Hepatitis: Reichard O

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.

Bruchfeld A, Lindahl K, Reichard O, Carlsson T, Schvarcz R. · Department of Renal Medicine, Karolinska University Hospital Huddinge and Solna, Karolinska Institute, Stockholm, Sweden. · J Viral Hepat. · Pubmed #16637862 No free full text.

Abstract: Standard therapy for chronic hepatitis C (HCV) is pegylated interferon in combination with ribavirin. There is limited experience with either drug in dialysis [end stage renal disease (ESRD)]. Six haemodialysis patients, four with HCV genotype 1, one with genotype 4 and one genotype 2 were treated with pegylated interferon-alfa-2b (n = 4) and pegylated interferon-alfa-2a (n = 2) for 24-48 weeks according to genotype with a dose of 50 or 135 mug/week respectively. All patients were given reduced ribavirin doses, initially 200-400 mg/day. Ribavirin trough plasma concentrations were measured with a HPLC method previously developed for earlier treatment studies, aiming at a target concentration of 10-15 micromol/L. Interferon related side-effects were common, in one patient peg-alfa-2b was permanently reduced to 50 mug every 9-10 days with improvement in tolerance. Average ribavirin dose was 170-300 mg/day. Ribavirin-induced anaemia was treated with high doses of erythropoietin and low doses of iron. Blood-transfusions were not needed. All patients became HCV-RNA-PCR negative during treatment which was completed or nearly completed in four patients. One patient terminated therapy prematurely due to pronounced interferon related side-effects and another died of myocardial infarction probably not related to therapy. Three patients have remained HCV-RNA negative with extended follow-up, two of whom have had a successful kidney transplant. Pegylated interferons are likely to become a valuable addition for HCV therapy in ESRD and are possible to combine with ribavirin. However the pharmacokinetics and tolerability of both peg-alfa-2a and 2b need to be studied more closely in prospective studies before definite dosing recommendations can be made.

Carlsson T, Weiland O, Reichard O. · Dept. of Infectious Diseases, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden. · Scand J Gastroenterol. · Pubmed #12408530 No free full text.

Abstract: BACKGROUND: The early decline of hepatitis C virus (HCV) RNA levels during therapy may predict the outcome and can be utilized to improve treatment regimens. We studied the HCV RNA levels during induction and standard interferon (IFN) and ribavirin treatment. METHODS: Patients received IFN 3 MU daily for 14 days followed by 3 MU three times a week (induction group; n = 10), or IFN 3 MU three times a week from start (standard group; n = 21), in combination with ribavirin 1000-1200 mg/day. HCV RNA was quantified day 0, 1, 2, 3, 7, 14, 28, 56 and 84 during treatment, and tested qualitatively at the end of treatment and at follow-up. RESULTS: The initial viral load decline was more pronounced in the induction group, and in patients infected with genotype non-1. The sustained response rate was not significantly different between the study groups. At day 1, the mean viral load decline from baseline was significantly greater in patients who became sustained responders than in those who became non-responders; 1.4 log (96%) versus 0.3 log (55%) (P < 0.05). All sustained responders had a viral load decline of at least 0.7 log (79%) after the first IFN dose. CONCLUSIONS: Our short-term induction treatment did not improve the long-term treatment outcome significantly, although a trend was seen. An absent or low initial viral load decline can be used to predict non-response in the individual patient.

Carlsson T, Reichard O, Weiland O. · Department of Infectious Diseases, Karolinska Institutet, Stockholm, Sweden. · Scand J Infect Dis. · Pubmed #11760165 No free full text.

Abstract: We studied HCV kinetics during the first 84 d of interferon-alpha (IFN) treatment. IFN was administered either at a dose of 3 million units daily for the first 14 d and thereafter 3 times per week (t.i.w.) (induction treatment), or at a dose of 3 million units t.i.w. throughout (standard treatment). No patient had received HCV treatment previously, and all had a pretreatment viral load of < 1.2 x 10(6) IU/ml at screening. Ten patients were given induction treatment and 21 received the standard t.i.w. regimen. Twenty patients were infected with genotype 1. At Day 2, the median HCV RNA level in the induction group was significantly lower compared to that of the standard treatment group. This significant difference persisted during the study period for patients infected with genotype 1, but was not maintained from Day 14 onwards for patients with genotype non-1. At Day 84, 80% (8/10) of patients in the induction group, compared to 16% (3/19) in the standard treatment group, had undetectable (< 600 IU/ml) HCV RNA levels (p < 0.05). We conclude that induction treatment resulted in a significantly greater decline in HCV RNA levels than standard treatment.

Carlsson T, Lindahl K, Schvarcz R, Wejstal R, Uhnoo I, Shev S, Reichard O. · Department of Infectious Diseases, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden. · J Viral Hepat. · Pubmed #11115051 No free full text.

Abstract: Interferon (IFN) alpha in combination with ribavirin (RIB) is standard therapy for patients with chronic hepatitis C virus (HCV) infection. However, many patients do not respond with sustained HCV clearance to this therapy. At present, no accepted treatment strategy exists for these patients. Recent preliminary data have suggested that amantadine (AMA) is effective against HCV infection. In a pilot study, we treated 13 nonresponders and 10 response/ relapsers to previous IFN/RIB therapy with AMA 200 mg per day in combination with IFN 3 MU thrice weekly, and RIB 1000 mg per day for 24 weeks, with a 24-week follow-up period after end-of-treatment. At the end-of-treatment, 1 previous nonresponder and 5 previous response/relapsers were HCV RNA negative. At the end of follow-up, only 1 previous response/relapser remained HCV RNA negative and had a sustained response. During therapy, serum HCV RNA became undetectable in 4 previous nonresponders, of whom 3 had a breakthrough at week 24. Twenty-one patients continued therapy without dose reductions. One patient discontinued therapy prematurely due to sleeping disturbances, and another patient was withdrawn from therapy due to heavy alcohol intake. We conclude that the addition of AMA to IFN and RIB was well tolerated but had little, if any, impact on HCV RNA eradication in nonresponders or response/relapsers to previous IFN/RIB combination therapy.

Schvarcz R, Glaumann H, Reichard O, Weiland O. · Department of Infectious Diseases, Huddinge Hospital, Sweden. · J Viral Hepat. · Pubmed #10607236 No free full text.

Abstract: Long-term virological and histological outcome following interferon-alpha2b (IFN-alpha2b) and ribavirin treatment for 24 weeks was studied in 20 patients with chronic hepatitis C who were without a lasting response to IFN as monotherapy. Following combination therapy, sustained virological response (SR) was achieved in 12 patients (i.e. hepatitis C virus (HCV) RNA negative in serum 6 months post-treatment). Eleven of these patients remained HCV RNA negative in serum 2 years post-treatment. A virological long-term response (LTR) was more frequent in patients with a previous end-of-treatment response to IFN monotherapy than in non-responders. Liver histology at follow-up, >/=24 months post-treatment, showed substantial improvement in patients with a virological LTR to the combination treatment. In all nine patients biopsied at the 2-year follow-up, liver inflammation had disappeared totally (grade=0), and the stage (fibrosis) had improved. In contrast, no significant changes in grade or stage were noted in patients with a virological non-LTR to combination treatment. A significant improvement in inflammation was noted, in patients with a virological LTR, from 3.6 to 0.2 (P<0.01) and in fibrosis from 2.0 to 1.4 (P<0.05) whereas the corresponding scores for patients with a virological non-LTR did not change significantly, from 3.1 to 1.5 for inflammation and for fibrosis from 1.3 to 1.3. We conclude that patients with chronic hepatitis C who achieve a virological sustained response 6 months post-treatment with IFN-alpha2b and ribavirin will remain virological responders for a follow-up period of least 24 months, concomitant with a disappearance of inflammatory activity and a marked improvement of fibrosis in the liver.

Weiland O, Braconier JH, Frydén A, Norkrans G, Reichard O, Uhnoo I. · Department of Immunology, Microbiology, Pathology and Infectious Diseases, Division of Infectious Diseases, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden. · Scand J Infect Dis. · Pubmed #10447316 No free full text.

Abstract: A total of 172 Swedish patients treated with interferon-alpha for at least 24 weeks and followed-up > or =24 weeks after treatment was stopped were analysed for pre-treatment factors of importance for achieving a virological sustained response (SR). Furthermore, the predictive value for a virological SR of a positive or negative HCV RNA test at week 12 of treatment was evaluated. A low baseline viral load and genotype non-1b were pre-treatment factors indicating a favourable response. Thus, 44% (38/86) of patients with a low baseline viral load vs. only 16% (14/86) of those with a high viral load had a virological SR (p<0.0001). Of patients with a negative qualitative HCV RNA test after 12 weeks of interferon treatment, 46% (44/95) had virological SR, whereas only 5.9% (4/68) of those with a positive test had (p<0.0001). Prolonged ( > 6 months) treatment with interferon-alpha tended to increase the chance of virological SR (p<0.052).

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.

Gonzalez VD, Falconer K, Michaëlsson J, Moll M, Reichard O, Alaeus A, Sandberg JK. · Center for Infection Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 14186, Stockholm, Sweden. · Clin Immunol. · Pubmed #18495540 No free full text.

Abstract: Co-infection with HCV and HIV-1 is a problem of increasing importance and the role of innate cellular immunity in this co-infection is incompletely understood. Here, we have observed sharply elevated numbers of CD56(-)CD16(+) perforin(low) NK cells in HCV/HIV-1 co-infected subjects on antiretroviral therapy. Interestingly, this expansion of unconventional CD56(-) NK cells rapidly reverted when HCV was suppressed by IFNalpha and ribavirin treatment, and was not seen in mono-infected control groups. In vitro experiments suggested that this effect of treatment was due to suppression of HCV viremia rather than a direct effect of IFNalpha on these cells. In contrast, the conventional CD56(+) NK cells were largely unchanged in subjects with high HCV loads, although they exhibited slightly decreased perforin expression. With delayed kinetics, the CD56(bright) immuno-regulatory NK cell subset temporarily increased to supranormal levels in response to HCV treatment. In contrast to the NK compartment, the CD1d-restricted NKT cells were severely reduced by the co-infection and not restored by treatment. Together, our data suggest that the high HCV loads in HCV/HIV-1 co-infection alter the NK cell compartment in a way not observed in HCV mono-infection.

Sangfelt P, Uhnoo I, Reichard O, Weiland O. · Department of Infectious Diseases, Akademiska University Hospital, Uppsala University, Uppsala, Sweden. · Scand J Gastroenterol. · Pubmed #18365912 No free full text.

Abstract: OBJECTIVE: To evaluate compliance, serologic response and the cost-benefit of a low-dose intradermal hepatitis B vaccination programme, followed by intramuscular boosters in non-responders. MATERIAL AND METHODS: The study comprised a retrospective survey of 1521 health-care workers and 968 students. Response was defined as hepatitis B antibody titres > or =10 IU/L. Non-response included vaccinees with undetectable antibodies and a hypo-response if antibodies were detectable. RESULTS: Overall, 2145/2489 (86%) subjects completed the intradermal series, whereof 1840/2489 (74%) complied with the serological check-up. Response was achieved in 1517/1840 (82.5%), whereas 107/1840 (5.8%) had a hypo-response and 216/1840 (11.7%) had an undetectable response. In a logistic regression model, younger age (odds ratio 0.73 (95% CI: 0.65-0.82, p<0.001)) and female gender (odds ratio 2.16 (95% CI: 1.67-2.80; p<0.001)) were predictive of response. In hypo-responders and those with undetectable responses, 43/46 (94%) and 71/136 (52%), respectively, had a response after the first intramuscular booster. Hence, in compliant vaccinees an overall seroprotection rate of 94% was reached after a single intramuscular booster. A cost-benefit analysis indicated a cost reduction exceeding 50% compared to a standard intramuscular vaccine regimen. CONCLUSIONS: In the clinical setting, a low-dose intradermal hepatitis B vaccination programme, followed by intramuscular boosters to non-responders, is effective and cost saving.

Falconer K, Gonzalez VD, Reichard O, Sandberg JK, Alaeus A. · Karolinska Institutet, Department of Medicine Solna, Infectious Diseases Unit, SE-17176 Stockholm, Sweden. · J Clin Virol. · Pubmed #18093872 No free full text.

Abstract: BACKGROUND/OBJECTIVE: Spontaneous HCV clearance in HCV/HIV-1 coinfected patients is likely to be very rare given the damage to the immune system caused by HIV-1 infection. The search for immune correlates of spontaneous clearance is important for the understanding of pathogenesis as well as for the development of possible new treatment strategies. STUDY DESIGN/RESULTS: A cohort of HCV/HIV-1 coinfected patients was followed. Plasma HCV viral load was measured and T cell immunity in peripheral blood samples was assessed using multi-color flow cytometry. One HCV/HIV-1 coinfected patient spontaneously became HCV-RNA negative after being positive for several years. This patient displayed a normalized CD4 counts on successful HAART, low level of T cell activation and a high level of T cell function as compared to HCV/HIV-1 coinfected control subjects. CONCLUSIONS: A beneficial immune status including a low level of chronic T cell activation and a high level of T cell function may be one factor that contributes to improved chances of clearance of chronic HCV infection in HIV-1 infected patients.

Dalgard O, Bjøro K, Ring-Larsen H, Bjornsson E, Holberg-Petersen M, Skovlund E, Reichard O, Myrvang B, Sundelöf B, Ritland S, Hellum K, Frydén A, Florholmen J, Verbaan H, Anonymous00245. · Infectious Disease Department, Ullevål University Hospital, Oslo, Norway. · Hepatology. · Pubmed #17975791 No free full text.

Abstract: A recent nonrandomized pilot trial showed that hepatitis C virus (HCV) patients with genotype 2/3 and rapid virological response (RVR) had a 90% sustained virological response (SVR) rate after 14 weeks of treatment. We aimed to assess this concept in a randomized controlled trial. In the trial, 428 treatment-naïve HCV RNA-positive patients with genotype 2 or 3 were enrolled. Patients with RVR were randomized to 14 (group A) or 24 (group B) weeks of treatment. Patients were treated with pegylated interferon alpha-2b (1.5 microg/kg) subcutaneously weekly and ribavirin (800-1400 mg) orally daily. The noninferiority margin was set to be 10% between the two groups with a one-sided 2.5% significance level. RVR was obtained in 302 of 428 (71%), and 298 of these were randomized to group A (n = 148) or group B (n = 150). In the intention-to-treat analysis, SVR rates were 120 of 148 (81.1%) in group A and 136 of 150 (90.7%) in group B (difference, 9.6%; 95% confidence interval, 1.7-17.7). Among patients with an HCV RNA test 24 weeks after the end of treatment, 120 of 139 (86.3%) patients in group A achieved SVR compared with 136 of 146 (93.2%) in group B (difference, 6.9%; 95% confidence interval, -0.1 to +13.9). CONCLUSION: We cannot formally claim that 14 weeks of treatment is noninferior to 24 weeks of treatment. However, the SVR rate after 14 weeks of treatment is high, and although longer treatment may give slightly better SVR, we believe economical savings and fewer side effects make it rational to treat patients with genotype 2 or 3 and RVR for only 14 weeks.

Bernfort L, Sennfält K, Reichard O. · Centre for Medical Technology Assessment, University of Linköping, Stockholm, Sweden. · Scand J Infect Dis. · Pubmed #16798701 No free full text.

Abstract: The aim of the study was to assess the cost-effectiveness of peginterferon alfa-2b (pegIFN) compared to interferon alfa-2b (IFN), both in combination with ribavirin, as initial therapy for chronic hepatitis C in Sweden. A computer based Markov model describing the natural course of chronic hepatitis C was used to assess costs and quality-adjusted life-y (QALY) for the treatment strategies. Study population was a cohort of hepatitis C patients from the age of 43 y until death. Natural history and response data were obtained from the literature and from Swedish clinical experts. Costs were obtained from different health care providers in Sweden and based on Swedish clinical practice. In our base case analysis for genotype 1 patients, pegIFN plus ribavirin therapy generated 0.29 incremental QALYs and was cost saving (dominant strategy). Corresponding results for genotype 2/3 patients were 0.09 QALYs at an incremental cost of 941 euros (10,500 euros/QALY). A probabilistic sensitivity analysis was performed to study the stability of our results. From the results we conclude that for genotype 1 patients treatment with pegIFN and ribavirin increased quality-adjusted life expectancy and was cost-effective as initial therapy for hepatitis C. The cost-effectiveness for patients infected with genotype 2/3 was less obvious.

Bruchfeld A, Lindahl K, Reichard O, Carlsson T, Schvarcz R. · No affiliation provided · Nephrol Dial Transplant. · Pubmed #16517569 links to  free full text

This publication has no abstract.

Carlsson T, Reichard O, Norkrans G, Bläckberg J, Sangfelt P, Wallmark E, Weiland O. · Division of Infectious Diseases, Karolinska University Hospital (Solna and Huddinge), Karolinska Institutet, Stockholm, Sweden. · J Viral Hepat. · Pubmed #16108761 No free full text.

Abstract: SUMMARY: To optimize treatment of chronic hepatitis C early identification of patients who will not achieve a sustained virological response (SVR) is desirable. We investigated hepatitis C virus (HCV) RNA kinetics at day 1 (in 15 patients; genotypes 1 and non-1, 9 and 6 respectively) at weeks 1, 4 and 12 (in 53 patients; genotypes 1 and non-1, 19 and 34, respectively) during treatment with pegylated interferon alpha-2a and ribavirin. Patients with SVR had a significantly more pronounced mean log10 decline from baseline in HCV RNA levels at weeks 1 and 4 compared with patients who failed to achieve SVR (1.99 vs 0.85 at week 1, P = 0.0003 and 2.89 vs 1.72 at week 4, P = 0.0159), whereas no difference was noted after day 1. For patients with a 2-log10 decrease in HCV RNA levels at day 7, the positive predictive value (PPV) for a SVR was 92%, whereas week 12 was the best time point for predicting a later nonresponse [negative predictive value (NPV) 92%] in patients failing to achieve a 2-log10 drop. For patients with genotype non-1 and a 2-log10 decrease in HCV RNA levels the PPV for a SVR was 89% week 1, and 79% weeks 4 and 12. The corresponding NPV for patients with genotype non-1 were 43, 40 and 100% respectively. During treatment with pegylated interferon alpha-2a plus ribavirin the HCV RNA decline at week 1 was an accurate predictor of SVR in patients who had achieved a 2-log10 drop in HCV RNA levels, whereas the lack of such decline week 12 was an accurate marker of a nonresponse.

Duberg AS, Nordström M, Törner A, Reichard O, Strauss R, Janzon R, Bäck E, Ekdahl K. · Department of Infectious Diseases, Orebro University Hospital, Orebro, Sweden. · Hepatology. · Pubmed #15723449 No free full text.

Abstract: The aim of this study was to evaluate the association between hepatitis C virus (HCV) infection and non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), thyroid cancer (TC), chronic lymphatic leukemia (CLL), acute lymphatic leukemia (ALL), and Hodgkin's lymphoma (HL). A Swedish cohort of 27,150 HCV-infected persons notified during 1990-2000 was included in the study. The database was linked to other national registers to calculate the observation time, expressed as person-years, and to identify all incident malignancies in the cohort. The patients were stratified according to assumed time of previous HCV infection. The relative risk of malignancy was expressed as a standardized incidence ratio (SIR)-the observed number compared to the expected number. During 1990-2000 there were 50 NHL, 15 MM, 14 ALL, 8 TC, 6 CLL, and 4 HL diagnoses in the cohort. Altogether, 20 NHL, 7 MM, 5 TC, 4 CLL, 1 ALL, and 1 HL patient fulfilled the criteria to be included in the statistical analysis. The observation time was 122,272 person-years. The risk of NHL and MM was significantly increased in the stratum with more than 15 years of infection (SIR 1.89 [95% CI, 1.10-3.03] and 2.54 [95% CI, 1.11-5.69], respectively). The association was not significant in TC or CLL. In conclusion, we report the incidence of several malignancies in a nationwide cohort of HCV-infected persons. Although the delayed diagnosis of HCV probably has resulted in an underestimation of the risk, this study showed a significantly increased risk of NHL and MM.

Sangfelt P, Von Sydow M, Uhnoo I, Weiland O, Lindh G, Fischler B, Lindgren S, Reichard O. · Department of Medical Sciences, Section of Infectious Diseases, Akademiska Hospital, Uppsala, Sweden. · Scand J Infect Dis. · Pubmed #15119362 No free full text.

Abstract: In Stockholm, Sweden, the majority of pregnant women positive for hepatitis B surface antigen (HBsAg) are hepatitis Be antigen (HBeAg) negative. Newborns to HBeAg positive mothers receive vaccination and hepatitis B immunoglobulin (HBIg). Newborns to HBeAg negative mothers receive vaccine and HBIg only if the mothers have elevated ALT levels. The aim of this study was to retrospectively evaluate ALT levels as a surrogate marker for HBV DNA levels in HBeAg negative carrier mothers. Altogether 8947 pregnant women were screened for HBV markers from 1999 to 2001 at the Virology Department, Karolinska Hospital. Among mothers screened 192 tested positive for HBsAg (2.2%). 13 of these samples could not be retrieved. Of the remaining 179 sera, 8 (4%) tested positive for HBeAg and 171 (95.5%) were HBeAg negative. Among the HBeAg negative mothers, 9 had HBV DNA levels > 10(5) copies/ml, and of these 7 had normal ALT levels indicating low sensitivity of an elevated ALT level as a surrogate marker for high HBV DNA level. Furthermore, no correlation was found between ALT and HBV DNA levels. Hence, it is concluded that the use of ALT as a surrogate marker for high viral replication in HBeAg negative mothers could be questioned.

Balciuniene L, Carlsson T, Ambrozaitis A, Reichard O, Weiland O. · Vilnius University, Vilnius University Hospital for Infectious Diseases, Vilnius, Lithuania. · Scand J Infect Dis. · Pubmed #12751713 No free full text.

Abstract: Hepatitis C virus (HCV) RNA kinetics were studied at baseline weeks 4, 8 and 12 during interferon-alpha (IFN) monotherapy in 65 patients (mean age 39 y, range 19-66 y) with chronic HCV infection. IFN treatment was given either as initial induction (n = 34) or as standard dosing 3 times a week (n = 31). Patients with genotypes 2 and 3 had a significantly steeper decline in HCV RNA levels than patients with genotype 1 at weeks 4, 8 and 12 (p < 0.001 at all points measured). The decline in viral load was more pronounced in patients with induction therapy than with standard therapy at weeks 4, 8 and 12 (p < 0.02, 0.054 and 0.01, respectively). Patients with a sustained viral response had a 3-log decline in viral levels at week 4, with few exceptions. Two patients with non-response at week 12 (1 each with genotype 1 and non-1) responded after supplementation with ribavirin.

Sennfält K, Reichard O, Hultkrantz R, Wong JB, Jonsson D. · Center for Medical Technology Assessment, University of Linköping, Sweden. · Scand J Gastroenterol. · Pubmed #11495084 No free full text.

Abstract: BACKGROUND: Recent trials have shown that treatment with a combination of interferon alfa-2b and ribavirin results in sustained loss of detectable hepatitis C-virus (HCV) RNA in a higher proportion of patients than treatment with interferon alone. Combination therapy, however, is two to three times as expensive as monotherapy. METHODS: Based on data from recent randomized clinical trials and a previously published decision model, we developed a Markov model to estimate the cost-effectiveness of initial combination therapy with interferon and ribavirin versus interferon alone for previously untreated patients with chronic HCV infection in Sweden. Clinical praxis and quality adjustments were based on expert estimates and costs were gathered from different health care providers in Sweden. RESULTS: Combination therapy for 24 or 48 weeks, compared to interferon alone, prolonged quality adjusted life expectancy by 0.5 to 1.1 years at marginal cost-effectiveness ratios of US$ 1,400 to US$ 6,000 per DQALY (discounted quality-adjusted life-year) for patients with genotype 1. In genotype 1, 48 weeks compared to 24 weeks of combination therapy prolonged quality adjusted life expectancy by 0.6 years at a marginal cost-effectiveness ratio of $US 9,800 per DQALY. For patients with genotype non-1, combination therapy for 24 or 48 weeks, compared to interferon alone, prolonged quality adjusted life expectancy by 2.3 years, with combination therapy for 24 weeks being money-saving. The results were robust in sensitivity analyses. CONCLUSION: Combination therapy with interferon and ribavirin increased quality-adjusted life expectancy and was cost-effective for patients with chronic hepatitis C.

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.