Hepatitis: Uhnoo I

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.

Sangfelt P, Uhnoo I, Hollander A, Lindh G, Weiland O. · Department of Infectious Diseases, University Hospital, Uppsala, Sweden. · Scand J Infect Dis. · Pubmed #12195876 No free full text.

Abstract: Lamivudine and famciclovir combination therapy has been used in patients with chronic HBeAg-positive hepatitis B to enhance the antiviral effect and reduce the risk of development of resistance. Interferon-alpha (IFN-alpha) can theoretically be added to the regimen to further improve the antiviral effect. Twenty patients with HBeAg-positive chronic hepatitis B were given lamivudine and famciclovir combination therapy for 24 weeks. After 12 weeks of treatment, patients were randomized on a 1:1 basis to either the addition of IFN-alpha 2b or no addition for the last 3 months of therapy. The decline in HBV DNA levels, the loss of HBeAg and the HBeAg seroconversion rate were assessed. Patients with loss of HBeAg and/or development of anti-HBe were followed up for at least 1 y after stopping treatment. Four of 19 patients (21%) had lost HBeAg and/or developed anti-HBe 24 weeks after stopping treatment, 1 of whom had received additional IFN-alpha. During long-term follow-up post-treatment, 2/19 patients (10.5%) had a durable HBeAg seroconversion. The mean HBV DNA level declined by 5 logs during the first 12 weeks of treatment. Addition of IFN-alpha during the last 3 months of treatment did not result in any further decline in HBV DNA levels compared with the non-IFN-alpha-treated group, nor in any increase in the HBeAg seroconversion rate. In conclusion, lamivudine and famciclovir combination treatment induced seroconversion from HBeAg to anti-HBe in 4/19 patients, 2 of whom became long-term responders. Addition of IFN-alpha did not improve the seroconversion rate.

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.

Frey S, Dagan R, Ashur Y, Chen XQ, Ibarra J, Kollaritsch H, Mazur MH, Poland GA, Reisinger K, Walter E, Van Damme P, Braconier JH, Uhnoo I, Wahl M, Blatter MM, Clements D, Greenberg D, Jacobson RM, Norrby SR, Rowe M, Shouval D, Simmons SS, van Hattum J, Wennerholm S, Gress JO. · Saint Louis University Health Sciences Center, St. Louis, MO 63110, USA. · J Infect Dis. · Pubmed #10558961 No free full text.

Abstract: A randomized trial comparing 3 manufacturing consistency lots of a combination hepatitis A/hepatitis B vaccine to each other and to hepatitis A vaccine and hepatitis B vaccine given separately and concurrently was done to evaluate safety, tolerability, and immunogenicity. Healthy volunteers >/=11 years of age were divided into 4 groups. Each of 3 groups received a separate consistency lot of the combination vaccine, and 1 group received separate but concurrent injections of hepatitis A and hepatitis B vaccines. Injections were given at weeks 0 and 24. The combination vaccine was generally well tolerated. The hepatitis A portion of the combination vaccine produced clinically acceptable high seropositivity rates 4 and 52 weeks after the first injection. The hepatitis B portion of the vaccine did not produce clinically acceptable seropositivity rates 4 weeks after the second injection. Lack of antibody production may be attributed, at least in part, to immunologic interference.

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).

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.

Gisslén M, Ahlqvist-Rastad J, Albert J, Blaxhult A, Hamberg AK, Lindbäck S, Sandström E, Uhnoo I, Anonymous00090. · Department of Infectious Diseases, Sahlgrenska University Hospital, Göteborg, Sweden. · Scand J Infect Dis. · Pubmed #16562361 No free full text.

Abstract: On 2 earlier occasions, in 2002 and 2003, the Swedish Medical Products Agency (MPA) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly publicized recommendations for the treatment of HIV infection. A working group from the same expert team that produced the 2002 report has now revised the text again. Since the publication of the last treatment recommendations, 4 new medicines have become available: emtricitabine, atazanavir, fosamprenavir, and enfuvirtid. The last-mentioned belongs to a new class of HIV medications called fusion inhibitors (Box 1). It is likely that tipranavir will also be on the market soon. Simultaneously, the drug zalcitabin has been deregistered. The following updated recommendations parallel the earlier ones, but increased knowledge allows us to be more specific in our recommendations. Thus, it is now suggested that the initial treatment for HIV infection consist of 2 nucleoside reverse transcriptase inhibitors (NRTIs) and 1 non-nucleoside reverse transcriptase inhibitor (NNRTI); or 2 NRTIs and 1 protease inhibitor (PI). In the group of the NRTIs, stavudine is no longer recommended for this purpose. In the NNRTI group, efavirenz should be preferred to nevirapine, except under special circumstances. Finally, PIs ought to be boosted with ritonavir (PI/r). Also new are recommendations regarding treatment choices for patients co-infected with hepatitis B virus (HBV) or tuberculosis (TB). As in the case of the previous publication, recommendations are evidence-graded in accordance with the Oxford Centre for Evidence Based Medicine, 2001 (see http://www.cebm.net/levels_of_evidence.asp#levels), and have been supplemented with references to newly-added sections and data not referred to in earlier background documentation.

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.

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.