فهرست مطالب

Hepatitis - Volume:16 Issue: 4, Apr 2016

Hepatitis Monthly
Volume:16 Issue: 4, Apr 2016

  • تاریخ انتشار: 1395/02/22
  • تعداد عناوین: 11
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  • Hassan Soleimanpour, Saeid Safari, Kavous Shahsavari Nia, Sarvin Sanaie, Seyed Moayed Alavian* Page 1
    Context: The liver, one of the most important organs of the body, is known to be responsible for several functions. The functional contribution of the liver to the metabolism of carbohydrates, protein, drugs and toxins, fats and cholesterol and many other biological processes are still unknown. Liver disorders are classified into two types: acute and chronic. Different drugs are used in liver diseases to treat and control pain. Most pain relief medications such as opioids are metabolized via the liver; therefore, the adverse reactions of drugs are probably higher for patients with liver disease. The current study aimed to evaluate the effects of opioid drugs on patients with liver disease; therefore, it is necessary to select suitable opioids for such patients.
    Evidence Acquisition: This review was written by referring to research literature including 70 articles and four textbooks published from 1958 to 2015 on various reputable sites. Searches were carried out on the key phrases of narcotic pain relievers (opioids), acute and chronic hepatic failure, opioid adverse drug reactions, drug-induced liver injury (DILI) and other similar keywords. References included a variety of research papers (descriptive and analytical), intervention and review articles.
    Results
    In patients with liver disease, administration of opioid analgesics should be observed, accurately. As a general rule, lower doses of drugs should be administered at regular intervals based on the signs of drug accumulation. Secondly, the interactions of opioid drugs with different levels of substrates of the P450 cytochrome enzyme should be considered.
    Conclusions
    Pain management in patients with liver dysfunction is always challenging to physicians because of the adverse reactions of drugs, especially opioids. Opioids should be used cautiously since they can cause sedation, constipation and sudden encephalopathy effects. Since the clearance of these drugs in patients with hepatic insufficiency is decreased, the initial dose must be decreased, the intervals between doses should be increased and some patients need to be continuously assessed.
    Keywords: Opioids, Liver Disease, Adverse Drug Reactions
  • Soheil Tavakolpour, Shahnaz Sali* Page 2
    Context: Hepatocellular carcinoma (HCC) is a common disorder throughout the world that can develop due to various factors, including genetics. Tumor necrosis factor-α (TNF-α) is the most frequently studied cytokine related to the risk of developing HCC, and an association between the 308 position of the TNF-α promoter (TNF-α-308) and HCC risk has been confirmed in various reports.
    Evidence Acquisition: The PubMed, Scopus, and Google Scholar databases were searched through July 12, 2015, for studies on associations between TNF-α-308 and the risk of HCC. To determine this association, odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.
    Results
    A total of 23 case-control studies were investigated, involving 3,389 cases and 4,235 controls. The overall conclusion was that the A allele was more frequent in case groups compared to control groups (13.4% vs. 8.4%). Thus, the A allele was significantly associated with increased HCC risk (OR = 1.77; 95% CI = [1.26-2.50]; P value
    Conclusions
    This meta-analysis indicated that the TNF-α-308 G/A polymorphism is significantly associated with increased susceptibility to HCC. However, to confirm this finding, more studies are needed on TNF-α-308 G/A polymorphisms associated with HCC.
    Keywords: Tumor Necrosis Factor, α Hepatocellular Carcinoma, Polymorphisms, TNF, α 308, Meta, Analysis
  • Soheil Tavakolpour, Seyed Moayed Alavian*, Shahnaz Sali Page 3
    Context: Due to the close relationship between the immune system and the hepatitis B virus (HBV) replication, it is essential to monitor patients with current or past HBV infection under any type of immunosuppression. Cancer chemotherapy, immunosuppressive therapies in autoimmune diseases, and immunosuppression in solid organ and stem cell transplant recipients are the major reasons for hepatitis B virus reactivation (HBVr). In this review, the challenges associated with HBVr are discussed according to the latest studies and guidelines. We also discuss the role of treatments with different risks, including anti-CD20 agents, tumor necrosis factor-alpha (TNF-α) inhibitors, and other common immunosuppressive agents in various conditions.
    Evidence Acquisition: Through an electronic search of the PubMed, Google Scholar, and Scopus databases, we selected the studies associated with HBVr in different conditions. The most recent recommendations were collected in order to reach a consensus on how to manage patients at risk of HBVr.
    Results
    It was found that the positive hepatitis B surface antigen (HBsAg), the high baseline HBV DNA level, the positive hepatitis B virus e antigen (HBeAg), and an absent or low hepatitis B surface antibody (HBsAb) titer prior to starting treatment are the most important viral risk factors. Furthermore, rituximab, anthracycline, and different types of TNF-α inhibitors were identified as the high-risk therapies. By analyzing the efficiency of prophylaxis on the prevention of HBVr, it was concluded that those with a high risk of antiviral resistance should not be used in long-term immunosuppressants. Receiving HBV antiviral agents at the commencement of immunosuppressant therapy or chemotherapy was demonstrated to be effective in decreasing the risk of HBVr. Prophylaxis could also be initiated before the start of therapy. For most immune suppressive regimes, antiviral therapy should be kept up for at least 6 months after the cessation of immunosuppressive drugs. However, the optimal time of prophylaxis keeping should be increased in cases associated with rituximab or hematopoietic stem cell transplants. According to the latest studies and guidelines from different bodies, recommendations regarding screening, monitoring, and management of HBVr are outlined.
    Conclusions
    Identification of patients at the risk of HBVr before immunosuppressive therapy is an undeniable part of treatment. Starting the antiviral therapy, based on the type of immunosuppressive drugs and the underlying disease, could lead to better management of disease.
    Keywords: Hepatitis B Virus_Reactivation_Immunosuppression_Rituximab_Prophylaxis
  • Mostafa Salehivaziri, Farzin Sadeghi, Amir Almasi Hashiani, Mohammad Gholami Fesharaki, Seyed Moayed Alavian* Page 4
    Context: The hepatitis B virus (HBV) is a major global public health problem, affecting more than 2 billion people worldwide. Accurate and updated data on HBV prevalence is important for further planning to control the infection. The aim of this study was to update the prevalence estimate of HBV infection in the general population of Iran.
    Evidence Acquisition: A systematic review was done for data on the prevalence of HBV infection in the general Iranian population published between Jan. 1, 1990, and Jan. 1, 2016, in both international and national databases, including PubMed, Scopus, Web of Science, Scientific Information Database, IranMedex, and Magiran. All papers with clearly described time and location of the study, proper sampling strategies, and proper analysis methods were included in the present study. Data were extracted by two independent reviewers. Prevalence of HBV infection with a 95% confidence interval (CI) was calculated using Stata software, version 13.
    Results
    The polled estimated prevalence of HBV infection in the general population of Iran was 2.2 % (95% CI: 1.9% - 2.6%). The highest prevalence of HBV infection (8.9%, 95% CI: 7.6% - 10.2%) was reported from Golestan province, and the lowest prevalence (0.7%, 95% CI: 0.4% - 1.1%) was seen in Kermanshah province. The prevalence of HBV infection was estimated at 3% (95% CI: 2.2% - 3.8%) for Iranian males and 1.7% (95% CI: 1.2% - 2.3%) for Iranian females. The prevalence of HBV infection in the general population of Iran was 2.9% (95% CI: 2.5% - 3.4%) before 2010 and 1.3% (95% CI: 0.9% - 1.7%) after 2010.
    Conclusions
    In total, Iran was classified within the low–intermediate HBV prevalence areas (2% - 4%), while according to recent data (after 2010), Iran was classified within the low HBV prevalence areas (
    Keywords: Hepatitis B Virus_Iran_Meta_Analysis_Prevalence
  • Khashayar Hesamizadeh, Heidar Sharafi, Mohammad Saeid Rezaee, Zavareh, Bita Behnava, Seyed Moayed Alavian* Page 5
    Context: After the introduction of safe and highly effective hepatitis C virus (HCV) treatments, eradication of HCV in the next 20 years is the ultimate goal. Since 2011, the advent of first generation direct acting antivirals (DAAs) were started and followed by the introduction of a new wave of DAAs in 2013 which exhibit outstanding efficacy. It is obvious that the eradication of hepatitis C is not restricted to development of DAAs.
    Evidence Acquisition: An electronic search of available literature published was conducted in all peer-reviewed journal indexed in PubMed, Scopus and Google scholar. The literature search was done among articles related treatment of hepatitis C with DAAs in different patient groups with mass screening of the patients and cost benefit of new treatments as main key words.
    Results
    There are major steps that should be taken to eradicate HCV, including (1) the development of screening strategies, particularly for groups such as intravenous drug users and recipients of blood or blood products before the introduction of HCV screening in donors; (2) the development of strategies to overcome issues with the high cost of recently introduced treatments; (3) special attention to special patient groups, such as HIV/HCV co-infection, hemophilia, thalassemia, hemodialysis, and liver-transplant patients; and (4) development of preventive strategies, such as the development of an efficient HCV vaccine, special attention to harm reduction in high-risk groups, and promotion of mass awareness of HCV.
    Conclusions
    The eradication of HCV will require significant governmental financial investment for screening, prevention, and treatment of infected patients. Although, we have a long way to eradication of HCV, the next steps could be including proper planning to patient finding, availability of new treatments to all patients and development of HCV prevention strategies such as vaccines.
    Keywords: Hepatitis C, Diagnosis, Mass Screening, Treatment Outcome
  • Farzin Sadeghi, Mostafa Salehi, Vaziri, Amir Almasi, Hashiani, Mohammad Gholami, Fesharaki, Reza Pakzad, Seyed Moayed Alavian * Page 6
    Context: Hepatitis C virus (HCV) infection is a major global public health issue. The Eastern Mediterranean regional office (EMRO) of the world health organization (WHO) seems to have one of the highest prevalence rates worldwide, with at least 21.3 million HCV-infected patients.
    Objectives
    The aim of the present study was to review systematically all epidemiological data related to the prevalence of HCV genotypes in infected patients in EMRO countries.
    Data Sources: A systematic search was conducted of peer-reviewed journals indexed in electronic databases (PubMed, Scopus, ISI, PakMediNet, and IMEMR, and Persian-specific databases including SID, Iran Medex, and MagIran).
    Study Selection: A systematic search was performed with temporal limits (papers published between January 2000 up to June 2015), regarding the prevalence and distribution of HCV genotypes in EMRO countries.
    Data Extraction: The prevalence rates of HCV genotypes were pooled by metan command in Stata 14. Statistical heterogeneity was explored using the I-square at the 5% significance level. Publication bias was assessed, graphically and statistically, by funnel plot and Begg and Egger tests.
    Results
    A total of 563 records were identified through the electronic search. Of these records, 134 studies comprising 67681 HCV-infected individuals were included in the meta-analysis. In Iran, subtype 1a was the predominant subtype with a rate of 42% (95% CI, 39 - 46), followed by subtype 3a, 35% (95% CI, 31 - 38). In Pakistan, Subtype 3a was the most common subtype with a rate of 56% (95% CI, 49 - 62), followed by subtype 3b, 10% (95% CI, 7 - 12). In Saudi Arabia and Egypt, genotype 4 was the most prevalent genotype with a rate of 65% (95% CI, 59 - 72) and 69% (95% CI, 36 - 100) respectively. In Tunisia and Morocco, subtype 1b was the most common subtype with a rate of 69% (95% CI, 50 - 88) and 32% (95% CI, 7 - 56) respectively.
    Conclusions
    The genotype distribution of HCV takes diverse patterns in EMRO countries. Genotypes 1 and 3 were predominant in Iran and Pakistan, while genotype 4 and 1 were the most common genotypes in the Middle East Arab countries and North African Arab countries. Understanding the genotypes of HCV can help policy makers in designing good strategies for treatment.
    Keywords: Hepatitis C Virus_Genotype_Prevalence_Molecular Epidemiology_Systematic Review_Meta_Analysis
  • Fatemeh Zare, Mohammad Reza Fattahi*, Masood Sepehrimanesh, Ali Reza Safarpour Page 7
    Background
    Hepatitis C virus (HCV) infection is a major blood-borne infection which imposes high economic cost on the patients.
    Objectives
    The current study aimed to evaluate the total annual cost due to chronic HCV related diseases imposed on each patient and their family in Southern Iran.
    Patients and
    Methods
    Economic burden of chronic hepatitis C-related liver diseases (chronic hepatitis C, cirrhosis and hepatocellular carcinoma) were examined. The current retrospective study evaluated 200 Iranian patients for their socioeconomic status, utilization (direct and indirect costs) and treatment costs and work days lost due to illness by a structured questionnaire in 2015. Costs of hospital admissions were extracted from databases of Nemazee hospital, Shiraz, Iran. The outpatient expenditure per patient was measured through the rate of outpatient visits and average cost per visit reported by the patients; while the inpatient costs were calculated through annual rate of hospital admissions and average expenditure. Self-medication and direct non-medical costs were also reported. The human capital approach was used to measure the work loss cost.
    Results
    The total annual cost per patient for chronic hepatitis C, cirrhosis and hepatocellular carcinoma (HCC) based on purchasing power parity (PPP) were USD 1625.50, USD 6117.2, and USD 11047.2 in 2015, respectively.
    Conclusions
    Chronic hepatitis C-related liver diseases impose a substantial economic burden on patients, families and the society. The current study provides useful information on cost of treatment and work loss for different disease states, which can be further used in cost-effectiveness evaluations.
    Keywords: Hepatitis C, Cost, Economics, Cirrhosis, Hepatocellular Carcinoma
  • Nadia Mohamed El, Guendy, Reham Helwa, Medhat Salah El, Halawany, Shimaa Abdel Rahman Ali, Marwa Tantawy Aly, Nelly Hasan Alieldin, Shawky Abdel Hamid Fouad, Hany Saeid, Abdel, Hady Ali Abdel, Wahab* Page 8
    Background
    MicroRNAs (miRNAs) have been repeatedly shown to play important roles in liver pathologies, including hepatitis, liver cirrhosis, and liver cancer. Egypt has the highest hepatitis C virus (HCV) infection rate worldwide, predominantly involving genotype-4.
    Objectives
    In this study, we attempted to characterize the miRNA profile of the poorly studied genotype 4 of HCV in chronically infected Egyptian patients to obtain a better understanding of the disease and its complications and help in the design of better management protocols.
    Patients and
    Methods
    We analyzed the expression levels of a selected panel of 94 miRNAs in fresh liver biopsies collected from 50 Egyptian patients diagnosed with chronic HCV infection using quantitative real-time polymerase chain reaction (PCR) assay. Non-parametric tests were used to analyze the expression level of each miRNA and association with the clinicopathological features of enrolled patients in this study.
    Results
    Our results revealed differential expression levels of the analyzed miRNAs compared to the normal controls. Twenty-seven miRNAs (including miR-105, miR-147, miR-149-3p, and miR-196b) showed up-regulation, while 17 miRNAs (including miR-21, miR-122, miR-199a-3p, and miR-223) showed down-regulation. An inverse correlation was observed between levels of miR-95, miR-130a, and miR-142-5p with the blood albumin level. Increased expression levels of seven miRNAs (miR-29c, miR-30c, miR-126, miR-145, miR-199a, miR-199a-3p, and miR-222) were observed with severe chronic hepatic inflammation. Several deregulated miRNAs found in this study have been previously linked to chronic liver inflammation and the risk of hepatocellular carcinoma (HCC) development.
    Conclusions
    The identified expression profiles of some examined miRNAs might offer important points to consider for the treatment of naive patients and the management of chronically infected HCV patients in Egypt and around the world.
    Keywords: Hepatitis C, MicroRNAs, Genotype, 4, Real, Time Polymerase Chain Reaction, Liver Cirrhosis
  • Jamal Mirzaei, Masood Ziaee*, Seyed Ali Farsad, Mohammad Fereydooni, Gholamreza Anani Sarab, Mohammad Reza Rezvani Khorashad Page 9
    Background
    Hemophilic patients require long-life intravenous infusion of factor concentrates to treat bleedings. This could increase the risk of transmission of blood-borne infections like hepatitis C.
    Objectives
    The current study was aimed at investigating the immunity status against hepatitis A in hemophilic patients in south Khorasan and evaluating the necessity of hepatitis A vaccination for this population.
    Patients and
    Methods
    A cross-sectional descriptive study was conducted between 2014 and 2015 on all hemophilic patients of south Khorasan province, Iran (n = 108) for anti-HAV total, anti- HCV, HBs-Ag, anti-HIV, and anti-HTLV-I /II. Note that no one had already received a hepatitis A vaccine.
    Results
    As our results show, 77.8% of the participants (59% under 20 and 88.4% above 20 years old) were seropositive for anti-HAV total; 20.4% and 2.8% (three patients) of the cases were anti-HCV positive and anti-HTLV-1 positive, respectively, while none of the subjects were HBS-Ag or HIV-Ab positive. Seventeen of the patients (15.75%) showed a co-infection of HAV with HCV, and five HCV-infected patients (22.73%) had no immunity against hepatitis A. There was a significant relationship between age, rural life, and anti-HAV positive state in our patients (P 0.05) was detected.
    Conclusions
    More than 40% of the hemophilic patients under 20 years of age in the present study had no immunity against hepatitis A, and 23% of hepatitis C patients had not had a hepatitis A co-infection yet. Since hepatitis A can show a fulminant course in hepatitis C patients, vaccination against hepatitis A seems necessary in hemophilic patients in the region.
    Keywords: Prevalence, Hepatitis A, Viral Infections, Hemophilia, Hepatitis C
  • Bai, Quan An, Lin, Lin Lu, Chen Yuan, Yong, Ning Xin*, Shi, Ying Xuan* Page 10
    Background
    Leptin receptor (LEPR) polymorphisms have been reported to be associated with lipid metabolism and insulin resistance in various populations. However, whether LEPR polymorphisms are associated with the risks of non-alcoholic fatty liver disease (NAFLD) and coronary atherosclerosis in the Chinese Han population remains unknown.
    Objectives
    To investigate the association of LEPR polymorphisms at Q223R and K109R with the risks of NAFLD and coronary atherosclerosis in the Chinese Han population.
    Patients and
    Methods
    Genotypes of LEPR Q223R and K109R were determined by polymerase chain reaction followed by sequencing in patients with NAFLD (n = 554), coronary atherosclerosis (n = 421), and healthy controls (n = 550). Serum lipid profiles were determined using biochemical methods. Pearson’s χ2 test was used to check for Hardy-Weinberg equilibrium and to analyze the distributions of genotypes’ alleles between groups. Baseline characteristics were analyzed using student’s t-test, paired-samples t-test, or the χ2 test where appropriate.
    Results
    The LEPR Q223R A allele significantly reduced the risks of both NAFLD and coronary atherosclerosis (OR = 0.683, 95% CI: 0.527 - 0.884, P = 0.004 and OR = 0.724, 95% CI: 0.548 - 0.955, P = 0.022, respectively). Compared to controls, no significant differences in the genotype and allele frequencies of K109R were found in the NAFLD and coronary atherosclerosis populations, respectively. However, there was a significantly increased risk of coronary atherosclerosis in NAFLD patients who carried the K109R A allele (OR = 2.283, 95% CI: 1.556 - 3.348, P
    Conclusions
    LEPR Q223R polymorphisms may confer a significant risk of NAFLD and coronary atherosclerosis. The A allele in the K109R polymorphism might be considered an independent risk factor for coronary atherosclerosis in NAFLD patients.
    Keywords: Non, Alcoholic Fatty Liver Disease, Coronary Atherosclerosis, Single Nucleotide Polymorphism, LEPR
  • Yue, Li Xiong, Hu Li, Fen Liu, Dazhi Zhang, Hong Ren, Peng Hu* Page 11
    Background
    After treatment cessation, a high prevalence of relapse was reported in chronic hepatitis B (CHB) patients in China, especially in nucleot(s)ide analogues (NUCs)-experienced patients. Re-treatment for these patients remains unsolved.
    Objectives
    This study aims to evaluate the efficacy of PEGylated interferon in HBeAg positive patients with exposure to antiviral therapy.
    Patients and
    Methods
    A total of 55 treatment-experienced, HBeAg positive Chinese patients were enrolled in this study. Of these patients, 33 were NUCs-experienced and 22 were interferon-experienced. PEGylated interferon was administered to 34 patients; and 21 patients were retreated with conventional interferon.
    Results
    Of the 34 treatment-experienced patients who received PEGylated interferon, 52.9% achieved virologic response, and 41.2% achieved HBeAg loss and seroconversion. Patients who were treated with PEGylated interferon for 48 weeks achieved higher virologic response (80%); HBeAg loss (60%); HBeAg seroconversion (60%); and HBsAg loss (5%) than patients treated for 24 weeks with PEGylated interferon. Their responses were also higher than those who were treated with conventional interferon. HBeAg seroconversion in treatment-experienced patients was independently associated with 48-week PEGylated interferon therapy duration.
    Conclusions
    PEGylated interferon was effective in treatment-experienced patients with HBeAg positive CHB, and showed higher rates of virological response, HBeAg loss, and seroconversion. The results provide important information regarding the role of re-treatment with PEGylated interferon in treatment-experienced HBeAg positive patients.
    Keywords: Chronic Hepatitis B, PEGylated Interferon, Treatment, Experienced, Nucleot(s)ide Analogues