Hepatitis Monthly
Volume:16 Issue: 9, Sep 2016

Context: Despite the great breakthroughs we have witnessed in the last 50 years in the prevention, diagnosis, and treatment of hepatitis B, we are still far from eradicating or even curing the disease. Achieving further progress in controlling this disease will not be possible without discovering the exact pathogenesis behind it. One prime suspect in the pathogenesis of various diseases is oxidative stress. This review will exclusively explore hepatitis B in the context of oxidative stress to obtain a more comprehensive clinical perspective on its pathogenesis and eventual medical therapy.
Evidence Acquisition: We systematically searched PubMed, Google Scholar, Web of Science, EMBASE, and Scopus using an extensive list of keywords in the following three categories: 1) Hepatitis B and oxidation 2) Hepatitis B and antioxidant system 3) Effects of approved anti-hepatitis B drugs on redox status. All relevant articles were obtained and reviewed carefully after the exclusion criteria were deployed.
There is great evidence indicating extensive oxidative stress occurs in hepatitis B. This oxidative stress takes place on multiple levels, including lipid peroxidation, DNA oxidation, protein oxidation, and reactive oxygen and nitrogen species production. However, there are also conflicting results with regard to antioxidant therapy and antioxidant status in hepatitis B, some of which may be explained by the concept of “compensatory gaps.” Nevertheless, further studies are indicated to reach a more thorough judgment.
Despite the presence of vast oxidative stress in hepatitis B, antioxidant therapy is not always effective as a treatment strategy, especially considering that antioxidants can act as “double-edged swords” or antioxidants; if not used at the right time or place or in the right combination, these substances can easily become pro-oxidants. Therefore, several studies will be needed to determine suitable antioxidant therapies. We propose the “2-step Combined Antioxidant Adjuvant Therapy for hepatitis B (2CAAT Hep B)” as a new strategy for antioxidant adjuvant therapy. We also suggest developing an international platform and database for antioxidant adjuvant therapy in hepatitis B (IPAATH and IDAATH) to canalize this field of research in a standardized direction, especially when complexity is a problem.

Context: The hepatitis C virus (HCV) is classified into seven genotypes and more than 100 subtypes. The treatment regimen, duration and efficacy of HCV therapy may vary according to the HCV genotype. Therefore, the HCV genotype should be determined prior to antiviral therapy. The objective of the current study was to review systematically all studies reporting the distribution of HCV genotypes in the countries that make up the Middle East.
Evidence Acquisition: Articles were identified by searching electronic databases, including Scopus, PubMed and Google scholar, with timeline limits (articles published between 1995 and 2016). We carried out a systematic search regarding the distribution of HCV genotypes in Middle Eastern countries.
A total of 579 studies were identified by the electronic search. Of these, a total of 187 were identified as eligible papers including 60,319 patients who were meta-analyzed for pooled distribution of HCV genotypes. In Turkey, Israel, Cyprus, and Iran, genotype 1 was the most prevalent HCV genotype with rates of 82% (95% CI, 82%-83%), 68% (95% CI, 67%-69%), 68% (95% CI, 59%-77%), and 55% (95% CI, 54%-55%), respectively. In Egypt, Iraq, Saudi Arabia, and Syria, HCV genotype 4 was the most common genotype with rates of 86% (95% CI, 85%-88%), 60% (95% CI, 56%-64%), 56% (95% CI, 54%-55%), and 57% (95% CI, 54%-61%), respectively. On the basis of adjusted data, HCV genotype 4 was the most prevalent genotype in the Middle East region, with a rate of 74.7% (95% CI, 73.4%-76%), followed by genotype 1 at 15.1% (95% CI, 14.1%-16%).
Our results showed that HCV genotype 4 is the most prevalent genotype in the Middle East region. However, HCV genotype 1 is the most prevalent among non-Arab countries in the region including Turkey, Iran, Cyprus, and Israel.

Context: Direct acting antivirals (DAAs) have recently emerged as a promising therapeutic regimen for the treatment of hepatitis C virus (HCV) infection, which is a major public health problem. Among the known DAAs, daclatasvir (DCV), an inhibitor of the non-structural 5A protein, has been used in combination with several drugs for treatment of infection with HCV of different genotypes under different conditions. We conducted a systematic review and meta-analysis of combination therapy with DCV.
Evidence Acquisition: We performed a systematic search in PubMed, Scopus, Science Direct and Web of Science with appropriate keywords for DCV. Studies that evaluated any regimen containing DCV and reported the sustained virological response (SVR) 12 weeks after therapy based on the HCV genotype, treatment duration and use of ribavirin (RBV) were included. The selected studies were considered for meta-analysis using STATA 11.0.
We found six different regimens containing DCV: DCV/asunaprevir (ASV), DCV/ASV/beclubavir, DCV/pegylated interferon lambda or alpha/RBV with or without ASV, DCV/simeprevir, DCV/VX-135 and DCV/sofosbuvir (SOF). Most of these regimens were used for the treatment of HCV genotype 1 infections, and in most cases, treatment failure was noted in subtype 1a infections. Among all these regimens, DCV/SOF with or without RBV for 12 or 24 weeks was found to be an efficacious approach for treatment of different types of patients with infections with different HCV genotypes.
Among the treatment regimens containing DCV, DCV/SOF has the highest SVR rate for the treatment of infection with different HCV genotypes in different patient contexts; thus, this regimen shows promise for the treatment of HCV infections..

Recent studies have indicated that abnormal glucose levels and diabetes are negatively associated with the prognosis of patients with chronic hepatitis C virus (HCV) infection. The genetic polymorphism of the promoter region -1260 of a gene encoding the enzyme 1-alpha-hydroxylase (CYP27B1-1260) has been shown to have an impact on the signaling pathways involved in insulin secretion.
The aim is to investigate the effect of CYP27B1-1260 polymorphism on the fasting plasma glucose (FPG) levels in patients with chronic HCV undergoing antiviral therapy.
Patients and A total of 461 patients with chronic HCV infection and 300 volunteers without HCV infection were enrolled in an observational cohort study in the China-Japan Union hospital of Jilin University and the Second Hospital of Daqing, Changchun, Jilin Province. Both groups were further divided into normal and abnormal FPG subgroups. The frequencies of the three CYP27B1-1260 genotypes (AA, AC, and CC) were determined in each subgroup. FPG levels were monitored at baseline in HCV and control participants, and both during and after antiviral therapy in HCV infected patients. The frequency of each genotype was determined. Logistic regression analysis was performed to evaluate the risk factors associated with abnormal FPG levels in HCV infected patients undergoing antiviral therapy.
In HCV infected patients with abnormal FPG levels, the frequency of the genotype CC was significantly higher than that in patients with normal FPG levels (19% vs. 7%, P CYP27B1-1260 polymorphism is associated with abnormal glucose metabolism in HCV infected patients. HCV infected individuals with CYP27B1-1260 genotype CC appeared to have an increased risk of developing abnormal FPG levels.

Liver biopsy is an invasive procedure that is currently still necessary for predicting underlying hepatic injury related to chronic viral hepatitis B (CVHB). To date, none of the studied non-invasive methods have been able to replace liver biopsy. An apoptotic serum marker, M30, which has been reported to indicate ongoing liver fibrosis, has been popular in recent years.
We aimed to investigate the possible role of M30 in predicting CVHB-associated hepatic injury and its severity.
Forty-eight patients undergoing liver biopsy for evaluation of the severity of CVHB-related liver injury and 40 healthy controls were included in this cross-sectional study. M30 levels were determined for all CVHB patients and controls, and other laboratory parameters and demographic features were obtained from our hospital’s database.
The mean ages of patients and controls were 39.7 and 45.7 years, respectively, and 35% of the controls and 52% of the patients were male. In contrast to lower platelet counts, transaminase and M30 levels were both higher in the patient group than in the controls. Among the investigated parameters, only transaminase increased as the fibrosis stage changed from mild to moderate; however, none of the laboratory parameters, including M30, differed as the histological activity index (HAI) score increased.
M30 levels were higher in CVHB patients compared to healthy controls. However, M30 levels were similar in the mild and moderate stages of fibrosis, so they did not indicate the severity of underlying fibrotic or inflammatory processes in CVHB patients.

The prevalence of HCV infection in people with hemophilia is substantially higher than that in the general population (63% - 98%). Multiple transfusions and substitutive therapy have also been linked to a high risk of HBV and HIV transmission. However, the prevalence of other blood-borne viral infections in this population is less well known.
This study aimed to assess the prevalence of co-infection with HBV and other blood-borne viruses in Polish HCV-infected hemophiliacs.
Seventy-one individuals, the majority of whom were male (94.36%), who had congenital bleeding disorders (60 had hemophilia A, five had hemophilia B, and six had other factor deficiencies) and HCV infection, which was defined as the presence of positive anti-HCV antibodies, were included in this study. The study group was divided into two subgroups according to the year in which blood donors were first tested for HBsAg in Poland. The serological markers were screened using commercially available enzyme immunoassays according to the manufacturer’s instructions. The molecular tests were performed using real-time PCR technology with commercial assays according to the manufacturer’s instructions.
The spontaneous elimination rate of HCV RNA was 29.6%. The HCV genotype 1 was detected in 28 patients (65.1%), genotype 2 in one patient (2.3%), genotype 3 in 11 patients (25.6%), genotype 4 in two patients (4.7%), and a mixed infection with genotypes 1 and 4 was detected in one person (2.3%). Fifty-three patients (74.6%) were anti-HBc positive. Among the seven HBsAg() patients, three individuals were HBV-DNA positive. No occult hepatitis B was detected. In six HBsAg positive patients, the HCV RNA was positive, while one patient was also infected with HIV. The prevalence rate of past infection with HAV in the study group was 30.9%, with a tendency for a higher prevalence in older patients. The prevalence of CMV and EBV infection was high and similar to that seen in the general population. All the patients were HGV and HTLV-1 negative.
The diagnostics and management of infections with hepatotropic viruses, particularly HBV, are neglected in hemophilic patients. All patients with coagulation disorders and a history of exposure to non-inactivated blood products should be screened for blood-borne infections. The prevalence of other potentially blood-borne viral infections exhibited a pattern similar to that observed in the general population.

In patients with chronic hepatitis B (CHB), the relation of interkeukin-7 (IL-7) to either the T follicular helper cells (Tfh cells) or to a specific cellular immune response is not clear.
The present study aims to explore the possible relationship of IL-7 to Tfh cells and to hepatitis B virus (HBV)-specific cellular immune response in patients with CHB.
Ninety-one adult patients with CHB were divided into groups A, B, and C, according to the patients’ IL-7 levels (low, medium, and high). Tfh cells and HBV-specific cytotoxic T lymphocytes (CTLs) were detected with flow cytometry; IL-7 and IL-21 were determined with a double antibody sandwich enzyme-linked immunosorbent assay; and HBV DNA was determined by using a real-time fluorescent quantitative polymerase chain reaction.
The results showed that the levels of IL-7, Tfh cells, IL-21, and HBV-specific CTLs of patients in group C were significantly higher than those of patients in group B, (P This study suggests that the IL-7 level of CHB patients may be related to Tfh cells. In CHB patients, IL-7 possibly increases the level of Tfh cells and HBV-specific cellular immune responses and thereby reduces the HBV DNA level.

Hepatitis A is a common health concern both in developing and developed countries. Hygienic and socioeconomic parameters deeply impact the prevalence and transmission of this disease. Evaluating the epidemiological distribution and risk factors for Hepatitis A virus (HAV) is necessary for policy makers to improve local and national preventive measures.
The aim of this study was to compare the prevalence of hepatitis A infection in a sample of Iranian adolescents living in different provinces of Iran and to assess its family- and community-related risk factors.
In this cross-sectional study, serum samples of 10 to 18-year-old adolescents, who were studied in a national health survey, were examined for anti-HAV antibodies. A total of 2,494 subjects were included from 16 provinces by multistage random cluster sampling. Demographic and socioeconomic factors related to HAV transmission were extracted by valid questionnaires. A multilevel analysis using mixed-effects logistic regression (melogit) was used to evaluate the association of risk factors with HAV infection.
The weighted prevalence of HAV varied significantly across the studied provinces (P = 0.001), ranging from 50.43% in the Fars province to 78.81% in Markazi province. HAV was significantly more prevalent in children whose mothers worked outside of the home (OR, 1.73; 95% CI, 1.14-2.62; P = 0.009).
The risk of symptomatic HAV infection is considerable in adolescents of all studied provinces; thus, universal HAV vaccination is recommended for all adolescents, regardless of their socioeconomic level. However, the risk is higher in some provinces, which seem to be transitioning from intermediate to low endemicity.

Infection with the hepatitis B virus (HBV) is an important global health problem. Knowledge of the geographic distribution pattern of HBV infection can help to control the spread of the disease.
To determine the prevalence of HBV infections and risk factors for the disease for the first time in Birjand, Southeastern Iran.
This was an analytical cross-sectional study conducted in 2013 - 2014 of 5235 HBV cases in Birjand, South Khorasan Iran. Subjects aged 15 - 70 y were selected using the cluster sampling method. Blood samples were taken and tested at a reference laboratory for the hepatitis B core antibody (anti-HBc). Seropositive specimens were tested for the hepatitis B surface antigen (HBsAg).
The mean age (± SD) was 39.07 (± 14.04) y, and 786 (15%) subjects were anti-HBc positive. The prevalence of HBsAg was 1.6% (n = 85). The prevalence of anti-HBc seropositivity was significantly higher in subjects with a lower level of education (P = 0.09), older subjects (P = 0.001), intravenous (IV) drug users (P Although the frequency of HBsAg seropositivity in the present study was close to that observed in the overall Iranian population, the seroprevalence of anti-HBc was higher, possibly due to the exposure of the elderly to more risk factors. The risk factors were similar. These included a history of blood transfusions, cupping, hospital admission, endoscopy, or familial HBV/HCV infection, in addition to piercings and drug abuse.

Although hepatitis B infection is the major cause of chronic liver disease in Iran, no studies have employed economic evaluations of the medications used to treat Iranian patients with chronic hepatitis B (CHB). Therefore, the cost-effectiveness of the different treatment options for this disease in Iran is unknown.
The aim of this study was to compare the cost utility and cost-effectiveness of medication strategies tailored to local conditions in patients with HB e antigen (HBeAg)-negative CHB infection in Iran.
An economic evaluation of the cost utility of the following five oral medication strategies was conducted: adefovir (ADV), lamivudine (LAM), ADV LAM, entecavir (ETV), and tenofovir (TDF). A Markov microsimulation model was used to estimate the clinical and economic outcomes over the course of the patient’s lifetime and based on a societal perspective. Medical and nonmedical direct costs and indirect costs were included in the study and life-years gained (LYG) and quality-adjusted life-years (QALY) were determined as measures of effectiveness. The results are presented in terms of the incremental cost-effectiveness ratio (ICER) per QALY or LYG. The model consisted of nine stages of the disease. The transition probabilities for the movement between the different stages were based on clinical evidence and international expert opinion. A probabilistic sensitivity analysis (PSA) was used to measure the effects of uncertainty in the model parameters.
The results revealed that the TDF treatment strategy was more effective and less costly than the other options. In addition, TDF had the highest QALY and LYG in the HBeAg-negative CHB patients, with 13.58 and 21.26 (discounted) in all comparisons. The PSA proved the robustness of the model results. The cost-effectiveness acceptability curves showed that TDF was the most cost-effective treatment in 59% - 78% of the simulations of HBeAg-negative patients, with WTP thresholds less than $14010 (maximum WTP per QALY).
The use of TDF in patients with HBeAg-negative CHB seemed to be a highly cost-effective strategy. Compared with the other available medication options, TDF was the most cost-saving strategy. Thus, TDF may be the best option as a first-line medication. Patients can also be switched from other medications to TDF.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major health problem in the world. Hairdressers (barbers) are in continuous contact with scissors and blades, and are considered a high-risk group for these infections.
The aim of this study was to analyze the prevalence of hepatitis B and C infections in barbers in Tehran and to evaluate their attitudes and knowledge about the occupational risk of these infections.
Six hundred eleven barbers were included in this study. A group of 556 bakers were also selected from the same regions, as a low-risk control group. Serum levels of hepatitis B surface antigen (HBsAg), HBsAg-specific antibody (HBsAb), hepatitis B core antigen-specific antibody (HBcAb), and hepatitis C virus-specific (anti-HCV) antibody markers were measured with the enzyme-linked immunosorbent assay (ELISA). Participants were interviewed using a questionnaire consisting of four sections: demographic information, awareness, behavior, and personal attitudes.
There were no significant differences in the frequency of HBsAg between the two groups. However, the frequency of HCV Ab in barbers was significantly higher than that in bakers (P Being a barber alone is not a potential risk factor for HBV infection, while HCV infection is still an occupational health hazards for barbers. We suggest more extensive case-control studies with regard to rates of hepatitis B and C markers among barbers in other Iranian cities to assess the incidence of hepatitis B and C infections among this population.

A strong association between obesity and non-alcoholic fatty liver disease (NAFLD) has been reported.
This study was conducted to evaluate if new obesity indices, including a body shape index (ABSI) and body roundness index (BRI), have stronger associations with NAFLD than waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR).
In this cross-sectional study, we utilized the data of 4,872 participants aged 18 - 74 years from a cohort study conducted among 6,143 subjects in northern Iran. Logistic regression analysis was performed on NAFLD as the outcome and obesity measures (based on Z-score values) as potential predictors. Receiver operating characteristic (ROC) analyses were conducted, in which NAFLD was considered as a reference variable and obesity measures as classification variables. The discriminatory ability of the obesity measures was reported based on area-under-the-curves, and the related cut-off points of BRI and WHtR were determined using the Youden index (YI).
Based on our results, BRI (OR = 5.484 for men and OR = 3.482 for women) and WHtR (OR = 5.309 for men and OR = 3.854 for women) showed a higher association with NAFLD than ABSI (OR = 1.363 for men and OR = 1.003 for women) and WHR (OR = 3.123 for men and OR = 1.628 for women). The optimal cut-off points for BRI were 4.00 (sensitivity = 82.7%, specificity = 70.8%) for men and 5.00 (sensitivity = 83.3%, specificity = 71.7%) for women. The optimal cut-off points for WHtR were 0.533 (sensitivity = 82.7%, specificity = 70.8%) for men and 0.580 (sensitivity = 83.3%, specificity = 71.7%) for women.
While BRI and WHtR have equally strong associations with NAFLD, ABSI and WHR have weaker associations with NAFLD than BRI and WHtR.

Chronic hepatitis B (CHB) remains a major public health problem worldwide, and the prevalence of CHB patients with hepatic steatosis is gradually increasing. Noninvasive approaches for the assessment of hepatic steatosis have been developed as alternatives to liver biopsy.
This study evaluated the diagnostic performance of the fat attenuation parameter (FAP) measured by transient elastography (FibroTouch) and a new algorithm to assess hepatic steatosis in CHB patients, in comparison to liver biopsy as the gold standard.
Two hundred fifty-four CHB patients underwent simultaneous liver biopsy, biochemical blood testing, and FibroTouch examination. A new algorithm based on four factors (FAP; body mass index, BMI; high-density lipoprotein, HDL; apolipoprotein B, APOB) was defined as follows: fatty index = 10*ep/ (1), and P = -2.75 0.028 ln FAP (dB/m) 0.409 ln BMI (Kg/m2) - 2.482 ln HDL (mmol/L) 1.979 ln APOB (g/L). The performances of FAP and fatty index were assessed by area under the ROC curve (AUROC).
The difference in FAP was significant (P 0, ≥ 5%, ≥ 10%, ≥ 20%, and ≥ 30% were 224.1, 230.6, 235.5, 246.9, and 261.1 dB/m, and AUROCs were 0.833, 0.801, 0.915, 0.917, and 0.972, respectively. The optimal cutoff value of fatty index for the diagnosis of hepatic steatosis was 1.5 and the AUROC was 0.807.
FAP is an accurate, reliable, and noninvasive approach that can also be combined with other metabolic biomarkers to comprehensively detect and quantify hepatic steatosis.

Sinusoidal obstruction syndrome (SOS) is a severe adverse event of long-term chemotherapy in patients with colorectal cancer. It usually develops as liver congestion due to diffuse microscopic obstruction in liver parenchyma. In contrast, it sometimes appears as a liver mass occurring with local parenchymal hemorrhaging, and is often misdiagnosed as liver metastasis.
A 40-year-old woman with rectal cancer underwent high anterior resection and partial liver resection of segment 7 due to synchronous liver metastasis. She received oxaliplatin-based chemotherapy (mFOLFOX6) as adjuvant chemotherapy for 6 months. A 13-mm irregular low-echoic mass was detected by CT in segment 3 of the liver 12 months after the operation. The mass was again resected as a liver metastasis because it had increased in size. The pathological diagnosis was focal SOS, which showed sinusoidal dilation and congestion by hepatocyte trabeculae in the liver parenchyma.
Atypical irregular tumors should be considered as SOS when the patient has received oxaliplatin-based chemotherapy. A qualitative imaging modality diagnosis, such as with diffusion-weighted MRI, is superior to a morphological diagnosis in focal SOS. This imaging modality can prevent unnecessary operations.