Hepatitis Monthly
Volume:17 Issue: 6, Jun 2017

Context: Recurrence of hepatitis C virus (HCV) infection after liver transplantation (LT) can be prevented, using antiviral therapy and new treatment regimens. Combination of protease, NS5A, and NS5B inhibitors, with or without pegylated-interferon and ribavirin (PEG-IFN/RBV), results in significantly high rates of sustained virologic response (SVR) among post-LT patients with HCV infection. In this study, we aimed to assess the efficacy of direct-acting antiviral (DAA) regimens in post-LT patients with HCV infection.
Evidence Acquisition: We conducted a systematic search in electronic databases to detect eligible studies on DAA treatments after LT. We evaluated English-language studies, including clinical trials and cohort studies, which used antiviral DAA regimens (with or without PEG-IFN/RBV) and reported SVR rates at 12 weeks after the end of treatment (SVR12). After data extraction, the pooled SVRs were calculated, using STATA version 11.
A total of 35 studies with various HCV genotypes were included in our analysis. Due to the small sample size and lack of suitable data on HCV genotypes 2 - 6, the meta-analysis was only conducted among patients with HCV genotype 1; the results of other studies were also obtained. SVR12 rates ranged from 91% to 97% in patients with 12- or 24-week sofosbuvir (SOF)/simeprevir (SMV) ± RBV, SOF/ledipasvir (LDV) ± RBV, and SOF/daclatasvir (DCV) ± RBV regimens. The minimum SVR12 rate was found in patients receiving SMV plus PEG-IFN/RBV (59%; 95% Confidence Interval, 49 - 68).
Administration of new HCV DAA regimens can prevent post-LT HCV infection. The combination of SOF/DCV and SOF/LDV, with or without RBV, for 12 or 24 weeks can produce high rates of SVR12 in post-LT HCV patients in different settings.

Hepatitis C virus (HCV), as a global health concern, has infected around 1.6% of the world population. Introduction of direct-acting antiviral regimens such as sofosbuvir/ledipasvir (SOF/LDV) made the treatment of HCV infection superior to previous HCV antiviral therapies in terms of efficacy and feasibility. The current study aimed at assessing the efficacy and safety of generic SOF/LDV in the Iranian patients with HCV infection.
The current prospective, cohort study was conducted on patients with HCV infection referred to Middle East Liver Diseases Center in 2016. Patients without cirrhosis were treated with daily fixed-dose combination of SOF/LDV (Sobopasvir) for 12 weeks. In cases with compensated cirrhosis, patients were treated with SOF/LDV plus daily weight adjusted ribavirin (RBV) for 12 weeks. If the patient with cirrhosis was RBV-intolerant, he/she was treated with daily fixed-dose combination of SOF/LDV for 24 weeks.
In the current study, 30 patients with the mean age of 52.9 years were enrolled and treated with SOF/LDV. Most of the patients were male (73.3%), had cirrhosis (53.3%), infected with HCV-1a (46.7%), and had previous history of HCV antiviral therapy (62.1%). All the patients completed the course of treatment. Rapid virologic and sustained virologic responses were observed in 29 (96.7%, 95%CI = 83.3% - 99.4%) and also 29 (96.7%, 95%CI = 83.3% - 99.4%) cases, respectively. The only case of treatment failure was a relapse. No serious adverse-event was observed during the treatment course.
The generic SOF/LDV was efficacious and safe to treat Iranian patients with chronic HCV infection.

Prevalence of hepatitis C virus (HCV) in voluntary blood donors (VBD) in China has decreased progressively. However, it was still higher than those in developed countries and some developing countries.
A total of 38952 VBD in Shanghai, China, were recruited in the study. The donated blood specimens were examined for anti-HCV antibody by ELISA. Hepatitis B virus DNA, HCV RNA, or HIV-1 RNA was subsequently tested by nucleic acid test (NAT) in the specimens negative for anti-HCV. A 377-nt partial sequence in HCV NS5B region was amplified in the specimens positive for anti-HCV or positive by NAT. To conduct a phylogenetic analysis, 179 sequences most phylogenetically identical to the VBD strains with BLAST search were retrieved in the GenBank and thirty nine 377-nt partial sequences isolated contemporaneously in local intravenous drug users (IDU) were included.
Overall prevalence of anti-HCV antibody in VBD was 0.46% (179/38952). Varying along demographics, the prevalence was higher in those aged 18-30 years and first donors. A total of thirty seven 377-nt partial sequences were amplified in the specimens positive for anti-HCV, whereas they were not seen in those negative for anti-HCV while positive by NAT. HCV genotype 1b was most predominant in VBD, followed by 2a, 3a, 1a, 3b, 6n, and 6a; in contrast, genotypes 3a and 3b were dominant in IDU. In genotypes 3a, 3b, 6a, and 6n, VBD and IDU strains shared high sequence identities and clustered together. In genotype 1b, VBD strains were phylogenetically identical to the sequences isolated across China, of which some were clustered more closely with IDU strains than the retrieved sequences.
HCV prevalence in VBD in Shanghai remained low. However, there were diverse genotypes of HCV that were identified in VBD. HCV transmission from high-risk population to general population is likely to occur.

De novo lipogenesis (DNL) increases in NAFLD and nicotinamide phosphoribosyltransferase (NAMPT) up regulates two essential enzymes in this pathway. On the other hand, NAMPT function could be affected by the promoter region polymorphism and sex hormones.
This study explored the association of -4689 G/T polymorphism in the promoter region of NAMPT gene with markers of hepatic injury and DNL in patients with NAFLD in order to see whether or not these associations are the same for both sexes.
In this cross-sectional study, 62 consecutive patients (32 men and 30 women) with NAFLD were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to identify -4689 G/T polymorphism. DNL index of erythrocyte membrane as the marker of hepatic DNL was analyzed by gas chromatography. Fasting serum NAMPT, Caspase-cleaved cytokeratin 18 (cCK18), total soluble cytokeratin 18 (CK18), liver enzymes (AST, ALT, ALKP, GGT), and lipid-glucose profile were measured. Anthropometric measurements, Fibroscan, assessment of dietary intake and physical activity were also performed. Two-independent sample t test, chi-square test, one-way analysis of variance, and multiple linear regression were used to analyze the data.
Serum NAMPT and erythrocyte membrane DNL index were not significantly different among the three genotypes in both sexes. In men, serum AST (P = 0.04) and ALT (P = 0.03) were significantly higher in GT genotype than GG genotype. Serum CK18, cCK18, and CAP also had the highest levels in GT genotype but not statistically significant. In women, the markers of hepatic injury were not significantly different between GG and GT genotypes. Serum AST (P = 0.01), ALT (P = 0.01) and cCK18 (P = 0.001) levels were significantly higher in TT genotype. Serum GGT, CK18, and CAP also had the highest level in TT genotype but not statistically significant. These associations remained significant even after adjustment for confounding variables in multiple linear regression.
-4689 G/T polymorphism was not associated with hepatic DNL index but T allele in this polymorphism was associated with increased biomarkers of hepatic inflammation, apoptosis and necrosis in patients with NAFLD especially in men, as one T allele (GT genotype) was enough for increased biomarkers of hepatic injury in men but not in women.

Hepatitis B virus (HBV) can cause chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Coinfection with hepatitis C virus (HCV)/HBV leads to a higher risk of liver damage. Development of HBV awareness campaigns could reduce the prevalence of this disease and limit the consequences.
The aim of this study was to sensitize, detect, and identify HBV markers and propose vaccination for people not infected with HBV.
With the support of “SOS Hepatitis Burkina” association, an HBV screening program, available for all volunteers, was implemented in several localities of Ouagadougou and the surroundings. A rapid HBsAg detection test was performed on 2207 subjects, who voluntarily answered a series of questions. A rapid detection test of HCV antibodies was performed in HBsAg-positive cases. HBV markers were also determined in HBsAg-positive cases.
In a sample of 2207 individuals, aged 1 - 85 years (mean age, 31.4 ± 15.7 years), the prevalence of HBsAg was 9.8% (217/2207) after screening. Before screening, 6.8% (150/2207) of the participants claimed that they were vaccinated against HBV. Also, multivariate analysis revealed that HBV infection was significantly associated with age (21 - 30 years) and vaccination status (P = 0.03; OR, 1.67; 95% CI, 1.04 to 2.69 and P = 0.003; OR, 5.69; 95% CI, 1.80 to 18.00, respectively). Among 217 HBsAg-positive cases, the prevalence of HBV markers was reported as follows: AbHBs (0.9%), HBeAg (6.0%), AbHBe (87.6%), and AbHBc (100.0%). Based on the findings, HCV was detected in 0.9% (2/217) of HBsAg-positive subjects. In this study, 628 out of 1990 HBsAg-negative subjects were vaccinated for three doses, resulting in a vaccination rate of 31.6%.
The present study reported an HBsAg prevalence of 9.8% in the study population. This intervention could contribute to major vaccination coverage against HBV after screening. Therefore, raising awareness and development of screening campaigns on HBV can increase the vaccination coverage of the population. The findings also showed that absence of vaccination against HBV constitutes a high-risk factor for HBV infection.

Acute liver failure (ALF) caused by a sudden loss of liver function in patients without pre-existing liver disease is a rare condition and one of the emergencies in the field of hepatology. The common etiologies of ALF vary in different geographic areas and the course is highly variable among patients with different confounding factors. In this prospective study, ALF patients referred to our tertiary center were followed, and their data were analyzed for determinants of outcome.
From March 2014 through February 2015, all adult and pediatric patients with a diagnosis of ALF, who were admitted to the gastroenterology and hepatology wards of our center with a large liver transplant program, were included in the study. Survivors were followed for at least 3 months after discharge from the hospital.
A total number of 45 (23 males) patients were included in the present study. The most common etiology was acute hepatitis A (15.6%), followed by drug induced liver injury (13.3%), and autoimmune hepatitis (11.1%), while most cases were classified as indeterminate ALF (35.6%). Overall survival rate was 71 %; 24.4% (11 patients) died, 46.7% (21 patients) survived without transplant, and 28.9% (13 patients) were transplanted, but 2 of them did not survive.
Most cases of ALF in this study had unknown etiology. Acute hepatitis A was the most commonly identified cause. About half of the cases survived without transplantation with very good outcomes after 3 months, one-third received liver transplantation with excellent post-transplant survival.

The CIITA plays a pivotal role in immune response by controlling HLA class II gene expression, and NTCP is a functional receptor for HBV. These variants may affect outcomes of HBV infection.
The aim of this study was to determine the association of CIITA and NTCP gene variants with chronic HBV infection and disease progression.
Based on serological and clinical characteristics, 671 unrelated Han Chinese individuals were divided into three major groups: healthy subjects (170 cases), clearance subjects (199 cases), and subjects with chronic HBV infection (305 cases) consisted of 169 chronic hepatitis B, 68 liver cirrhosis, and 68 hepatocellular carcinoma patients. By logistic regression analysis, the rs2296651 AG AA genotype decreased significantly in the chronic HBV infection group when compared to healthy subjects in dominant genetic models (OR = 0.41, 95%CI: 0.23 - 0.74). The rs9302456 CT TT genotype and rs12882299 CT CC significantly increased the risk of chronic HBV infection when compared to healthy subjects in dominant genetic models (rs9302456: OR = 2.24, 95%CI: 1.17 - 4.29; rs12882299: OR = 1.97, 95%CI: 1.27 - 3.07). Using the chronic hepatitis B patients as control group, our study showed that there was no association between CIITA and NTCP gene variants and HBV progression.
Our study suggested that genetic variations in CIITA and NTCP were significantly associated with chronic HBV infection in Han Chinese populations, but not with HBV progression.

HCV NS5B is a major target for drugs that directly inhibit viral replication. Naturally occurring mutations that reduce susceptibility to NS5B inhibitors have been reported.
The present study aimed at screening treatment resistance mutations in the NS5B region in South Africa.
The study comprised 42 NS5B sequences (amino acids 228 - 335), derived from treatment-naïve HCV-infected patients at Dr George Mukhari Academic hospital. Nucleotide sequences were aligned, translated into amino acids, and compared to mutations associated with drug resistance described in the literature.
The most common mutation in this study was Q309R, which was present in all genotypes except genotype 1b. Mutation A333E was detected only in genotype 5a. The NS5B polymorphism C316N, which is associated with resistance to HCV-796, was found in 3 of 4 genotype 1b sequences. The resistance mutations D244N, S282T, C316Y, S326G, and T329I were not detected in any of the analyzed sequences. Position 309 was under positive selection in genotype 5a.
The data indicated the presence of previously described NS5B resistance mutations in South African treatment-naïve patients, suggesting that drug resistance testing would be useful prior to the initiation of antiviral therapy for HCV.