Hepatitis: Fischler B

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.

Fischler B. · Department of Pediatrics, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden. · Semin Fetal Neonatal Med. · Pubmed #17320495 No free full text.

Abstract: The prevalence of chronic hepatitis C infection in the general paediatric population varies between 0.1 and 15% around the world, with the highest numbers noted in endemic areas of Africa. The risk of viral transmission from an infected mother to her child is approximately 5% and there are currently no effective preventative measures to lower it. All children born to infected mothers should be tested for hepatitis C. The progression to liver damage in infected children is slow. However, in the perspective of 15-20 years of infection or in the presence of other risk factors, such as concomitant chronic disease, a progression to more severe liver damage can be seen. Thus, the use of antiviral treatment may be of importance. Treatment combinations of interferon and ribavirin seem to be at least as effective in children as in adults. However, the negative effect on growth of interferon requires specific attention by paediatricians.

Honkaniemi E, Gustafsson B, Fischler B, Nemeth A, Frost BM, Papadogiannakis N, Winiarski J. · Department of Paediatrics, Karolinska University Hospital, Huddinge, Clintec, Karolinska Institutet, S-141 86 Stockholm, Sweden. · Acta Paediatr. · Pubmed #17888058 No free full text.

Abstract: AIM: Aplastic anaemia following hepatitis may develop in as many as 1 of 3 patients with non-A, non-B and non-C hepatitis. Several causative factors have been discussed, such as viral infections and autoimmunity. Here we describe the natural history of this condition in 7 children and investigate possible hepatitis-causing agents. METHODS: We reviewed the medical records, bone marrow and liver biopsies of 7 children with severe hepatitis, with or without liver failure, who subsequently had developed aplastic anaemia. RESULTS: The median time from onset of hepatic symptoms until diagnosed onset of aplasia was 54 days. No associated viral infections could be identified. On liver biopsy, a majority had lobular inflammation but lacked signs of autoimmune hepatitis, findings compatible with a viral aetiology. Three of 6 children had low reticulocyte counts already at onset of hepatitis. All, but one patient is alive at median follow-up of 8 years. CONCLUSION: The unknown pathogenetic mechanism appears to target liver and bone marrow simultaneously, because half of the children concomitantly had low reticulocyte counts and severe liver failure.

Fischler B, Nyström J, Björnsdottir T, Lindh G, Hultgren C. · Department of Pediatrics, Karolinska University Hospital, Huddinge, Stockholm, Sweden. · J Pediatr Gastroenterol Nutr. · Pubmed #17592368 No free full text.

Abstract: OBJECTIVES: To study the hepatitis B-specific T cell-mediated immune response in chronically infected children and adolescents. PATIENTS AND METHODS: In all, 36 HBsAg-positive patients, 2 to 19 years old, were included. There were 9 HBeAg-positive patients with normal levels of alanine aminotransferase (ALT) (group 1), 18 HBeAg-positive patients with elevated ALT (group 2), and 9 HBeAg-negative, anti-HBe-positive patients (group 3). Four patients in group 2 were treated with interferon during the study. In all patients, HBcAg-specific T cell proliferation and ALT levels were prospectively studied in repeated samples for a mean follow-up time of 1.6 years. The baseline HBV-DNA and plasma cytokine levels were determined, and genotypes were analyzed. RESULTS: The percent of patients with at least 1 sample indicating T cell proliferation was 55% in group 1 and 89% in groups 2 and 3, respectively (P = 0.07 group 1 vs group 2, P = 0.013 group 1 vs the combined groups 2 and 3). Tendencies for positive correlations between the degree of T cell proliferation and ALT levels were noted in groups 1 and 3 and for negative correlations in HBeAg seroconverting patients of group 2. In patients with successful interferon treatment, a pattern of more vigorous T cell proliferation than in patients with spontaneous seroconversion was noted. CONCLUSIONS: A majority of patients showed signs of ongoing T cell proliferation. The continuation of the T cell-mediated immune response seems to be of importance in maintaining the HBeAg seroconversion over time.

Knisely AS, Strautnieks SS, Meier Y, Stieger B, Byrne JA, Portmann BC, Bull LN, Pawlikowska L, Bilezikçi B, Ozçay F, László A, Tiszlavicz L, Moore L, Raftos J, Arnell H, Fischler B, Németh A, Papadogiannakis N, Cielecka-Kuszyk J, Jankowska I, Pawłowska J, Melín-Aldana H, Emerick KM, Whitington PF, Mieli-Vergani G, Thompson RJ. · Institute of Liver Studies, King's College Hospital, London, UK. · Hepatology. · Pubmed #16871584 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is rare in young children. We attempted to see if immunohistochemical and mutational-analysis studies could demonstrate that deficiency of the canalicular bile acid transporter bile salt export pump (BSEP) and mutation in ABCB11, encoding BSEP, underlay progressive familial intrahepatic cholestasis (PFIC)--or "neonatal hepatitis" suggesting PFIC--that was associated with HCC in young children. We studied 11 cases of pediatric HCC in the setting of PFIC or "neonatal hepatitis" suggesting PFIC. Archival liver were retrieved and immunostained for BSEP. Mutational analysis of ABCB11 was performed in leukocyte DNA from available patients and parents. Among the 11 nonrelated children studied aged 13-52 months at diagnosis of HCC, 9 (and a full sibling, with neonatal hepatitis suggesting PFIC, of a tenth from whom liver was not available) had immunohistochemical evidence of BSEP deficiency; the eleventh child did not. Mutations in ABCB11 were demonstrated in all patients with BSEP deficiency in whom leukocyte DNA could be studied (n = 7). These mutations were confirmed in the parents (n = 14). With respect to the other 3 children with BSEP deficiency, mutations in ABCB11 were demonstrated in all 5 parents in whom leukocyte DNA could be studied. Thirteen different mutations were found. In conclusion, PFIC associated with BSEP deficiency represents a previously unrecognized risk for HCC in young children. Immunohistochemical evidence of BSEP deficiency correlates well with demonstrable mutation in ABCB11.

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.

Fischler B. · Department of Pediatrics, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden. · Scand J Infect Dis. · Pubmed #12374369 No free full text.

Abstract: The mother of an HCV-infected child had been subjected to neonatal exchange transfusion. It is likely that she contracted a chronic HCV infection which was later transmitted to her daughter. A similar route of infection is suggested in other HCV-infected patients lacking obvious risk factors.

Lazdina U, Hultgren C, Chen M, Fischler B, Weiland O, Mushahwar IK, Sällberg M. · Division of Clinical Virology, Karolinska Institutet at Huddinge University Hospital, Sweden. · J Med Virol. · Pubmed #11055243 No free full text.

Abstract: Immune responses to two recombinant envelope 2 (E2) proteins, representing genotypes 1 and 2 of the GB virus C, or the hepatitis G virus (GBV-C/HGV), were studied in mice and in 48 individuals with, or without, chronic, or past GBV-C/HGV infection. Immunised mice developed E2-specific antibodies (mean titres, 1:1,167 to 1:9,360), recognising linear antigenic regions and proliferative and IL-2, IL-6 and gammaIFN cytokine responses regardless of the viral genotype. Individuals with past GBV-C infection had E2 antibody titres from 1:1,500 to 1:7,500 that did not recognise the E. coli derived E2 protein or linear antigenic regions. Proliferative E2-specific responses were detected in peripheral blood mononuclear cells from 6/22 (27%) persons with, and in none without GBV-C markers (P<0.05). Thus, E2-specific immune responses are mainly crossreactive between different variants of GBV-C/HGV, although proliferative responses appear to be rare.

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.

Chen M, Fischler B, Hultgren C, Halasz R, Nemeth A, Sällberg M. · Divisions of Clinical Virology and Basic Oral Science, Karolinska Institutet at Huddinge University Hospital, S-141 86 Huddinge, Sweden. · J Clin Microbiol. · Pubmed #10565950 links to  free full text

Abstract: GB virus C (GBV-C) markers were analyzed in two to three generations in three families with documented vertical transmission of GBV-C. None of the maternal grandparents had GBV-C markers, whereas the male spouses had GBV-C envelope 2 antibodies. Evidence was found for intrafamilial transmission but not for GBV-C transmission over three generations.

Halasz R, Fischler B, Nemeth A, Lundholm S, Sällberg M. · Department of Immunology, Microbiology, Pathology, and Infectious Diseases, Huddinge University Hospital, Karolinska Institute, Sweden. · Clin Infect Dis. · Pubmed #10194074 No free full text.

Abstract: The role of GB virus C/hepatitis G virus (GBV-C/HGV) in adult and pediatric liver disease is unclear. We detected serum GBV-C/HGV RNA by reverse transcriptase polymerase chain reaction in 1 (3%) of 38 cholestatic infants, in 4 (4%) of 95 children without liver disease, and in none of 30 children with autoimmune hepatitis. One cholestatic infant had antibodies, presumably maternal, to GBV-C/HGV. Sequence analysis of a nonstructural 3 region fragment suggested that mother-to-infant transmission was the route of infection for the cholestatic infant. The four infected children without liver disease had normal liver function test results and lacked risk factors for bloodborne infections. Thus, the detection of GBV-C/HGV RNA among children with and without liver disease suggests that chronic GBV-C/ HGV infections may be established early in life, possibly by mother-to-infant transmission. This may explain in part the high prevalence of serum GBV-C/HGV RNA and antibodies in healthy adults.

Halasz R, Barkholt L, Lara C, Hultgren C, Ando Y, Broomé U, Fischler B, Nemeth A, Ericzon BG, Sönnerborg A, Sällberg M. · Division of Clinical Virology, F68, Department of Immunology, Microbiology, Pathology, and Infectious Diseases, Karolinska Institutet, Huddinge University Hospital, S-141 86 Huddinge, Sweden. · Gut. · Pubmed #9895390 links to  free full text

Abstract: BACKGROUND: The role of the recently discovered GB virus C (GBV-C)/hepatitis G virus in fulminant hepatic failure (FHF) has been debated. Although GBV-C RNA has been detected in many cases of FHF, recent data suggest that the relation between GBV-C and FHF may be accidental. AIMS: To retrospectively investigate the possible relation between the presence of GBV-C markers (RNA or antibodies to the GBV-C envelope 2 (E2) glycoprotein) and FHF. METHODS: The presence of GBV-C RNA was determined in serum samples from 58 patients diagnosed with FHF using a reverse transcriptase polymerase chain reaction. Amplified genetic fragments were directly sequenced by the dideoxy chain termination method. Antibodies to GBV-C in serum samples were detected by enzyme immunoassay based on a recombinant GBV-C E2 protein. RESULTS: Nine (16%) patients with FHF had GBV-C RNA and 13 (22%) [corrected] had GBV-C E2 antibodies, which are higher frequencies than in healthy subjects (p<0.01 and p<0.05 respectively). Six of nine [corrected] patients with GBV-C markers during FHF tested negative for these markers before therapy with blood and/or blood products. Sequence analysis of the GBV-C NS3 region fragments of six FHF patients showed no common sequence pattern or motif. CONCLUSIONS: The frequencies of both GBV-C RNA and antibodies are higher in patients with FHF than in healthy subjects. However, these increased frequencies may in many cases be explained by the use of contaminated blood and/or blood products given as therapy.

Fischler B, Einberg AP. · No affiliation provided · Acta Paediatr. · Pubmed #17850397 No free full text.

This publication has no abstract.