Hepatitis Research and Treatment http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. 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 Mon, 18 Apr 2016 14:18:45 +0000 http://www.hindawi.com/journals/heprt/2016/8325467/ 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. Fritz Klein, Ruth Neuhaus, Dennis Eurich, Jörg Hofmann, Sandra Bayraktar, Johann Pratschke, and Marcus Bahra Copyright © 2016 Fritz Klein et al. All rights reserved. A Novel Structurally Stable Multiepitope Protein for Detection of HCV Thu, 28 Jan 2016 14:33:27 +0000 http://www.hindawi.com/journals/heprt/2016/6592143/ 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. Alexsandro S. Galdino, José C. Santos, Marilen Q. Souza, Yanna K. M. Nóbrega, Mary-Ann E. Xavier, Maria S. S. Felipe, Sonia M. Freitas, and Fernando A. G. Torres Copyright © 2016 Alexsandro S. Galdino et al. All rights reserved. Seroprevalence and Predictors of Hepatitis B Virus Infection among Pregnant Women Attending Routine Antenatal Care in Arba Minch Hospital, South Ethiopia Sun, 24 Jan 2016 11:18:30 +0000 http://www.hindawi.com/journals/heprt/2016/9290163/ 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. Tsegaye Yohanes, Zerihun Zerdo, and Nega Chufamo Copyright © 2016 Tsegaye Yohanes et al. All rights reserved. Atherosclerosis as Extrahepatic Manifestation of Chronic Infection with Hepatitis C Virus Wed, 13 Jan 2016 13:17:28 +0000 http://www.hindawi.com/journals/heprt/2016/7629318/ 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. Theodoros Voulgaris and Vassilios A. Sevastianos Copyright © 2016 Theodoros Voulgaris and Vassilios A. Sevastianos. All rights reserved. Prevalence of Hepatitis E Virus among Adults in South-West of Iran Tue, 23 Jun 2015 05:49:40 +0000 http://www.hindawi.com/journals/heprt/2015/759589/ 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. Fatemeh Farshadpour, Reza Taherkhani, and Manoochehr Makvandi Copyright © 2015 Fatemeh Farshadpour et al. All rights reserved. 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 Thu, 22 Jan 2015 08:46:29 +0000 http://www.hindawi.com/journals/heprt/2015/439867/ 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. Olusegun Adekanle, Dennis A. Ndububa, Samuel Anu Olowookere, Oluwasegun Ijarotimi, and Kayode Thaddeus Ijadunola Copyright © 2015 Olusegun Adekanle et al. All rights reserved. Interleukin-16 Gene Polymorphisms Are Considerable Host Genetic Factors for Patients’ Susceptibility to Chronic Hepatitis B Infection Wed, 26 Nov 2014 12:49:50 +0000 http://www.hindawi.com/journals/heprt/2014/790753/ 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. Sara Romani, Seyed Masoud Hosseini, Seyed Reza Mohebbi, Shabnam Kazemian, Shaghayegh Derakhshani, Mahsa Khanyaghma, Pedram Azimzadeh, Afsaneh Sharifian, and Mohammad Reza Zali Copyright © 2014 Sara Romani et al. All rights reserved. Hepatitis B Awareness among Medical Students and Their Vaccination Status at Syrian Private University Wed, 12 Nov 2014 07:08:29 +0000 http://www.hindawi.com/journals/heprt/2014/131920/ 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. Nazir Ibrahim and Amr Idris Copyright © 2014 Nazir Ibrahim and Amr Idris. All rights reserved. Portraying Persons Who Inject Drugs Recently Infected with Hepatitis C Accessing Antiviral Treatment: A Cluster Analysis Wed, 01 Oct 2014 10:08:28 +0000 http://www.hindawi.com/journals/heprt/2014/631481/ 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. Jean-Marie Bamvita, Elise Roy, Geng Zang, Didier Jutras-Aswad, Andreea Adelina Artenie, Annie Levesque, and Julie Bruneau Copyright © 2014 Jean-Marie Bamvita et al. All rights reserved. High Dose of Lamivudine and Resistance in Patients with Chronic Hepatitis B Tue, 30 Sep 2014 07:02:39 +0000 http://www.hindawi.com/journals/heprt/2014/615621/ 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. Hamid Ullah Wani, Saad Al Kaabi, Manik Sharma, Rajvir Singh, Anil John, Moutaz Derbala, and Muneera J. Al-Mohannadi Copyright © 2014 Hamid Ullah Wani et al. All rights reserved. Prediction of Sustained Virological Response to Telaprevir-Based Triple Therapy Using Viral Response within 2 Weeks Sun, 28 Sep 2014 11:53:15 +0000 http://www.hindawi.com/journals/heprt/2014/748935/ 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. Hideyuki Tamai, Ryo Shimizu, Naoki Shingaki, Yoshiyuki Mori, Shuya Maeshima, Junya Nuta, Yoshimasa Maeda, Kosaku Moribata, Yosuke Muraki, Hisanobu Deguchi, Izumi Inoue, Takao Maekita, Mikitaka Iguchi, Jun Kato, and Masao Ichinose Copyright © 2014 Hideyuki Tamai et al. All rights reserved. Serum Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 (ITIH4) in Children with Chronic Hepatitis C: Relation to Liver Fibrosis and Viremia Sun, 14 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/heprt/2014/307942/ 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. Mostafa M. Sira, Behairy E. Behairy, Azza M. Abd-Elaziz, Sameh A. Abd Elnaby, and Ehab E. Eltahan Copyright © 2014 Mostafa M. Sira et al. All rights reserved. Seroepidemiology of Hepatitis B and C Viruses in the General Population of Burkina Faso Tue, 05 Aug 2014 05:51:43 +0000 http://www.hindawi.com/journals/heprt/2014/781843/ 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. Issoufou Tao, Tegwindé R. Compaoré, Birama Diarra, Florencia Djigma, Theodora M. Zohoncon, Maléki Assih, Djeneba Ouermi, Virginio Pietra, Simplice D. Karou, and Jacques Simpore Copyright © 2014 Issoufou Tao et al. All rights reserved. Spectrum of Histomorphologic Findings in Liver in Patients with SLE: A Review Mon, 21 Jul 2014 11:05:15 +0000 http://www.hindawi.com/journals/heprt/2014/562979/ 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. Shrruti Grover, Archana Rastogi, Jyotsna Singh, Apurba Rajbongshi, and Chhagan Bihari Copyright © 2014 Shrruti Grover et al. All rights reserved. Prevalence of Hepatitis C Virus Genotypes in District Bannu, Khyber Pakhtunkhwa, Pakistan Mon, 30 Jun 2014 07:28:12 +0000 http://www.hindawi.com/journals/heprt/2014/165826/ 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. Shamim Saleha, Anwar Kamal, Farman Ullah, Nasar Khan, Asif Mahmood, and Sanaullah Khan Copyright © 2014 Shamim Saleha et al. All rights reserved. MHC Class I Presented T Cell Epitopes as Potential Antigens for Therapeutic Vaccine against HBV Chronic Infection Mon, 26 May 2014 07:24:52 +0000 http://www.hindawi.com/journals/heprt/2014/860562/ 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. Joseph D. Comber, Aykan Karabudak, Vivekananda Shetty, James S. Testa, Xiaofang Huang, and Ramila Philip Copyright © 2014 Joseph D. Comber et al. All rights reserved. Histological and Clinical Characteristics of Patients with Chronic Hepatitis C and Persistently Normal Alanine Aminotransferase Levels Wed, 07 May 2014 00:00:00 +0000 http://www.hindawi.com/journals/heprt/2014/760943/ 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. Bakht Roshan and Grace Guzman Copyright © 2014 Bakht Roshan and Grace Guzman. All rights reserved. Transplacental Transfer of Hepatitis B Neutralizing Antibody during Pregnancy in an Animal Model: Implications for Newborn and Maternal Health Thu, 27 Mar 2014 11:25:09 +0000 http://www.hindawi.com/journals/heprt/2014/159206/ 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. Li Ma, Malgorzata G. Norton, Iftekhar Mahmood, Zhong Zhao, Lilin Zhong, Pei Zhang, and Evi B. Struble Copyright © 2014 Li Ma et al. All rights reserved. Prevalence and Seroincidence of Hepatitis B and Hepatitis C Infection in High Risk People Who Inject Drugs in China and Thailand Thu, 27 Mar 2014 07:16:14 +0000 http://www.hindawi.com/journals/heprt/2014/296958/ 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. J. Brooks Jackson, Liu Wei, Fu Liping, Apinun Aramrattana, David D. Celentano, Louise Walshe, Yi Xing, Paul Richardson, Ma Jun, Geetha Beauchamp, Deborah Donnell, Yuhua Ruan, Liying Ma, David Metzger, and Yiming Shao Copyright © 2014 J. Brooks Jackson et al. All rights reserved. Hepatitis B Vaccination and Screening Awareness in Primary Care Practitioners Thu, 06 Mar 2014 07:29:40 +0000 http://www.hindawi.com/journals/heprt/2014/373212/ 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. Adnan Said and Janice H. Jou Copyright © 2014 Adnan Said and Janice H. Jou. All rights reserved. Involvement of Differential Relationship between HCV Replication and Hepatic PRR Signaling Gene Expression in Responsiveness to IFN-Based Therapy Sun, 29 Dec 2013 16:00:55 +0000 http://www.hindawi.com/journals/heprt/2013/917261/ 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. Nobukazu Yuki, Shinji Matsumoto, Michio Kato, and Toshikazu Yamaguchi Copyright © 2013 Nobukazu Yuki et al. All rights reserved. Predictors of Health-Related Quality of Life in Outpatients with Cirrhosis: Results from a Prospective Cohort Sun, 22 Dec 2013 11:04:20 +0000 http://www.hindawi.com/journals/heprt/2013/479639/ 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 (<4 points) and mortality were analyzed using multivariable logistic regression. Results. In total, 92 patients were included (mean age 61 years, 59% male). Nineteen patients died (mean duration of follow-up 20 months). The mean Child-Pugh score was 6.9. Twenty percent had a poor HRQOL judged by the Chronic Liver Disease Questionnaire score and 45% had covert hepatic encephalopathy. The only predictors of poor HRQOL were the Child-Pugh score (), nonalcoholic etiology of cirrhosis (), and body mass index (). The body mass index predicted poor HRQOL independently of the presence of ascites and albumin level. Conclusions. The body mass index was associated with a low HRQOL. This suggests that malnutrition may be an important target in the management of patients with cirrhosis. Maja Thiele, Gro Askgaard, Hans B. Timm, Ole Hamberg, and Lise L. Gluud Copyright © 2013 Maja Thiele et al. All rights reserved. Transforming Growth Factor-β1 Gene Polymorphism (T29C) in Egyptian Patients with Hepatitis B Virus Infection: A Preliminary Study Wed, 18 Dec 2013 09:34:51 +0000 http://www.hindawi.com/journals/heprt/2013/293274/ 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. Roba M. Talaat, Mahmoud F. Dondeti, Soha Z. El-Shenawy, and Omaima A. Khamiss Copyright © 2013 Roba M. Talaat et al. All rights reserved. Circulating Cytokines and Histological Liver Damage in Chronic Hepatitis B Infection Thu, 31 Oct 2013 09:17:22 +0000 http://www.hindawi.com/journals/heprt/2013/757246/ 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. Kittiyod Poovorawan, Pisit Tangkijvanich, Chintana Chirathaworn, Naruemon Wisedopas, Sombat Treeprasertsuk, Piyawat Komolmit, and Yong Poovorawan Copyright © 2013 Kittiyod Poovorawan et al. All rights reserved. Parvovirus B19 Associated Hepatitis Tue, 22 Oct 2013 15:09:59 +0000 http://www.hindawi.com/journals/heprt/2013/472027/ 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. Chhagan Bihari, Archana Rastogi, Priyanka Saxena, Devraj Rangegowda, Ashok Chowdhury, Nalini Gupta, and Shiv Kumar Sarin Copyright © 2013 Chhagan Bihari et al. All rights reserved. Measuring the Response of Extrahepatic Symptoms and Quality of Life to Antiviral Treatment in Patients with Hepatitis C Mon, 07 Oct 2013 17:16:53 +0000 http://www.hindawi.com/journals/heprt/2013/910519/ 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. David Isaacs, Nader Abdelaziz, Majella Keller, Jeremy Tibble, and Inam Haq Copyright © 2013 David Isaacs et al. All rights reserved. Elevation in Serum Concentration of Bone-Specific Alkaline Phosphatase without Elevation in Serum Creatinine Concentration Secondary to Adefovir Dipivoxil Therapy in Chronic Hepatitis B Virus Infection Mon, 09 Sep 2013 18:03:11 +0000 http://www.hindawi.com/journals/heprt/2013/739247/ Of 168 patients with chronic hepatitis B virus (HBV) infection-related liver disease, 20 patients who had received 100 mg of lamivudine plus 10 mg/day of adefovir dipivoxil (ADV) (ADV group) and 124 patients who had received 0.5 mg/day of entecavir or 100 mg/day of lamivudine (non-ADV group) for >1 year were enrolled. For comparative analyses, 19 well-matched pairs were obtained from the groups by propensity scores. At the time of enrollment, serum creatinine and phosphate concentrations were similar between the ADV and non-ADV groups; however, urinary phosphate () and serum bone-specific alkaline phosphatase (BAP) () concentrations were significantly higher in the ADV group than in the non-ADV group. Serum BAP was significantly higher at the time of enrollment than before ADV administration in the ADV group (), although there was no significant change in serum BAP concentration in the non-ADV group. There was a significant positive correlation between the period of ADV therapy and ΔBAP (, ). Serum BAP concentration increased before increase in serum creatinine concentration and was useful for early detection of adverse events and for developing adequate measures for continuing ADV for chronic HBV infection-related liver disease. Hiroshi Abe, Nobuyoshi Seki, Tomonori Sugita, Yuta Aida, Haruya Ishiguro, Tamihiro Miyazaki, Munenori Itagaki, Satoshi Sutoh, and Yoshio Aizawa Copyright © 2013 Hiroshi Abe et al. All rights reserved. Tryptophan-Kynurenine Metabolism and Insulin Resistance in Hepatitis C Patients Wed, 04 Sep 2013 14:13:36 +0000 http://www.hindawi.com/journals/heprt/2013/149247/ Chronic hepatitis C virus (HCV) infection is associated with 50% incidence of insulin resistance (IR) that is fourfold higher than that in non-HCV population. IR impairs the outcome of antiviral treatment. The molecular mechanisms of IR in HCV are not entirely clear. Experimental and clinical data suggested that hepatitis C virus per se is diabetogenic. However, presence of HCV alone does not affect IR. It was proposed that IR is mediated by proinflammatory cytokines, mainly by TNF-alpha. TNF-alpha potentiates interferon-gamma-induced transcriptional activation of indoleamine 2,3-dioxygenase, the rate-limiting enzyme of tryptophan- (TRP-) kynurenine (KYN) metabolism. Upregulation of TRP-KYN metabolism was reported in HCV patients. KYN and some of its derivatives affect insulin signaling pathways. We hypothesized that upregulation of TRP-KYN metabolism might contribute to the development of IR in HCV. To check this suggestion, we evaluated serum concentrations of TRP and KYN and HOMA-IR and HOMA-beta in 60 chronic HCV patients considered for the treatment with IFN-alpha. KYN and TRP concentrations correlated with HOMA-IR and HOMA-beta scores. Our data suggest the involvement of KYN and its metabolites in the development of IR in HCV patients. TRP-KYN metabolism might be a new target for prevention and treatment of IR in HCV patients. G. F. Oxenkrug, W. A. Turski, W. Zgrajka, J. V. Weinstock, and P. Summergrad Copyright © 2013 G. F. Oxenkrug et al. All rights reserved. Interferon-α-Induced Changes to Natural Killer Cells Are Associated with the Treatment Outcomes in Patients with HCV Infections Tue, 13 Aug 2013 08:34:28 +0000 http://www.hindawi.com/journals/heprt/2013/374196/ Aim. We analyzed the pretreatment natural killer (NK) cell functions with the aim of predicting the sustained virological response (SVR) or the interleukin (IL) 28B polymorphism that is strongly associated with the treatment response. Methods. The peripheral NK cells from chronic hepatitis patients with HCV genotype 1 and high virus titers were activated using a Toll-like receptor (TLR) 4 ligand and IFN-α. The cell surface markers were evaluated using a flow cytometric analysis, and IFN-γ production was evaluated using an enzyme-linked immunosorbent assay (ELISA). The genotyping of the polymorphisms in the IL28B gene region (rs8099917) on chromosome 19 was performed on the DNA collected from each patient. Results. The production of IFN-γ was significantly higher in the SVR patients compared with the no-response (NR) patients, whereas the cell surface markers were similar between the SVR and the NR patients. There were no significant differences found in the IL28B genotype distribution associated with the production of IFN-γ. Conclusion. Differences in the NK cell functions were observed between the SVR patients and the NR patients, suggesting that NK cells play a potential role in the treatment response independent of the IL28B genotype. Shinji Shimoda, Kosuke Sumida, Sho Iwasaka, Satomi Hisamoto, Hironori Tanimoto, Hideyuki Nomura, Kazufumi Dohmen, Kazuhiro Takahashi, Akira Kawano, Eiichi Ogawa, Norihiro Furusyo, Koichi Akashi, and Jun Hayashi Copyright © 2013 Shinji Shimoda et al. All rights reserved. Evaluation of the Significance of Pretreatment Liver Biopsy and Baseline Mental Health Disorder Diagnosis on Hepatitis C Treatment Completion Rates at a Veterans Affairs Medical Center Thu, 16 May 2013 12:26:49 +0000 http://www.hindawi.com/journals/heprt/2013/653976/ Objectives. This study was performed to define the overall treatment response rates and treatment completion rates among the population of Hepatitis C infected patients at an urban VA Medical Center. Additionally, we examined whether pretreatment liver biopsy is a positive predictor for treatment completion and if the presence of mental health disorders is a negative predictor for treatment completion. Methods. Retrospective chart review was performed on the 375 patients that were treated for HCV and met the study inclusion parameters between January 1, 2003 and April 1, 2008 at our institution. Clinical data was obtained from the computerized patient record system and was analyzed for respective parameters. Results. Sustained virological response was achieved in 116 (31%) patients. 169 (45%) patients completed a full treatment course. Also, 44% of patients who received a pre-treatment liver biopsy completed treatment versus 46% completion rates for patients who did not receive a pretreatment liver biopsy. Baseline ICD9 diagnosis of a mental health disorder was not associated with higher treatment discontinuation rates. Conclusions. In conclusion, pretreatment liver biopsy was not a positive predictor for treatment completion, and the presence of mental health disorders was not a negative predictor for treatment completion. Joseph Kluck, Rose M. O’Flynn, David E. Kaplan, and Kyong-Mi Chang Copyright © 2013 Joseph Kluck et al. All rights reserved.