Hepatitis: Lindh M

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.

Söderström A, Lindh M, Ekholm K, Conradi N, Horal P, Krantz M, Hultgren C, Norkrans G. · Department of Infectious Diseases, Göteborg University, Sweden. · Scand J Infect Dis. · Pubmed #15764189 No free full text.

Abstract: Further knowledge about factors predicting response to interferon treatment for chronic hepatitis B in children is required, in particular as the benefits of therapy are uncertain. In the present study, baseline characteristics were related to virological and histological responses in 27 children given interferon-alpha for 24 weeks after steroid priming. HBe seroconversion was seen in 8 of 27 HBeAg positive patients and was accompanied by a sustained virological response (SR), with a median 4.1 log HBV DNA reduction. Pretreatment viraemia level was the only baseline parameter associated with SR. After 12 weeks of IFN (mid-treatment), viraemia was significantly reduced in all patients, with a median of 3.0 (range 0.6-5.2) log decline in SR compared with 0.6 (range -0.5-3.6) log decline in non-sustained responders (NSR). HBV DNA levels below 1 million copies/ml at week 12 predicted sustained response with a positive predictive value of 75% and a negative predictive value of 89%. During the latter half of the IFN treatment HBV DNA tended to increase by a mean of 0.4-0.5 log for all patient groups. Flares during IFN treatment were rare or mild as measured by ALT. Pretreatment anti-HBc IgM was associated with liver damage but not with response. Histological inflammation scores were improved in SR. Thus, pretreatment HBV DNA levels were associated with IFN response, and the virological response at week 12 predicts SR and may be useful in the decision to continue or modify therapy.

Söderström A, Lindh M. · · Lakartidningen. · Pubmed #19530423 No free full text.

This publication has no abstract.

Liu WC, Lindh M, Buti M, Phiet PH, Mizokami M, Li HH, Sun KT, Young KC, Cheng PN, Wu IC, Chang TT. · Department of Life Sciences, Mingdao University, Changhua, Taiwan. · Intervirology. · Pubmed #18812698 No free full text.

Abstract: OBJECTIVES: Eight genotypes (A-H) of hepatitis B virus (HBV) are known with variations in nucleotide sequences greater than 8%. Several recent publications found that the clinical course and outcome of antiviral therapy depended on the genotype of the infecting HBV strain. Large epidemiological studies will require the availability of a system which is rapid, reliable and can be performed on a large number of samples. METHODS: To establish a simple and accurate genotyping method, the study collected 369 HBV complete genomic sequences from the GenBank database. Type-specific primers were also designed that separated HBV genotypes A to G by multiplex polymerase chain reaction. RESULTS: By comparison with the traditional restriction fragment length polymorphism method, over 93% of 441 samples were accurately genotyped by current assay, with a higher detection rate and sensitivity to detect mixed HBV infections. CONCLUSIONS: This methodology can be applied only to areas prevalent with HBV genotypes A to G. However, it provides an efficient alternative for clinical diagnosis and large-scale studies.

Hellström U, Lindh M, Krogsgaard K, Sylvan S. · Department of Communicable Disease Control and Prevention, Karolinska Hospital, Stockholm, Sweden. · J Gastroenterol Hepatol. · Pubmed #17931371 No free full text.

Abstract: BACKGROUND AND AIM: The treatment of hepatitis B virus (HBV) remains complex, with somewhat unpredictable responses. The aim of this study was to determine the predictive value of the pretreatment presence of circulatory antibodies towards a synthetic peptide mimicking the amino acids 94-117 of the preS1 protein of HBV and the capacity to respond to alpha-inteferon (IFN-alpha) treatment. METHODS: The anti preS1(94-117) antibodies were measured by a peptide-based enzyme-linked immunosorbent assay (ELISA) and the response to INF-alpha therapy was judged by the effect on the viral kinetics as measured by an assay based on quantitative polymerase chain reaction during the treatment and follow up. RESULTS: We found a significant (P < 0.001) correlation between the pretreatment presence of anti preS1(94-117) antibodies and a decrease in viral levels on follow up after the end of IFN-alpha therapy. The combined response of HBV DNA suppression (P < 0.001), hepatitis B e antigen (HBeAg) loss (P < 0.0001), anti-HBe seroconversion (P < 0.005) and AST aminotransferase normalization (P < 0.01) was also highly associated with the pretreatment presence of anti preS1(94-117) antibodies. CONCLUSION: The positive predictive value (PPV) of anti preS1(94-117) in determining a virological response was 83% and the negative predictive value (NPV) was 100%, indicating that in the absence of pretreatment anti preS1 reactivity virtually no patient has the capacity to respond to IFN-alpha therapy. Our findings may help to improve the efficacy of INF-alpha therapy for chronic hepatitis B (CHB) by guiding the selection of patients for treatment and optimizing the clinical management of the individual patient.

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.

Malmström S, Hannoun C, Lindh M. · Department of Clinical Virology, Göteborg University, Guldhedsgatan 10 B, 413 46 Göteborg, Sweden. · J Virol Methods. · Pubmed #17416427 No free full text.

Abstract: Hepatitis B virus infected patients on long-term lamivudine treatment are exposed to a 15-32% risk compounded annually of developing resistance mutations. Such resistance results in a progression of the liver damage caused by chronic hepatitis B, and may also impair the effect of other antivirals through cross-resistance. At present lamivudine is used frequently as monotherapy because of its relatively low price and negligible side effects. Thus, simple methods for identifying resistance mutations are required. A method based on real-time polymerase chain reaction with TaqMan chemistry is described. The method combines both primer specificity, in order to target wild type and mutant viral strains at codon 180, and a mixture of three minor groove binding probes distinguishing the YMDD wild type and the YVDD and YIDD variants at codon 204. The accuracy of the method was verified by concordance with results of direct sequencing and restriction fragment length polymorphism when examining 27 samples from five patients, in whom lamivudine resistance was known to have developed. This method is rapid, cost effective, and should prove useful for monitoring patients treated with lamivudine.

Liu WC, Mizokami M, Buti M, Lindh M, Young KC, Sun KT, Chi YC, Li HH, Chang TT. · Institute of Basic Medical Sciences, Department of Medicine, National Cheng Kung University, Tainan City 704, Taiwan, Republic of China, and Liver Unit, Hospital General Universitari Vall d'Hebron, Barcelona, Spain. · J Clin Microbiol. · Pubmed #17021067 links to  free full text

Abstract: Both the viral titer and the genotype significantly determine clinical outcomes and responses to antiviral treatment in chronic hepatitis B virus (HBV) infection. A method was developed for large-scale A-to-G genotyping with simultaneous viral quantification. The assay was run on a LightCycler instrument using hybridization probes. The genotype was determined from the melting points of the probes in a two-step manner. Set 1 amplicons differentiated genotypes B, E, and F from A, C, D, and G and simultaneously quantified viremia by real-time PCR. Melting curve analysis using the set 2-1 amplicon or the set 2-2 amplicon reaction mixture was then used to differentiate these genotype groups into single genotypes. HBV DNA quantification was consistent with that of the Amplicor assay and linear in a range from 10(2) to 10(13) copies/ml. By comparison with the restriction fragment length polymorphism method, 92.3% of 441 samples were accurately genotyped by the current assay. The method should be useful for genotyping and quantification of HBV DNA in areas where all genotypes exist.

Lindh M, Hannoun C, Malmström S, Lindberg J, Norkrans G. · Department of Clinical Virology, Göteborg University, Guldhedsgatan 10 B, 413 46 Göteborg, Sweden. · J Clin Microbiol. · Pubmed #16825388 links to  free full text

Abstract: The COBAS AMPLICOR hepatitis B virus assay targets a conserved region of the genome and is widely used to monitor treatment of hepatitis B in order to identify emerging resistance. However, the assay failed to recognize increasing viremia levels when YMDD mutations were paralleled by mutations in the segment targeted by the COBAS AMPLICOR probe.

Kullberg-Lindh C, Ascher H, Saalman R, Olausson M, Lindh M. · Department of Pediatrics, Queen Silvia Children's Hospital, Göteborg, Sweden. · Pediatr Transplant. · Pubmed #16499593 No free full text.

Abstract: Effective immunosuppression has improved the results following liver transplantation, but also increased the risk for opportunistic infections. Epstein-Barr virus (EBV) infection in transplant patients can cause various symptoms including the life-threatening premalignant condition, post-transplantation lymphoproliferative disorder (PTLD). Serum specimens from 24 consecutive children (mean 7.6 specimens/patient), who had undergone liver transplantation in Göteborg from January 1995 to May 2002, were analyzed retrospectively for EBV DNA by real-time TaqMan polymerase chain reaction (PCR). The results were related to clinical picture, immunosuppression, graft rejection and infections with other agents. Eleven patients (46%) developed primary EBV infection at a mean time of 4.8 months after transplantation, and six (25%) reactivated EBV infection at a mean of 4.0 months after transplantation. Four of the 11 patients with primary infection had symptomatic EBV infection: two had PTLD and two hepatitis. One patient in the group with reactivated infection developed PTLD. EBV DNA levels were significantly higher in the group with primary symptomatic infection compared with the patients with primary asymptomatic infection (mean 65 500 copies/mL; range 14 200-194 300 vs. 3700 copies/mL; range 100-9780). In patients with symptomatic infection EBV DNA levels did not differ between PTLD and hepatitis patients. The data suggest that quantitative analysis of EBV DNA in serum by real-time PCR is useful for identification of EBV-related disease.

Lindh M, Hannoun C. · Department of Clinical Virology, Guldhedsgatan 10 B, 413 46 Göteborg, Sweden. · J Clin Virol. · Pubmed #16157261 No free full text.

Abstract: BACKGROUND: Genotype of hepatitis C virus (HCV) is of major importance for the outcome of treatment. The response rate is considerably lower for genotype 1, the predominant genotype in western countries. OBJECTIVES: To develop and evaluate a new, simple method for genotyping of HCV based on real-time polymerase chain reaction (PCR) and Taqman probes targeting the 5' non-coding region. STUDY DESIGN: The method was compared with Innolipa on 220 serum samples representing genotypes 1-4, and was applied on a further 614 clinical samples. RESULTS: Taqman typing of the 220 samples showed genotype 1 in 69, genotype 2 in 58, genotype 3 in 57 and genotype 4 in 19, while 17 were non-reactive. There was a complete concordance with Innolipa with the exception of seven samples, which were of genotype 1 by Taqman, but genotype 4 by Innolipa. Sequencing of these samples showed a subtype 4 variant which differed at two positions compared with subtypes 4b/c/d, which are targeted by the probe. By adding a modified probe, these genotype 4 variants could also be identified. Out of 614 consecutive clinical samples, 524 could be typed by the Taqman assay; 45.2% were genotype 1, 19.3% genotype 2, 33.8% genotype 3 and 1.7%, genotype 4. CONCLUSION: The method was overall accurate and provides an attractive alternative for genotyping because processing time and costs are significantly reduced. Inclusion of probes targeting genotypes 5 and 6 is required for the method to be useful in areas where these genotypes are present.

Lindh M, Hannoun C. · Department of Clinical Virology, Göteborg University, Guldhedsgatan 10B, 413 46 Göteborg, Sweden. · J Clin Microbiol. · Pubmed #16081992 links to  free full text

Abstract: The Cobas Taqman assay for hepatitis B virus (HBV) DNA showed linear detection over 7 logs for genotypes A to D. The coefficient of variation was 1.2% at > or =1,000 IU/ml and 22.0% at 10 IU/ml. In 97 clinical samples, the log HBV DNA/ml differed by 0.11 between Cobas Amplicor and Cobas Taqman (r2 = 0.97).

Hannoun C, Söderström A, Norkrans G, Lindh M. · Department of Clinical Virology, Göteborg University, Guldhedsgatan 10B, 413 46 Göteborg, Sweden. · J Gen Virol. · Pubmed #16033963 links to  free full text

Abstract: Hepatitis B virus (HBV) is a major cause worldwide of liver disease, including hepatocellular carcinoma. There are eight known genotypes (A-H), of which genotype A has been divided into two subtypes: A2, prevalent in Europe, and A1, which is prevalent in sub-Saharan Africa, but also occurs in southern Asia. In this study, which includes 14 new complete genomes of non-European genotype A HBV, it was found that West African strains seem to constitute a new subgroup, A3. The high degree of genetic diversity within Africa indicates that genotype A originates from Africa. Based on a 2 % genetic distance between Asian and Somali sequences, it seems that the A1 subtype has spread from East Africa to southern Asia during the last 1000-2000 years. Moreover, it is proposed here that the A2 subtype originates from southern Africa and was imported to Europe around 500 years ago or later. The finding of T-1809/1812 close to the precore start codon and T-1862 and A-1888 in the precore region in HBV e antigen-positive children with signs of a mimimal immune response indicates that these substitutions are stable variants, rather than mutations emerging during infection in individual carriers.

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.

Thorén F, Romero A, Lindh M, Dahlgren C, Hellstrand K. · Department of Clinical Virology, Göteborg University, Guldhedsgatan 10b, S-413 46 Göteborg, Sweden. · J Leukoc Biol. · Pubmed #15371490 links to  free full text

Abstract: The persistent infection caused by hepatitis C virus (HCV) is presumably explained by a deficient immune response to the infection, but the basis for the inefficiency of immune-mediated virus eradication is not known in detail. This study addresses mechanisms of relevance to dysfunction of cytotoxic lymphocytes in HCV infection, with a focus on the role of phagocyte-derived oxygen radicals. We show that NS3, a nonstructural, HCV-encoded protein, induces a prolonged release of oxygen radicals from mononuclear and polymorphnuclear phagocytes by activating a key enzyme in radical formation, the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The NS3-activated phagocytes, in turn, induced dysfunction and/or apoptosis in three major subsets of lymphocytes of relevance to defense against HCV infection: CD3+/56- T cells, CD3-/56+ natural killer (NK) cells, and CD3+/56+ NKT cells. Two inhibitors of the NADPH oxidase, histamine and diphenylene iodonium, suppressed the NS3-induced oxygen radical production and efficiently protected lymphocytes against NS3-induced apoptosis and dysfunction. In conclusion, we propose that NS3, by triggering oxygen radical formation in phagocytes, may contribute to the dysfunction of antiviral lymphocytes in HCV-infected liver tissue and that strategies to circumvent oxidative stress may be useful in preventing HCV-associated carcinogenesis and facilitating lymphocyte-mediated clearance of infected cells.

Iwarson S, Lindh M, Widerström L. · Department of Infectious Diseases, Sahlgrenska University Hospital, Göteborg, Sweden. · J Travel Med. · Pubmed #15109480 No free full text.

This publication has no abstract.

Söderström A, Norkrans G, Lindh M. · Department of Infectious Diseases, Sahlgrenska University Hospital, Ostra, Göteborg, Sweden. · Scand J Infect Dis. · Pubmed #14723355 No free full text.

Abstract: Little is known about how pregnancy influences viremia levels in women with chronic hepatitis B virus infection. In this study, we first retrospectively analysed changes in HBV DNA levels during and after 55 pregnancies in HBsAg-positive women, of whom 9 were HBeAg-positive. Secondly, HBV DNA levels in 3 HBeAg-positive mothers whose babies became chronic HBV carriers, were compared with levels in 18 mothers whose babies were not infected by HBV. We found that HBV DNA ranged from 10(8.1) to 10(9.5) copies/mL in HBeAg-positive, and from undetectable (< 100) to 10(6.8) copies/mL in HBeAg-negative mothers. HBV DNA increased by a mean of 0.4 log late in pregnancy or early post partum; in 4 out of 16 HBeAg negative mothers by > 1 log during pregnancy. Post partum ALT increased in both HBeAg-positive and negative women. HBV DNA was 10(9.4)-10(10.4) copies/mL in 3 HBeAg-positive mothers whose babies were, as compared to < 100-10(10.4) copies/mL in 18 whose babies were not, vertically infected. Although the majority of HBeAg-negative women had low and relatively stable HBV DNA during pregnancy, viremia was also relatively high in some HBeAg-negative mothers, and both viremia and ALT increased significantly late in pregnancy or shortly after delivery. Vertical transmission was only seen in HBeAg-positive mothers with very high levels of viremia. The value of measuring HBV DNA in the pregnant woman to modify immunoprophylaxis to her infant needs further study.

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.

Söderström A, Norkrans G, Conradi N, Krantz M, Horal P, Lindh M. · Department of Infectious Diseases, Göteborg University, Sweden. · J Pediatr Gastroenterol Nutr. · Pubmed #12394372 No free full text.

Abstract: BACKGROUND: Despite high viral load, children with chronic hepatitis B virus (HBV) infection may lack significant biochemical signs of liver dysfunction. Failure to develop abnormal liver chemistriesis is probably due to immunologic hyporeactivity. Despite the absence of biochemical abnormalities in these patients, there is still a risk for long-term complications. The pathogenic importance of viral load and genetic variability is less well studied in children than in adults. METHODS: We evaluated viremia levels, genotypes, and mutations related to histologic evidence of liver damage in 71 HBV carriers, aged 2 to 18 years, all of non-Swedish origin. RESULTS: None of the of 22 children who were hepatitis B e antigen (HBeAg) negative had severe liver disease or had HBV DNA levels greater than 10 copies/mL (mean 10 ); 3 (14%) of them had increased alanine aminotransferase (ALT). The 49 HBeAg-positive children had a mean HBV DNA level of 10 copies/mL, and increased ALT was seen in 28 (55%). Core promoter mutations (at nt 1764) or precore mutations (at codon 1, 2, or 28) were rare; they were seen in four and one HBeAg-positive children, and in four and nine HBeAg-negative children, respectively, without association to liver damage. C-1858 was associated with more liver inflammation. Genotype did not significantly influence liver damage. Children with horizontal transmission had a faster rate of seroconversion and more inflammation of the liver. CONCLUSIONS: Severe HBeAg-negative hepatitis with high HBV DNA levels and mutations in the core promoter or precore regions seems to be less common in children than in adults. C-1858 strains may be more pathogenic, but this requires further study. Epidemiologic factors influence the course of infection.

Lagging LM, Aneman C, Nenonen N, Brandberg A, Grip L, Norkrans G, Lindh M. · Department of Infectious Diseases, Göteborg University, Sweden. · Scand J Infect Dis. · Pubmed #12238573 No free full text.

Abstract: Nosocomial spread of HCV and other blood-borne pathogens continues to occur in the Western world despite the screening of blood products. Using molecular and epidemiological methods we investigated an outbreak of HCV involving 3 patients following percutaneous coronary intervention at a Swedish hospital. The most likely mode of transmission was contamination of a multidose vial of saline used for the flushing of intravenous catheters. It may, therefore, be prudent to restrict the use of such vials, in addition to promoting vigorous adherence to standard hygiene procedures in order to prevent the recurrence of similar outbreaks in the future.

Hannoun C, Krogsgaard K, Horal P, Lindh M, Anonymous00190. · Department of Clinical Virology, Göteborg University, Göteborg, Sweden. · J Infect Dis. · Pubmed #12198608 No free full text.

Abstract: Little is known about coinfection among several hepatitis B virus (HBV) genotypes, although previous reports of recombination and genotype shifts indicate that this should occur. In the present study, we designed a method to identify mixtures of genotype A and another genotype, regardless of whether one of them predominates. Using this method, signs of genotypic coinfection were found in 20 (67%) of 30 hepatitis B e antigen-positive patients treated with interferon (IFN). In 8 of these patients, coinfection or genotype shifts were detectable by direct sequencing or standard preS genotyping. In most of these cases, genotype changes were detected after a >2-log decrease or increase of the HBV DNA level. The presence of genotype mixtures did not significantly influence IFN response. Because quasi-species selection may occur at or shortly after transmission, patients might acquire HBV infection from subjects who appear to be infected with a different genotype. This should be considered when tracing the source of HBV infection.

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.

Iwarson S, Lindh M, Widerström L. · Department of Clinical Virology, Institute of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. · Scand J Infect Dis. · Pubmed #11928839 No free full text.

Abstract: We studied the immune response of an inactivated hepatitis A vaccine (Havrix 1440) given to middle-aged travellers 4-6 y after a single, primary dose. Anti-HAV antibodies in serum were checked before and 28-35 d after the booster. All 25 vaccinees showed an impressive anamnestic booster response (geometric mean titres 32 and 2993 mIU/ml before and after the booster, respectively). The study confirms experimental data indicating that I dose of inactivated hepatitis A vaccine induces a long-term proliferative T-cell response in addition to producing anti-HAV antibody. As recall memory for this vaccine is elicited several years after a single dose there is probably no need for a second vaccine dose.