[Hepatitis B is an occupational risk for health personnel. Preventive vaccination is recommended].
Explore the source record for details and available documents.
Blood-Borne Pathogens↗
Biomedical subjects
O Weiland
Publications and source records attributed to O Weiland.
Utility of an anonymous questionnaire for the identification of a primary transmission route and possible secondary transmission in adults with acute hepatitis B virus infection.
By letting adults with acute hepatitis B virus (HBV) infection answer an anonymous questionnaire covering risks associated with the acquisition and further transmission of HBV infection, we found that a likely relevant transmission route could be identified in most patients. Despite being informed of the diagnosis, 50% of the patients exposed others via sexual contact during their contagious period.
Adult↗
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↗
Ribavirin treatment for patients with chronic hepatitis C: results of a placebo-controlled study.
BACKGROUND/AIMS: Small, uncontrolled studies of ribavirin for patients with chronic hepatitis C have reported efficacy in chronic hepatitis C. We have evaluated the efficacy and safety of a 24-week course of oral ribavirin in patients with chronic hepatitis C, compared to placebo. METHODS: A total of 114 patients were randomised to ribavirin or placebo. Ribavirin was administered in doses of 1000 or 1200 mg/day for 24 weeks. Efficacy was determined in the intention-to-treat population: 76 received ribavirin and 38 placebo. RESULTS: Ribavirin was significantly more effective than placebo in reducing and normalising serum ALT levels: 42/76 (55%) of ribavirin-treated patients vs 2/38 (5%) placebo recipients had either normalisation of the ALT levels or a reduction from baseline of at least 50% (p < 0.001). ALT levels were normal in 22/76 (29%) of ribavirin-treated patients vs 0/38 placebo recipients (p < 0.001). Twenty-four weeks after stopping ribavirin, the majority of patients had abnormal ALT levels. There was no difference between the treatment groups in reduction or disappearance of HCV-RNA levels. HCV RNA disappeared during treatment in 3% of ribavirin-treated patients and 3% of placebo recipients. More ribavirin than placebo patients showed improvement in total Knodell score (45% vs 31%), but these differences were not statistically significant. Analysis of each component of a histology activity index revealed no statistically significant differences between treatment groups. Ribavirin patients had fewer lymphoid aggregates than did placebo recipients at the post-treatment assessment (p = 0.05). Ribavirin was associated with reversible haemolytic anaemia: a fall in haemoglobin occurred in 3% of placebo- and 32% (25/78) of ribavirin-treated patients, respectively (p < 0.001). CONCLUSIONS: These data indicate that ribavirin was no more effective than placebo in reducing or eliminating HCV-RNA levels, and was not significantly more effective than placebo in improving hepatic histology after 6 months of treatment. The role of a 6-month treatment of chronic hepatitis C with ribavirin alone, without a significant effect on HCV RNA, is therefore limited.
Administration, Oral↗
Restriction of hepatitis C virus heterogeneity during prolonged interferon-alpha therapy in relation to changes in virus load.
To determine how interferon-alpha (IFN-alpha) treatment changes the heterogeneity of the hepatitis C virus (HCV) population, the hypervariable region 1 (HVR1) was directly sequenced, and the virus load was quantified in 15 patients who had received IFN-alpha for 15 months. Before treatment, 13 patients exhibited heterogeneous HVR1 sequences. In 7 subjects who did not respond or did not sustain a response to treatment, significantly decreased heterogeneity of the HVR1 was found at the end of treatment (P=.01). In 6 of these patients, the virus load decreased in parallel with the changes in HVR1 heterogeneity. At follow-up, both the virus load and the heterogeneity increased in 4 patients, and the virus load, but not the heterogeneity, increased in 2. In the seventh patient, the virus load steadily increased during treatment and follow-up. These results suggest that a selection of HVC strains may occur during prolonged IFN-alpha treatment, concomitant with general suppression of the viral replication.
Amino Acid Sequence↗
Factors influencing the response to interferon therapy in chronic hepatitis C. Studies on viral genotype and induction of 2',5'-oligoadenylate synthetase in the liver and peripheral blood cells.
BACKGROUND: The mechanism behind the antiviral action of interferon (IFN) therapy in chronic hepatitis C virus (HCV) infection is not well understood, and, furthermore, few factors have been shown to be good predictors of a favourable response to IFN treatment in chronic HCV infection. METHODS: Freshly explanted liver cells and peripheral blood mononuclear cells (PBMC) from 80 patients with chronic HCV infection were used to study the capacity of IFN to induce the enzyme 2',5'-oligoadenylate synthetase (2'5'-AS) in vitro. The HCV genotype was determined in 53 patients. The induction of 2'5'-AS was correlated to the results of IFN-alpha treatment in 36 patients. RESULTS: Normalization of transaminases during IFN treatment was significantly associated with 2'5'-AS levels in liver cells cultured in the absence of IFN. A similar tendency, although not statistically significant, was found for IFN-induced levels of 2'5'-AS in liver cells. No such associations were found when PBMC were analysed. Six patients showed a sustained biochemical response. These six did not deviate significantly from the remaining patients with regard to base-line or IFN-induced levels of 2'5'-AS in liver cells or PBMC. Eradication of HCV RNA during IFN treatment did not correlate with 2'5'-AS levels in liver cells. Comparison of HCV genotype and clinical response showed that patients with genotype 3a had the most favourable outcome. No association was found between liver histology and treatment outcome. CONCLUSION: These data imply that direct effects of IFN on liver cells are of importance for the response to IFN treatment.
2',5'-Oligoadenylate Synthetase↗
[Half of the patients respond to interferon treatment. Combination therapy is an alternative in chronic hepatitis C].
Explore the source record for details and available documents.
Chronic Disease↗
Combined treatment with interferon alpha-2b and ribavirin for chronic hepatitis C in patients with a previous non-response or non-sustained response to interferon alone.
Ten patients with chronic hepatitis C, six of whom had not responded and four of whom had responded in a non-sustained fashion to interferon-alpha treatment alone, were given interferon alpha-2b and ribavirin in combination during 24 weeks. Interferon alpha-2b was given subcutaneously, at a dose of 3 MU thrice weekly, together with ribavirin orally, at a dose of 1,000-1,200 mg/day. All four patients with a prior non-sustained response to interferon alone had normal alanine aminotransferase (ALT) levels at the end of treatment as well as during follow-up (> or = 24 weeks post treatment). Furthermore, all four lost serum HCV-RNA at the end of treatment and three continued to be negative during follow-up. Among patients with a prior non-response to interferon alone three of six had normal ALT levels at the end of treatment and one at follow-up. Two of six became HCV-RNA negative at cessation of treatment, one of whom was negative also at follow-up. All former non-sustained responders and one of six non-responder patients thus showed a sustained biochemical response with eradication of HCV-RNA from serum in all cases but one. It is concluded that combination therapy with interferon alpha-2b and ribavirin offers a chance of sustained biochemical response with eradication of the viremia in patients who have not shown a persistent response to interferon-alpha alone.
Adult↗
Risk factors for hepatitis A, B and C virus infection among Swedish expatriates.
The influence of different risk factors for viral hepatitis A, B and C, particularly if sexual contact with the indigenous population was related to an increased risk of having hepatitis B virus (HBV) markers, was assessed by multivariate analysis in a logistic regression model in a prospectively enrolled series of 563 adult Swedish expatriates. The most frequently reported recognised risk factors for the acquisition of viral hepatitis (as reported in a self-administered questionnaire) were having received an inoculation during medical or dental treatment, reported by 45% of all subjects, and having had sexual contact with the indigenous population, reported by 35%. Whilst the prevalences of hepatitis A virus (HAV) and hepatitis C virus (HCV) markers in these expatriates were of the same magnitude as previously reported in the general Swedish population, 8% and 0.3%, respectively, the prevalence of markers for a past or present HBV infection was about twice as high (5%). The presence of HBV markers was associated with being a health care professional or having received inoculations during medical or dental treatment in Africa. No significant association was found between having HBV markers and having had sexual contact with the indigenous population.
Adolescent↗
Distinguishing acute from symptomatic chronic hepatitis C virus (HCV) infection by site-directed serology of the HCV structural proteins.
To distinguish acute from symptomatic chronic hepatitis C virus (HCV) infection, site-directed serology was done on the complete core, envelope 1, and envelope 2 proteins using multiple peptide assays. Serum samples were obtained from 7 patients with clinically confirmed acute HCV infections and from 36 patients with symptomatic chronic HCV infections. At onset of symptoms, all patients with acute infection had HCV RNA in serum, 1 had > 2 strong core peptide reactivities (A405 > 1.0), and the number of core reactivities increased with time in 6 patients. In contrast, 35 of 36 chronic-phase patients with HCV RNA in serum had 3-12 strong core reactivities (P < .001). Envelope 2 antibodies were found in 2 acute-phase and in 32 chronic-phase HCV patients (P < .01). Thus, a serum sample with HCV RNA from a patient with hepatitis can be classified as acute or chronic using site-directed serology of the HCV structural proteins.
Acute Disease↗
Hepatitis E virus infections in patients with acute hepatitis non-A-D in Sweden.
A total of 12 patients previously treated for acute hepatitis of unknown aetiology were retrospectively found to be anti-hepatitis E virus (HEV) IgG-positive. Four patients were anti-HEV IgM- and IgG-positive consistent with an acute HEV infection. All 4 had travelled to or were immigrants from HEV-endemic countries. One anti-HEV IgM-negative patient seroconverted from anti-HEV IgG-negative to positive and 3 from anti-HEV IgG-positive to negative in 2 consecutive serum samples. Of the remaining 4 patients without anti-HEV IgM, 3 had a history of recent travel to an HEV-endemic country. Most patients were young adults and all but 1 recovered from the hepatitis. One patient with a fulminant hepatitis was anti-HEV IgG-positive when tested 4 months after a journey to Turkey. She died from her fulminant hepatitis shortly after admission. All the other patients but 1 normalized their serum liver enzymes within 1-2 months after the onset of disease.
Acute Disease↗
Two-year biochemical, virological, and histological follow-up in patients with chronic hepatitis C responding in a sustained fashion to interferon alfa-2b treatment.
Fourteen patients with chronic hepatitis C who had a sustained response to a 60-week interferon alfa-2b treatment course were followed, biochemically and virologically, 2 years after treatment cessation. Biopsies were repeated in 12 of 14 for histological and virological evaluation at 2-year follow-up. All 14 patients had normal serum alanine transaminase (s-ALT) levels and were negative for hepatitis C virus (HCV) RNA in serum during treatment and at short-term follow-up 6 months post-treatment. At 2-year follow-up, 13 patients still had normal ALT levels (< 0.6 mukat/L for women; < 0.8 mukat/L for men), 1 a near normal level (0.76 mukat/L); all were HCV RNA negative in serum, and 11 of 12 also in the liver. Liver histology improved during treatment and remained stable during the 2-year follow-up. The authors conclude that most sustained responders, who have normal ALT levels and are nonviremic at short-term follow-up 6 months after interferon treatment, will continue to have a durable long-term response without relapse of the viremia.
Adult↗
Efficacy of human leucocyte alpha-interferon treatment for chronic hepatitis C virus infection.
A total of 42 Swedish patients with biopsy-proven chronic hepatitis C virus (HCV) infection were treated with a natural human leucocyte alpha-interferon (HuIFN-alpha-Le), Alfanative (BioNative AB, Umeå, Sweden) in an open uncontrolled study. Two patients were withdrawn from treatment within 2 weeks due to non-compliance and were omitted from further analysis, and 40 patients (17 females), mean age 39 years (range 24-71) completed the study. All patients were HCV RNA-positive in serum prior to treatment, with raised alanine aminotransferase (ALT) levels > 1.5 times the upper normal limit known for more than 6 months. Interferon was given at a dose of 3 MU t.i.w. for an intended 24 weeks and follow-up was a further 24 weeks after treatment. Biochemical non-responders were withdrawn from treatment within 12-16 weeks but continued follow-up. Overall 21/40 (52.5%) patients had a complete biochemical response with normal ALT levels at the end of treatment. Sustained response during follow-up was seen in 8 (20%) whereas 13 (32.5%) had a non-sustained response. At the end of treatment 23 (58%) patients had undetectable serum HCV RNA and 9 (23%) at follow-up. Patients with sustained, non-sustained and non-response had a mean pretreatment HCV RNA level of 3.2 x 10(5), 2.5 x 10(6) and 3.2 x 10(6) genomes/ml, respectively, differences that did not reach statistical significance. Of the patients 3, 9, 10 and 14 had genotype 1b, 3a, 1a, and 2b, respectively, and 4 had mixed genotypes. Of the 23 patients with genotype 2b or 3a, 7 had a sustained response vs. none of the 13 patients with genotype 1a or 1b (p = 0.03). No patients with cirrhosis had a sustained response whereas 4/18 with chronic persistent and 4/18 with chronic active hepatitis had such a response. It is concluded that some 50% of patients treated with HuIFN-alpha-Le responded with normalisation of ALT levels but that only 20% had a durable response 24 weeks post-treatment, and that patients with genotypes 3a or 2b seem to respond better than patients with other genotypes.
Adult↗
Efficacy of human leucocyte alpha-interferon treatment for chronic hepatitis C virus infection.
A total of 42 Swedish patients with biopsy-proven chronic hepatitis C virus (HCV) infection were treated with a natural human leucocyte alpha-interferon (HuIFN-alpha-Le), Alfanative (BioNative AB, Umeå, Sweden) in an open uncontrolled study. Two patients were withdrawn from treatment within 2 weeks due to non-compliance and were omitted from further analysis, and 40 patients (17 females), mean age 39 years (range 24-71) completed the study. All patients were HCV RNA-positive in serum prior to treatment, with raised alanine aminotransferase (ALT) levels > 1.5 times the upper normal limit known for more than 6 months. Interferon was given at a dose of 3 MU t.i.w. for an intended 24 weeks and follow-up was a further 24 weeks after treatment. Biochemical non-responders were withdrawn from treatment within 12-16 weeks but continued follow-up. Overall 21/40 (52.5%) patients had a complete biochemical response with normal ALT levels at the end of treatment. Sustained response during follow-up was seen in 8 (20%) whereas 13 (32.5%) had a non-sustained response. At the end of treatment 23 (58%) patients had undetectable serum HCV RNA and 9 (23%) at follow-up. Patients with sustained, non-sustained and non-response had a mean pretreatment HCV RNA level of 3.2 x 10(5), 2.5 x 10(6) and 3.2 x 10(6) genomes/ml, respectively, differences that did not reach statistical significance. Of the patients 3, 9, 10 and 14 had genotype 1b, 3a, 1a, and 2b, respectively, and 4 had mixed genotypes. Of the 23 patients with genotype 2b or 3a, 7 had a sustained response vs. none of the 13 patients with genotype 1a or 1b (p = 0.03). No patients with cirrhosis had a sustained response whereas 4/18 with chronic persistent and 4/18 with chronic active hepatitis had such a response.
Adult↗
Combination treatment with interferon alfa-2b and ribavirin for chronic hepatitis C in patients who have failed to achieve sustained response to interferon alone: Swedish experience.
BACKGROUND: Only 10-20% of patients treated with interferon alfa alone attain long-term benefits. More effective regimens are needed. METHODS: Twenty Swedish patients with chronic hepatitis C virus infection, ten with a prior non-response and ten with a non-sustained response to interferon alfa treatment alone, were treated with interferon alfa-2b and ribavirin in combination for 24 weeks, then followed up for another 24 weeks. Patients received interferon alfa-2b subcutaneously 3 MU thrice weekly and oral ribavirin 1000-1200 mg/day. RESULTS: All ten patients with a prior non-sustained response to interferon alone had a sustained biochemical response with normal aminotransferase levels at follow-up; nine also had a sustained viral response with a negative HCV-RNA test in serum. Among the ten patients with a prior biochemical non-response to interferon alone, five had normal aminotransferase levels at the end of therapy; four were negative for HCV RNA in serum. At follow-up, three had normal aminotransferase levels and a negative HCV-RNA test in serum. No major adverse effect was seen, apart from fatigue and an expected fall in hemoglobin levels from a mean of 155 g/l to 124 g/l at the end of therapy. All patients completed the treatment schedule, but the ribavirin dose was reduced in one patient because of a fall in hemoglobin to 99 g/l. CONCLUSIONS: These results indicate that combination treatment with interferon alfa-2b and ribavirin offers a chance of sustained biochemical response and virus eradication in a subset of patients who fail to achieve sustained response with interferon alfa alone.
Adult↗
Genotyping of hepatitis C virus isolates by a modified polymerase chain reaction assay using type specific primers: epidemiological applications.
A polymerase chain reaction (PCR)-based assay using primers against the hepatitis C core gene has been described [Okamoto et al. (1992a): Journal of General Virology 73:673-679]. Within the two major HCV genotypes 1 and 2, the Okamoto system identifies two subtypes each (1a, 1b and 2a, 2b, respectively). Typing is achieved by a primary PCR with consensus primers followed by a nested PCR with type specific primers. The original assay was modified by addition of a parallel second PCR identifying the recently described major genotype 3. The assay also identifies in duplicate subtype 1b (type II by Okamoto), suggested to respond poorly to interferon. Reaction conditions were reviewed and melting temperatures of all typing primers equalised to increase strigency. The modified system functioned well and typing results were supported by partial core sequencing. The following distribution of genotypes was found in 53 hepatitis C virus (HCV) infected Swedish blood donors: genotype 1a (57%), 3 (19%), 1b (13%), and 2b (11%). In six recipients of HCV infected blood identified in a retrospective study, the recipient HCV genotype was identical to donor HCV genotype. Furthermore, in HCV positive couples identical genotype was observed when only one partner had an external risk factor; whereas genotypes were often diverse if both sex partners had parenteral risk factors. Finally, a cluster of hepatitis C cases in a haemodialysis unit was evaluated retrospectively. Eight patients had genotype 1b, two had mixed 1a and 1b, and one had type 1a. The modified HCV genotyping assay was of value in examining different epidemiological situations and can be expanded presumably to include future genotypes.
Base Sequence↗
Colorimetric detection of competitive PCR products for quantification of hepatitis C viremia.
A method based on competitive polymerase chain reaction (PCR) and colorimetric detection of the amplified products was developed to quantify hepatitis C virus (HCV) genomes. Serum samples were obtained from patients who were treated with interferon alpha (IFN-alpha). After reverse transcription of the HCV RNA, the cDNA was coamplified with a serially diluted cloned HCV competitor DNA using nested PCR. The competitor DNA consisted of the amplified region of the wild type HCV cDNA with an internal region substituted with the lac operator (lacO) sequence. The PCR products were quantitated specifically by a colorimetric solid-phase assay. The results suggest that the method is well suited for analysing the kinetics of the anti-HCV effects during IFN-alpha treatment. The quantification assay is simple, reliable and suitable for quantitating HCV genomes in a large number of clinical samples.
Base Sequence↗
Interferon therapy in chronic hepatitis C virus infection.
Antiviral treatment of chronic hepatitis C with interferon is reviewed. Alpha-interferon, both recombinant alpha-2a, -2b and human lymphoblastoid interferon given at a dose of > or = 3MU t.i.w. for 6-12 months will result in normalisation of ALT levels (complete response) in some 50-60% of treated patients with chronic hepatitis C virus (HCV) infection. Approximately half of the complete responders to interferon will relapse within 6 months once treatment is withdrawn (non-sustained response). Longer treatment schedules (6 vs. 12 months) seem to diminish the relapse rate and increase the percentage of sustained response. In patients with sustained response to interferon treatment with continuously normal ALT levels > or = 6 months after treatment stop a concomitant eradication of the viraemia is usually seen, whereas a non-sustained or non-response to interferon usually will indicate a continuous viraemia. Factors predictive of a favourable response are low pretreatment HCV RNA levels in serum, genotypes other than type II according to Okamoto, short disease duration, female gender and less pronounced liver damage, whereas high serum HCV RNA levels, having genotype II and cirrhosis, are predictive of a less favourable response. Patients with a sustained response and eradication of the viraemia will also improve their liver inflammation with diminishing scores for portal inflammation, piecemeal necrosis, lobular inflammation and also fibrosis after treatment. For non-responders and non-sustained responders to interferon, ribavirin especially in combination with interferon will offer some hope for the future.
Chronic Disease↗