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Abstract Micro-elimination of hepatitis C virus (HCV) infection through rapid uptake of government-funded direct-acting antiviral therapy within an Australian prison setting is demonstrated. During a 22-month period, 119 patients initiated treatment for chronic HCV infection, with HCV in-prison viremic prevalence declining from 12% to 1%.

Cloud computing provides the flexible architecture where data and resources are dispersed at various locations and are accessible from various industrial environments. Cloud computing has changed the using, storing, and sharing of resources such as data, services, and applications for industrial applications. During the last decade, industries have rapidly switched to cloud computing for having more comprehensive access, reduced cost, and increased performance. In addition, significant improvement has been observed in the internet of things (IoT) with the integration of cloud computing. However, this rapid transition into the cloud raised various security issues and concerns. Traditional security solutions are not directly applicable and sometimes ineffective for cloud-based systems. Cloud platforms’ challenges and security concerns have been addressed during the last three years, despite the successive use and proliferation of multifaceted cyber weapons. The rapid evolution of deep learning (DL) in the artificial intelligence (AI) domain has brought many benefits that can be utilized to address industrial security issues in the cloud. The findings of the proposed research include the following: we present a comprehensive survey of enabling cloud-based IoT architecture, services, configurations, and security models; the classification of cloud security concerns in IoT into four major categories (data, network and service, applications, and people-related security issues), which are discussed in detail; we identify and inspect the latest advancements in cloud-based IoT attacks; we identify, discuss, and analyze significant security issues in each category and present the limitations from a general, artificial intelligence and deep learning perspective; we provide the technological challenges identified in the literature and then identify significant research gaps in the IoT-based cloud infrastructure to highlight future research directions to blend cybersecurity in cloud.

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The Asian-Pacific Association for the Study of the Liver (APASL) convened an international working party on the “APASL consensus statements and recommendation on management of hepatitis C” in March, 2015, in order to revise “APASL consensus statements and management algorithms for hepatitis C virus infection (Hepatol Int 6:409–435, 2012)”. The working party consisted of expert hepatologists from the Asian-Pacific region gathered at Istanbul Congress Center, Istanbul, Turkey on 13 March 2015. New data were presented, discussed and debated to draft a revision. Participants of the consensus meeting assessed the quality of cited studies. Finalized recommendations on treatment of hepatitis C are presented in this review.

Extrahepatic manifestations are a feature of chronic hepatitis C virus (HCV) infection. In the course of chronic HCV infection, about 70% of patients have one or more extrahepatic manifestations. The latter are often the first and only clinical sign of infection. Experimental and clinical data support a causal association for many extrahepatic manifestations and HCV infection, which include mixed cryoglobulinemia, non-Hodgkin lymphomas (NHL), cardiovascular disease, insulin resistance, type 2 diabetes, neurological and psychiatric disease and other rheumatic diseases. All these extrahepatic conditions influence the morbidity, quality of life and mortality of HCV-infected patients. Currently, interferon-free therapeutic regimens with direct-acting antiviral agents (DAA) offer the possibility of treatment to almost the entire infected population, irrespective of stage of cirrhosis and associated serious comorbidities, always maintaining a high efficacy and tolerability. Several studies have shown a close association between HCV clearance by DAAs and an improvement or reduction in the risk of extrahepatic manifestations. Patients with HCV after a sustained virologic response (SVR) by DAA treatment have a lower risk than non-responders of developing cryoglobulinemic vasculitis and B-cell non-Hodgkin’s lymphomas. Furthermore, the SVR by DAA also reduces the risk of acute coronary syndrome, cardiovascular disease, insulin resistance and type 2 diabetes, and it improves atherosclerosis. HCV clearance by DAA also improves the quality of life and survival of patients with chronic HCV infection with associated extrahepatic diseases. Thus, DAAs should be initiated as early as possible in HCV patients with extrahepatic manifestations.

Hepatitis C virus (HCV) infection is the major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of HCC initiation, growth, and metastasis appear to be highly complex due to the decade-long interactions between the virus, immune system, and overlapping bystander effects of host metabolic liver disease. The lack of a readily accessible animal model system for HCV is a significant obstacle to understand the mechanisms of viral carcinogenesis. Traditionally, the primary prevention strategy of HCC has been to eliminate infection by antiviral therapy. The success of virus elimination by antiviral treatment is determined by the SVR when the HCV is no longer detectable in serum. Interferon-alpha (IFN-α) and its analogs, pegylated IFN-α (PEG-IFN-α) alone with ribavirin (RBV), have been the primary antiviral treatment of HCV for many years with a low cure rate. The cloning and sequencing of HCV have allowed the development of cell culture models, which accelerated antiviral drug discovery. It resulted in the selection of highly effective direct-acting antiviral (DAA)-based combination therapy that now offers incredible success in curing HCV infection in more than 95% of all patients, including those with cirrhosis. However, several emerging recent publications claim that patients who have liver cirrhosis at the time of DAAs treatment face the risk of HCC occurrence and recurrence after viral cure. This remains a substantial challenge while addressing the long-term benefit of antiviral medicine. The host-related mechanisms that drive the risk of HCC in the absence of the virus are unknown. This review describes the multifaceted mechanisms that create a tumorigenic environment during chronic HCV infection. In addition to the potential oncogenic programming that drives HCC after viral clearance by DAAs, the current status of a biomarker development for early prediction of cirrhosis regression and HCC detection post viral treatment is discussed. Since DAAs treatment does not provide full protection against reinfection or viral transmission to other individuals, the recent studies for a vaccine development are also reviewed.

Hepatitis C virus (HCV) is currently classified into 8 genotypes and 86 subtypes. The objective of this study was to characterize novel HCV subtypes and to investigate the impact of subtypes on treatment outcome. Full-genome sequencing was performed on HCV plasma samples with <85% sequence homology of NS3, NS5A, and/or NS5B to HCV genotype (GT) 1-8 reference strains. A total of 14 653 patients with GT1-6 HCV infection were enrolled in clinical studies of sofosbuvir-based regimens. For the majority of the patients, a specific subtype could be assigned based on a close genetic relationship to previously described subtypes. However, for 19 patients, novel subtypes were identified with <85% homology compared with previously described subtypes. These novel subtypes had the following genotypes: 9 in GT2, 5 in GT4, 2 in GT6, and 1 each in GT1, GT3, and GT5. Despite the presence of polymorphisms at resistance-associated substitution positions, 18 of the 19 patients treated with sofosbuvir-containing therapy achieved SVR12. Nineteen novel HCV subtypes were identified, suggesting an even greater genetic diversity of HCV subtypes than previously recognized.

The positive sense RNA virus, hepatitis C virus (HCV), is affiliated with the Flaviviridae family. Approximately 1% of people around the globe experience the impact of the HCV, which can coax them into potentially fatal conditions, including cirrhosis and carcinoma. The second-highest hepatitis C infection burden lies in Pakistan. The case of a HCV-infected patient who additionally has obesity or concurrent medical conditions like diabetes, HBV infection, or HIV infection is susceptible to becoming direr. Direct-acting antiviral medications replaced interferons as a staple of the treatment plan since they have fewer, milder side effects and a higher SVR rate in patients. The present study sought to assess the modifications to glucose homeostasis in non-diabetic chronic HCV-infected patients getting DAA treatment and the factors that independently pertain to insulin resistance. The study enrolled 250 patients, with 190 individuals having HCV-positive PCR results. The analysis included CBC, LFTs, glycaemic and insulin measurements, and the insulin resistance index calculation. Key cardiometabolic risk factors crucial for defining MASLD were assessed, including BMI measurement, evaluation of type 2 diabetes, and lipid profile analysis. The same tests were repeated following DAA therapy, and HOMA-IR was computed to compare pre-and post-treatment results. Among the 250 recruited patients, 190 were detected as HCV positive by the PCR assay, 57% (110 patients) were women, 43% (80 patients) were men, and patients were 47 years old on average. The patients showed high BMI (average 26.28 kg/m 2 ) and signs of severe insulin resistance (HOMA-IR > 2.5). Multivariable logistic regression analysis pointed out that elevated baseline levels of triglycerides, ALT, ALP, cholesterol, and total bilirubin were independently associated with high insulin resistance. A notable improvement in HOMA-IR from 13.63 ± 2.63 to 3.16 ± 1.52 ( p  < 0.005) was spotted after administering interferon-free antiviral therapy for 3 months. The presence of high BMI, hyperlipidemia, and elevated levels of ALP, ALT, and AST in non-diabetic HCV-infected patients were independently associated with IR. In patients who previously had a higher IR index, there was a decrease in the HOMA-IR index after infection clearance by direct-acting antivirals.

Background. Persistent infection with hepatitis C virus (HCV) causes profound alterations of the cytokine and chemokine milieu in peripheral blood. However, it is unknown to what extend these alterations affect the progression of liver disease and whether HCV clearance normalizes soluble inflammatory mediators. Methods. We performed multianalyte profiling of 50 plasma proteins in 28 patients with persistent HCV infection and advanced stages of liver fibrosis or cirrhosis and 20 controls with fatty liver disease. The patients were treated for 24 weeks with sofosbuvir and ribavirin and underwent sampling longitudinally. Ten patients experienced viral relapse after treatment cessation. Results. The cytokine and chemokine expression pattern was markedly altered in patients with chronic HCV infection as compared to healthy controls and patients with nonalcoholic steatohepatitis. Distinct soluble factors were associated with the level of fibrosis/cirrhosis, viral replication, or treatment outcome. The baseline expression level of 10 cytokines distinguished patients with a sustained viral response from those who experienced viral relapse. While the majority of upregulated analytes declined during and after successful therapy, HCV clearance did not lead to a restoration of parameters that were suppressed. Conclusions. Chronic HCV infection appears to disrupt the milieu of soluble inflammatory mediators even after viral clearance. Thus, HCV cure does not lead to complete immunological restitution.