PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (663)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
1.  Duct-to-Duct Biliary Anastomosis Yields Similar Outcomes to Roux-en-Y Hepaticojejunostomy in Liver Transplantation for Primary Sclerosing Cholangitis 
Hepatitis Monthly  2015;15(5):e18811.
Background:
While Roux-en-Y hepaticojejunostomy (RYH) is the common anastomotic technique for liver transplantation (LT) in patients with primary sclerosing cholangitis (PSC), duct-to-duct (DD) reconstruction may be used if the recipient common bile duct is normal. There are conflicting observational data on the rate of success of DD reconstruction versus RYH, in PSC.
Objectives:
The aim of this study was to assess the safety and efficacy of DD anastomosis, compared to RYH reconstruction, among adults transplanted for PSC.
Patients and Methods:
All adult patients, who underwent primary LT for PSC between 1990 and 2012, were evaluated, according to type of biliary reconstruction. Recipient and graft survival, postoperative medical and surgical complications, and postoperative resource utilization rates were compared between the two groups.
Results:
Totally, 73 patients fulfilled the inclusion criteria. Of them, 58 had RYH and 15 had DD reconstruction. A total of 53 subjects (73%) were male, with the mean age ± standard deviation at LT of 43.3 ± 14.4 years. Rates of recipient mortality, graft failure, biliary complications, acute cellular rejection, and reoperation were similar in both groups. Postoperative cholangiography was used more frequently in patients with DD reconstruction (33.3% vs. 8.6%, P = 0.026).
Conclusions:
In selected recipients with PSC, DD reconstruction is a safe and efficacious technique, with long-term clinical outcomes comparable to RYH.
doi:10.5812/hepatmon.15(5)2015.18811
PMCID: PMC4451269  PMID: 26045700
Primary Sclerosing Cholangitis; Liver Transplantation; Roux-en-Y Anastomosis
2.  Efficacy of Tenofovir Disoproxil Fumarate Therapy in Nucleoside-Analogue Naive Iranian Patients Treated for Chronic Hepatitis B 
Hepatitis Monthly  2015;15(5):e25749.
Background:
Tenofovir disoproxil fumarate (TDF) is a new effective treatment option for patients with chronic hepatitis B (CHB).
Objectives:
To evaluate TDF efficacy in nucleos(t)ide analogues (NAs)-naive Iranian patients with CHB.
Patients and Methods:
The NA-naive patients received TDF for at least six months. The primary endpoint was the proportion of patients achieving a complete virological response (CVR) during the treatment. Multivariate Cox regression analysis determined predictive factors independently associated with the time to CVR. The secondary endpoints were biochemical and serological responses, frequency of virological breakthrough, genotypic resistance development, safety and tolerability.
Results:
In all, 93 patients (64.5% hepatitis B e antigen [HBeAg]-negative) were eligible. Of these, 70 patients completed 24 months of treatment. The cumulative CVR rates in HBeAg-negative and HBeAg-positive patients were 87% versus 53% at 24 months, respectively. The multivariate Cox regression model showed only HBeAg positivity at baseline and a high baseline HBV DNA level were independent factors predicting a CVR. No patient achieved hepatitis B surface antigen (HBsAg) and HBeAg loss or seroconversion and no virologic breakthrough occurred. A new amino acid substitution (rtD263E) was observed to develop in 60% of patients with viremia.
Conclusions:
The cumulative CVR rates showed that patients with HBeAg-negative have better virologic respond than those with HBeAg-positive during the same period. The rtD263E mutation might be associated with partial resistance to TDF.
doi:10.5812/hepatmon.15(5)2015.25749
PMCID: PMC4451271  PMID: 26045705
Chronic Hepatitis B; Tenofovir; nucleoside analogue
3.  Clinical Values of Elevated Serum Cytokeratin-18 Levels in Hepatitis: A Meta-Analysis 
Hepatitis Monthly  2015;15(5):e25328.
Background:
As an important intermediate filament protein within liver cells, cytokeratin-18 (CK-18) has been confirmed as a potential indicator in various hepatitis progressions.
Objectives:
We sought to clarify the connection between serum CK-18 levels and hepatitis pathogenesis in the present meta-analysis.
Materials and Methods:
With the application of various computerized databases, including PubMed, Embase, Cochrane Library, Google Scholar, Web of Science, China BioMedicine (CBM), China National Knowledge Infrastructure (CNKI), published papers that assessed the relationship between serum CK-18 levels and hepatitis were obtained. The main key words used are “Hepatitis”, “hepatitides”, “Cytokeratin-18”, “Keratin-18” and “CK-18”. Statistical analysis was conducted using the STATA software (version 12.0).
Results:
Eight case-control studies published between 2010 and 2014 were confirmed eligible, according to our selection criteria. The results of the meta-analysis showed that serum levels of CK-18 in hepatitis patients were higher compared to healthy controls (standardized mean difference (SMD) = 3.71, 95%CI: 2.27-5.14, P < 0.001). Subgroup analysis by ethnicity and disease implicated that high serum CK-18 levels might be a risk factor for non-alcoholic steatohepatitis (NASH), chronic hepatitis C (CHC), and chronic hepatitis B (CHB) (all P < 0.05) among Asians (SMD = 2.89, 95%CI: 2.35-3.43, P < 0.001), Africans (SMD = 0.69, 95%CI: 0.12-1.26, P = 0.017), and Caucasians (SMD = 4.86, 95%CI: 1.82-7.89, P = 0.002).
Conclusions:
Serum CK-18 levels in hepatitis patients were higher, compared with healthy controls. Our results revealed the clinical values of CK-18, in combination with other apoptosis markers, in identifying the development of hepatitis.
doi:10.5812/hepatmon.15(5)2015.25328
PMCID: PMC4451272  PMID: 26045704
Cytokeratin-18; Fatty Liver; Hepatitis; Meta-Analysis
4.  Knowledge, Attitude, and Behavior of Hepatitis B Virus Infection Among Chinese Dental Interns 
Hepatitis Monthly  2015;15(5):e25079.
Background:
Blood is frequently involved in dental treatment procedures, which increases the exposure of dentists to a variety of blood-borne pathogens and microorganisms such as Hepatitis B Virus.
Objectives:
The current study aimed to assess Chinese dental and medical interns’ knowledge, attitude and behavior (KAB) towards Hepatitis B Virus (HBV) infection and to evaluate which exact KAB phase respondents were involved in.
Patients and Methods:
A self-administered questionnaire survey was conducted on 313 fifth to eighth year students. Descriptive statistics and bivariate analyses were used to identify correlations between KAB and the results obtained from different grades.
Results:
Despite the fact that Chinese dental interns had good general knowledge level, they lacked the experience with active and artificial immunities against HBV. Graduates forgot basic knowledge and applied the methods without understanding the terms. Compared with the medical interns, dental interns were less willing to treat patients with HBV infection. All three required vaccination doses were received by a significant number of dental interns. However the frequency of antibody titer status check and the use of eye wear or face mask were not satisfying.
Conclusions:
It is therefore recommended that Chinese dental interns continue improving knowledge level, assume more positive attitude by accumulating clinical experience, and pay more attention to the overlooked procedures. The results of the current study can help the Chinese dental interns on theoretical studies and clinical practices regarding HBV.
doi:10.5812/hepatmon.15(5)2015.25079
PMCID: PMC4451273  PMID: 26045703
Hepatitis B; Knowledge; Attitudes; Behaviors; China
5.  LRRFIP1 Inhibits Hepatitis C Virus Replication by Inducing Type I Interferon in Hepatocytes 
Hepatitis Monthly  2015;15(5):e28473.
Background:
Hepatitis C virus infection is one of the leading causes of end stage liver diseases. The innate immune response slows down viral replication by activating cytokines such as type I interferon (IFN-α/β), which trigger the synthesis of antiviral proteins and modulate the adaptive immune system. Recently, leucine-rich repeat (in Flightless I) interacting protein-1 (LRRFIP1) was reported contributing to the production of interferon-β in macrophages.
Objectives:
The aim of this study was to assess the role of LRRFIP1 in induction of IFN-β and inhibition of HCV infection in hepatocytes.
Materials and Methods:
Induction of IFN-β by LRRFIP1 in Huh7 and Huh7.5.1 was determined by real-time PCR and western blotting in vitro. Inhibition of HCV replication by LRRFIP1 overexpression in hepatocytes was assessed.
Results:
LRRFIP1 increased the expression of IFN-β in hepatocytes with or without HCV infection. Induction of IFN-β by LRRFIP1 was enhanced with the presence of hepatitis C virus. Overexpression of LRRFIP1 in hepatocytes inhibited HCV replication. However, HCV infection did not regulate intracellular expression of LRRFIP1.
Conclusions:
LRRFIP1 and its mediated production of type I interferon play a role in controlling HCV infection. The findings of this study provide new target for HCV treatment and contribute to development of anti-HCV drugs.
doi:10.5812/hepatmon.15(5)2015.28473
PMCID: PMC4451274  PMID: 26045710
LRRFIP1 Protein, Human; Hepacivirus; Interferon Type I
6.  Are Platelets Count Useful for Detecting the Grade of Steatosis? 
Hepatitis Monthly  2015;15(5):e28957.
doi:10.5812/hepatmon.15(5)2015.28957
PMCID: PMC4451275  PMID: 26045711
Blood Platelets; Fibrosis; Fatty Liver
7.  Molecular Mechanisms for Alcoholic Hepatitis Based on Analysis of Gene Expression Profile 
Hepatitis Monthly  2015;15(5):e27336.
Background:
Alcoholic hepatitis (AH) is an acute manifestation of alcoholic liver disease with high mortality rates.
Objectives:
Our aim was to study the molecular mechanisms of AH.
Materials and Methods:
The differentially expressed genes (DEGs) in liver between AH and control cases were identified by analyzing the GSE28619 microarray data using t-test. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) enrichment analyses were performed using DAVID online tool. The protein-protein interaction (PPI) network was constructed using Search Tool for the Retrieval of Interacting Genes (STRING) and the subnetwork was identified by BioNet. Both PPI network and subnetwork were visualized using the Cytoscape software.
Results:
Total 908 DEGs (551 up- and 357 down-regulated DEGs) were obtained. The up-regulated DEGs were significantly enriched in 15 pathways and 112 GO biological processes. The down-regulated DEGs were significantly enriched in 22 pathways and 84 GO biological processes. The PPI network with 608 nodes and 2878 interactions was constructed and the subnetwork with 53 nodes and 131 interactions was also identified. The hub DEGs (TSPO, PPIB, NME1 and NME2) were extracted in this subnetwork.
Conclusions:
TSPO might contribute to the liver damage and AH progression induced by mitochondrial dysfunction through oxidative stress of liver. TSPO interacted with PPIB might play important roles in liver damage in AH. The interaction between NME1 and NME2 might contribute to the transformation from AH to hepatocellular carcinoma.
doi:10.5812/hepatmon.15(5)2015.27336
PMCID: PMC4451276  PMID: 26045708
Protein-Protein Interaction Map; Alcoholic Hepatitis; Disease
8.  A Comprehensive Long-Term Prognosis of Chronic Hepatitis C Patients With Antiviral Therapy: A Meta-Analysis of Studies From 2008 to 2014 
Hepatitis Monthly  2015;15(5):e27181.
Context:
Attaining a sustained virological response with antiviral therapy is a sign of clinical cure for chronic hepatitis C patients. The aim of this meta-analysis was to evaluate the long-term efficiency and outcome of antiviral therapy in patients with hepatitis C who attained a sustained virological response.
Evidence Acquisition:
A literature search was performed on published articles between January 2008 and February 2014. Patients with Hepatitis C who received interferon with or without ribavirin therapy were enrolled. Relative risks were estimated using either fixed or random effect models.
Results:
Patients who attained sustained virological response had a less risk (85%) for all-cause mortality and about 63% reduced risk of hepatocellular carcinoma incidence than those who did not achieve sustained virological response. Based on deeply analysis, the stage of liver fibrosis was a risk factor at baseline for the incidence of hepatocellular carcinoma.
Conclusions:
Sustained virological response can reduce all-cause mortality and the incidence of hepatocellular carcinoma of patients with hepatitis C. Advanced liver fibrosis is still a risk factor for the incidence of hepatocellular carcinoma, in spite of hepatitis C patients attained a sustained virological response.
doi:10.5812/hepatmon.15(5)2015.27181
PMCID: PMC4451277  PMID: 26045707
Chronic Hepatitis C; Meta-Analysis; Antiviral Therapy
9.  Saturated Fatty Acid Inhibits Viral Replication in Chronic Hepatitis B Virus Infection With Nonalcoholic Fatty Liver Disease by Toll-Like Receptor 4-Mediated Innate Immune Response 
Hepatitis Monthly  2015;15(5):e27909.
Background:
Chronic Hepatitis B (CHB) infection is common in patients with Non-Alcoholic Fatty Liver Disease (NAFLD). The replication level of Hepatitis B Virus (HBV) was inversely correlated with hepatic steatosis. Toll-Like Receptor (TLR) 4-mediated innate immunity plays a pivotal role in the occurrence of NAFLD and controls HBV replication.
Objectives:
This study aimed to investigate whether the TLR4-mediated innate immunity stimulates the pathogenesis of CHB in patients with NAFLD and to determine whether TLR4 plays a role in inhibiting HBV replication.
Materials and Methods:
The HBV transgenic mice were randomized into the HBV and HBV/NAFLD groups. HepG2.2.15 cells were treated with different concentrations (0 – 200 μM) of Stearic Acid (SA) to induce steatosis. The total RNA of the liver tissue was extracted for Real-Time Polymerase Chain Reaction (RT-PCR) detection, and immunohistochemistry or western blot was conducted for further validation. The Enzyme-Linked Immunosorbent Assay (ELISA) analysis was applied to evaluate the production of Interleukin 6 (IL-6), Tumor necrosis factor α (TNF-α) and Interferon β (IFN-β). Moreover, viral dynamics were analyzed using HBV DNA and HBV-related antigens (HBsAg and HBeAg).
Results:
Non-alcoholic fatty liver disease was induced in HBV-transgenic mice fed with High Fat Diet (HFD) for 8 - 24 weeks. Oil red-O staining positive droplets and the content of Triglyceride (TG) were increased in HepG2.2.15 cells treated with SA. TLR4, Myeloid differentiation factor 88 (MyD88), IL-6 and TNF-α expression levels were significantly higher in the HBV/NAFLD group and the steatotic HepG2.2.15 cells than those in their respective controls. Compared to the HBV group, significant reductions in serum levels of HBsAg, HBeAg, and HBV DNA titers occurred in the HBV/NAFLD group at 24 weeks, but the IFN-β level was remarkably increased. Similar data were also obtained from the steatoric HepG2.2.15 cells.
Conclusions:
Saturated Fatty Acids (SFAs) served as a potential ligand for TLR4 and activated TLR4 signaling pathway, which might be involved in the pathogenesis. Thus, SFAs can accelerate the mechanism of inhibiting HBV replication in CHB with NAFLD.
doi:10.5812/hepatmon.15(5)2015.27909
PMCID: PMC4451278  PMID: 26045709
Diet, High-Fat; Stearic Acid; Toll-like receptor 4; Hepatitis B Virus; Nonalcoholic Fatty Liver Disease
10.  Seroprevalence of Hepatitis E Among Hemodialysis Patients: A Report From Hamadan, Iran 
Hepatitis Monthly  2015;15(5):e26260.
Background:
Previous studies have documented a high prevalence of hepatitis E among patients undergoing maintenance hemodialysis. Available studies reporting on the seroprevalence of hepatitis E in hemodialysis patients in Iran, an endemic region for the disease, are sparse.
Objectives:
The present study aimed to determine the prevalence rate of anti-hepatitis E antibody in hemodialysis patients in Hamadan, Iran.
Patients and Methods:
In this cross-sectional study, all 153 consecutive patients undergoing hemodialysis in two centers were enrolled. Patients’ demographic and clinical data were collected, using a standard questionnaire and from medical records. Serum immunoglobulin G concentrations against hepatitis E were determined using the enzyme linked immunosorbent assay method.
Results:
Thirty patients (19.2%), were seropositive. Seropositive patients were not significantly different from seronegative patients, with regard to age, sex, level of education, access to filtered water, and duration and frequency of hemodialysis. The proportions of patients with hepatitis B, C, and HIV infection were comparable between the two groups.
Conclusions:
One in five patients undergoing maintenance dialysis in Hamadan is seropositive for hepatitis E immunoglobulin G antibody. Future studies are needed to investigate the factors contributing to the observed high prevalence rate and the possibility of parenteral transmission of hepatitis E.
doi:10.5812/hepatmon.15(5)2015.26260
PMCID: PMC4451279  PMID: 26045706
Hepatitis E; Seroprevalence; Immunoglobulin; Renal Dialysis
11.  Distribution and Epidemiologic Trends of HBV Genotypes and Subtypes in 14 Countries Neighboring China 
Hepatitis Monthly  2015;15(5):e24422.
Background:
The number of cases of HBV infection reported by the WHO for each district and country is positively correlated with the number of HBV sequences in the database isolated from the corresponding district and country.
Objectives:
This study determined distribution characteristics of HBV genotypes and subtypes in 14 countries neighboring China. The progress made in genomic research involving HBV was also reviewed.
Materials and Methods:
Nine hundred fifty-one complete genome sequences of HBV from 14 countries neighboring China were selected from NCBI. The sequence-related information was analyzed and recorded. One hundred seventy-two sequences of HBV genotype B were screened for alignment using DNA star and MEGA 5.1.
Results:
Dominant HBV genotypes in the countries neighboring China were genotypes B, C and D and dominant subtypes were adw2 and adrq+. The association between genotype and serotype of HBV in these countries was shown to differ from previous research results. As shown by sequence alignment, the sequence divergence between five subgenotypes (B3, B5, B7, B8 and B9) was below 4%. The B subgenotypes shared six common specific amino acid sites in the S region.
Conclusions:
The B3, B5, B7, B8 and B9 subgenotypes can be clustered into quasi-sub-genotype B3 and the open reading frame of HBV has a start codon preference; however, whether a mutation in the start codon in the pre-S2 region has an impact on survival and replication of HBV remains to be determined.
doi:10.5812/hepatmon.15(5)2015.24422
PMCID: PMC4451280  PMID: 26045702
Serotype; Epidemiology; Genomics
12.  Dichlorvos Induced Autoimmune Hepatitis: A Case Report and Review of Literature 
Hepatitis Monthly  2015;15(4):e25469.
Introduction:
Drug-induced liver injury is a frequent cause of hepatic dysfunction. Several drugs have been identified to cause autoimmune hepatitis (AIH). Environmental chemicals are capable of triggering a certain degree of liver injury. However, toxin induced AIH is rare.
Case Presentation:
We reported a woman with chronic (long-term) exposures to dichlorvos, which resulted in liver injury and cirrhosis. She was diagnosed after a second liver biopsy, which was correlated with laboratory findings. At the same time, she experienced hepatic cortical blindness during her first admission.
Conclusions:
Chronic (long-term) exposures to dichlorvos can lead to AIH. A detailed inquiry of medical history and liver biopsy are necessary for the diagnosis of toxin-induced AIH. Corticosteroid therapy is associated with favorable evolution.
doi:10.5812/hepatmon.25469
PMCID: PMC4449892  PMID: 26034503
Dichlorvos; Autoimmune Hepatitis; Drug-Induced Liver Injury
13.  Distribution and Predominance of Genotype 3 in Hepatitis C Virus Carriers in the Province of Kahramanmaras, Turkey 
Hepatitis Monthly  2015;15(4):e25142.
Background:
The hepatitis C virus (HCV) has six major genotypes and more than 100 subtypes, and the determination of the responsible genotype, collection of epidemiological data, tailoring antiviral therapy, and prediction of prognosis have an important place in disease management.
Objectives:
The aim of the present study was to determine the distribution of HCV genotypes across geographic regions and compare these data with those obtained from other geographic locations.
Patients and Methods:
The HCV genotypes were identified in HCV RNA positive blood samples, obtained from different centers. The HCV genotype was determined using molecular methods [Real-Time Polymerase Chain Reaction (RT-PCR)] in 313 patients, who were found to be positive for HCV RNA. The presence of HCV RNA was investigated using the RT-PCR method in serum samples delivered to the Microbiology Laboratory at Kahramanmaras Necip Fazıl City Hospital, Kahramanmaras, Turkey, from the centers located in Kahramanmaras City center and peripheral districts of the province, between March 2010 and August 2014. The HCV genotype analysis was performed in HCV RNA positive samples, using RT-PCR reagents kit. Urine samples from the patients were tested for amphetamine with an Amphetamines II (AMPS2) kit, cocaine was tested with a Cocaine II (COC2) kit, opiates were tested with an Opiates II (OPI2) kit, and cannabinoids were tested with a Cannabinoids II (THC2) kit in Roche/Hitachi Cobas c501 device.
Results:
The blood samples collected from 313 patients were included in the study. Of these patients, 212 (67.7%) were male and 101 (32.3%) were female. The mean age of the patients was 41.29 ± 20.32 years. In terms of HCV genotype distribution, 162 patients (51.7%) had genotype 1, 144 patients (46%) had genotype 3, four patients (1.3%) had genotype 2, and three patients (1%) had genotype 4. The results of urine drug tests were available in only 65 patients (20.2%). Of these, 61 (93.8%) patients had HCV genotype 3.
Conclusions:
In conclusion, the prevalence of HCV genotype 1 was 51.7%, which was lower than the rates reported in other studies in Turkey, while the prevalence of HCV genotype 3 was 46%, which was remarkably higher than the reported Turkish data. In addition, the prevalence rate for genotype 3 reported in the present study is the highest that has ever been reported in the literature.
doi:10.5812/hepatmon.15(4)2015.25142
PMCID: PMC4426333  PMID: 25972903
Hepatitis C; Genotype; Real-Time Polymerase Chain Reaction; Turkey
14.  The Impact of Fragility Fractures on Health-Related Quality of Life in Patients With Primary Sclerosing Cholangitis 
Hepatitis Monthly  2015;15(4):e25539.
Background:
Osteoporosis occurs frequently in patients with chronic cholestatic liver diseases, yet data are scarce regarding the prevalence of osteoporosis and fragility fractures and their impact on Health-Related Quality of Life (HRQoL) in Primary Sclerosing Cholangitis (PSC).
Objectives:
We aimed to assess Bone Mineral Density (BMD), physical activity and incidence of fragility fractures in patients with PSC. We also sought associations between prior fractures and HRQoL.
Patients and Methods:
The study was performed on 33 patients (11 females, 22 males) aged 35.3 ± 13 years. HRQoL was assessed by Short Form (SF)-36, Primary Biliary Cirrhosis (PBC)-40 and PBC-27 questionnaires. BMD was measured by densitometry in the lumbar spine and hip. Physical activity was assessed by questionnaire.
Results:
In 32% of patients, BMD measured in the hip or spine was below 1.0 Standard Deviation. A history of fragility fractures (distal forearm and ribs) was reported in six patients (18%). In SF-36 assessment, patients with fractures had lower scores in the role functioning, general health and vitality domains and Physical Component Summary (PCS) than those without fractures. Prior fractures adjusted for gender and PSC duration were associated with lower PCS and Mental Component Summary (MCS) scores. Symptoms and fatigue (assessed by PBC) and prior fractures were inversely associated with MCS (P = 0.007).
Conclusions:
In middle-aged subjects with PSC, we found a high rate of non-vertebral fractures and a moderately decreased BMD in lumbar spine and hip. Fragility fractures had an impact on physical and mental aspects of HRQoL.
doi:10.5812/hepatmon.25539
PMCID: PMC4426354  PMID: 25972904
Health; Quality of Life; Osteoporosis; Cholangitis, Sclerosis
15.  Economic Burden of Hepatitis B Virus-Related Diseases: Evidence From Iran 
Hepatitis Monthly  2015;15(4):e25854.
Background:
Hepatitis B infection is still the main cause of chronic liver disease in Iran, which is associated with significant economic and social costs.
Objectives:
This study aimed to estimate the financial burden caused by CHB infection and its complications in Iran.
Patients and Methods:
Prevalence-based and bottom-up approaches were used to collect the data. Data on direct medical costs were extracted from outpatient medical records in a referral gastroenterology and hepatology research center, inpatient medical records in several major hospitals in Tehran and Shiraz in 2013, and the self-reports of specialists. Data on direct non-medical and indirect costs were collected based on the patients’ self-reports through face-to-face interviews performed in the mentioned centers. To calculate the indirect costs, friction cost approach was used. To calculate the total cost-of-illness in Iran, the total cost per patient at each stage of the disease was estimated and multiplied by the total number of patients.
Results:
The total annual cost for the activate population of CHB patients and for those receiving treatment at various disease stages were respectively 450 million and 226 million dollars, with 64% and 70% of which allocated to direct costs respectively, and 36% and 30% to indirect costs respectively. The total direct costs alone for each group were respectively 1.17% and 0.6% of the total health expenditure. Furthermore, the cost spent on drugs encompasses the largest proportion of the direct medical cost for all stages of the disease.
Conclusions:
According to the perspectives of payers, patients, and community, CHB infection can be considered as one of the diseases with a substantial economic burden; the disease, specifically in extreme cases, can be too expensive and costly for patients. Therefore, patients should be protected against more severe stages of the disease through proper treatment and early diagnosis.
doi:10.5812/hepatmon.15(4)2015.25854
PMCID: PMC4427913  PMID: 25977694
CHB; Cost of Illness; Diseases
16.  The Factors Affecting Bone Density in Cirrhosis 
Hepatitis Monthly  2015;15(4):e26871.
Background:
Bone loss is common in cirrhosis. However, the prevalence of osteopenia and osteoporosis has been heterogeneous in different reports. Reduction in bone formation with or without increase in bone resorption appears to be responsible for bone loss in these patients.
Objectives:
We aimed to investigate bone loss in patients with cirrhosis at different anatomical sites and key factors that might affect it.
Patients and Methods:
In this cross-sectional study, 97 patients with cirrhosis who were referred to Razi Hospital, Rasht, Iran, from 2008 to 2010, were studied. Cirrhosis was diagnosed using biopsy and/or clinical and paraclinical findings. Bone mineral densitometry was done in L2 through L4 lumbar spine (LS) and femoral neck (FN), using dual-energy X-ray absorptiometry (DEXA) (QDR 1000, Hologic DEXA Inc, Waltham, Massachusetts, the United States). Statistical analysis was performed using SPSS 18. A P value < 0.05 was considered statistically significant.
Results:
A total of 97 patients with cirrhosis (55.7% male) and the mean age of 51 ± 13 years and median body mass index (BMI) of 22.7 kg/m2 were recruited over a two-year period. Etiologies of cirrhosis were hepatitis C (40.2%), hepatitis B (26.8%), cryptogenic (21.6%), and other causes (11.4%). Child A, B, and C, were seen in 16.5%, 47.4%, and 36.1% of patients, respectively. The DEXA results were abnormal in 78.4% of our participants (osteopenia, 45.4%; osteoporosis, 33%). BMI and calculated glomerular filtration rate (GFRc) had moderate positive and Child score had moderate negative significant correlation with T score in both anatomical sites. There was no significant association between abnormal DEXA and the causes of cirrhosis. The univariate analysis showed that the risk of abnormal results in DEXA was significantly higher in those with low BMI, current smoking, higher Child score, and low GFRc; however, in multivariate analysis, the abnormal results were more frequent in those with lower vitamin D, higher Child score, and less GFRc.
Conclusions:
Abnormal DEXA was highly prevalent among patients with cirrhosis. The risk of this finding was increased by lower vitamin D levels, advanced disease, and impaired renal function.
doi:10.5812/hepatmon.15(4)2015.26871
PMCID: PMC4428083  PMID: 25977695
Bone Density; Osteoporosis; Liver Cirrhosis
17.  Association of PNPLA3 I148M Variant With Chronic Viral Hepatitis, Autoimmune Liver Diseases and Outcomes of Liver Transplantation 
Hepatitis Monthly  2015;15(4):e26459.
Context:
The PNPLA3 I148M variant has been recognized as a genetic determinant of liver fat content and a genetic risk factor of liver damage progression associated with steatohepatitis. The I148M variant is associated with many chronic liver diseases. However, its potential association with inflammatory and autoimmune liver diseases has not been established.
Evidence Acquisition:
We systemically reviewed the potential associations of I148M variant with chronic viral hepatitis, autoimmune liver diseases and the outcome of liver transplantation, explored the underlying molecular mechanisms and tried to translate them into more individualized decision-making and personalized medicine.
Results:
There were associations between I148M variant and chronic viral hepatitis and autoimmune liver diseases and differential associations of I148M variant in donors and recipients with post-liver transplant outcomes. I148M variant may activate the development of steatosis caused by host metabolic disorders in chronic viral hepatitis, but few researches were found to illustrate the mechanisms in autoimmune liver diseases. The peripherally mediated mechanism (via extrahepatic adipose tissue) may play a principal role in triglyceride accumulation regardless of adiponutrin activity in the graft liver.
Conclusions:
Evidences have shown the associations between I148M variant and mentioned diseases. I148M variant induced steatosis may be involved in the mechanism of chronic viral hepatitis and genetic considered personalized therapies, especially for PSC male patients. It is also crucial to pay attention to this parameter in donor selection and prognosis estimation in liver transplantation.
doi:10.5812/hepatmon.15(4)2015.26459
PMCID: PMC4449891  PMID: 26034504
PNPLA3; Polymorphism; Hepatitis B, Chronic; Hepatitis C, Chronic; Autoimmune Hepatitis; Liver Transplantation
18.  Protective Effect of Salep on Liver 
Hepatitis Monthly  2015;15(4):e28137.
Background:
Salep is used for various purposes in food industries and traditional medicine. Therefore, evaluation of its effect on the liver seems to be necessary.
Objectives:
The aim of this study was to assess salep effect on liver.
Materials and Methods:
In this experimental study, various concentrations of Salep were intraperitoneally administered to five groups of Wistar rats (control, placebo and 20, 40 and 80 mg/kg salep). After one month, liver enzymes and liver tissue were evaluated and compared between different groups.
Results:
Significant decreased level of liver enzymes, MDA (Malondialdehyde) and TOC (Total Oxidation Capacity) were found in various concentrations of salep administration. On the other hand, a significant increase was found in TAC (Total Antioxidant Capacity) level with various doses of salep.
Conclusions:
Elevated level of total protein and albumin and decreased level of liver enzyme by salep extract were found in this study. Therefore, this plant may be a useful medicine for patients with liver diseases.
doi:10.5812/hepatmon.15(4)2015.28137
PMCID: PMC4449893  PMID: 26034505
Rat; Liver; Enzymes; Salep
19.  Prevalence of National Responsiveness to HBV Vaccine After 22 Years of Iranian Expanded Program on Immunization (EPI): A Systematic Review and Meta-Analysis Study 
Hepatitis Monthly  2015;15(5):e23618.
Context:
Hepatitis B Virus expanded program on immunization (EPI) started on 1993 in Iran. Most surveys have assessed the level of response to vaccine by measuring the titers of anti-HBs. This meta- analysis aimed to summarize the Iranian published data on the rate of vaccine-responders versus non-responders. Moreover, the impact of variables such as age, gender, type of vaccine, etc. on the levels of responsiveness was evaluated.
Evidence Acquisition:
All published papers on this topic in Iranian and international journals with affiliation of “Iran” were reviewed using standard keywords up to 2014. We included our study to healthy participants with no previous HBV infection and who had already received a complete course of HB vaccine. The estimated prevalence and 95% confidence intervals in 28 eligible articles for HBV vaccine responders (anti-HBs > 10 IU/mL) and non-responders (10 <) were analyzed by random effect method due to between-study heterogeneity.
Results:
The age of subjects was between 6 months and 15 years old. Overall, 5991 (51.5%) were male and 4571 (48.5%) females. Overall, 80% were responders to vaccine versus 20% nonresponders. With increase in age, the number of responders to vaccine decreased significantly (P = 0.001). There was no strong difference between responders versus nonresponders to vaccine for gender, types of vaccine, ethnicity and living area.
Conclusions:
The results arose from this meta-analysis highlighted the safety of vaccine and its effectiveness in stimulating immune response of vaccines, despite being different in generation, manufacturers and types. Moreover, there was no substantial difference between Iranian and other international investigations in the rate of nonresponsiveness to HBV vaccine.
doi:10.5812/hepatmon.15(04)2015.23618
PMCID: PMC4451270  PMID: 26045701
HBV Vaccine; Anti-HBs; Expanded Program on Vaccination; Responder; Nonresponder
20.  HAV Immunity in Iranian Medical Students 
Hepatitis Monthly  2015;15(3):e26219.
Background:
Hepatitis A, a fecal-oral transmitted disease, which has been considered endemic in developing countries, seems to change its pattern in developing countries because of their improved socioeconomic status.
Objectives:
In the present study, we aimed to determine the need of vaccination in 270 students at AJA University of Medical Sciences.
Materials and Methods:
The serum level of anti-HAV antibody was checked in 270 students of AJA University of medical students, and effect of different factors, including age, gender, pre-university entrance exam region, familial education, familial income, clean water availability, and previous history of jaundice were tested.
Results:
Of total 270 students, 30 were female. Their age ranged between 18 and 30 years old with the mean age of 20.58 years and just 34% of students had positive level of anti-HAV antibody. Age and sex had no role in positive serum level of anti-HAV antibody. According to analyzed data, lack of clean water availability, pre-university entrance exam region, lower family education, and poor health status estimation increased statistically the risk of HAV infection.
Conclusions:
Because 66% of students were anti-HAV antibody negative and they will work as health care workers in future, our study suggest vaccinating all students accepted at AJA University of Medical Sciences.
doi:10.5812/hepatmon.26219
PMCID: PMC4359362  PMID: 25825590
Hepatitis A; Jaundice; Liver Failure; Acute
21.  Association of Tumor Necrosis Factor-alpha Polymorphisms and Risk of Coronary Artery Disease in Patients With Non-alcoholic Fatty Liver Disease 
Hepatitis Monthly  2015;15(3):e26818.
Background:
Cardiovascular events account for the main cause of death in patients with non-alcoholic fatty liver disease (NAFLD), and are largely influenced by genetic factors. Although multiple studies showed that tumor necrosis factor-alpha (TNF-α) polymorphisms are risk factors in the progression of NAFLD, few papers on the association of the polymorphisms and the developing coronary artery disease (CAD) in NAFLD patients have been reported.
Objectives:
The present study was designed to evaluate the association of TNF-α polymorphisms at residues -238 and -308, with the risk of developing CAD in Chinese patients with NAFLD.
Patients and Methods:
The TNF-α polymorphisms at residues 238 and 308 were genotyped in B-type ultrasonography proven NAFLD patients with (n = 246), without (n = 247) CAD and healthy controls (n = 304), using polymerase chain reaction (PCR). Serum lipid profiles were determined using biochemical methods. Statistical analyses were performed using SPSS statistical software, version 20.0 for Mac.
Results:
We found a significant association between TNF-α-238 guanine to alanine (GA) polymorphism and carriers of variant allele A between NAFLD patients with and without CAD (P < 0.05). Carriers of the A allele of TNF-α-238 had higher serum triglycerides (TG) and low density lipoprotein (LDL) levels in NAFLD patients with CAD (P = 0.025 and 0.001, respectively) and a higher TG level in NAFLD patients without CAD (P = 0.017), than their non-carrier counterparts.
Conclusions:
In the Chinese Han population that we studied, NAFLD patients who carry the TNF-α-238 GA polymorphism have an increased risk of developing CAD. Mechanisms underlying this potentially important association require further investigation.
doi:10.5812/hepatmon.26818
PMCID: PMC4359363  PMID: 25825591
Tumor Necrosis Factor-alpha; Polymorphism; Genetic; Non-alcoholic Fatty Liver Disease; Coronary Artery Disease
22.  Pegylated Interferon α Therapy in Chronic Delta Hepatitis: A One-Center Experience 
Hepatitis Monthly  2015;15(3):e24366.
Background:
The only established therapy for chronic viral delta hepatitis, the most severe form of viral hepatitis is treatment with pegylated-interferon α (Peg IFN α).
Objectives:
In this study, we aimed to determine the efficacy of pegylated-interferon α 2a (Peg-IFN α 2a) and 2b (Peg IFN α 2b) in the treatment of patients infected with chronic delta hepatitis virus.
Patients and Methods:
The sample size was based on available patients potentially to be recruited. Data of 63 patients receiving either Peg IFN alpha 2a or Peg IFN alpha 2b were retrospectively assessed in the present cohort study performed in Turkey. Of 56 patients completed the study, 41 received Peg IFN α 2a and 15 received Peg IFN α 2b for 12 months. Patients were evaluated for biochemical and virological responses at the end of given treatment and six months after the treatment.
Results:
Stage of fibrosis was found high in both groups (85.4% vs. 86.7%), while cirrhosis was higher in the group of Peg IFN α 2b (53.3% vs. 34.1%). At the end of treatment, either hepatitis delta virus RNA (HDV RNA) alone or both HDV RNA and hepatitis b virus DNA (HBV DNA) had negative results in 32% of patients. Although HDV RNA negativity was sustained in 30.3% of patients, negativity of both HDV RNA and HBV DNA was decreased to 19.6% six months after completion of the treatment. HBV DNA became positive in one third of patients with response at six months after completion of the treatment (10.7% of all patients). HDV RNA negativity at month six was found as a predictor of positive response. No significant difference was found between Peg IFN α 2a and Peg IFN α 2b for virological response rate.
Conclusions:
Treatment with Peg IFN α achieved a sustained negativity of HDV RNA in about one third of patients. Duration of Peg IFN α therapy might be prolonged to at least 24 months or more to prevent the occurrence of Hepatitis B virus (HBV) relapse encountered six months after completion of the treatment.
doi:10.5812/hepatmon.24366
PMCID: PMC4385268  PMID: 25861318
Hepatitis D; Interferon; Therapeutics
23.  Targeting Human Telomerase Reverse Transcriptase by a Simple siRNA Expression Cassette in HepG2 Cells 
Hepatitis Monthly  2015;15(3):e24343.
Background:
Human telomerase reverse transcriptase (hTERT) has become an ideal target for development of anticancer therapy. Small interfering RNAs (siRNAs) are very powerful reagents for gene silencing and show promise for cancer gene therapy. However, only a small number of siRNAs have been demonstrated to be effective. For gene therapy targeting hTERT, it is essential to develop a robust system to fully explore the power of siRNAs.
Objectives:
We explored a siRNA expression cassette (SEC) to screen highly effective RNAi-targeted sequences for gene therapy of hepatocellular carcinoma (HCC).
Materials and Methods:
An SEC was developed by flanking H1 and U6 promoters in opposite directions at the siRNA-encoding sequence. Eight SECs specific to hTERT were designed by overlap extension polymerase chain reaction (PCR) and transfected into HepG2 cells with calcium phosphate. The telomerase activity was determined by telomeric repeat amplification protocol (TRAP) silver staining and TRAP real-time PCR analysis. The mRNA and protein expression levels of hTERT were determined by reverse transcription (RT)-PCR and western blot, respectively. Cell viability was determined by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and cell apoptosis was measured by the annexin-V/propidium iodide (PI) assay coupled with flow cytometry.
Results:
Eight hTERT-specific SECs (SEC-1-8) were successfully constructed. In comparison to that of the negative control SEC, the hTERT-specific SECs, especially, SEC-4, SEC-5, SEC-7 and SEC-8 significantly reduced the activity of hTERT in HepG2 cells at 48 hours after transfection. Moreover, the mRNA and protein expression levels of hTERT as well as the cell viability were significantly reduced by SECs. Knockdown of hTERT by SECs in HepG2 cells led to cell apoptosis.
Conclusions:
Our developed simple SEC was a powerful strategy for screening highly effective RNAi-targeted sequences and showed promise for gene therapy of HCC.
doi:10.5812/hepatmon.24343
PMCID: PMC4385270  PMID: 25861317
hTERT; siRNA; Telomerase; Hepatocellular Carcinoma; Gene Therapy
24.  Dystrophic-Anagen Effluvium Occurring During Pegylated Interferon-α-2a/Ribavirin Therapy 
Hepatitis Monthly  2015;15(3):e24804.
Introduction:
Various types of dermatological manifestations have been reported due to hepatitis C virus (HCV) infection and anti­HCV therapy. Some of them have been described during IFN-based therapies. PEG-IFN-α-2a/RBV combination is used as the international standard of treatment for HCV infection for a long time. The combination therapy yields an adverse-event profile similar to standard interferon (IFN) therapy. Some of these adverse effects are rheumatologic, neuropsychiatric and dermatological manifestations including alopecia.
Case Presentation:
We reported a 43-year-old woman with dystrophic anagen effluvium (DAE), rheumatoid arthritis and Hashimoto thyroiditis, which were developed under the combination therapy for chronic HCV infection.
Conclusions:
Although some cases of alopecia areata (AA) and telogen effluvium (TE) were reported in literature, no case of DAE associated with PEG-INF-α-2a /RBV combination therapy was reported previously.
doi:10.5812/hepatmon.24804
PMCID: PMC4360537  PMID: 25821474
Alopecia; Interferon; Therapy; Chronic Hepatitis C
25.  An Index to Predict Ribavirin-Induced Anemia in Asian Patients With Chronic Genotype 1 Hepatitis C 
Hepatitis Monthly  2015;15(3):e27148.
Background:
Single-nucleotide polymorphisms (SNP) in the inosine triphosphate pyrophosphatase (ITPA) gene correlate with ribavirin (RBV)-induced anemia in patients with chronic hepatitis C (CHC) receiving combination therapy. Managing anemia is an early priority in the treatment process.
Objectives:
The aim was to develop a predictive index based on ITPA SNP status to identify CHC patients at risk of anemia.
Patients and Methods:
A total of 418 eligible East Asian patients diagnosed with CHC genotype 1 (G1) received combination therapy in this study. Participant DNA was genotyped for a functional ITPA SNP (C/C, A/A or C/A) on chromosome 20 at rs1127354. A predictive index was constructed by incorporating independent factors identified for severe anemia events (hemoglobin < 10 g/dL). Areas under the receiver-operating characteristic curves (AUCs) represented the diagnostic accuracies of the predictive index in randomly assigned development and validation cohorts.
Results:
Multiple logistic regressions identified age (≥ 50 y: OR = 9.7, 95% CI = 5.0 - 18.6), ITPA rs1127354 (C/C: OR = 3.3, 95% CI = 1.8 - 5.8) and baseline hemoglobin (< 14.0 g/dL: OR 6.4, 95% CI = 3.3 - 12.1; 14.0 - 14.9: OR = 2.4, 95% CI = 1.2 - 4.6) as predictors of severe anemia throughout the treatment. For severe anemia, the predictive index incorporating age, ITPA SNP status and baseline hemoglobin yielded diagnostic accuracies (AUCs) of 0.830 (95% CI = 0.783 - 0.871) in the development (n = 324) and 0.902 (0.826 - 0.925) in the validation (n = 81) cohorts.
Conclusions:
In patients with CHC G1 and receiving combination therapy, ITPA SNP-based index was an accurate and practical solution for prediction of severe anemia.
doi:10.5812/hepatmon.27148
PMCID: PMC4377223  PMID: 25834588
Polymorphism; Inosine Triphosphate; Hepatitis C; Ribavirin; Anemia

Results 1-25 (663)