Patient-reported outcomes of sleep, mood and quality of life after treatment of chronic hepatitis C infection using direct-acting antiviral agents.

OBJECTIVES: The aim was to investigate the effect of hepatitis C virus (HCV) infection treatment with direct-acting antiviral (DAA) drugs on patients' mood, sleep quality and quality of life (QoL). METHODS: Chronic HCV-infected patients receiving DAAs were evaluated prospectively. Patients were evaluated before the beginning of treatment and 12-24 weeks after finishing their treatment duration using the Pittsburgh Sleep Quality Index, Beck depression inventory questionnaire and SF-36 health-related QoL questionnaires. RESULTS: A total of 120 patients with a mean age of 41.03 ± 7.68 years were evaluated (68.3% males). The mean follow-up duration was 141.79 ± 27.88 days after finishing the treatment. Significant improvement in the scores of sleep quality (5.13 ± 1.5 vs. 3.43 ± 1.35), mood (12.77 ± 4.02 vs. 9.27 ± 3.14) and QoL (77.49 ± 5.15 vs. 83.95 ± 3.39) post treatment compared with pretreatment were observed (p < 0.05). Changes in patients' sleep and mood were not related to their QoL change (p > 0.05). DISCUSSION: DAAs for the treatment of HCV have a significant effect on improving their sleep, mood and QoL. The changes in sleep quality, mood and QoL of patients were independent and were not affected by each other.

[Evaluation of miR-122 level in the plasma of chronically HCV infected patients].

MicroRNAs (miRNAs) are small non-coding RNA molecules, which have an important function in regulating RNA stability and gene expression. They also can circulate in a cell-free form in the blood thatmakes them potential disease markers. The liver contains various classes of miRNAs in which miR-122 accounts for about 70% of all miRNAs and it has been proved that its level increases in case of liver damage. Here, we investigated plasma levels of miR-122 as a useful disease parameter in patients with chronic hepatitis C (CHC) infection. Thirty five hemophilia and thalassemia patients with CHC were studied. The total RNA was extracted from plasma samples, and miR-122 levels were measured by qPCR and then compared with the specific liver markers. The plasma levels of alanine transaminase (ALT) and aspartate transaminase(AST) were correlated with plasma miR-122 level in CHC patients, and the level of circulating miR-122 in healthy individual groups were rarely lower than those of patients with CHC. In our study, miR-122 levels correlated well with markers of liver inflammatory activity. Plasma miR-122 can be assumed to be another marker in liver similar to the currently used specific markers such as ALT and AST for evaluation of liver damage in hepatitis C virus (HCV) infected patients. Moreover, the correlation between miR-122 and ALT was shown to be higher than between miR-122 and AST.

Hepatitis delta virus facilitates the selection of hepatitis B virus mutants in vivo and functionally impacts on their replicative capacity in vitro.

To identify molecular interactions between hepatitis B virus (HBV) and hepatitis delta virus (HDV), HBV sequences were analysed in HBV/HDV-infected patients. Characteristic amino acid substitutions were found in cytosolic domains of hepatitis B surface antigen (HBsAg), in contrast to HBV-mono-infected controls. The functional impact of HDV on the replication of wild-type and mutant HBV was assessed in vitro. HDV co-transfection significantly reduced the replication of HBV strains containing precore or basal core promoter mutations, and HBV polymerase or surface antigen mutants affected HDV replication in vitro. Conclusively, our study revealed distinct HBsAg mutational patterns in HBV/HDV-infected patients and novel functional interactions between HBV and HDV.

Clearance of HBV DNA in immunized children born to HBsAg-positive mothers, years after being diagnosed with occult HBV infection.

In a previous study, we observed immunoprophylaxis failure due to occult hepatitis B virus (HBV) infection (OBI) despite the presence of adequate levels of anti-HBs in 21 (28%) of 75 children born to HBsAg-positive mothers. The aim of the study was to explore the maintenance of this cryptic condition in this population. Of 21 OBI-positive children, 17 were enrolled. HBV serological profiles were determined by enzyme-linked immunosorbent assay. Highly sensitive real-time and standard PCR followed by direct sequencing were applied in positive cases. The mean age (±SD) of studied patients was 6.57 ± 2.75 years. All children still were negative for HBsAg. All but one (94%) were negative for HBV DNA. Only two children were positive for anti-HBc. The results of the most recent anti-HBs titration showed that 4 (23.5%) and 13 (76.5%) had low (<10 IU/mL) and adequate (>10 IU/mL) levels of anti-HBs, respectively. The only still OBI-positive patient had an HBV DNA level of 50 copy/mL, carried the G145R mutation when tested in 2009 and again in 2013 in the 'a' determinant region of the surface protein. Further follow-up showed that after 18 months, he was negative for HBV DNA. In high-risk children, the initial HBV DNA positivity early in the life (vertical infection) does not necessarily indicate a prolonged persistence of HBV DNA (occult infection). Adequate levels of anti-HBs after vaccine and hepatitis B immune globulin immunoprophylaxis following birth could eventually clear the virus as time goes by. Periodic monitoring of these children at certain time intervals is highly recommended.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm - volume 3.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.

Strategies to manage hepatitis C virus infection disease burden - volume 3.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries in Europe, the Middle East and Asia, and the relative impact of two scenarios was considered: increased treatment efficacy while holding the annual number of treated patients constant and increased treatment efficacy and an increased annual number of treated patients. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. A 90% reduction in total HCV infections within 15 years is feasible in most countries studied, but it required a coordinated effort to introduce harm reduction programmes to reduce new infections, screening to identify those already infected and treatment with high cure rate therapies. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. Among European countries, the majority of patients were born between 1940 and 1985. A wider range of birth cohorts was seen in the Middle East and Asia (between 1925 and 1995).

Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 3.

Detailed, country-specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus (HCV) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7 001 000 cases) and Indonesia (3 187 000 cases). Injection drug use (IDU) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden.

Seroepidemiology and clinical features of hepatitis delta among HBsAg carriers: a study from Hepatitis Clinic of Iranian Blood Transfusion Organization.

BACKGROUND: Hepatitis B is a significant health problem and more than 350 million individuals are infected with hepatitis B virus (HBV) globally. About 5% of these individuals are coinfected with hepatitis D virus (HDV). HBV-HDV coinfection increases the rate of fulminant hepatitis, chronic hepatitis and cirrhosis. This study aimed to evaluate the epidemiology of HDV in individuals positive for hepatitis B surface antigen (HBsAg) who were referred to Tehran Blood Transfusion Hepatitis Clinic from 2011 to 2012. MATERIALS AND METHODS: HBsAg-positive individuals attending this clinic were tested for anti-HDAg antibodies (anti-HDAbs). All samples positive for anti-HDAb were also tested for detection of HDV RNA by reverse transcription-polymerase chain reaction (RT-PCR). A questionnaire consisting of demographic characteristics and potential risk factors for acquisition of HDV was filled for each individual. RESULTS: Among 1038 individuals, HBsAg was detected in 660 (63.6%) cases following blood donation and in 378 (36.4%) cases following blood testing. In this study, 23 [2.2%, 95% confidence interval (CI) = 1.3-3.2%] patients were HDV-seropositive. In HDV-seropositive patients, 14 (60.9%, 95% CI = 39.1-78.3%) were positive for HDV RNA. HDV-seropositive cases were more likely to have evidence of severe forms of hepatitis than the group of individuals without anti-HDAb (P < 0.01). Familial history of hepatitis D infection was more observed in HDV-seropositive patients than in individuals negative for anti-HDAb (P < 0.01). CONCLUSION: The seroprevalence of HDV in HBsAg-positive individuals in this study was about 2% which seems to be lower than the global prevalence of HDV.

Targeting microRNA-122: walking on cutting edge of hepatitis C virus infection therapy.

Hepatitis C virus (HCV) infection, with an estimated 170 million carriers worldwide, remains a major cause of chronic liver disease. Current anti-HCV treatments have significant side effects and have met with only partial success. Therefore, a more effective therapeutic modality for HCV infection is needed. The stability and propagation of HCV is dependent on the interaction between its genome and a highly abundant liver microRNA (miRNA), known as microRNA-122 (miR-122). As a conserved host factor that would not be expected to evolve resistance mutations, miR-122 makes an attractive antiviral target. In this review we will discuss how targeting miR-122, using antisense oligonucleotides (ASOs), can be a new anti-HCV treatment.

Seroepidemiology of human T-cell lymphotropic virus among Iranian adult thalassemic patients.

BACKGROUND: A large number of transfusion-dependent thalassemic patients is at a substantial risk for transfusion-transmitted infections. Human T-cell lymphotropic virus (HTLV) is a blood-borne pathogen and can be transmitted via cellular products. We aimed to evaluate the seroprevalence of HTLV in transfusion-dependent thalassemic patients referred to Tehran Adult Thalassemia Clinic. METHODS: From 2008 to 2010, 257 transfusion-dependent thalassemic patients who referred to Tehran Adult Thalassemia Clinic were enrolled. The seroprevalence of HTLV, hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV were assessed using enzyme-linked immunosorbant assay (ELISA). Also, the samples with positive result for anti-HTLVAb (by ELISA) were reassessed using Western blot for HTLV. RESULTS: Among the 257 transfusion-dependent thalassemic patients who were tested for anti-HTLVAb, 29 (11.3%, 95% CI = 7.8-15.6%) were found to be anti-HTLVAb positive by ELISA and Western blot. No case was detected to be HBsAg positive, whereas 16% had HBV seroconversion criteria, and more than 95% had anti-HBsAb in their sera. Also, 103 (40.1%) patients were HCV seropositive, 13 (5.1%) patients of which were co-infected with HCV/HTLV. Among the HTLV-infected patients, 44.8% were co-infected with HCV, whereas 39.5% of HTLV-seronegative individuals were HCV mono-infected (P > 0.05). CONCLUSION: This study showed that transfusion-dependent thalassemic patients were in higher risk for transmission of different blood-borne pathogens such as HTLV. The screening of HTLV in Iranian blood donors is recommended.

Hepatitis B virus-induced hepatocellular carcinoma: the role of the virus x protein.

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases and has the fourth highest mortality rate worldwide. Chronic hepatitis B virus (HBV) infection has been identified as a major risk factor in HCC. Currently available evidence support a critical role of hepatitis B virus x (HBx) gene and protein in the pathogenesis of HBV-induced HCC. HBx protein is a multifunctional regulator that modulates cellular signal transduction pathways, transcriptional regulations, cell cycle progress, DNA repair, apoptosis, and genetic stability by interacting with different host factors. This review describes the current state of knowledge about the biological roles of this protein in the development of HCC.

Hepatitis B virus surface protein mutations clustered mainly in CTL immune epitopes in chronic carriers: results of an Iranian nationwide study.

Mutations within the coding region of hepatitis B surface antigen (HBsAg) have been found naturally in chronic carriers. To characterize the mutations of HBsAg from Iranian chronic carriers who were vaccine and/or medication naive. The surface genes from 360 patients were amplified and directly sequenced. The distribution of amino acid substitutions was classified according to different immune epitopes of the surface protein. All isolates belonged to genotype D. 222 (61.6%) of 360 patients contained at least one amino acid substitution. 404 (74.5%) of 542 amino acid changes occurred in different immune epitopes of HBsAg, of which 112 (27.7%) in 32 residues of B-cell epitopes (62 in the 'a' determinant); 111 (27.4%) in 32 residues of T helper; and 197 (48.7%) in 32 residues inside cytotoxic T lymphocyte (CTL) epitopes. One Th (186-197) and two CTL (28-51 and 206-215) epitopes were found to be hotspot motifs for the occurrence of 213 (52.7%) substitutions. 20 stop codons were identified in different epitopes. There was a significant association between amino acid substitutions and anti-HBe seropositivity; however, the correlation between such changes with viral load and ALT levels was not significant. In chronic hepatitis B virus(HBV) carriers, positive selection in particular outside the 'a' determinant appeared to exert influence on the surface proteins. These changes could be immune escape mutations naturally occurring due to the host immune surveillance especially at the T-cell level.

Therapeutic potential of RNA interference: a new molecular approach to antiviral treatment for hepatitis C.

Hepatitis C virus (HCV) infection remains a major cause of chronic liver disease with an estimated 170 million carriers worldwide. Current treatments have significant side effects and have met with only partial success. Therefore, alternative antiviral drugs that efficiently block virus production are needed. During recent decades, RNA interference (RNAi) technology has not only become a powerful tool for functional genomics but also represents a new therapeutic approach for treating human diseases including viral infections. RNAi is a sequence-specific and post-transcriptional gene silencing process mediated by double-stranded RNA (dsRNA). As the HCV genome is a single-stranded RNA that functions as both a messenger RNA (mRNA) and replication template, it is an attractive target for the study of RNAi-based viral therapies. In this review, we will give a brief overview about the history and current status of RNAi and focus on its potential application as a therapeutic option for treatment for HCV infection.

Renal grafts from anti-hepatitis B core-positive donors: a quantitative review of the literature.

BACKGROUNDS AND AIMS: Organ shortage is a major problem in transplantation. The use of organs from hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (HBcAb)-positive donors could significantly increase the donor pool. However, little information is available about the impact of HBcAb status of renal donors on viral transmission to recipients. To address this issue, the present quantitative review of relevant studies has been performed. MATERIALS AND METHODS: Electronic databases including Medline, EMBASE, ISI, and Scopus were systematically searched for studies that evaluated risk of hepatitis B virus (HBV) transmission through renal transplantation from HBsAg-/HBcAb+ donors. Eligible studies were identified according to predefined criteria. The final outcome was one of HBV markers seroconversion defined as HBsAg, hepatitis B surface antibody (HBsAb), or HBcAb detection in previously seronegative end-stage renal disease (ESRD) patients after transplantation, and without other identified major sources of infection. RESULTS: Nine studies with 1385 eligible kidney recipients were included. In total, 45 subjects showed seroconversion of HBV markers as follows: HBsAg (n = 4) (0.28%; 95% confidence interval [CI] 0.006; 0.57), HBcAb (n = 32), HBsAb (n = 5), and either HBcAb or HBsAb (n = 4). The total rate of seroconversion after renal transplantation was calculated to be 3.24% (95% CI: 2.31-4.18). CONCLUSION: Our review indicates that the risk of HBV transmission from HBcAb-positive kidney donors is extremely low. Therefore, kidneys from these donors can be transplanted safely into ESRD patients.