Hepatitis: Wejstål R

Lindh M, Uhnoo I, Bläckberg J, Duberg AS, Friman S, Fischler B, Karlström O, Norkrans G, Reichard O, Sangfeldt P, Söderström A, Sönnerborg A, Weiland O, Wejstål R, Wiström J. · Department of Infectious Diseases, Sahlgrenska University Hospital, Göteborg, Sweden. · Scand J Infect Dis. · Pubmed #18584530 No free full text.

Abstract: The main goal for treatment of chronic hepatitis B is to prevent complications such as liver cirrhosis or hepatocellular carcinoma. Knowledge from population studies of the long-term risk of chronic HBV infection, as well as the recent introduction of pegylated interferon and additional nucleoside analogues has changed the therapeutic situation. Recently, a Swedish expert panel convened to update the national recommendations for treatment. The panel recommends treatment for patients with active HBV infection causing protracted liver inflammation or significant liver fibrosis, verified by liver histology. In general, pegylated interferon alpha-2a is recommended as first-line treatment, in particular for HBeAg-positive patients with HBV genotypes A or B. Among nucleoside analogues, entecavir is the first choice and adefovir or tenofovir can be used as alternatives. Lamivudine monotherapy is not recommended due to the high risk of resistance development. Combinations of nucleoside analogues such as tenofovir and lamivudine or emtricitabine are alternatives for patients with non-response or infection with resistant variants, or as first choice for patients with advanced liver disease. Nucleoside analogue treatment should be monitored to detect primary non-response and virological breakthrough. Special recommendations are given for HBV/HIV coinfected patients, immunosuppressed patients, children, and for treatment before and after liver transplantation. The present guideline is translated from Swedish, where it is published on the MPA and RAV websites (www.mpa.se and www.rav.nu.se) including 7 separate papers based on thorough literature search. The complete reference list can be received from the Medical Products Agency upon request.

Wejstål R, Alaeus A, Fischler B, Reichard O, Uhnoo I, Weiland O, Anonymous00099. · Department of Infectious Diseases, Sahlgrenska University Hospital/Ostra, Göteborg, Sweden. · Scand J Infect Dis. · Pubmed #14514142 No free full text.

Abstract: In 1999 a Swedish national expert panel published recommendations for the treatment of chronic hepatitis C (HCV) infection. Recently, pegylated interferon (peg-IFN) products have been introduced, and an increased knowledge concerning treatment of acute HCV and HCV-human immunodeficiency virus (HIV) coinfection has been gained. As a result of this, an update of the Swedish recommendations was developed following an expert meeting in October 2002. The panel now recommends the use of peg-IFN together with ribavirin as the standard treatment. Owing to the excellent response rates in HCV genotype 2 and 3 infections, these patients can be treated for 24 weeks without preceding liver biopsy. For patients with genotype 1 infection (with a slightly below 50% sustained response rate after 48 weeks treatment) and only mild histological disease, treatment can be postponed until future better treatment options become available. In patients who fail to achieve a 99% reduction (2 log drop) in viral titre after 12 weeks of treatment, discontinuation of therapy is recommended. Patients previously treated with IFN monotherapy and not having achieved a sustained virological response are recommended the same combination treatment as treatment-naive patients. IFN monotherapy is recommended in patients with acute hepatitis C. For children with chronic HCV infection, combination treatment is mainly recommended in clinical trials. For HCV-HIV coinfected patients, combination treatment is recommended and preferably given when blood CD4 counts are above 350/ml and before antiretroviral treatment (ART) is needed. Concurrent ART or prominent liver fibrosis requires frequent monitoring because of the increased risk for mitochondrial toxicity and liver failure.

Wejstål R, Fischler B, Glaumann H, Norkrans G, Reichard O, Sönnerbor A, Uhnoo I, Weiland O, Anonymous00027, Anonymous00028. · Department of Infectious Diseases, Sahlgrenska University Hospital/Ostra, Göteborg, Sweden. · Scand J Infect Dis. · Pubmed #11055647 No free full text.

This publication has no abstract.

Wejstål R. · Institute of Internal Medicine, Department of Infectious Diseases, Sahlgrenska University Hospital/Ostra, Götenborg, Sweden. rune.wejstå · J Hepatol. · Pubmed #10622568 No free full text.

Abstract: Sexual transmission of hepatitis C virus (HCV) occurs; however, to what extent is still unclear. In this presentation relevant data from the literature concerning the following key issues will be presented: presence of HCV in the seminal fluid and vaginal secretions; presence of HCV infection in sexually promiscuous individuals; presence of HCV infection among sexual partners to HCV-infected individuals; and molecular biology evidence of sexual transmission. An anti-HCV prevalence of 2-12% is seen in sexually promiscuous individuals, which is higher than that usually seen among blood donors. In case-control studies, HCV infection is associated with sexual promiscuity and sex with a partner who has a past history of hepatitis. In most studies, HCV infection is common among sexual partners of HCV-infected subjects. Genotyping and genome sequencing provide further evidence for intraspousal transmission of HCV Despite these findings, stable sexual partners of hemophiliacs or recipients of HCV-contaminated immunoglobulin preparations rarely become infected. These discrepancies are not fully understood. Other sexual behaviours or confounding non-sexual transmission routes could play a part.

Wejstål R, Lindberg J. · Sahlgrenska Universitetssjukhuset/Ostra, Göteborg. · Lakartidningen. · Pubmed #10024820 No free full text.

Abstract: Hepatitis G virus, or GB virus type C, is a recently discovered RNA virus, remotely related to hepatitis C virus. The infection is frequently found, and seems to be blood-borne, occurring among intravenous drug abusers and transmitted from mother to child. Although long-term viraemia is common, in most cases the infection resolves spontaneously. Whether the viral infection causes liver disease or has other manifestations remains unknown.

Reichard O, Glaumann H, Frydén A, Norkrans G, Wejstål R, Weiland O. · Department of Infectious Diseases at Danderyd, University Hospital, Karolinska Institutet, Stockholm, Sweden. · J Hepatol. · Pubmed #10365802 No free full text.

Abstract: BACKGROUND/AIMS: This study aimed to determine the long-term outcome of hepatitis C virus (HCV)-infected patients who respond to interferon treatment with clearance of serum HCV RNA. METHODS: We performed a long-term biochemical, virological, and histological follow-up of all sustained virological responders, defined as those who became HCV RNA negative at follow-up 6 months after the end of treatment, from 3 controlled interferon trials performed in Sweden between 1988 and 1994. RESULTS: At biochemical and virological long-term follow-up performed in 26 sustained virological responders 3.5-8.8 years (mean +/- SD, 5.4+/-1.6 years) after the end of IFN therapy, 22 patients (85%) had normal serum ALT levels, and 24 patients (92%) were HCV RNA negative in serum. Liver biopsies performed in 23 patients 2.1-8.7 years (mean +/- SD, 5.0+/-1.8 years) after end of treatment showed no or minimal inflammation, whereas mild and probably irreversible fibrosis was seen in a few patients. CONCLUSION: In this well-defined material of sustained responders to IFN therapy, the long-term prognosis was excellent. Nearly all had a durable response, not only biochemically and virologically, but more importantly also histologically with normalisation or near normalisation of previous histological lesions.

Lindh M, Alestig E, Arnholm B, Eilard A, Hellstrand K, Lagging M, Wahlberg T, Wejstål R, Westin J, Norkrans G. · Department of Infection and Virology, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden. · J Clin Microbiol. · Pubmed #17581934 links to  free full text

Abstract: We monitored early viral response during the treatment of hepatitis C virus (HCV) infection with the aim of identifying predictors of treatment outcome. We studied 53 patients with genotype 1 infection who received 180 microg/week pegylated interferon alfa-2a and 1,000 or 1,200 mg/day ribavirin depending on body weight and serially assessed HCV RNA in serum, using the Cobas TaqMan assay. Thirty-one patients (58%) achieved sustained viral response (SVR). SVR was obtained in 100% (10/10) of patients with pretreatment viremia concentrations below 400,000 IU/ml, in 100% (14/14) of patients with more than 1.5 log reduction of HCV RNA after 4 days of treatment, and in 95% (22/23) of patients with a rate of decline in viremia higher than 0.70 log units/week during the second phase. Non-SVR was seen in all patients with a second-phase decline rate lower than 0.35 log units/week. Patients with slopes between 0.50 and 0.80 log units/week achieved SVR (4/4) unless the treatment dose was modified (3/3). We conclude that the second-phase slope appears to be an accurate and useful predictor of treatment response. On the basis of these findings, we propose a model of tailored treatment which takes into account the second-phase slope and the amount of HCV RNA after 21 days of treatment.

Lindh M, Lagging M, Westin J, Wejstål R, Norkrans G. · Department of Clinical Virology, Göteborg University, Guldhedsgatan 10B, 41346, Göteborg, Sweden. · Eur J Clin Microbiol Infect Dis. · Pubmed #15772819 No free full text.

This publication has no abstract.

Westin J, Nordlinder H, Lagging M, Norkrans G, Wejstål R. · Department of Infectious Diseases, Sahlgrenska University Hospital/Ostra, Göteborg University, SE-416 85 Göteborg, Sweden. · J Hepatol. · Pubmed #12445426 No free full text.

Abstract: BACKGROUND/AIMS: Steatosis is common in patients with hepatitis C virus (HCV) infection. Its influence on disease progression is only partially understood. The aim of this study was to evaluate the impact of steatosis on fibrosis progression over time in relation to HCV genotype. METHODS: We retrospectively analyzed 98 patients who underwent dual liver biopsies prior to antiviral treatment. The median follow-up time was 5.8 years. Biopsy specimens were assessed for necroinflammatory activity, fibrosis and steatosis. RESULTS: The prevalence and grade of steatosis were strongly associated with HCV genotype 3, independent of sex, age, body mass index and alcohol consumption. Progressive fibrosis was more prevalent in patients whose initial biopsy showed steatosis, an effect seen mainly in genotype 3 infected patients. Low-grade steatosis was observed in overweight patients, but high-grade steatosis was associated with genotype 3, independent of body mass index. CONCLUSIONS: Our data confirm the association between HCV genotype 3 and steatosis. Furthermore, we showed that steatosis in genotype 3 infected patients is a risk factor for progression of fibrosis. Therefore, patients with genotype 3 and steatosis ought to be recommended for early therapeutic intervention.

Lagging LM, Garcia CE, Westin J, Wejstål R, Norkrans G, Dhillon AP, Lindh M. · Department of Clinical Virology, Göteborg University, Göteborg, Sweden. · J Clin Microbiol. · Pubmed #12409402 links to  free full text

Abstract: An enzyme immunoassay has recently been developed for the hepatitis C virus (HCV) core antigen. To evaluate the possible association between core antigen and HCV RNA levels with regards to the change in liver histology over time as well as study the effect of duration of storage on viral load results, sequential sera were analyzed from 45 patients with chronic HCV infection who had undergone two or more liver biopsies. A relatively strong association was found between the core antigen and HCV RNA concentrations (r(s) = 0.8), with a core antigen level of 1 pg/ml corresponding to approximately 1,000 IU/ml. All 42 sera with detectable HCV RNA at the time of the second biopsy had core antigen concentrations above 1 pg/ml, and the three sera without detectable HCV RNA had concentrations below 1 pg/ml. No association was found between HCV RNA or core antigen levels and the stage of fibrosis in biopsy samples, progression of fibrosis, necro-inflammatory grade, steatosis, genotype, alanine aminotransferase level, or alcohol consumption. A significant association was demonstrated between the storage time of the samples and both the HCV RNA and core antigen concentrations. The median log HCV RNA concentrations (international units/milliliter) were 3.92 for the sera obtained at the time of the first biopsy (median storage time, 13.0 years) and 4.41 for the sera obtained at the time of the second biopsy (median storage time, 6.6 years) compared to 5.96, the median for 102 different routine clinical patient samples.

Lagging LM, Westin J, Svensson E, Aires N, Dhillon AP, Lindh M, Wejstål R, Norkrans G. · Department of Clinical Virology, Göteborg University, Göteborg, Sweden, Department of Infectious Diseases, Göteborg University, Sweden. · Liver. · Pubmed #12028408 No free full text.

Abstract: BACKGROUND/METHODS: In order to evaluate the progression of liver fibrosis associated with Hepatitis C virus (HCV) infection, two liver biopsy specimens obtained prior to antiviral therapy from 98 patients with HCV were scored and evaluated using statistical methods appropriate for ordered categorical data. RESULTS/CONCLUSIONS: Greater progression of fibrosis was seen with increasing time between the biopsies. Likewise, the change in fibrosis score was significantly more pronounced in the 11 patients whose first biopsy was obtained within the first year after acquiring HCV. A multivariate logistic regression analysis of possible explanatory factors for the fibrosis outcome showed that interface hepatitis in both biopsies, the time interval between the biopsies, and age at first biopsy were associated with change in the fibrosis score. In addition we found that higher age at the time of infection was associated with development of cirrhosis, that moderate intake of alcohol was associated with fibrosis progression, and that an inflammatory response in the form of moderate interface hepatitis in the first biopsy was not necessarily associated with greater progression of fibrosis if the second biopsy showed mild interface hepatitis. However, having moderate interface hepatitis later in the course of infection as reflected by the second biopsy may be detrimental. If moderate interface hepatitis early in the course of the disease is followed by less interface hepatitis later there is less fibrosis; and if moderate interface hepatitis persists, there is more fibrosis eventually.

Westin J, Lagging LM, Spak F, Aires N, Svensson E, Lindh M, Dhillon AP, Norkrans G, Wejstål R. · Department of Infectious Diseases, Göteborg University, Göteborg Sweden. · J Viral Hepat. · Pubmed #12010513 No free full text.

Abstract: Although excessive alcohol consumption in combination with hepatitis C virus (HCV) infection is known to increase the risk of liver cirrhosis, the effect of moderate alcohol intake remains to be elucidated. The aim of this study was to evaluate the effect of moderate alcohol consumption on fibrosis progression in HCV infection. A group of 78 patients with HCV infection and moderate alcohol consumption were analysed retrospectively. All patients had undergone two liver biopsies, with a median time between biopsies of 6.3 years, and had not received any antiviral therapy. Their lifetime drinking history was recorded. All patients except one had daily alcohol consumption below 40 g of ethanol (median 4.8 g/day, interquartile range 1.1-11.6 g/day) during the period between the biopsies. The patients whose liver fibrosis had deteriorated had a higher total alcohol consumption and higher drinking frequency between the biopsies. The degree of fibrosis progression was greater in patients with a total alcohol intake and drinking frequency above the median level for the group. A multiple logistic regression analysis showed that drinking frequency and time between biopsies were independently associated with fibrosis progression. Hence, even moderate alcohol intake seems to increase fibrosis progression in HCV-infected patients. From that point of view, total abstention ought to be recommended. If this is not achieved, occasional use of alcohol is probably less harmful than daily drinking for patients with low or moderate alcohol consumption.

Lagging LM, Meyer K, Westin J, Wejstål R, Norkrans G, Lindh M, Ray R. · Department of Clinical Virology, Göteborg University, Guldhedsgatan 10B, S-413 46 Göteborg, Sweden. · J Infect Dis. · Pubmed #11930327 No free full text.

Abstract: Infection with hepatitis C virus (HCV) generally progresses to chronic disease, although a minority of patients appear to clear viremia spontaneously. In this investigation, serum samples were analyzed for virological parameters, serum alanine aminotransferase (ALT) levels, and neutralizing antibody response against pseudotyped vesicular stomatitis virus (VSV) generated using chimeric envelope glycoprotein 1 (E1) or 2 (E2) of HCV. Testing of sequential serum samples that were collected beginning at the onset of acute-phase disease demonstrated intermittent viremia, elevated ALT levels, and detectable neutralization activity against VSV in 9 of 10 patients. Serum neutralization activity did not exhibit a correlation with the genotype of the infecting HCV or with virus load. On the other hand, patients with chronic HCV infection consistently had detectable amounts of virus present but no significant variation in ALT levels, and serum samples from a majority (>90%) of patients failed to show detectable neutralization activity.

Westin J, Lindh M, Nenonen N, Lagging LM, Norkrans G, Wejstål R. · Department of Infectious Diseases, Sahlgrenska University Hospital, Götehorg, Sweden. · Scand J Infect Dis. · Pubmed #11233844 No free full text.

Abstract: Adding the nucleoside analog ribavirin (RBV) to interferon (IFN) for treatment of HCV has improved the sustained response rates, but the mechanism by which RBV mediates viral clearance is not fully understood. In this study, a highly sensitive method (Codes Amplicor HCV Monitor) was used to monitor the early (first 12 weeks of therapy) and long-term virological response in 20 patients who were treated first with IFN and later, due to non-sustained response, with IFN-RBV. All 10 IFN relapsers displayed a prompt virological response at week 4 to both IFN and IFN-RBV therapy; nine of them showed a sustained response to IFN-RBV. Out of 10 IFN non-responders, five showed a sustained response to IFN-RBV. Four of these were HCV RNA-negative at week 4 of IFN-RBV therapy and two of them had a transient early virological response (RNA-negative at weeks 4-8) to IFN alone. Overall, of the 14 patients (nine IFN relapsers, five IFN non-responders) with a sustained response to IFN-RBV, 11 and 13 had HCV RNA below 2000 copies/ml at week 4 of IFN and IFN-RBV, respectively, as compared with one and one of six patients without a sustained response to IFN-RBV (p < 0.02). Thus, addition of RBV to IFN increased both viral clearance during the first 12 weeks of therapy and the rate of sustained response. Loss of viremia at week 4 of IFN was associated with a sustained response to IFN-RBV and was seen in 11 of 13 patients (85%) with genotypes 2 or 3, as compared with one of seven patients (14%) with genotype 1 (p = 0.0044).

Mellgren A, Norkrans G, Hagberg L, Dunlop O, Wejstål R, Gisslén M. · Department of Infectious Diseases, Sahlgrenska University Hospital, Göteborg, Sweden. · Acta Neurol Scand. · Pubmed #10987376 No free full text.

Abstract: OBJECTIVES: To investigate if HIV-1-infected patients without acquired immunodeficiency syndrome (AIDS) have cerebral dysfunction as reflected by impaired reaction times compared to patients with chronic hepatitis C. MATERIAL AND METHODS: Forty-one HIV-1-infected patients not fulfilling the AIDS criteria, were tested with three reaction time tests and compared to controls with chronic hepatitis C, matched according to gender and age. RESULTS: HIV-1-infected individuals had, in mean, 5-47 ms longer reaction time than patients with hepatitis C (statistically significant in two of three tests). All but 9 HIV-1-infected individuals had, however, reaction times within the normal range defined by the control group (mean +/- 2 SD). No correlation was found between reaction time and immune status measured as CD4-cell count. CONCLUSION: This study indicates that a subgroup of HIV-1-infected individuals have slower reaction time compatible with cerebral deterioration early in the course of the infection.

Widell A, Verbaan H, Wejstål R, Kaczynski J, Kidd-Ljunggren K, Wallerstedt S. · Department of Medical Microbiology, University Hospital, Malmö, Sweden. · Scand J Infect Dis. · Pubmed #10826899 No free full text.

Abstract: Viral markers of chronic hepatitis were tested for in 95 frozen serum samples from 299 patients from Malmö, Sweden, with hepatocellular carcinoma (HCC), diagnosed between 1977 and 1994. Hepatitis B analysis included anti-HBc, HBsAg and, if anti-HBc positive, HBV DNA. Hepatitis C infection analysis included anti-HCV screening, RIBA, HCV RNA and HCV genotyping. HCV genotyping was also carried out in 9 HCV-viraemic HCC-patients from Gothenburg. HCV genotype distribution in HCC cases was compared with Swedish HCV-infected blood donors. Among the 95 patients from Malmö, 28 (29%) had anti-HBc, but only 5 (5%) were chronic HBV carriers, compared with 16 (17%) with chronic hepatitis C (p = 0.021). HCV-related HCC was more common among immigrants (8/16 vs. 8/79; p < 0.001). Genotyping of 25 HCV-infected cases showed genotype 1a in 6 (24%), genotype 1b in 13 (52%), genotype 2b in 4 (16%), and genotype 3a in 2 (8.0%) patients. Genotype 1b was more common among HCC patients than among blood donors (p < 0.001), but 8 of 13 genotype 1b-infected patients were from countries where genotype 1b is predominant. Among native Swedes there was no difference between the HCV genotypes infecting blood donors and those found in HCC patients.

Wejstål R, Månson AS, Widell A, Norkrans G. · Department of Infectious Diseases, Sahlgrenska University Hospital/Ostra, Göteborg, Sweden. · Clin Infect Dis. · Pubmed #10825044 No free full text.

Abstract: Hepatitis G virus (HGV) infection is more common than hepatitis C virus (HCV) infection and is frequently found in healthy individuals. Although parenteral spread of HGV is well recognized, other routes of transmission probably occur as well. In a prospective study of mother-to-infant transmission of hepatitis viruses, 69 pregnant women with antibodies to HCV and their 81 newborn children were included. Serum levels of HCV RNA and HGV RNA were detected by polymerase chain reaction (PCR) assays, and antibodies to HCV and HGV envelope protein E2 were detected by enzyme-linked immunosorbent assay. Fifty-nine of the mothers had HCV viremia, whereas 16 had HGV viremia. HCV transmission from viremic mothers occurred in 2.8%-4.2% of the cases, whereas HGV transmission from viremic mothers occurred in 75.0%-80.0% of the cases (P < .001). Sequencing of the PCR products of HGV from the mother-infant serum pairs showed minor differences in most cases but sequence homology in each pair. Although the rate of perinatal HGV transmission highly exceeded that of perinatal HCV transmission, HGV did not seem to induce hepatitis in the children.

Wejstål R, Fischler B, Glaumann H, Norkrans G, Reichard O, Sönnerborg A, Uhnoo I, Weiland O. · Infektionskliniken, Sahlgrenska Universitetssjukhuset/Ostra, Göteborg. · Lakartidningen. · Pubmed #10584541 No free full text.

This publication has no abstract.

Westin J, Lindh M, Lagging LM, Norkrans G, Wejstål R. · Department of Infectious Diseases, Sahlgrenska University Hospital, Ostra, Göteborg, Sweden. · Scand J Infect Dis. · Pubmed #10528872 No free full text.

Abstract: Hepatitis C virus (HCV) strains are divided into 6 genotypes and several subtypes. Recent studies reported a change in the relative frequency of genotypes within certain regions. We studied the HCV genotype in 312 Swedish patients with chronic hepatitis C, using a core region primer-specific PCR, and grouped the patients according to parenteral risk factors. The date of infection could be estimated in 127 cases. Genotypes 1a (35%) and 3 (31%) were the most common genotypes, followed by genotype 2 (17%), while only 6% had genotype 1b. Genotype 3 was relatively more frequent among subjects infected sexually or by intravenous drug use. The genotype distribution was different from that in studies from other parts of the world, with a lower frequency of genotype 1 (especially 1b) and a higher frequency of genotype 3. The frequency of genotype 1b has decreased and genotype 3 increased over time. The reasons for a different distribution of genotypes in Sweden, compared with other countries, might be a relatively recent introduction of HCV into the population, or a different pattern of transmission.

Westin J, Lagging LM, Wejstål R, Norkrans G, Dhillon AP. · Department of Infectious Diseases, Sahlgrenska University Hospital, Göteborg, Sweden. · Liver. · Pubmed #10395036 No free full text.

Abstract: AIMS/BACKGROUND: Assessing the histopathological degree of liver damage is essential to the routine care of patients with chronic hepatitis C virus (HCV) infection. Several scoring systems have been proposed in attempts to standardize the histological assessment. One scoring system has been proposed by Ishak et al. Although widely endorsed, its interobserver reliability has not been evaluated. METHODS: 95 liver biopsies from patients with chronic HCV infection were scored by three independent observers. Interface hepatitis, confluent necrosis, focal necrosis, portal inflammation, and fibrosis were assessed. RESULTS: Confluent necrosis, which is more common in acute hepatitis, was not seen in any biopsy. For each of the remaining variables of inflammation (periportal hepatitis, focal necrosis, and portal inflammation) we found agreement in 95-96% for all three observers. Kappa scores ranged from 0.11 to 0.41 and weighted kappa scores from 0.18 to 0.53. For staging we noted 84% agreement, kappa scores of 0.26-0.47, and weighted kappa scores of 0.57-0.69. CONCLUSION: The Ishak system is associated with good interobserver reliability if a deviance of one categorical level in each variable of the system is accepted as agreement. Compared to the Knodell system it provides more detailed information but is less reliable regarding fibrosis.