS: The observed shift in Hp phenotype distribution in chronic hepatitis C may point to a role of Hp in the natural evolution of hepatitis C.

Adult↗
PubMed1995

Rapid genotyping of hepatitis C virus RNA-isolates obtained from patients residing in western Europe.

Two rapid genotyping methods for hepatitis C virus (HCV), the line probe assay (Inno-LiPA) and the subtype-specific core amplification system [Okamoto et al., (1992b) Journal of General Virology 73:673-679], were applied to 58 HCV isolates which were typed as type 1 (n = 37) and type 2 (n = 21) by sequence analysis of the 5' untranslated region (5'UTR). The line probe assay targets the 5'UTR and recognized 12 subtype 1a, 25 subtype 1b, 18 subtype 2a, 2 subtype 2b and 1 subtype 2d in accordance with sequence analysis of this region. Subtype-specific core amplification revealed 7 discrepancies among the 37 type 1 isolates when compared to LiPA. A different subtype was observed in 3 isolates (1a versus 1b), 2 isolates remained untyped and 2 isolates showed a coinfection of subtype 1a and 1b. The first 5 discrepancies were confirmed by sequence analysis of the core region whereas the coinfection could not be confirmed. Of the 21 type 2 isolates only one could be typed by subtype-specific core amplification. HCV RNA was detected in all 21 cases after the general first round of polymerase chain reaction (PCR). Direct sequencing of the core region indicated sequence variation as a source of failure. It is concluded that LiPA results are conclusive for typing of HCV. However, LiPA is hampered occasionally for subtyping by lack of subtype-specific sequence variation in 5'UTR. Subtyping results by subtype-specific core amplification were accurate. However, it seems that this assay is not suitable for the identification of genotype 2 isolates that circulate in patients living in Western Europe.

Adult↗
PubMed1995

Sequence analysis of hepatitis C virus genotypes 1 to 5 reveals multiple novel subtypes in the Benelux countries.

Hepatitis C virus (HCV) isolates from a cohort of 315 patients from the Benelux countries (Belgium, The Netherlands, Luxembourg) were genotyped by means of reverse hybridization Inno-LiPA (line probe assay). Genotypes 1a, 1b, 2a, 2b, 3a, 4a and 5a were detected. From the cohort, isolates representing all types and those showing an aberrant LiPA pattern were further analysed by sequencing parts of the 5' UTR, core (nt 1 to 326; aa residues 1 to 108) and core/E1 (nt 477 to 924; aa residues 159 to 308) regions. Molecular evolutionary analysis of the core and core/E1 regions allowed discrimination between known and additional subtypes, especially within types 2 and 4. The core region is not suitable for classification of new subtypes because of the relatively high level of conservation. The core/E1 region displays a higher level of sequence variation and allows much more distinct discrimination between subtypes. Genotypes 2 and 4 are particularly heterogeneous, with at least 7 and 10 subtypes, respectively. In contrast to previous reports from Europe, HCV isolates from the cohort constituted a highly heterogeneous population of virus variants, especially within genotypes 2 and 4.

Belgium↗
PubMed1994

Suicide associated with alfa-interferon therapy for chronic viral hepatitis.

We report on two attempted suicides and one successful suicide during or shortly after alfa-interferon therapy for chronic viral hepatitis. While on therapy, all three patients developed a psychiatric disorder leading to their suicidal behavior. In a survey of 15 European hospitals, three cases of attempted and two of successful suicide during alfa-interferon therapy for chronic viral hepatitis, were additionally reported. None of the patients had a psychiatric history. Alfa-interferon is known to lead to neuropsychiatric symptoms, and our observations strongly suggest that these mental disorders could lead to suicidal behavior. Therefore it is important that physicians, patients and their families are informed about the potential risk of the emotional and psychiatric disturbances that can occur during alfa-interferon therapy.

Adult↗
PubMed1994

Sequence analysis of the 5' untranslated region in isolates of at least four genotypes of hepatitis C virus in The Netherlands.

The RNAs of hepatitis C virus (HCV) isolates from 62 patients with chronic HCV infection were analyzed by direct sequencing of the 5' untranslated region. Two important sequence motifs were recognized: one between positions -170 and -155 and the other between positions -132 and -117. These motifs are partly complementary. All three previously published genotypes were observed; 34 (55%) isolates were classified as type 1 (including prototype [from the United States] and HCV-BK [from Japan] sequences), 11 (18%) were classified as type 2 (including HC-J6 and HC-J8), and 12 (19%) were classified as type 3 (including EB1); one patient was infected with genotypes 1 and 2. Four (6%) isolates showed aberrant sequences and were therefore provisionally classified as genotype 4. These results indicate the significance of sequence variation among the 5' untranslated regions of different HCV genotypes and indicate that this region could possibly be used for consistent genotyping of HCV isolates.

Adult↗
PubMed1993

Detection of hepatitis C virus RNA in patients with chronic hepatitis C virus infections during and after therapy with alpha interferon.

In 24 patients with hepatitic C virus (HCV) infection who participated in a randomized trial with alpha 2B interferon, HCV RNA analysis by the polymerase chain reaction with two separate primer sets was performed at weeks 0, 4, and 24 and during a follow-up period of 6 to 9 months. Prior to therapy all patients were HCV RNA positive. During therapy, HCV RNA decreased to an undetectable level (< 1 chimpanzee infectious dose per ml) in nine patients at week 4. After week 4, no additional cases of HCV RNA disappearance (< 1 chimpanzee infectious dose per ml) were observed. During follow-up, HCV RNA could not be detected in four of the six patients with a sustained alanine aminotransferase response. These results suggest the probable predictive value of HCV RNA levels for detecting the failure of therapy in an early stage of HCV infection.

Adolescent↗
PubMed1980

Evidence for the functional heterogeneity of the two sites of transferrin in vitro.

A recently developed crossed immunoelectrophoretic method for displaying and quantitating the four possible molecular species of transferrin has been utilized to assess the relative effectiveness of each site of rabbit and human diferric transferrin in providing iron to rabbit reticulocytes. The site which appears to reside in the N-terminal half of the rabbit protein was found to be at least 5 times more effective than its counterpart. However, both sites may serve as iron donors in monoferric as well as diferric rabbit transferrins. It is also possible that iron may be removed from rabbit transferrin in pairwise as well as sequential fashion. In human diferric transferrin, the site in the C-terminal domain functions as the better iron donor for rabbit reticulocytes.

Animals↗
PubMedDate not supplied

Treatment of chronic hepatitis C: practical aspects.

The initial enthusiasm about the potential of alpha-interferon therapy for chronic hepatitis C might be weaning in view of the low virus clearance rate of about 15%. At the same time, the potential of interferon to induce sustained remission of the disease is rapidly growing by 3 modalities: a) prolongation of therapy from 6 to 12 months in order to reduce relapse; b) combination of interferon with ribavirin to reduce early non-response, breakthrough and relapse; c) high dose induction therapy; Benefit-risks/cost ratios vary for the different stages of chronic hepatitis C. Consensus exists on the indication of therapy for chronic hepatitis with fibrosis, whereas benefits in very early and very late stages of chronic hepatitis C are doubtful; patients with cirrhosis are clearly in need of therapy but remission is less than 10% and such patients are encouraged to participate in controlled trials assessing combination and/or newer therapy modalities. For decompensated cirrhosis, liver transplantation is the treatment option of choice.

Antiviral Agents↗