Heidar Sharafi

Background: Patients with hereditary bleeding disorders (HBDs) have always been vulnerable to transfusion-transmitted infections (TTIs) such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections due to being regular recipients of blood and blood products. This study aimed to detect the trends in the prevalence of HBV, HCV, and HIV infections by birthyear in Iranian patients with HBDs to show the efficacy of national interventions implemented to administrate control and to prevent these infections, i.e., blood safety, newborn HBV vaccination, and safe replacement treatments. Methods: In this retrospective study, the trends in the prevalence of hepatitis B core antibody (HBcAb), HCV antibody (HCV-Ab), and HIV antibody (HIV-Ab) in Iranian patients with HBDs born before 2012 were assessed using patients’ clinical archives. The determinants of HBV, HCV, and HIV infections were investigated in bivariable and multivariable logistic regression analyses. Results: Out of 1475 patients with HBDs, most were male (87.7%) and diagnosed with hemophilia A (52.1%) and severe bleeding disorder (63.7%). The prevalence of HBcAb, HCV-Ab, and confirmed HIV-Ab was 22.9%, 59.8%, and 1.2%, respectively. The trends in HBcAb, HCV-Ab, and HIV-Ab were all decreasing by birthyear and reached a stable level of 0% for patients with birthyears in 1999, 2000, and 1984, respectively. In multivariable analysis, birthyear was significantly associated with HBcAb prevalence. In the multivariable analysis, type of HBD; birthyear; bleeding severity; histories of receiving packed cells, fresh frozen plasma, and cryoprecipitate before 1996; and history of receiving factor concentrate before 1997 were highly associated with the prevalence of HCV-Ab. Moreover, in the bivariable analysis, birthyear and type of HBD were associated with HIV-Ab prevalence. Conclusion: This study demonstrated the decreasing trends in HBV, HCV, and HIV seroprevalence in Iranian patients with HBDs following preventive interventions such as HBV vaccination, blood safety measures, and the provision of safe replacement treatments.

Background: Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide. Genetic predisposition increases susceptibility to NAFLD. The PNPLA3 rs738409 and TM6SF2 rs58542926 polymorphisms are genetic risk factors for NAFLD. Objectives: This study aimed to investigate the association of rs738409 and rs58542926 polymorphisms with NAFLD among the Iranian population in two groups: (1) Population-based NAFLD (PB-NAFLD), and (2) clinic-based NAFLD (CB-NAFLD). Methods: This case-control study included a group of healthy individuals without NAFLD as the control group and two case groups, PB-NAFLD and CB-NAFLD. All individuals underwent clinical and laboratory assessments and were also diagnosed using ultrasonography. Genotyping for rs738409 and rs58542926 polymorphisms was carried out by the PCR-RFLP method. Results: A total of 110 control, 108 PB-NAFLD, and 73 CB-NAFLD individuals were included in the study. The distribution of rs738409 GG+CG in the PB-NAFLD was 39.8% while it was 52.7% in the control group (P = 0.06, OR = 0.59). The distribution of rs738409 GG in the CB-NAFLD was 19.2%, while it was 8.2% in the control group (P = 0.04, OR = 2.66). The distribution of rs58542926 genotypes was not significantly different between the NAFLD and control groups. In multivariate analysis, metabolic syndrome (OR = 2.85) and BMI > 25 (OR = 3.32) were independent determinants of NAFLD in the PB-NAFLD group, and BMI > 25 (OR = 7.15) was an independent determinant of NAFLD in the CB-NAFLD group. Conclusions: In this study, the PNPLA3 rs738409 polymorphism was associated with NAFLD in the CB-NAFLD cohort; however, the same was not observed for the PB-NAFLD cohort. The TM6SF2 rs58542926 polymorphism was not associated with NAFLD in the Iranian population.

Background: High-risk behaviors in people with severe mental illnesses, such drug injection by shared equipment and unprotected sex, expose them to the risk of blood-borne infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Objectives: This study aimed to determine the prevalence of HBV and HCV serum markers in people with severe mental illnesses in Tehran, Iran. Methods: In this cross-sectional study, people with mental illnesses, such as schizophrenia, bipolar disorder, and depression, were studied. The participants were recruited using a non-random convenience sampling method from Roozbeh and Razi hospitals in Tehran between December 2019 and March 2020. Blood samples were evaluated for HCV-Ab, HBs Ag, HBs Ab, and HBc Ab using an enzyme immunoassay technique. Results: A total of 257 participants were recruited for this study; their mean age was 35.77 years, and 70.0% of whom were male. Bipolar disorder (40.5%) and schizophrenia (35.8%) were the most frequent severe mental disorders in the participants. The prevalence of HBV and HCV seromarkers was as follows: HBs Ag: 0.3% (95% CI: 0.0 - 2.0%), HBc Ab: 7.3% (95% CI: 4.6 - 11.3%), HBs Ab: 18.7% (95% CI: 14.1 - 24.0%), and HCV Ab: 3.1% (95% CI: 1.3 - 6.9%). In logistic regression analysis, tattooing (OR = 4.94, 95% CI: 1.73 - 14.13) and age (OR= 1.06, 95% CI: 1.01 - 1.11) were associated with HBV infection (HBc Ab positivity), and only tattooing (OR= 6.33, 95% CI: 1.19 - 33.80) was significantly associated with exposure to HCV. Conclusions: The results of this study showed that the prevalence of HBsAg positivity in people with severe mental illness was not higher than that in the general population of Iran; however, HCV Ab positivity was more prevalent in people with severe mental illness than in the general population of Iran. Preventive, diagnostic, and therapeutic interventions for HCV infection are needed in this population in Iran.

Introduction: To realize the global goals of eliminating hepatitis B virus (HBV) and hepatitis C virus (HCV) by 2030, it is necessary to monitor the status of disease among target populations and undertake the required interventions. This study is the third round of surveys to determine the prevalence of hepatitis B and C infections among incarcerated individuals in different provinces of Iran. Methods: This study was conducted in five provinces of Iran (including Kurdistan, Ardabil, West Azerbaijan, Markazi, and Semnan) in 2019. The subjects of the study were selected from incarcerated people in prisons of all provinces that had not been studied in the previous two rounds of the surveys (in 2015 and 2016) in Iran. In this study, 15 prisons were selected and 2475 incarcerated individuals were enrolled into the study based on the multistage sampling method; the selected subjects were surveyed and their dried blood spot (DBS) samples were collected to test HBsAg and HCV-Ab. In cases with a reactive result for HCV-Ab, an HCV-RNA test was also performed on their serum samples. The relationships between independent variables and outcomes were evaluated via logistic regression. Results: Of all participants (2475 subjects) enrolled in the study, 54.18% were selected from northern provinces and 45.82% from the central provinces. The prevalence of HCV-Ab and HBsAg among incarcerated individuals was 5.66% (95% CI: 4.81% to 6.64%) and 2.42% (95% CI: 1.89% to 3.11%), respectively. Among HCV-seropositive individuals, 73.68% (95% CI: 64.70% to 81.01%) had current HCV infection (detectable HCV-RNA). The results showed that histories of imprisonment, drug use, unprotected sexual contact, drug injection, tattooing, and younger age in the first-time drug use in incarcerated individuals significantly increased the risk of HCV transmission. Among these behaviors, drug injection was more likely than other behaviors to result in contracting HCV in incarcerated individuals (OR: 22.91; 95% CI: 14.92–35.18; p < 0.001). Conclusion: To achieve international and national strategies targeted to eliminate HCV and HBV by 2030, it is necessary to pay special attention to prisons in Iran. It is recommended to continue HBV vaccination of eligible people in prisons. Developing screening and treatment protocols for individuals with HCV infection in prisons can help the country to achieve HCV elimination goals.

Background: Although several regimens have been approved for the treatment of hepatitis C virus (HCV) infection, sofosbuvir-based regimens are not approved for the treatment of HCV infection in patients with severe renal impairment. Methods: This study was conducted on hemodialysis patients infected with HCV. The patients received a constant dose of sofosbuvir/daclatasvir (SOF/DCV). Sustained virologic response (SVR) was evaluated 12 weeks after completion of treatment. Results: Fifty-one hemodialysis patients with HCV infection were selected and treated with a combination of SOF/DCV. Eleven patients expired during the anti-HCV treatment due to causes not related to liver disease or antiviral therapy. Finally, 40 patients finished the treatment, and 36 cases were evaluated for SVR. Among those tested for SVR, 35 (97.2%, 95% CI: 85.5 - 99.9%) achieved SVR and one (2.8%, 95% CI: 0.1 - 14.5%) relapsed. No patient reported severe adverse events. Conclusions: The combination of SOF/DCV showed great efficacy and safety in hemodialysis patients with severe renal impairment and chronic HCV infection.

Background: Hepatitis C virus (HCV), non-structural 5A (NS5A), and non-structural 5B (NS5B) resistance-associated substitutions (RASs) are the main causes of failure to direct-acting antiviral agents (DAAs). NS5A and NS5B RASs can occur in patients with HCV infection naturally and before exposure to DAAs.Objectives: This study aimed to evaluate naturally-occurring NS5A and NS5B RASs in Iranian patients with HCV genotype 1a (HCV-1a) and -3a infections.Methods: In this cross-sectional study, viral RNA was extracted from serum specimens. NS5A and NS5B regions were amplified using RT-PCR followed by DNA sequencing. The results of nucleotide sequences were aligned against reference sequences of HCV-1a and -3a and the amino acid substitutions were analyzed using geno2pheno [hcv] web application.Results: Among 135 patients with hepatitis C, NS5A amino acid substitutions/RASs were identified in 26.4% and 15.9% of patients with HCV-1a and -3a infections, respectively. The identified amino acid substitutions/RASs in the NS5A region of patients with HCV-1a infection were M28T/V/I 11.1%, Q30R/H 4.2%, L31M 1.4%, and H58Y/P/C/D/Q/S/T 16.7%. Y93H substitution was not found in HCV-1a sequences. In patients with HCV-3a infection, NS5A amino acid substitutions/RASs were A30T/K 9.5%, L31F 1.6%, P58S/T/C 3.2%, Y93H 3.2%, and Y93N 3.2%. No resistance substitutions were identified in NS5B sequences from patients with HCV-1a and -3a infections.Conclusion: In this study, baseline amino acid substitutions/RASs were only identified in the NS5A region in Iranian patients with HCV-1a and -3a infections, and the prevalence of these amino acid substitutions/RASs were in accordance with similar studies. There were no RASs in the HCV-1a and -3a NS5B region.

Context: Hepatic manifestations of Coronavirus Disease 2019 (COVID-19) are common among people living with Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV). Objectives: This systematic review aimed to summarize the evidence on COVID-19 patients living with HBV or HCV co-infections. Data Sources: We searched multiple electronic databases and preprint servers from December 1, 2019, to August 9, 2020. Study Selection: Studies were included if they reported quantitative empirical data on COVID-19 patients living with HBV or HCV co-infections. Data Extraction: Descriptive analyses were reported, and data were synthesized narratively. The quality assessment was completed using the Joanna Briggs Institute critical appraisal tools. Results: Out of the 941 uniquely identified records, 27 studies were included. Of the eligible studies, 232 COVID-19 patients were living with HBV and 22 were living with HCV. Most patients were male, and the mean age was 49.8 and 62.8 years in patients living with HBV and HCV, respectively. Among the reported cases of SARS-CoV-2-HBV co-infection, the proportions of death were 4.7% and 15% in cross-sectional and case series/report studies, respectively. The death proportion was 8.3% among the reported cases of SARS-CoV-2-HCV co-infection. Among COVID-19 patients, 34.1% and 76.2% reported at least one comorbidity besides HBV and HCV infections, mainly hypertension and type 2 diabetes mellitus. The most common COVID-19-related symptoms in both HBV and HCV groups were fever, cough, dyspnea, fatigue, and gastrointestinal symptoms. Conclusions: While understanding the pathogenesis of SARS-CoV-2 requires further investigations, the careful assessment of hepatic manifestations and chronic infections, such as HBV and HCV upon the admission of COVID-19 patients could help reduce multimorbidity among HBV or HCV patients and lead to more favorable health outcomes among them.

Context: Hepatocellular carcinoma (HCC), as the most common type of primary liver cancer (accounting for 70% - 90% of all liver cancers), is the seventh most common malignancy worldwide. Glutathione S-transferases (GSTs) are a specific group of enzymes that are responsible for the detoxification of carcinogens. According to the available literature, genetic variations in this group of enzymes may be associated with the risk of HCC. In this study, we aimed to assess the association of GSTM1 and GSTT1 null deletions and GSTP1 rs1695 polymorphism with the risk of HCC. Methods: We systematically searched electronic databases, including PubMed, Scopus, and Web of Science, using appropriate keywords to gather relevant data until March 2019. Studies that met the inclusion criteria were included in the meta-analysis, using either fixed- or random-effects models based on the presence of heterogeneity. Results: This meta-analysis pooled 19 studies for GSTM1 null deletions, 14 studies for GSTT1 null deletions, and five studies for GSTP1 rs1695 polymorphism. In terms of heterogeneity, the pooled odds ratio (OR) was calculated in a random-effects model for both Asian and non-Asian populations. HCC was found to be associated with GSTM1 null deletions (OR = 1.26, 95% CI: 1.00 - 1.58, P = 0.05) and GSTT1 null deletions (OR = 1.39, 95% CI: 1.10 - 1.74, P = 0.005); however, no significant association was found between HCC and GSTP1 rs1695 polymorphism (OR = 1.14, 95% CI: 0.86 - 1.50, P = 0.36). Conclusions: We found that GSTM1 and GSTT1 null deletions increased the risk of HCC; however, the GSTP1 rs1695 polymorphism did not have a similar effect.