Hepatitis Research and Treatment
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Open Access journal
ISSN (Print) 2090-1364 - ISSN (Online) 2090-1372
Published by Hindawi [334 journals]
- Add-on Pegylated Interferon Alpha-2a Therapy in Chronic Hepatitis B
Japanese Patients Treated with Entecavir
Abstract: Entecavir requires long-term administration. Pegylated interferon (PEG-IFN) therapy leads to significant reduction of hepatitis B surface antigen (HBs Ag) levels. This study aimed to assess the safety and efficacy of adding PEG-IFN-α-2a to entecavir toward cessation of entecavir. A total of 23 patients treated with entecavir underwent add-on PEG-IFN-α-2a therapy (90 μg per week) for 48 weeks. Viral response (VR) was defined as more than 50% reduction of baseline hepatitis B surface antigen (HBs Ag) level at 72 weeks from the start of therapy. Complete response (CR) was defined as the decline of HBs Ag levels
PubDate: Tue, 11 Apr 2017 00:00:00 +000
- Prevalence of Hepatitis B Virus Infection among Pregnant Women Attending
Antenatal Clinics in Vientiane, Laos, 2008–2014
Abstract: The Lao People’s Democratic Republic (PDR) is still considered a highly endemic country for hepatitis B, mainly due to perinatal transmission of hepatitis B virus (HBV), despite efforts made since 2004 for universal immunization of newborns. The prevalence of HBV surface antigen (HBsAg) carriage in pregnant women is a relevant marker for the risk of mother-to-child HBV transmission. This study aimed to assess the changes in prevalence of HBV infection among pregnant women attending the Mahosot Prenatal Clinic (Vientiane Capital). Methods. A retrospective study was performed in the Mahosot Hospital Laboratory to collect and analyze all the results of HBsAg testing in pregnant women from 2008 to 2014. Results. Of a total of 13,238 tested women of mean age of 26 years, 720 women (5,44% [95 CI: 5.1–5.8%]) were found HBsAg positive, the annual prevalence ranging from 4.6% to 6.2%. A slight but steady and significant decrease in prevalence over the 7 years of the study could be documented. Conclusion. Although below the 8% hyperendemic threshold, the HBsAg prevalence observed in pregnant women in Vientiane reflects a high risk of HBV perinatal transmission and call for a widespread infant immunization with an HBV vaccine birth dose.
PubDate: Wed, 29 Mar 2017 08:18:16 +000
- Assessment of Immunization to Hepatitis B Vaccine among Children under
Five Years in Rural Areas of Taiz, Yemen
Abstract: Background. Hepatitis B virus (HBV) infection poses a major health problem worldwide. approximately 1 million deaths annually due to cirrhosis and hepatocellular carcinoma. Objectives. This study was conducted to determine the coverage rate of HBV vaccine and assess the vaccine protective response among children under five years old in rural areas of Yemen. Methods. A cross-sectional study was conducted from January to December 2015 in four districts of countryside Yemen. The target population was children aged from 6 to 59 months. 227 children were enrolled in the study. Questionnaire was used to collect of data. Serum samples were tested for anti-HBs antibodies by enzyme linked immunosorbent assay (ELISA). Anti-HBs level ≥ 10 IU/L was considered a protective response to the vaccine. Results. The coverage rate of HBV vaccine among children was 87.3%. A total of 143 (72.2%) children responded to the vaccine with anti-HBs level ≥ 10 IU/L, while 55 (27.8%) of the children had nonprotective anti-HBs levels of
PubDate: Mon, 06 Mar 2017 10:54:38 +000
- Combinations of siRNAs against La Autoantigen with NS5B or hVAP-A Have
Additive Effect on Inhibition of HCV Replication
Abstract: Hepatitis C virus is major cause of chronic liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Presently available direct-acting antiviral drugs have improved success rate; however, high cost limits their utilization, especially in developing countries like India. In the present study, we evaluated anti-HCV potential of several siRNAs targeted against the HCV RNA-dependent RNA polymerase NS5B and cellular factors, La autoantigen, PSMA7, and human VAMP-associated protein to intercept different steps of viral life cycle. The target genes were downregulated individually as well as in combinations and their impact on viral replication was evaluated. Individual downregulation of La autoantigen, PSMA7, hVAP-A, and NS5B resulted in inhibition of HCV replication by about 67.2%, 50.7%, 39%, and 52%, respectively. However, antiviral effect was more pronounced when multiple genes were downregulated simultaneously. Combinations of siRNAs against La autoantigen with NS5B or hVAP-A resulted in greater inhibition in HCV replication. Our findings indicate that siRNA is a potential therapeutic tool for inhibiting HCV replication and simultaneously targeting multiple viral steps with the combination of siRNAs is more effective than silencing a single target.
PubDate: Wed, 29 Jun 2016 15:15:07 +000
- Two-Year Follow-Up Analysis of Telaprevir-Based Antiviral Triple Therapy
for HCV Recurrence in Genotype 1 Infected Liver Graft Recipients as a
First Step towards Modern HCV Therapy
Abstract: Objective. The introduction of protease inhibitors telaprevir and boceprevir in 2011 had extended the antiviral treatment options especially in genotype 1 infected hepatitis C relapsers and nonresponders to interferon/ribavirin therapy. The aim of this study was to analyze the long-term treatment efficiency of telaprevir-based triple therapy for patients with hepatitis C reinfection after orthotopic liver transplantation. Patients and Methods. We included 12 patients with histologically confirmed graft fibrosis due to hepatitis C reinfection. The treatment duration was scheduled as 12 weeks of telaprevir-based antiviral triple therapy followed by 36 weeks of dual therapy with pegylated interferon/ribavirin. The patients were followed up for two years after the end of triple therapy. Results. Of the 12 patients, 6 (50%) completed the full 48 weeks of antiviral treatment. An end of treatment response and a sustained virological response 52 weeks after the end of the antiviral treatment course were achieved in 8/12 (67%) and 7/12 (58%) patients, respectively. Conclusion. Telaprevir-based triple therapy was shown to be a long-term effective but complex treatment option for individual patients with hepatitis C graft. With the recent improvements in hepatitis C therapy options telaprevir may not be recommended as a standard therapy for this indication anymore.
PubDate: Mon, 18 Apr 2016 14:18:45 +000
- A Novel Structurally Stable Multiepitope Protein for Detection of HCV
Abstract: Hepatitis C virus (HCV) has emerged as the major pathogen of liver diseases in recent years leading to worldwide blood-transmitted chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Accurate diagnosis for differentiation of hepatitis C from other viruses is thus of pivotal importance for proper treatment. In this work we developed a recombinant multiepitope protein (rMEHCV) for hepatitis C diagnostic purposes based on conserved and immunodominant epitopes from core, NS3, NS4A, NS4B, and NS5 regions of the virus polyprotein of genotypes 1a, 1b, and 3a, the most prevalent genotypes in South America (especially in Brazil). A synthetic gene was designed to encode eight epitopes in tandem separated by a flexible linker and bearing a his-tag at the C-terminal end. The recombinant protein was produced in Escherichia coli and purified in a single affinity chromatographic step with >95% purity. Purified rMEHCV was used to perform an ELISA which showed that the recombinant protein was recognized by IgG and IgM from human serum samples. The structural data obtained by circular dichroism (CD) spectroscopy showed that rMEHCV is a highly thermal stable protein at neutral and alkaline conditions. Together, these results show that rMEHCV should be considered an alternative antigen for hepatitis C diagnosis.
PubDate: Thu, 28 Jan 2016 14:33:27 +000
- Seroprevalence and Predictors of Hepatitis B Virus Infection among
Pregnant Women Attending Routine Antenatal Care in Arba Minch Hospital,
Abstract: Hepatitis B virus (HBV) is a serious cause of liver disease affecting millions of people throughout the world. When HBV is acquired during pregnancy, prenatal transmission can occur to the fetus. Therefore, this study is aimed at estimating seroprevalence and associated factors of HBV infection among pregnant women attending Antenatal Clinic (ANC) of Arba Minch Hospital, Southern Ethiopia. A facility based cross-sectional study was conducted on 232 pregnant women visiting ANC from February to April, 2015. Data regarding sociodemographic and associated factors were gathered using questionnaire. Serum samples were tested for hepatitis B surface antigen (HBsAg) by Enzyme Linked Immunosorbent Assay. Data was analyzed using SPSS version 20. The overall seroprevalence of HBV infection was 4.3% (95% CI: 2.2–6.9%). Multivariate analysis showed that history of abortion (AOR = 7.775; 95% CI: 1.538–39.301) and having multiple sexual partners (AOR = 7.189; 95% CI: 1.039–49.755) were independent predictors of HBsAg seropositivity. In conclusion, the prevalence of HBV infection is intermediate. Therefore, screening HBV infection should be routine part of ANC; health information on having single sexual partner for women of childbearing age and on following aseptic techniques during abortion should be provided to health facilities working on abortion.
PubDate: Sun, 24 Jan 2016 11:18:30 +000
- Atherosclerosis as Extrahepatic Manifestation of Chronic Infection with
Hepatitis C Virus
Abstract: Chronic hepatitis C virus infection is associated with significant morbidity and mortality, as a result of progression towards advanced natural course stages including cirrhosis and hepatocellular carcinoma. On the other hand, the SVR following successful therapy is generally associated with resolution of liver disease in patients without cirrhosis. Patients with cirrhosis remain at risk of life-threatening complications despite the fact that hepatic fibrosis may regress and the risk of complications such as hepatic failure and portal hypertension is reduced. Furthermore, recent data suggest that the risk of HCC and all-cause mortality is significantly reduced, but not eliminated, in cirrhotic patients who clear HCV compared to untreated patients and nonsustained virological responders. Data derived from studies have demonstrated a strong link between HCV infection and the atherogenic process. Subsequently HCV seems to represent a strong, independent risk factor for coronary heart disease, carotid atherosclerosis, stroke, and, ultimately, CVD related mortality. The advent of new direct acting antiviral therapy has dramatically increased the sustained virological response rates of hepatitis C infection. In this scenario, the cardiovascular risk has emerged and represents a major concern after the eradication of the virus which may influence the life expectancy and the quality of patients’ life.
PubDate: Wed, 13 Jan 2016 13:17:28 +000
- Prevalence of Hepatitis E Virus among Adults in South-West of Iran
Abstract: Background. Knowledge regarding prevalence of HEV in general population can be an indicator of the public health and hygiene. Therefore, this study was conducted to evaluate the prevalence of HEV among adults in South-West of Iran. Methods. Blood samples were taken from 510 participants, 206 (40.4%) males and 304 (59.6%) females from February to July 2014. Detection of anti-HEV IgG and IgM antibodies was carried out by ELISA test. Results. The overall anti-HEV IgG and IgM prevalence rates were 46.1% and 1.4%, respectively. Anti-HEV IgG and IgM seropositivity were not statistically associated with gender and race/ethnicity. Meanwhile, there were significant differences between the age groups regarding HEV IgG and IgM seropositivity. HEV IgG seroprevalence increased with age from 14.3% in subjects aged 18–30 years to 71.4% in persons over 71 years old, and considerably individuals aged 61 to 70 years had the highest HEV prevalence (90.9%). Also, 5.7% in the age group 18–30 years and 2.2% in the age group 31–40 years were positive for anti-HEV IgM antibodies and the highest rate was observed in subjects aged 18–30 years. Conclusion. In conclusion, high HEV IgG seroprevalence of 46.1% was observed among adults in South-West of Iran.
PubDate: Tue, 23 Jun 2015 05:49:40 +000
- Knowledge of Hepatitis B Virus Infection, Immunization with Hepatitis B
Vaccine, Risk Perception, and Challenges to Control Hepatitis among
Hospital Workers in a Nigerian Tertiary Hospital
Abstract: Background. Studies had reported high rate of hepatitis B infection among hospital workers with low participation in vaccination programmes, especially those whose work exposes them to the risk of HBV infection. The study assessed knowledge of hepatitis B virus infection, risk perception, vaccination history, and challenges to control hepatitis among health workers. Methods. A descriptive cross-sectional study. Consenting health care workers completed a self-administered questionnaire that assessed respondents’ general knowledge of HBV, vaccination history and HBsAg status, risk perception, and challenges to control hepatitis. Data was analysed using descriptive and inferential statistics. Results. Three hundred and eighty-two health care workers participated in the study. There were 182 males and 200 females. The respondents comprised 94 (25%) medical doctors, 168 (44%) nurses, 68 (18%) medical laboratory technologists, and 52 (14%) pharmacists. Over 33% had poor knowledge with 35% not immunized against HBV. Predictors of good knowledge include age less than 35 years, male sex, being a medical doctor, previous HBsAg test, and complete HBV immunisation. Identified challenges to control hepatitis include lack of hospital policy (91.6%), poor orientation of newly employed health workers (75.9%), and low risk perception (74.6%). Conclusion. Hospital policy issues and low risk perception of HBV transmission have grave implications for the control of HBV infection.
PubDate: Thu, 22 Jan 2015 08:46:29 +000
- Interleukin-16 Gene Polymorphisms Are Considerable Host Genetic Factors
for Patients’ Susceptibility to Chronic Hepatitis B Infection
Abstract: Host genetic background is known as an important factor in patients’ susceptibility to infectious diseases such as viral hepatitis. The aim of this study was to determine the effect of genetic polymorphisms of interleukin-16 (IL-16) cytokine on susceptibility of hepatitis B virus (HBV) infected patients to develop chronic HBV infection. Genotyping was conducted using PCR followed by enzymatic digestion and RFLP (restriction fragment length polymorphism) analysis. We genotyped three single nucleotide polymorphisms (SNPs) in the Il-16 gene (rs11556218 T>G, rs4778889 T>C, and rs4072111 C>T) to test for relationship between variation at these loci and patients’ susceptibility to chronic HBV infection. Allele frequency of Il-16 gene rs4072111 and rs11556218 was significantly different between chronic HBV patients and healthy blood donors. Genotype frequency of rs4778889 polymorphism of Il-16 gene was significantly different when chronic HBV patients and HBV clearance subjects were compared. Our results showed that Il-16 gene polymorphisms are considerable host genetic factors when we chase biomarkers for prognosis of HBV infected patients.
PubDate: Wed, 26 Nov 2014 12:49:50 +000
- Hepatitis B Awareness among Medical Students and Their Vaccination Status
at Syrian Private University
Abstract: Background. Hepatitis B virus (HBV) is a potentially life-threating infection and a well-recognized occupational hazard for health-care workers including medical students. Methods. A cross-sectional study was conducted at Syrian Private University (SPU), Faculty of Medicine, to assess the knowledge and awareness about hepatitis B, the status of hepatitis B vaccination, and the reasons for not getting vaccinated among the first- and the fifth-year medical students. Results. The present study demonstrates surprising results and raises issues about the high number of medical students that are not vaccinated or not sure about their vaccination status, which puts them at a higher risk of being infected in the future. Another important issue is the medical students’ overall knowledge about this life-threating infection. The students have not been totally educated about the gravity of the situation which requires the need of further HBV education. It is highly recommended that SPU provides the HBV vaccine to all nonvaccinated students attending the faculty of medicine at no cost to encourage them to take the HBV vaccine and to reform some of its educational curriculum to effectively limit the hazardous effects of this disease and elaborate on the serious health consequences of HBV.
PubDate: Wed, 12 Nov 2014 07:08:29 +000
- Portraying Persons Who Inject Drugs Recently Infected with Hepatitis C
Accessing Antiviral Treatment: A Cluster Analysis
Abstract: Objectives. To empirically determine a categorization of people who inject drug (PWIDs) recently infected with hepatitis C virus (HCV), in order to identify profiles most likely associated with early HCV treatment uptake. Methods. The study population was composed of HIV-negative PWIDs with a documented recent HCV infection. Eligibility criteria included being 18 years old or over, and having injected drugs in the previous 6 months preceding the estimated date of HCV exposure. Participant classification was carried out using a TwoStep cluster analysis. Results. From September 2007 to December 2011, 76 participants were included in the study. 60 participants were eligible for HCV treatment. Twenty-one participants initiated HCV treatment. The cluster analysis yielded 4 classes: class 1: Lukewarm health seekers dismissing HCV treatment offer; class 2: multisubstance users willing to shake off the hell; class 3: PWIDs unlinked to health service use; class 4: health seeker PWIDs willing to reverse the fate. Conclusion. Profiles generated by our analysis suggest that prior health care utilization, a key element for treatment uptake, differs between older and younger PWIDs. Such profiles could inform the development of targeted strategies to improve health outcomes and reduce HCV infection among PWIDs.
PubDate: Wed, 01 Oct 2014 10:08:28 +000
- High Dose of Lamivudine and Resistance in Patients with Chronic Hepatitis
Abstract: Background. Lamivudine is the most affordable drug used for chronic hepatitis B and has a high safety profile. With the daily dose of 100 mg there is progressive appearance of resistance to lamivudine therapy. In our study we used 150 mg of lamivudine daily as a standard dose which warrants further exploration for the efficacy of the drug. Aims of the Study. To assess the efficacy of lamivudine 150 mg daily on resistance in patients with chronic hepatitis B. Methods. This retrospective study consists of 53 patients with chronic hepatitis B treated with 150 mg of lamivudine daily. The biochemical and virological response to the treatment were recorded at a 1-year and 2-, 3-, 4-, and 5-year period and time of emergence of resistance to the treatment was noted. Results. The mean age of the patients was 54 years with 80% being males. The resistance to lamivudine 150 mg daily at 1 year and 2, 3, and 5 years was 12.5%, 22.5%, 37.5%, and 60%, respectively, which is much less compared to the standard dose of 100 mg of lamivudine. Conclusions. Lamivudine is safe and a higher dose of 150 mg daily delays the resistance in patients with chronic hepatitis B.
PubDate: Tue, 30 Sep 2014 07:02:39 +000
- Prediction of Sustained Virological Response to Telaprevir-Based Triple
Therapy Using Viral Response within 2 Weeks
Abstract: The aim of the present study was to predict sustained virological response (SVR) to telaprevir with pegylated interferon (PEG-IFN) and ribavirin using viral response within 2 weeks after therapy initiation. Thirty-six patients with genotype 1 hepatitis C virus (HCV) and high viral load were treated by telaprevir-based triple therapy. SVR was achieved in 72% (26/36) of patients. Significant differences between the SVR group and non-SVR group were noted regarding response to prior PEG-IFN plus ribavirin, interleukin (IL)28B polymorphism, amino acid substitution at core 70, cirrhosis, hyaluronic acid level, and HCV-RNA reduction within 2 weeks. Setting 4.56 logIU/mL as the cut-off value for HCV-RNA reduction at 2 weeks, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 77%, 86%, 95%, 50%, and 79%, respectively, and for neither the IL28B minor allele nor core 70 mutant were 80%, 71%, 91%, 50%, and 78%, respectively. In conclusion, evaluation of viral reduction at 2 weeks or the combination of IL28B polymorphism and amino acid substitution at core 70 are useful for predicting SVR to telaprevir with PEG-IFN and ribavirin therapy.
PubDate: Sun, 28 Sep 2014 11:53:15 +000
- Serum Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 (ITIH4) in Children with
Chronic Hepatitis C: Relation to Liver Fibrosis and Viremia
Abstract: Liver fibrosis and viremia are determinant factors for the treatment policy and its outcome in chronic hepatitis C virus (HCV) infection. We aimed to investigate serum level of inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and its relation to liver fibrosis and viremia in children with chronic HCV. ITIH4 was measured by ELISA in 33 treatment-naive children with proved chronic HCV and compared according to different clinical, laboratory and histopathological parameters. Liver histopathological changes were assessed using Ishak score and compared with aspartate transaminase-to-platelet ratio (APRI) and FIB-4 indices as simple noninvasive markers of fibrosis. ITIH4 was measured in a group of 30 age- and sex-matched healthy controls. ITIH4 was significantly higher in patients than in controls ( pg/mL versus pg/mL; ). ITIH4, but not APRI or FIB-4, had a significant direct correlation with fibrosis stage (, 0.961, and 0.389, resp.), whereas, the negative correlation of ITIH4 with HCV viremia was of marginal significance (). In conclusion, ITIH4 significantly correlated with higher stages of fibrosis indicating a possible relation to liver fibrogenesis. The trend of higher ITIH4 with lower viremia points out a potential antiviral properties and further studies in this regard are worthwhile.
PubDate: Sun, 14 Sep 2014 00:00:00 +000
- Seroepidemiology of Hepatitis B and C Viruses in the General Population of
Abstract: Objectives. In Burkina Faso, few studies reported the prevalence of HBV and HCV in the general population. This study aimed to evaluate the prevalence of hepatitis B and C viruses in the general population and to determine the most affected groups in relation to the risk factors associated with the infection. Method. A voluntary testing opened to anyone interested was held at Saint Camille Medical Centre in Ouagadougou. Rapid tests were carried out on 995 persons who voluntarily answered a range of questions before the venous blood sampling. Results. The results revealed that the antigen HBs carriers in the general population represented 14.47% (144/995) and the prevalence of HCV was 1.00% (10/995). The difference between HBV’s prevalence in men (18.58%) and that in women (11.60%) was statistically significant . The most affected groups were undergraduated students (19.57%) and persons working in the informal sector (15.98%). The least affected group was high level students (8.82%). Conclusion. Burkina Faso is a country with a high prevalence of HBV, while the incidence of HCV is still low in the general population. Therefore, more campaigns on the transmission routes of HBV and HCV are needed to reduce the spread of these viruses in sub-Saharan Africa.
PubDate: Tue, 05 Aug 2014 05:51:43 +000
- Spectrum of Histomorphologic Findings in Liver in Patients with SLE: A
Abstract: Collagen vascular diseases (CVDs) like systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjogren syndrome (SS), and scleroderma are immunologically mediated disorders that typically have multisystem involvement. Although clinically significant liver involvement is rare, liver enzyme abnormalities are common in these patients. The reported prevalence of hepatic involvement in SLE, histopathologic findings, and its significance is very variable in the existing literature. It is important to be familiar with the causes of hepatic involvement in SLE along with histomorphological features which aid in distinguishing hepatitis of SLE from other hepatic causes as they would alter the patient management and disease course. Histopathology of liver in SLE shows a wide morphological spectrum commonly due to a coexisting pathology. Drug induced hepatitis, viral etiology, and autoimmune overlap should be excluded before attributing the changes to SLE itself. Common histopathologic findings in SLE include fatty liver, portal inflammation, and vascular changes like hemangioma, congestion, nodular regenerative hyperplasia, arteritis, and abnormal vessels in portal tracts.
PubDate: Mon, 21 Jul 2014 11:05:15 +000
- Prevalence of Hepatitis C Virus Genotypes in District Bannu, Khyber
Abstract: Determination of an individual’s hepatitis C virus (HCV) genotypes prior to antiviral therapy has become increasingly important for the clinical management and prognosis of HCV infection. Therefore, this study was conducted to investigate the prevalence of HCV genotypes in HCV infected patients of district Bannu in Khyber Pakhtunkhwa region of Pakistan. Serum samples of 117 seropositive patients were screened for HCV-RNA by using reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) and then PCR positive samples were subjected to HCV genotyping. Out of 117 seropositive samples, 110 samples were found positive by PCR analysis. Genotype 3a was the most prevalent one detected in 38% of patients, followed by genotype 3b in 21% of patients, and then genotype 2a in 12% of patients. However 21% of HCV-PCR positive samples could not be genotyped by method used in this study. Genotype 3a was the most prevalent genotype in patients of all age groups and its prevalence was found high among patients with increasing age (>34 years). Moreover, genotypes 3a and 3b were found to be the most prevalent genotypes in patients with history of shaving by barbers, receiving multiple injections, and dental procedures. In conclusion there is need of further investigation of genotypes of HCV by using more sensitive assays and considering large sample size in district Bannu.
PubDate: Mon, 30 Jun 2014 07:28:12 +000
- MHC Class I Presented T Cell Epitopes as Potential Antigens for
Therapeutic Vaccine against HBV Chronic Infection
Abstract: Approximately 370 million people worldwide are chronically infected with hepatitis B virus (HBV). Despite the success of the prophylactic HBV vaccine, no therapeutic vaccine or other immunotherapy modality is available for treatment of chronically infected individuals. Clearance of HBV depends on robust, sustained CD8+ T activity; however, the limited numbers of therapeutic vaccines tested have not induced such a response. Most of these vaccines have relied on peptide prediction algorithms to identify MHC-I epitopes or characterization of T cell responses during acute infection. Here, we took an immunoproteomic approach to characterize MHC-I restricted epitopes from cells chronically infected with HBV and therefore more likely to represent the true targets of CD8+ T cells during chronic infection. In this study, we identified eight novel MHC-I restricted epitopes derived from a broad range of HBV proteins that were capable of activating CD8+ T cells. Furthermore, five of the eight epitopes were able to bind HLA-A2 and A24 alleles and activated HBV specific T cell responses. These epitopes also have potential as new tools to characterize T cell immunity in chronic HBV infection and may serve as candidate antigens for a therapeutic vaccine against HBV infection.
PubDate: Mon, 26 May 2014 07:24:52 +000
- Histological and Clinical Characteristics of Patients with Chronic
Hepatitis C and Persistently Normal Alanine Aminotransferase Levels
Abstract: Patients with chronic hepatitis C virus (HCV) infection and persistently normal alanine aminotransferase (PNALT) are generally described to have mild liver disease. The aim of this study was to compare clinical and histological features in HCV-infected patients with PNALT and elevated ALT. Patients presenting to the University of Illinois Medical Center, Chicago, who had biopsy proven HCV, an ALT measurement at the time of liver biopsy, at least one additional ALT measurement over the next 12 months, and liver biopsy slides available for review were identified. PNALT was defined as ALT ≤ 30 on at least 2 different occasions over 12 months. Of 1200 patients with HCV, 243 met the study criteria. 13% (32/243) of patients had PNALT while 87% (211/243) had elevated ALT. Significantly more patients with PNALT had advanced fibrosis (F3 and F4) compared to those with elevated ALT (). There was no significant difference in the histology activity index score as well as mean inflammatory score between the two groups. In conclusion, in a well-characterized cohort of patients at a tertiary medical center, PNALT did not distinguish patients with mild liver disease.
PubDate: Wed, 07 May 2014 00:00:00 +000
- Transplacental Transfer of Hepatitis B Neutralizing Antibody during
Pregnancy in an Animal Model: Implications for Newborn and Maternal Health
Abstract: Despite the success of postexposure prophylaxis (PEP) of the newborn in preventing mother-to-child transmission of hepatitis B virus), in non-US clinical trials, administering hepatitis B immune globulin (HBIG) to mothers at the end of pregnancy (in addition to passive-active PEP of the newborn) only partially improved outcomes. That is, a significant percentage of newborns became infected during their first year of life. We used a relevant animal model for human IgG transplacental transfer to study dose, time and subclass dependence of HBV neutralizing antibody (nAb) maternal, and fetal levels at the end of pregnancy. Pregnant guinea pigs received 50 or 100 IU/kg HBIGIV 2–5 days before delivery. Human total IgG, IgG subclasses, and nAb in mothers and their litters were measured. In vitro analyses of guinea pig Fc neonatal receptor binding to HBIGIV, as well as to all human IgG subclasses, were also performed. Our study showed that nAb transferred transplacentally from the pregnant guinea pigs to their litters; no transfer occurred during parturition. The amount of the transferred nAb was dose and time dependent. Thus, selection of an efficacious dose in the clinic is important: microdosing may be underdosing, particularly in cases of high viraemia.
PubDate: Thu, 27 Mar 2014 11:25:09 +000
- Prevalence and Seroincidence of Hepatitis B and Hepatitis C Infection in
High Risk People Who Inject Drugs in China and Thailand
Abstract: We determined the prevalence and incidence of HBV and HCV infection in people who inject drugs (PWIDs) at high risk for HIV in China and Thailand and determined the association of HBV and HCV incidence with urine opiate test results and with short-term versus long-term buprenorphine-naloxone (B-N) treatment use in a randomized clinical trial (HPTN 058). 13.8% of 1049 PWIDs in China and 13.9% of 201 PWIDs in Thailand were HBsAg positive at baseline. Among HBsAg negative participants, the HBsAg incidence rate was 2.7/100 person years in China and 0/100 person years in Thailand. 81.9% of 1049 PWIDs in China and 59.7% of 201 in Thailand were HCV antibody positive at baseline. The HCV confirmed seroincidence rate among HCV antibody negative PWIDs was 22/100 person years in China and 4.6/100 person years in Thailand. Incident HBsAg was not significantly different in the short-term versus long-term B-N arm in China or Thailand. Participants with positive opiate results in at least 75% of their urines during the time period were at increased risk of incident HBsAg (HR = 5.22; 95% CI, 1.08 to 25.22; ) in China, but not incident HCV conversion in China or Thailand.
PubDate: Thu, 27 Mar 2014 07:16:14 +000
- Hepatitis B Vaccination and Screening Awareness in Primary Care
Abstract: Introduction. The goals of Healthy People US 2020 have called for increased screening and vaccination of high-risk groups for Hepatitis B (HBV). Methods. We performed a survey of 400 randomly chosen primary care practitioners (PCPs) in Wisconsin to assess their knowledge, attitudes, and practices regarding screening and vaccination for HBV. Results. Screening rates of patients at risk of sexual transmission were low, with 61% of respondents stating that they screen patients who had more than 1 sex partner in 6 months and 86% screening patients with a history of sex with prostitutes. Screening rate for persons with a history of intravenous drug use was 94%. Children of immigrants were screened by 65%, persons on hemodialysis by 73%, and prison inmates by 69%. Screening increased with provider experience with HBV. Deficiencies in vaccination rates mirrored screening practices. Major barriers to screening were cost, someone else’s responsibility, time constraints, or lack of knowledge. Conclusions. Without improved education and practices of PCPs about HBV screening and vaccination, the goals of healthy people 2020 regarding HBV will not be met. Barriers to screening and vaccination need to be addressed. Cost-effectiveness of alternative strategies such as universal vaccination under the age of 50 should be explored.
PubDate: Thu, 06 Mar 2014 07:29:40 +000
- Involvement of Differential Relationship between HCV Replication and
Hepatic PRR Signaling Gene Expression in Responsiveness to IFN-Based
Abstract: Aim. To gain an insight into the effect of HCV replication-associated interference with the IFN system on hepatic mRNA expression involved in IFN production. Methods. Relative mRNA expression of TLR3/RIG-I signaling genes involved in IFN-β production was correlated with positive- and negative-strand HCV RNAs in pretreatment liver tissues responsive and nonresponsive to peginterferon and ribavirin for chronic hepatitis C genotype 1. Treatment response was analyzed for per protocol population at weeks 12 () and 24 () and at 24 weeks aftertreatment (). Results. HCV replication had no relation to the expression of TLR3, RIG-I, TRIF, IPS-1, IRF3, and IFN-β mRNAs in responders. In striking contrast, positive- and/or negative-strand HCV showed positive correlations with TLR3, RIG-I, TRIF, IPS-1, and IRF3 mRNAs in week-12 nonresponders; with RIG-I, TRIF, IPS-1, and IRF3 mRNAs in week-24 nonresponders; and with TLR3, RIG-I, and IRF3 mRNAs in posttreatment nonresponders. Thus mRNA expression of TLR3/RIG-I signaling genes was increased in relation to viral replication in nonresponders. Conclusions. The findings in IFN nonresponders may imply a host feedback response to severe impairment of the IFN system associated with HCV replication.
PubDate: Sun, 29 Dec 2013 16:00:55 +000
- Predictors of Health-Related Quality of Life in Outpatients with
Cirrhosis: Results from a Prospective Cohort
Abstract: Background. Cirrhosis may lead to a poor health-related quality of life (HRQOL), which should be taken into consideration when addressing the cirrhotic outpatient. Methods. Prospective cohort study evaluating predictors of HRQOL in outpatients with cirrhosis. Patients with overt hepatic encephalopathy at baseline were excluded. HRQOL was evaluated at baseline using the six point Chronic Liver Disease Questionnaire. Predictors of low quality of life scores (
PubDate: Sun, 22 Dec 2013 11:04:20 +000
- Transforming Growth Factor-β1 Gene Polymorphism (T29C) in Egyptian
Patients with Hepatitis B Virus Infection: A Preliminary Study
Abstract: The interindividual variations in the capacity of transforming growth factor-β1 (TGF-β1) production have been ascribed to genetic polymorphisms in TGF-β1 gene. As pathogenesis of HBV has a genetic background, this preliminary study was designed to assess the impact of TGF-β1 (T29C) on the susceptibility of Egyptians to HBV infection. Genotyping was performed using single stranded polymorphism-polymerase chain reaction (SSP-PCR) in 65 Egyptian hepatitis B patients and 50 healthy controls. TGF-β1 plasma levels were measured using Enzyme-linked immunosorbent assay (ELISA). The frequency of CC genotype was significantly higher () in HBV patients compared to controls. On the contrary, TC genotype did not show significant difference in both groups. TT genotype was significantly higher () in controls than HBV patients. Our current preliminary data revealed that the frequency of the genotypes in the controls were within Hardy-Weinberg equilibrium (HWE) while the patients group was out of HWE (). TGF-β1 was significantly (; ) deceased in the sera of patients as compared to normal subjects. Depending on our preliminary work, CC genotype may act as a host genetic factor in the susceptibility to HBV infection in Egyptians. Taken together, the current data pointed to the importance of polymorphism of TGF-β1 gene (T29C) in HBV infection.
PubDate: Wed, 18 Dec 2013 09:34:51 +000
- Circulating Cytokines and Histological Liver Damage in Chronic Hepatitis B
Abstract: Each phase of hepatitis B infection stimulates distinct viral kinetics and host immune responses resulting in liver damage and hepatic fibrosis. Our objective has been to correlate host inflammatory immune response including circulating Th1 and Th2 cytokines in patients with chronic hepatitis B infection with liver histopathology. Sixty-four patients with chronic hepatitis B without previous treatment were recruited. The liver histology and histological activity index were assessed for various degrees of necroinflammation and hepatic fibrosis. We determined circulating levels of the Th1 and Th2 cytokines. Forty-six males and 18 females at a median age of 34.5 years were studied. HBeAg was present in 28/64 (43.75%) of the patients. In patients negative for HBeAg, IL-10 and IFN-gamma were significantly correlated with degrees of necroinflammation (, , resp.; ). Moreover, TNF-alpha was significantly correlated with degrees of fibrosis (; ), and IL-10 and TNF-alpha were significantly correlated with significant fibrosis (, , resp.; ). These correlations were found in the HBeAg negative group as opposed to the HBeAg positive group. In HBeAg negative patients, circulating cytokines IL-10 and IFN-gamma were correlated with degrees of necroinflammation, whereas IL-10 and TNF-alpha were correlated with significant fibrosis.
PubDate: Thu, 31 Oct 2013 09:17:22 +000
- Parvovirus B19 Associated Hepatitis
Abstract: Parvovirus B19 infection can present with myriads of clinical diseases and syndromes; liver manifestations and hepatitis are examples of them. Parvovirus B19 hepatitis associated aplastic anemia and its coinfection with other hepatotropic viruses are relatively underrecognized, and there is sufficient evidence in the literature suggesting that B19 infections can cause a spectrum of liver diseases from elevation of transaminases to acute hepatitis to fulminant liver failure and even chronic hepatitis. It can also cause fatal macrophage activation syndrome and fibrosing cholestatic hepatitis. Parvovirus B19 is an erythrovirus that can only be replicate in pronormoblasts and hepatocytes, and other cells which have globosides and glycosphingolipids in their membrane can also be affected by direct virus injury due to nonstructural protein 1 persistence and indirectly by immune mediated injury. The virus infection is suspected in bone marrow aspiration in cases with sudden drop of hemoglobin and onset of transient aplastic anemia in immunosuppressed or immunocompetent patients and is confirmed either by IgM and IgG positive serology, PCR analysis, and in situ hybridization in biopsy specimens or by application of both. There is no specific treatment for parvovirus B19 related liver diseases, but triple therapy regimen may be effective consisting of immunoglobulin, dehydrohydrocortisone, and cyclosporine.
PubDate: Tue, 22 Oct 2013 15:09:59 +000
- Measuring the Response of Extrahepatic Symptoms and Quality of Life to
Antiviral Treatment in Patients with Hepatitis C
Abstract: Background. HCV infection is associated with musculoskeletal manifestations such as chronic widespread pain, sicca syndrome, polyarthritis, and a reduced HRQOL. Little data is available on the effect of treatment on these manifestations. This study measured changes in extrahepatic symptoms and HRQOL before and after antiviral treatment in a large UK patient cohort. Methods. 118 patients completed HQLQ and rheumatological questionnaires before and after treatment with pegylated interferon-α and ribavirin, with specific regard to chronic widespread pain, sicca syndrome, and sustained virological response. Results. There was significant improvement in HQLQ domains of physical functioning, physical disability, social functioning, limitations and health distress due to hepatitis, and general health. There was significant deterioration in domains of positive well-being, health distress, and mental health. There was a significant decline prevalence of CWP (26.3% versus 15.3%, ). Sicca syndrome prevalence fell insignificantly (12.7% versus 11%). SVR was associated positively with all HRQOL changes and significantly with CWP remission. Conclusions. HCV antivirals significantly improve poor HRQOL scores and CWP. Before treatment, both were common, coassociated, and unaccounted for through mixed cryoglobulinemia alone. Although a role of the hepatitis C virus in CWP cannot be deduced by these results, symptomatic improvement via antiviral treatment exists for this subset of patients.
PubDate: Mon, 07 Oct 2013 17:16:53 +000