Hepatitis C Virus Infection in Persons Who Inject Drugs in the Middle East and North Africa: Intervention Strategies.

There is a high incidence and prevalence of hepatitis C viral infection in persons with or without substance use disorders (SUDs) in the Middle East and North Africa (MENA) region, but only a small number receive comprehensive care. Highly effective direct-acting antiviral (DAA) medications are available at substantially lower costs; however, complete elimination of the hepatitis C virus (HCV) can only be achieved if integrated care strategies target those at highest risk for HCV infection and transmission and improve access to care. Due to the high prevalence of SUD in the MENA region, strategies to eliminate HCV must focus on integrated healthcare across multiple subspecialties, including addiction medicine, psychiatry, infectious diseases, hepatology, and social work. In this invited manuscript, we review the epidemiology of HCV in the MENA region and highlight intervention strategies to attain the WHO's goal of HCV eradication by 2030.

Sorafenib use in hepatitis B virus- or hepatitis C virus-related hepatocellular carcinoma: A propensity score matching study.

Sorafenib is the recommended first-line treatment option for patients with advanced hepatocellular carcinoma (HCC). Hepatitis C virus (HCV)-related advanced HCC (HCV-HCC) seemed to have a better response than hepatitis B virus (HBV)-related HCC (HBV-HCC) in sorafenib use, but it was undetermined. Hence, we aimed to investigate the effect of sorafenib between HBV-HCC and HCV-HCC patients in Taiwan. From August 2012 to December 2016, 575 consecutive advanced HCC patients received sorafenib under the reimbursement of Taiwan national health insurance in our hospital. Radiologic assessment was performed at a 2-month interval. Those patients with tumor progression or liver function deterioration were disallowed for further sorafenib use. Patients with HBV or HCV infection were, retrospectively, enrolled and followed till December 2018. There were 277 (62.4%) HBV-HCC patients and 167 (37.6%) HCV-HCC patients. Before sorafenib, 192 (69.3%) HBV-HCC patients who had used nucleoside analogs (NAs) for HBV management, whereas only 5 (3%) HCV-HCC patients received interferon-based antiviral therapy. Overall survival (OS) of HCV-HCC patients was significantly superior to HBV-HCC patients without NAs (8.8 months vs. 4.9 months, p = 0.006), but was noninferior to HBV-HCC patients with NAs (8.8 months vs. 10.7 months, p = 0.54). Using propensity score matching, progression-free survival (2.0 months vs. 2.1 months, p = 0.374) and OS (10.5 months vs. 9.6 months, p = 0.746) between HBV-HCC and HCV-HCC groups were not different. Antiviral therapy might increase survival benefits of advanced HBV-HCC patients underwent sorafenib use, leading to a comparable OS to HCV-HCC patients in Taiwan.

A hepatitis B virus causes chronic infections in equids worldwide.

Preclinical testing of novel therapeutics for chronic hepatitis B (CHB) requires suitable animal models. Equids host homologs of hepatitis C virus (HCV). Because coinfections of hepatitis B virus (HBV) and HCV occur in humans, we screened 2,917 specimens from equids from five continents for HBV. We discovered a distinct HBV species (Equid HBV, EqHBV) in 3.2% of donkeys and zebras by PCR and antibodies against EqHBV in 5.4% of donkeys and zebras. Molecular, histopathological, and biochemical analyses revealed that infection patterns of EqHBV resembled those of HBV in humans, including hepatotropism, moderate liver damage, evolutionary stasis, and potential horizontal virus transmission. Naturally infected donkeys showed chronic infections resembling CHB with high viral loads of up to 2.6 × 109 mean copies per milliliter serum for >6 mo and weak antibody responses. Antibodies against Equid HCV were codetected in 26.5% of donkeys seropositive for EqHBV, corroborating susceptibility to both hepatitis viruses. Deltavirus pseudotypes carrying EqHBV surface proteins were unable to infect human cells via the HBV receptor NTCP (Na+/taurocholate cotransporting polypeptide), suggesting alternative viral entry mechanisms. Both HBV and EqHBV deltavirus pseudotypes infected primary horse hepatocytes in vitro, supporting a broad host range for EqHBV among equids and suggesting that horses might be suitable for EqHBV and HBV infections in vivo. Evolutionary analyses suggested that EqHBV originated in Africa several thousand years ago, commensurate with the domestication of donkeys. In sum, EqHBV naturally infects diverse equids and mimics HBV infection patterns. Equids provide a unique opportunity for preclinical testing of novel therapeutics for CHB and to investigate HBV/HCV interplay upon coinfection.

Identification of Potential HCV Inhibitors Based on the Interaction of Epigallocatechin-3-Gallate with Viral Envelope Proteins.

Hepatitis C is affecting millions of people around the globe annually, which leads to death in very high numbers. After many years of research, hepatitis C virus (HCV) remains a serious threat to the human population and needs proper management. The in silico approach in the drug discovery process is an efficient method in identifying inhibitors for various diseases. In our study, the interaction between Epigallocatechin-3-gallate, a component of green tea, and envelope glycoprotein E2 of HCV is evaluated. Epigallocatechin-3-gallate is the most promising polyphenol approved through cell culture analysis that can inhibit the entry of HCV. Therefore, various in silico techniques have been employed to find out other potential inhibitors that can behave as EGCG. Thus, the homology modelling of E2 protein was performed. The potential lead molecules were predicted using ligand-based as well as structure-based virtual screening methods. The compounds obtained were then screened through PyRx. The drugs obtained were ranked based on their binding affinities. Furthermore, the docking of the topmost drugs was performed by AutoDock Vina, while its 2D interactions were plotted in LigPlot+. The lead compound mms02387687 (2-[[5-[(4-ethylphenoxy) methyl]-4-prop-2-enyl-1,2,4-triazol-3-yl] sulfanyl]-N-[3(trifluoromethyl) phenyl] acetamide) was ranked on top, and we believe it can serve as a drug against HCV in the future, owing to experimental validation.

Synthesis and In Vitro anti-HCV and Antitumor Evaluation of Schisandronic Acid Derivatives.

BACKGROUND: Schisandronic acid (SA), a triterpenoid from fruits of Schisandra sphenanthera, inhibited pan-genotypic HCV entry into human hepatocytes by interfering with virion-cell membrane fusion. It was a promising lead compound for the development of novel HCV entry inhibition agents. OBJECTIVE: The aim of the present study is to search for compounds with more potent anti-HCV and antitumor activities and explore SARs. A series of novel derivatives of SA were designed and synthesized and evaluated for in vitro, their anti-HCV and antitumor activities. METHODS: SA derivatives were synthesized by reduction, condensation, esterification or amidation. The anti-HCV activity of title compounds was tested by inhibition on HCVcc infection of Huh7 cells, and a preliminary MOA study was conducted by determining inhibition on HCVpp entry into Huh7 cells. The antitumor activity in vitro was determined by MTT methods. RESULTS: In total, 24 novel derivatives were synthesized. Most of the compounds inhibited HCVcc infection. Compounds 5h and 6 showed the most potent anti-HCVcc activities and inhibition of HCVpp entry into Huh7 cells without obvious cytotoxicity. Most of the title compounds showed potent in vitro antitumor activities against Bel7404 and SMMC7721 tumor cell lines. Compounds 5j and 6 exhibited more potent antitumor activity than positive control SA and DOX. CONCLUSION: Structural modification of SA could lead to the discovery of potent anti-HCV or antitumor agents. Compounds 5h, 5j and 6 were promising lead compounds for development of novel HCV entry inhibition or antitumor agents.

Bioactive Natural Antivirals: An Updated Review of the Available Plants and Isolated Molecules.

Viral infections and associated diseases are responsible for a substantial number of mortality and public health problems around the world. Each year, infectious diseases kill 3.5 million people worldwide. The current pandemic caused by COVID-19 has become the greatest health hazard to people in their lifetime. There are many antiviral drugs and vaccines available against viruses, but they have many disadvantages, too. There are numerous side effects for conventional drugs, and active mutation also creates drug resistance against various viruses. This has led scientists to search herbs as a source for the discovery of more efficient new antivirals. According to the World Health Organization (WHO), 65% of the world population is in the practice of using plants and herbs as part of treatment modality. Additionally, plants have an advantage in drug discovery based on their long-term use by humans, and a reduced toxicity and abundance of bioactive compounds can be expected as a result. In this review, we have highlighted the important viruses, their drug targets, and their replication cycle. We provide in-depth and insightful information about the most favorable plant extracts and their derived phytochemicals against viral targets. Our major conclusion is that plant extracts and their isolated pure compounds are essential sources for the current viral infections and useful for future challenges.

Canola oilseed- and Escherichia coli- derived hepatitis C virus (HCV) core proteins adjuvanted with oil bodies, induced robust Th1-oriented immune responses in immunized mice.

Induction of broad Th1 cellular immune responses and cytokines is crucial characteristics for vaccines against intracellular infections such as hepatitis C virus (HCV). Plants (especially oilseed tissues) and plant-immunomodulators (like oil bodies) offer cost-effective and scalable possibilities for the production of immunologically relevant and safe vaccine antigens and adjuvants, respectively. Herein, we provide data of the murine immunization by transgenic canola oilseed-derived HCV core protein (HCVcp) soluble extract (TSE) and Escherichia coli- derived rHCVcp in combination with Canola oil bodies (oil) compared to that of the Freund's (FA) adjuvant. Mice immunized by TSE+ oil developed both strong humeral (IgG) and Th1-biased cellular responses, manifested by high levels of IFN-γ and lower IgG1/IgG2a ratio and IL-4 secretion. Results of the intracellular cytokine staining indicated that TSE+ oil immunization in mice triggered both CD4+ and CD8+ T cells to release IFN-γ, while CD4+ cells were mostly triggered when FA was used. Analyses by qRT-PCR indicated that a combination of rHCVcp/TSE with oil body induced high levels of IL-10 cytokines compared to that of the FA adjuvant. These characteristics are important properties for the design of an HCV vaccine candidate and indicate the potential of Canola-derived antigen and oil bodies in addressing these concerns.

Study on the anti-tumor mechanism related to immune microenvironment of Bombyx Batryticatus on viral and non-viral infections of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant primary liver cancer with poor prognosis. Most previous studies on anti-HCC effects of traditional Chinese medicines (TCM) have focused on the mechanism of direct action and few researchers considered that TCM can inhibit tumor progression and improve prognosis of HCC patients through regulating tumor microenvironment (TME). In this study, network pharmacology combined bioinformatics methods were employed to analysis mechanism of Bombyx batryticatus (B. batryticatus, one of the most frequently used traditional Chinese animal medicines, has been used in some Asian countries for centuries as an anticancer agent, anti-inflammatory agent, and antioxidant.) in regulating TME of HCC. The results showed that 24 core targets and 2 compounds were identified from overlapping between differential expression genes related to HCC in the cancer genome atlas (TCGA) database and targets of B. batryticatus in TCMSP database. For further analyzing the role of TME heterogeneity of HCC on anti-HCC mechanism of B. batryticatus, the correlation of core targets related with overall survival of HCC with TME cells in hepatitis C or hepatitis B virus-associated hepatocellular carcinoma (VIR) and non-hepatitis C or hepatitis B virus-associated hepatocellular carcinoma (NVIR) were calculated, respectively. The results showed that AKR1C3, SPP1 were significantly related with macrophages in VIR and other targets including NR1I2, CYP1A2 and CYP3A4 were significantly associated with macrophages in NVIR; the target protein AKR1C3 was significantly negative correlated with macrophages M1 in VIR (cor=-0.35, P-value<0.001) and the correlation between AKR1C3 and macrophages M1 was poor in NVIR group (cor = 0.064, P-value = 0.36). Additionally, survival curve of AKR1C3 showed that poor prognosis in VIR group can be related to high level of AKR1C3 (HR = 2.32, 95 % CI: 1.18-4.56, P-value = 0.012), and no signified gene can be found in NVIR group (P-value>0.05). In conclusion, the molecular mechanism of anti-HCC of B. batryticatus can be related to the tumor microenvironment to some extent. B. batryticatus may exert its anti-cancer effects and improve prognosis of patients by regulating macrophages M1 in VIR and NVIR through acting on different targets.

Inga edulis fruits: a new source of bioactive anthocyanins.

The extraction conditions and chromatographic analysis from seeds of Inga edulis were optimized and provided one anthocyanin from aqueous fraction and a mixture of three anthocyanins from methanolic fraction. The pure anthocyanin obtained was subjected to structural modifications and the products obtained were subjected to chemical and pharmacological assays, as well as quantum chemical calculations based on DFT and TD-DFT methods. Hence, the anthocyanin fractions were evaluated for their chemical-pharmacological potential through chemical and biological assays: antioxidant activity by the DPPH, determination of the Solar Protection Factor (SPF) and cytotoxic activity (hepatocellular carcinoma infected with hepatitis C virus). The results indicated that even the anthocyanin and derivatized compounds having high antioxidant potential showed an SPF lower than six, which is lower than the minimum accepted by current Brazilian legislation. In addition, none of compounds presented significant cytotoxic activity against the tumour cell line studied.

Estimating the national cost burden of in-hospital needlestick injuries among healthcare workers in Japan.

BACKGROUND: Needlestick injury (NSI) is one of the most burdensome professional hazards in any medical setting; it can lead to transmission of fatal infectious diseases, such as hepatitis B, hepatitis C and human immunodeficiency virus. In the United States, the annual cost burden was estimated as somewhere between $118 million to $591 million; in the United Kingdom it is approximated to be £500,000 (US$919,117.65) per the National Health Service. METHOD: This is the first published paper on the national cost burden of NSIs in Japan. A systematic literature review was conducted to review previous study design in global studies and to extract parameter values from Japanese studies. We conducted abstract searches through PubMed and the Japan Medical Abstracts Society (Ichushi), together with grey literature and snowball searches. A simple economic model was developed to calculate cost burden of NSIs from a societal perspective over a one-year time horizon. We assumed all NSIs are reported and perfect adherence in post NSI management that presented in the labour compensation scheme. Local guidelines were also referenced to extract resource utilization. Lastly, a deterministic sensitivity analysis was conducted and a scenario analysis which considered a payer perspective was also included. RESULT AND CONCLUSION: The national cost burden of in-hospital NSIs is estimated as ¥33.4 billion (US$302 million) annually, based on an average cost per NSI of ¥63,711 (US$577) and number of NSIs at 525,000/year. 70% of the cost is due to initial laboratory tests, followed by productivity loss, estimated at 20% of the total cost. Cost of contaminated NSIs remains at 5% of the total cost. Change in number of NSIs significantly influences outcomes. Variation in post-exposure management practices suggests a need for NSI specific National guidelines and holistic labour compensation scheme development in Japan.

Risk factors for hepatitis C infection among adult patients in Kedah state, Malaysia: A case-control study.

Hepatitis C infection is a global public health problem. This study was designed to identify the risk factors associated with hepatitis C infection among adult patients in Kedah state, Malaysia. A matched, hospital-based, case-control study was conducted at a tertiary hospital. Cases were adult (aged ≥ 18 years) patients with positive serology test results for hepatitis C virus antibody and detectable hepatitis C virus RNA from January 2015 to December 2018, and controls were age-, sex- and ethnicity-matched patients who were not infected with hepatitis C virus. Self-administered questionnaires were used to collect data on demographic characteristics and previous exposure to selected risk factors among the study participants. Associations between hepatitis C and demographic and risk factors were assessed using univariable and multivariable logistic regression analyses. A total of 255 case-control patient pairs were enrolled. The multivariable analysis indicated that having a history of blood or blood product transfusion before 1992 (adjusted odds ratio [AOR] = 6.99, 95% confidence interval [CI]: 3.73-13.81), injection drug use (AOR = 6.60, 95% CI: 3.66-12.43), imprisonment (AOR = 4.58, 95% CI: 1.62-16.40), tattooing (AOR = 3.73, 95% CI: 1.37-12.00), having more than one sexual partner (AOR = 2.06, 95% CI: 1.16-3.69), piercing (AOR = 1.71, 95% CI: 1.04-2.80), and having only secondary education (AOR = 1.92, 95% CI: 1.06-3.57) were independently associated with hepatitis C. No associations were found between health care occupation, needle-prick injury, surgical procedures, haemodialysis, acupuncture, cupping, or contact sports and hepatitis C infection. These findings demonstrate that hepatitis C risk is multifactorial. Having a history of blood or blood product transfusion before 1992, injection drug use, imprisonment, tattooing, having more than one sexual partner, piercing, and having only secondary education were associated with increased odds of hepatitis C.

Herbal Medicine Containing Aristolochic Acid and the Risk of Primary Liver Cancer in Patients with Hepatitis C Virus Infection.

BACKGROUND: We investigated the association between taking herbal medicine (HM) containing aristolochic acid (AA) and the risk of primary liver cancer (PLC) among patients with hepatitis C virus (HCV) infection. METHODS: This is a prospective study for the long-term follow-up of a nationwide population-based cohort of patients ages 18 years or older diagnosed with HCV infection during 1997 to 2010. A total of 223,467 HCV-infected patients were identified using the National Health Insurance Research Database in Taiwan. The use of HM containing AA was evaluated among patients who had visited traditional Chinese medicine clinics beginning from 1997 to 1 year prior to the diagnosis of PLC or dates censored (2003). We tracked each individual patient from 1997 to 2013 to identify incident cases of PLC since 1999. RESULTS: During the follow-up period of 3,052,132 person-years, we identified 25,502 PLC cases; this corresponded to an overall incidence rate of 835.5 PLCs per 100,000 person-years. The adjusted HRs were 1.21 [95% confidence interval (CI), 1.18-1.24], 1.48 (95% CI, 1.37-1.59), 1.50 (95% CI, 1.34-1.68), and 1.88 (95% CI, 1.61-2.19) for estimated AA usage groups: 1 to 250, 251 to 500, 501 to 1,000, and more than 1,000 mg, respectively, relative to no AA exposure (reference group). CONCLUSIONS: The current findings suggest that among HCV-positive patients, increasing exposure to AA poses an increased risk of acquiring PLC. IMPACT: AA may increase the risk of PLC in HCV-positive populations.

Testing for hepatitis C virus infection in UK prisons: What actually happens?

Prisons are a key demographic in the drive to eradicate hepatitis C virus (HCV) as a major public health threat. We have assessed the impact of the recently introduced national opt-out policy on the current status of HCV testing in 14 prisons in the East Midlands (UK). We analysed testing rates pre- and post-introduction of opt-out testing, together with face-to-face interviews with prison healthcare and management staff in each prison. In the year pre-opt-out, 1972 people in prison (PIP) were tested, compared to 3440 in the year following opt-out. From July 2016 to June 2017, 2706 people were tested, representing 13.5% of all prison entrants (median 16.6%, range 7.6%-40.7%). Factors correlating with testing rates were as follows: pre-admission location of the PIP (another prison or the community, OR 2.2, 95% CI 1.9-2.3, P < 0.001); whether the PIP could access health care independently of prison officers (OR 1.7, 95% CI 1.5-1.8, P < 0.001); the absence of out-reach services for HCV treatment (OR 1.3, 95% CI 1.2-1.5, P < 0.001), whether >50% of PIP reported ease of access to a nurse (OR 2.0, 95% CI 1.8-2.2, P < 0.001), and whether prison health care was supplied by private or NHS providers (OR 1.3, 95% CI 1.2-1.5, P < 0.001). Testing rates remained far below the minimum national opt-out target of 50%. Inadequacy of healthcare facilities and constraints imposed by adherence to prison regimens were cited by healthcare and management staff at all prisons. Without radical change, the prison estate may be intrinsically incapable of supporting NHSE to deliver the HCV elimination strategy.

Cerebral patterns of neuropsychological disturbances in hepatitis C patients.

Neuropsychiatric symptoms and cognitive impairment have been consistently reported in patients with hepatitis C virus (HCV) infection. Since the mechanisms behind remain to be established, the present study attempted to assess whether neuropsychological impairments in HCV-infected patients are accompanied by structural alterations in the brain. Therefore, 19 anti-HCV-antibody-positive women with mild liver disease and 16 healthy controls underwent extensive neuropsychological testing and cranial magnetic resonance imaging (MRI) examination. Nine of the patients and five controls were followed up after 6-7 years. Voxel-based morphometry and magnetization transfer imaging were utilized to study HCV-associated structural gray and white matter changes. The HCV-infected patients had significantly worse fatigue and depression scores and significantly poorer performance on attention and memory tests than controls. The patients displayed gray matter (GM) atrophy in the bilateral insula and thalamus and a profound GM volume increases in the cerebellum. Microstructural GM changes in the insula were also evident by a reduced magnetization transfer ratio. Structural white matter changes were observed along several descending and crossing fiber tracts. Follow-up at 7 years revealed increased GM atrophy in the left amygdala and left parahippocampal regions over time. We conclude that our data provide evidence for structural alterations in the brains of patients with chronic HCV infection. Disturbances of cerebellothalamocortical regions and circuits, linking cerebellar projections to the prefrontal cortex through the thalamus, underpin the emotional and cognitive dysfunction characteristically observed in these patients.

Berberine inhibits hepatitis C virus entry by targeting the viral E2 glycoprotein.

BACKGROUND: Despite the advent of direct-acting antivirals (DAAs), HCV remains an important public health problem globally. There is at present no effective vaccine against the virus, and the DAAs in current use cannot prevent de novo infection, including in liver transplant setting wherein donor livers inevitably become re-infected. Developing inhibitors to HCV entry using nature-derived small molecules may help to expand/complement the current treatment options. PURPOSE: In this study, we explored the effect of the plant alkaloid berberine (BBR) on HCV early viral entry. METHODS: Cell culture-derived HCV (HCVcc), viral pseudoparticles bearing HCV glycoproteins (HCVpp), and entry-related assays were employed to assess BBR's bioactivity. Molecular docking was used to predict BBR-HCV glycoproteins interaction, and the compound's antiviral activity was confirmed against HCVcc infection of primary human hepatocytes (PHHs). RESULTS: BBR specifically impeded HCVcc attachment and entry/fusion steps without inactivating the free virus particles or affecting the expression of host cell entry factors and post-entry viral replication. BBR also effectively inhibited infection by viral pseudoparticles expressing HCV E1/E2 glycoproteins and molecular docking analysis pointed at potential interaction with HCV E2. Finally, BBR could suppress HCVcc infection of PHHs. CONCLUSIONS: We identified BBR as a potent HCV entry inhibitor, which merits further evaluation particularly for use in transplant setting against graft re-infection by HCV.

An update on hepatitis C virus genotype distribution in Jordan: a 12-year retrospective study from a tertiary care teaching hospital in Amman.

BACKGROUND: Nucleic acid hybridization (NAH) of hepatitis C virus (HCV) is a practical and reliable tool for virus genotyping. Genotype assignment is an important factor in the prediction of treatment success in chronic hepatitis C patients. The aim of this study was to determine the genotype distribution among HCV clinical isolates in Jordan between 2007 and 2018. METHODS: Electronic and paper-based clinical data registry records from 2007 to 2018 at the Jordan University Hospital (JUH) were retrospectively examined for individuals with HCV genotype, HCV viral load, and alanine aminotransferase (ALT) testing results. Genotype determination was based on NAH technique using the HCV 5' untranslated region (5' UTR) with 386 requests available from 342 unique individuals. RESULTS: A total of 263 out of 342 unique individuals (76.9%) had genotyping results available for final analysis with 259 individuals each having a single genotyping result. The most common HCV genotypes in the study were: genotype 4 (n = 142, 54.0%), genotype 1 (n = 87, 33.1%), genotype 3 (n = 16, 6.1%), genotype 2 (n = 9, 3.4%), other undetermined genotypes (n = 5, 1.9%) and mixed infections (n = 4, 1.5%). Sub-genotyping results were available for 46 individuals as follows: sub-genotype 4c/d (n = 13, 28.3%), sub-genotype 1a (n = 11, 23.9%), sub-genotype 1b (n = 10, 21.7%), sub-genotype 4a (n = 8, 17.4%), sub-genotype 3a (n = 2, 4.3%), sub-genotypes 2a/c and 4 h (n = 1, 2.2% for both). Individuals infected with genotype 1 showed higher viral load when compared to those infected with genotype 4 (p = 0.048, t-test). Younger HCV-infected individuals (< 52 years) had higher ALT levels compared to older individuals (p = 0.036, t-test). Self-reported risk factors for HCV acquisition included: history of previous surgery, invasive dental procedures, and blood transfusion, delivery at home, circumcision at home and wet cupping therapy (hijama). CONCLUSIONS: High genetic diversity of HCV was found in Jordan, with genotypes 4 and 1 as the most prevalent genotypes co-circulating in the country. Potential impact of virus genotype on disease markers (viral load, ALT) was detected and needs further assessment. The study can be helpful to plan for future prevention and management of HCV infection in Jordan.

Hepatitis C: Is eradication possible?

Hepatitis C has a relevant global impact in terms of morbidity, mortality and economic costs, with more than 70 million people infected worldwide. In the resolution, "Transforming our world: the 2030 Agenda for Sustainable Development" was included as a focus area in the health-related goal with world leaders pledging to "combat" it by 2030. In response, WHO drafted the Global Viral Hepatitis Strategy carrying the ambitious targets to reduce the number of deaths by two-thirds and to increase treatment rates up to 80%. Despite the availability of highly effective therapeutic regimens based on direct-acting antivirals many barriers to HCV eradication still remain. They are related to awareness of the infection, linkage to care, availability of the therapeutic drug regimens and reinfection. Overall, if an effective prophylactic vaccine will not be available, HCV eradication appears difficult to achieve in the future.

Oenothein B, dimeric hydrolysable tannin inhibiting HCV invasion from Oenothera erythrosepala.

The envelope proteins of the hepatitis C virus (HCV), E1 and E2, have been revealed to be essential for invasion of HCV. Thus, we were engaged in the search for the inhibitors against HCV invasion through the assay system using the model virus expressing recombinant HCV envelopes, E1 and E2. Now, we disclosed dimeric hydrolysable tannin oenothein B (1) from MeOH extract of Oenothera erythrosepala as an active principle for inhibition of HCV invasion and its potency was almost the same as that of monomeric hydrolysable tannin, tellimagrandin I (2). Furthermore, by use of stereoselectively prepared 1-ß- and 1-α-O-methyl tellimagrandin Is (4 and 5), the introduction of methyl moiety into 1-hydroxy group of 2 was clarified to result in slightly reduction of activity and ß-isomer was revealed to exhibit a little stronger activity than α-one.

Effect of vitamin D supplementation on sustained virological response in genotype 1/4 chronic hepatitis C treatment-naïve patients from India.

BACKGROUND & OBJECTIVES: The effect of vitamin D supplementation on response to antiviral therapy in hepatitis C virus (HCV) genotype 1 and 4 infection still remains unclear, with studies yielding inconsistent results. The aim of the present study was to assess the effect of vitamin D supplementation on treatment outcome in patients with genotype 1/4 chronic hepatitis C (CHC) infection. METHODS: Sixty consecutive, treatment-naïve, genotype 1 and 4 chronic HCV patients were included in the study. The patients were randomized into two groups: Vitamin D supplemented group received pegylated (PEG)-interferon α-2a 180 µg per week plus ribavirin (RBV) (1000-1200 mg/d) together with vitamin D3 (2000 IU/d) and control group received identical therapy without vitamin D (32 patients). RESULTS: There were no significant differences between the two groups in terms of age, sex, body mass index and baseline laboratory values. Lower vitamin D levels were associated with higher grades of fibrosis in liver histology (vitamin D >20 ng/ml - 70% vs vitamin D <20 ng/ml - 37%, P<0.05). Vitamin D supplemented group had similar rapid viral response (40 vs 28%, P=0.36), complete early viral response (53.2 vs 40%, P=0.34), end of treatment response (64 vs 46%, P=0.17) and sustained virological response (SVR) (60 vs 44%, P=0.19) as compared to control group. Interleukin 28B polymorphism [odds ratio (OR)-15.37, 95% confidence interval (CI)-2.32-101.76, P=0.04] and baseline serum vitamin D levels (OR-6.36, 95% CI-1.36-29.61 P=0.02) were independent predictors of SVR in genotype 1/4 CHC. Vitamin D supplementation was not found to be predictor of response in genotype 1/4 CHC on multivariate analysis (OR-2.79, 95% CI- 0.63-12.34, P=0.74). INTERPRETATION & CONCLUSIONS: The present study showed that addition of vitamin D to PEG/RBV combination therapy in treatment-naïve patients who were infected with HCV genotype 1/4 had no effect on the rates of rapid, early and sustained viral responses.

Inhibitory Effects of Amentoflavone and Orobol on Daclatasvir-Induced Resistance-Associated Variants of Hepatitis C Virus.

Hepatitis C virus (HCV) is recognized as a major causative agent of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Despite rapid progress in the development of direct-acting antivirals (DAA) against HCV infection in recent years, cost-effective antiviral drugs with more affordable prices still need to be developed. In this study, we screened a library of natural compounds to identify natural HCV inhibitors. The library of the pure compounds extracted from Chinese herbs deposited in the chemical bank of National Research Institute of Chinese Medicine (NRICM), Taiwan was screened in the cell culture-derived HCV (HCVcc) system. We identified the flavone or flavan-based compounds amentoflavone, 7,4[Formula: see text]-dihydroxyflavanone, and orobol with the inhibition of viral entry, replication, and translation of the HCV life cycle. Amentoflavone and orobol also showed inhibitory effects on resistant-associated variants to the NS5A inhibitor daclatasvir. The results of this study have the potential to benefit patients who are intolerant to the adverse effect of pegylated interferon or who harbor resistant strains refractory to treatment by current direct-acting antiviral agents.