Hepatitis Monthly
Year:2016 | Volume:16 | Issue:4|Papers Count:10

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. Nonparametric 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.

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 HCVinfected 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.

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-a) 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, anthracy cline, and different types of TNF-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 immune suppressants. 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 hem at opoieticstem 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.

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, Iran Medex, 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 Iranwas2.2% (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 (<2%), indicating that preventive measures conducted in Iran have been effective.

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, cirrhosisandhepatocellular carcinoma (HCC) basedonpurchasing 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.

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.

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 retreatment with PEGylated interferon in treatment-experienced HBeAg positive patients.

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 LEPRQ223R 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 c2 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 c2 test where appropriate.Results: The LEPRQ223R A allele significantly reduced the risks of both NAFLD and coronary atherosclerosis (OR=0.683, 95% CI: 0.527 - 0.884, P=0.004 andOR=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<0.001).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.

Context: Hepatocellular carcinoma (HCC) is a common disorder throughout the world that can develop due to various factors, including genetics. Tumor necrosis factor-a(TNF-a) is the most frequently studied cytokine related to the risk of developing HCC, and an association between the 308 position of the TNF-a promoter (TNFa-308) and HCCrisk 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-a 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<0.002). In addition to the allelic model, the dominant model (AA+AGvs. GG) was significantly associated with HCCrisk (OR=1.80; CI= [1.29-2.51]; P value<0.001). In the sensitivity analysis for co-dominant (AA vs. GG) and recessive models (AA vs. AG+GG), no trustworthy associations with the risk of HCC development were observed.Conclusions: This meta-analysis indicated that the TNF-a 308 G/A polymorphism is significantly associated with increased susceptibility to HCC. However, to confirm this finding, more studies are needed on TNF-a 308 G/A polymorphisms associated with HCC.

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.