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OBJECTIVE: To evaluate the impact of hepatitis C virus (HCV) infection and treatment status on COVID-19-related hospitalizations in Georgia. METHODS: We analyzed 2020-2021 Georgian health-registry data for COVID-19-positive individuals and categorized by HCV infection and treatment status. Logistic regression was used to assess the strengths of the associations. RESULTS: Treated HCV individuals had lower odds of COVID-19-related hospitalization compared to anti-HCV-negatives, while untreated HCV-viremic and anti-HCV-positive non-viremic individuals had higher odds. CONCLUSIONS: HCV treatment prior to COVID-19 infection was associated with lower odds of COVID-19-related hospitalization, highlighting the benefits of HCV management in the context of the pandemic.

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Background Patients on hemodialysis (HD) are most likely to contract hepatitis C (HCV) infection, which is associated with significant morbidity and disease progression. Direct-acting antivirals (DAAs) are safe and tolerable in chronic kidney disease (CKD) with a 90-100% cure rate, and limited data exist regarding their efficacy in end-stage renal disease (ESRD), particularly for HD patients in South Asia. The study aimed to assess the outcome of a 12-week sofosbuvir (SOF) and velpatasvir (VEL) treatment regimen on ESRD patients with chronic HCV infection undergoing HD in the Pakistani Asian population. Methodology This prospective cohort study was conducted between January 2022 and January 2023 at the outpatient nephrology and gastroenterology clinic of Sheikh Zayed Medical College and Hospital, Rahim Yar Khan, Pakistan. This study included a total of 220 ESRD patients fulfilling the inclusion criteria, aged 20-55 years, who had been undergoing weekly HD sessions for at least two years, with acquired HCV infection. Data on demographic and clinical characteristics were collected through patient interviews. Laboratory and dialysis profiling was executed to assess ESRD and discover the underlying cause by ultrasound abdomen, blood pressure measurement by sphygmomanometer, random blood sugar for diabetes, and taking note of the duration and frequency of dialysis. HCV RNA PCR was done at selected intervals to evaluate the virological response to treatment. Sustained virological response (SVR), liver cirrhosis status, and number of weekly HD sessions were compared at one year of SOF/VEL regimen. Results The mean age of patients with ESRD was 41.8 with a standard deviation (SD) of 9.3 years, and HCV diagnosis was 1.3 years with SD of 0.4 years; 52.7% (n=116) were males, 47.3% (n=104) were females, 75% (n=165) were urban dwellers, and 93.6% (n=206) were married. CKD that requires dialysis was caused mainly by hypertension (78, 35%), diabetes mellitus type 2 (52, 24%), bilateral small kidney disease (40, 18%), and others (34, 16%). One hundred and six (48.2%) received dialysis thrice weekly, 83 (37.7%) twice, and 31 (14.1%) once weekly. The study monitored the rapid virological response (RVR) at four weeks of SOF/VEL regimen in 89.5% of ESRD patients, observed end-of-treatment response (ETR) at 12 weeks in 93.2%, and noted 91.4% SVR response at one year. Only four (1.8%) relapses were observed in the study, which was statistically insignificant. The status of liver cirrhosis showed a 50% improvement, decreasing from 40% to 20%. The frequency of weekly HD sessions decreased from thrice to twice-thrice a week. Conclusion The prevalence of contracting HCV is high among CKD and dialysis ESRD patients. All-oral DAA therapy has revolutionized HCV treatment with co-morbidities. Renal functions improved after the SOF/VEL regimen for chronic HCV infection in ESRD patients undergoing HD, with the number of weekly dialysis sessions reduced and SVR reaching 91.4%. Thus, a single-tablet, pan-genotypic DAA regimen of SOF/VEL for 12 weeks is safe, effective, and tolerable regardless of the underlying etiology of ESRD, complications of cirrhosis, HCV genotype, or previous treatment exposure. The successful treatment of HCV and achieving SVR lowers the risk of ESRD complications, improves extra-hepatic manifestations, and greatly enhances survival. Further studies are warranted after the availability of other DAAs to confirm findings with no limitations.

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BACKGROUND: Direct acting antivirals(DAAs) are effective in reducing inflammatory ant fibrotic markers in patients with chronic hepatitis C virus(HCV) infection and to prevent liver-related complications. Two-dimensional shear wave elastography(2D-SWE) is an effective technique for the assessment of liver fibrosis. AIM: To evaluate changes in liver stiffness(LS) in HCV cirrhotic patients undergoing DAA therapy and to identify non-invasive parameters that predict the occurrence of liver-related events. METHODS: We enrolled 229 patients who received DAAs between January 2015 and October 2018. Ultrasound parameters and laboratory data were assessed before treatment and 24(T1) and 48(T2) weeks after end of treatment. Patients were followed up every 6 months to evaluate the development of HCC and other liver related complications. Multiple Cox regression analysis was used to determine parameters associated with the development of complications. RESULTS: Model for End-stage Liver Disease(MELD) score(HR 1.16; CI 95% 1.01-1.33; p = 0.026) and a change in LS at T2(1-year Delta LS) < 20%(HR 2.98; CI 95% 1.01-8.1; p = 0.03) were independently associated with HCC risk. One-year Delta-LS <20% was independently associated with the development of ascites(HR 5.08; CI 95% 1.03 - 25.14; p = 0.04). CONCLUSIONS: Dynamic changes of 2D-SWE-measured LS after DAA therapy may be a useful tool to identify patients who are at higher risk of liver related complications.

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We herein report a case of hepatitis C virus (HCV)-associated cryoglobulinemic livedo reticularis in a woman in her 60s that improved with direct-acting antivirals (DAAs). Hyperpigmentation was observed in both lower legs, and a skin biopsy confirmed livedo reticularis, suggesting a relationship with cryoglobulinemia and HCV infection. DAAs with an NS5A inhibitor+NS3/4A protease inhibitor (glecaprevir/pibrentasvir) were administered for eight weeks, and a sustained virological response (SVR) was obtained. The disappearance of serum cryoglobulin was confirmed approximately two years after an SVR was obtained and livedo reticularis was improved. DAA therapy can be an effective therapeutic option for extrahepatic complications associated with HCV infection.

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PREAMBULAR NOTA BENE: As a tribute to Dr Mike Bray, the following review of literature willbe mainly based on published data andconcepts, but will also contain my personal views, and in this respect could be more considered as a bioassay. Even though a cost-effective and excellent prophylactic vaccine exists since many years to protect against hepatitis B virus (HBV) infection, academic-researcher/drug-developers/stakeholders are still busy with the R&D of novel therapies that could eventually have an impact on its worldwide incidence. The Taiwanese experience have univocally demonstrated the effectiveness of constrained national HBV prophylactic vaccination programs to prevent the most dramatic HBV-induced end-stage liver disease, which is hepatocellular carcinoma; but yet the number of individuals chronically infected with the virus, for whom the existing prophylactic vaccine is no longer useful, remains high, with around 300 million individuals around the globe. In this review/bioassay, recent findings and novel concepts on prospective therapies against HBV infections will be discussed; yet it does not have the pretention to be exhaustive, as "pure immunotherapeutic concepts" will be mainly let aside (or referred to other reviews) due to a lack of expertise of this writer, but also due to the lack of, or incremental, positive results in clinical trials as-off today with these approaches.

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BACKGROUND: HLA-E binding to NKG2A/CD94 induces inhibitory signals that modulate NK cells cytotoxicity against infected targets. HCV-derived peptides stabilize HLA-E molecule that favours its higher expression. However, HLA-E stability and expression vary in different genotypes where the presence of HLA-E*01:03 allele is associated with higher HLA-E expression on targets that enhances NK cells inhibition and increases the chance of virus to escape from innate immune system. Here, we aimed to investigate whether HLA-E polymorphism affects HCV infection status or its treatment in major thalassemia patients who are more vulnerable to hepatitis C. METHODS AND MATERIALS: Study included 89 cases of major thalassemia positive for HCV-antibody; of those 17 patients were negative for HCV-PCR (spontaneously cleared) and 72 patients were HCV-PCR positive (persistent hepatitis under different anti-viral treatment). 16 major thalassemia patients without hepatitis, negative for HCV-antibody were also considered as patients control group. Genomic DNAs extracted from whole bloods were genotyped for HLA-E locus using a sequence specific primer-PCR strategy. RESULTS: In thalassemia patients, HLA-E*01:03 allele increased susceptibility to HCV infection [p = 0.02; 4.74(1.418-15.85)]. In addition, HLA-E*01:03/*01:03 genotype predicted more resistance to HCV treatment compared to other genotypes [p = 0.037; 3.5(1.1-11.4)]. In other words, we found that the presence of HLA-E*01:01 allele favors better response to anti-HCV therapy [p = 0.037; 3.5(1.1-11.4)]. CONCLUSION: From a mechanistic point of view, the associations between HLA-E polymorphisms and susceptibility to HCV infection or its therapeutic resistance in thalassemia patients may suggest potential roles for the innate and adaptive immune responses to this infection, which are manifested by the acts of HLA-E - NKG2A/CD94 axis in the modulation of NK cell inhibitory function as well as HLA-E associated CD8+ T cell cytolytic activity against HCV, respectively. Notably, from a clinical point of view, paying attention to these associations may not only be useful in increasing the effectiveness of current anti-HCV regimens comprising direct acting antivirals (DAAs) in more complicated patients, but may also suggest antiviral prophylaxis for patients more vulnerable to HCV infection.

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OBJECTIVES: Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous disease. Literature supports an association between OLP and Hepatitis C virus (HCV) infection. The current treatment for HCV infection with direct-acting antivirals (DAAs) is highly effective and safe. The aim of this study is to evaluate the clinical impact of viral eradication with DAAs in patients with HCV and OLP. MATERIALS AND METHODS: For this cohort observational study, 18 patients with HCV and OLP were recruited; all patients received DAAs. Nineteen patients with OLP without HCV were recruited as controls. Both groups received an oral clinical examination, taking photographs of the oral mucosa, at three time points. Size and type of lesions, clinical and efficacy scores, were evaluated at each time point with ImageJ software. Changes were assessed by a general linear model repeated measures analysis. Kruskal-Wallis H and Mann-Whitney U tests were used to evaluate the differences between subgroups. RESULTS: All patients of the study group reached a sustained virological response. The study group showed a correlation between viral load and clinical status (p < 0.05), higher clinical scores at baseline (p = 0.001) and higher efficacy index than controls (p < 0.001), improving over time (p < 0.001); controls did not show significant changes (p = 0.196). One patient of the experimental group developed oral squamous cell carcinoma (OSCC) of the tongue during the DAAs treatment. CONCLUSIONS: In this study, patients with HCV and OLP showed a worst clinical oral status than controls at baseline. However, treatment for virus eradication can improve the oral lichen planus clinical course. CLINICAL RELEVANCE: HCV eradication can improve the clinical course of patients with HCV-related OLP.

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Background: Chronic immune stimulation by hepatitis C virus (HCV) may cause occurrence of several autoantibodies in infected patients, with or without features of clinically overt autoimmune diseases. The recent introduction of direct-acting antivirals (DAAs) has dramatically changed the natural history of chronic HCV infection. The aim of this study was to assess the effects of DAA therapy on serum autoantibodies in chronic hepatitis C (CHC) patients. Methods: The medical records of 113 CHC patients were reviewed to assess autoantibody behavior following DAA-directed HCV eradication. Statistical analysis was performed to assess correlations between DAA treatment and autoantibody titers, HCV genotypes, and viral loads. Results: Anti-nuclear (ANA), anti-smooth muscle cell (ASMA) and anti-mitochondrial (AMA) antibody testing was available in 77 patients; 31 out of 77 patients (40%) had one or more serum autoantibodies prior to treatment. Measurement of autoantibody titers before and after HCV eradication was performed in 20 of 31 patients. DAA treatment significantly affected ANA and ASMA titers, leading to disappearance or reduction of autoantibody titers; conversely, AMA were not influenced by DAA treatment. No correlations were observed between autoantibody specificity and both HCV genotypes and viral loads at baseline. Likewise, serum autoantibody titers were independent of HCV genotypes. Conclusions: DAA-directed HCV clearance may interrupt chronic immune stimulation by removing the drive for autoantibody induction. The isolated persistence of autoantibodies in the small fraction of patients who did not show clearance following DAA treatment may require long-term vigilance.

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For the treatment of chronic hepatitis B virus (HBV) infection, pegylated interferon-alfa and nucleoside/nucleotide analogs (entecavir and tenofovir) are currently available. These drugs allow viral suppression and normalization of the liver enzyme alanine aminotransferase (ALT) and prevent the liver disease from progressing. However, several therapeutic strategies that are still in clinical development aim at a functional cure. Their aim is that the HBV envelope protein HBsAg is no longer detectable in the serum ("resolved" hepatitis B). This review article provides an overview of current and possible future antiviral therapies against chronic HBV infection. A literature search paying special attention to the current guidelines as well as current conference contributions served as the basis.The currently available antiviral therapies only very rarely lead to the elimination of HBsAg (functional cure). It is also largely unclear in which patients discontinuation of long-term therapy with entecavir or tenofovir is feasible. New therapeutic strategies in clinical development lead to a functional cure in a higher proportion of patients. However, a combination of several antiviral strategies is likely required to achieve a functional cure in the majority of patients. Such therapies may presumably be available in the next 5-10 years.

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BACKGROUND: Coadministration of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection and first generation anticonvulsants is currently not recommended due to a drug-drug interaction that could potentially lead to subtherapeutic DAA levels and subsequent treatment failure. Currently, there is limited data evaluating this interaction and timely treatment of HCV infection with DAAs is imperative to prevent liver-related morbidity and mortality. METHODS: A retrospective case series evaluating clinical cure of chronic HCV infection, defined as sustained virologic response (SVR) 12 weeks after completion of DAA therapy, in patients from three inner-city clinics who remained on first generation anticonvulsants during the treatment course. RESULTS: A total of five patients received standard dose DAAs for treatment of chronic HCV infection while being maintained on first generation anticonvulsants. The most common HCV genotype was 1a (80%), followed by 1b (20%). The majority of patients were treated with glecaprevir/pibrentasvir (80%) for eight weeks and one patient was treated with ledipasvir/sofosbuvir for 12 weeks. Anticonvulsant regimens consisted of carbamazepine, phenytoin, phenytoin plus phenobarbital, phenytoin plus levetiracetam, and phenobarbital plus lacosamide. All five patients achieved sustained virologic response (SVR) despite this drug-drug interaction. CONCLUSION: Although every effort to prevent concomitant use of DAAs and potent inducers should be made, clinical cure may still be achieved in patients whom cannot avoid this coadministration.

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A new coronavirus strain called as SARS-CoV-2 has emerged from Wuhan, China in late 2019 and it caused a worldwide pandemic in a few months. After the Second World War, it is the biggest calamity observed as there is no specific US Food and Drugs Administration (USFDA) approved drug or vaccine available globally for the treatment. Several clinical trials are ongoing for therapeutic alternatives, however with little success rate. Considering that the time is crucial, the drug repurposing and data obtained from in silico models are one of the most important approaches to identify possible lead inhibitors against SARS-CoV-2. More recently, the Direct Acting Antivirals (DAAs) are emerged as the most promising drugs to control viral infection. The Main Protease (Mpro), a key enzyme in the SARS-CoV-2 replication cycle, is found close homolog to the Hepatitis C Virus (HCV) protease and could be susceptible of blocking its activity by DAAs. In the current study, the DAAs were investigated as antivirals using structure based computational approach against Mpro of SARS-CoV-2 to propose them as new therapeutics. In total, 20 DAAs of HCV, including a reference compound O6K were docked against Mpro. The docked structures were examined and resulted in the identification of six highly promising DAAs i.e. beclabuvir, elbasvir, paritaprevir, grazoprevir, simeprevir, and asunapevir exhibiting high theoretical binding affinity to Mpro from SARS-CoV-2 in comparison to other DAAs. Furthermore, the post docking analysis revealed that Cys145, Glu166, His163, Thr26, His41, and Met165 played potential role for the binding of these DAAs inside binding site of Mpro. Furthermore, the correlation between binding energies were found in accord with the results from the reported IC50s for some DAAs. Overall, the current study provides insight to combat COVID-19 using FDA-approved DAAs as repurposed drugs.

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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.

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BACKGROUND Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection showed the presence of resistant-associated substitutions (RASs). The aim of the present study was to carry out a follow-up of patients with baseline RASs to report the impact of RASs on DAA therapy outcome. METHODS In a cohort study, we analyzed NS5A and NS5B RASs among nine thalassemia cases by baseline RASs. In a 2-year follow-up, we analyzed viral markers and biochemical and hematological parameters of the participants and their sustained virologic response (SVR). Statistical analyses were performed using SPSS software version 22. RESULTS RASs for HCV subtype 1a included M28V, L31M, and H58P. For subtype 1b: L28M, R30Q, S24F, and C316N. And for subtype 3a: C316S, and S24F. In patients with cirrhosis (n = 5), ALT (p = 0.001) and AST (p = 0.007) levels were significantly reduced after treatment, and creatinine level slightly increased (p = 0.025). However, no significant data was observed in non-cirrhotic patients following the treatment. CONCLUSION The present study did not show any adverse effects of DAA therapy among patients with thalassemia suffering from chronic HCV infection with baseline RASs. Furthermore, reduction in ferritin and liver stiffness levels after DAA therapy could show the efficacy of DAA in such patients.

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BACKGROUND: Resistance-associated substitutions (RASs) to HCV direct-acting antivirals (DAAs) can contribute to virologic failure and limit retreatment options. People who inject drugs (PWID) are at highest risk for transmission of resistant virus. We report on RASs at baseline and after virologic failure in DAA-naive and protease inhibitor-experienced PWID. METHODS: We sequenced the NS3/4A, NS5A, and NS5B regions from 150 PWID with genotype 1 (GT1) viruses; 128 (85.3%) GT1a, 22 (14.7%) GT1b. RESULTS: Among the 139 (92.7%) DAA-naive PWID, 85 of 139 (61.2%) had baseline RASs-67 of 139 (48.2%) in NS3 (predominantly Q80K/L); 25 of 139 (18.0%) in NS5A; and 8 of 139 (5.8%) in NS5B. Of the 11 protease inhibitor-experienced participants, 9 had baseline NS3 RASs (V36L N = 1, Q80K N = 9) and 4 had baseline NS5A RASs (M28V N = 2, H58P N = 1, A92T N = 1). Among the 11 participants who had posttreatment samples with detectable virus (7 treatment failures, 1 late relapse, 3 reinfections), 1 sofosbuvir/ledipasvir failure had a baseline H58P. Two sofosbuvir/ledipasvir-treated participants developed new NS5A mutations (Q30H, Y93H, L31M/V). Otherwise, no RASs were detected. CONCLUSIONS: Our results demonstrate RAS prevalence among DAA-naive PWID is comparable to that in the general population. Only 2 of 150 (1.3%) in our longitudinal cohort developed treatment-emergent RASs. Concern for transmission of resistant virus may therefore be minimal.

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Hepatitis C virus (HCV) infection induces a long-term inflammatory response and oxidative-stress in the liver microenvironment, leading to hepatic fibrosis and metabolic alterations. Direct-acting-antiviral-agents (DAAs) induce HCV-clearance, even though liver damage is only partially restored. In this context, understanding the impact of viral-eradication on liver metabolic activities could allow optimizing the metabolic care of the patient. The present prospective longitudinal study aims at characterizing the urinary metabolic profile of HCV-induced severe liver fibrosis and the metabolic changes induced by DAAs and HCV-clearance by nuclear magnetic resonance-based metabolomics. The urinary metabolic profile of 23 HCV males with severe liver fibrosis and 20 age-matched healthy-controls was analyzed by NMR-based-metabolomics before starting DAAs, at the end-of-therapy, after one and three months of follow-up. The urinary metabolic profile of patients with severe liver fibrosis was associated to pseudouridine, hypoxanthine, methylguanidine and dimethylamine, highlighting a profile related to oxidative damage, and to tyrosine and glutamine, related to a decreased breakdown of aromatic aminoacids and ammonia detoxification, respectively. 1-methylnicotinamide, a catabolic intermediate of nicotinamide-adenine-dinucleotide, was significantly increased in HCV-patients and restored after HCV-clearance, probably due to the reduced hepatic inflammation. 3-hydroxy-3-methylbutyrate, an intermediate of leucine-catabolism which was permanently restored after HCV-clearance, suggested an improvement of skeletal muscle protein synthesis. Finally, 3-hydroxyisobutyrate and 2,3-dihydroxy-2-methylbutyrate, intermediates of valine-catabolism, glycine and choline increased temporarily during therapy, resulting as potential biomarkers of DAAs systemic effects.

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BACKGROUND: Hepatitis C virus (HCV) acts in the host as a complicated mixture of related variants with the potency to genetically escape host immune responses. Direct acting antivirals (DAAs) have been approved for HCV treatment with shorter duration, better cure rates and lower side effects. However, naturally occurring resistance associated substitutions (RASs) create some obstacles to this antiviral therapy success. OBJECTIVE: In this study, we aimed at the determination of the naturally occurring NS3/4A RASs in HCV/human immunodeficiency virus (HIV)infected patients. METHODS: A total of 120 DAA-naïve HCV-HIV co-infected patients were included. HCV NS3/4Agenome region was amplified with PCR and mutation analysis was performed by Sanger sequencing technique. The amino acid sequence diversity of the region was analyzed using geno2pheno HCV. RESULTS: Phylogenetic analysis showed that 73 cases were infected by 3a and 47 subjects by subtype1a. The overall RASs among studied subjects were observed in 6 (5%) individuals from 120 studied cases who were infected with HCV 1a. V36M/L, Q80L, S122G/L, R155T/G, A156S, D168Y/N and S174A/N/T mutations were detected in this study. CONCLUSION: Although the prevalence of RASs was totally low in this study, the presence of several cases of double and triple mutants among this population suggests prior evaluation of protease inhibitors related mutations before initiation of standard treatment and also an investigation on a large population could be of high value.

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BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in Africa. In Africa, the major causes of HCC include chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV). Knowledge of the changes in the incidence of viral hepatitis-associated HCC over time and the factors responsible for such changes is key in informing policies for the prevention of viral hepatitis-associated HCC in Africa. AIM: The study aimed to systematically summarize the changes in the prevalence of viral hepatitis among HCC patients and the overall effect of the prevalence of viral hepatitis on the incidence of HCC over the past four decades in Africa (1980-2019). METHODS: A literature search was conducted in MEDLINE (PubMed), Google Scholar, Science Direct, Scopus, Web of Science, and African wide web for articles published on viral hepatitis-associated HCC in Africa from 1980 to 2019. The abstracts of the articles were screened for eligibility and those meeting the inclusion criteria were retrieved and reviewed. RESULTS: A total of 272 studies were included in the analysis. Viral hepatitis-related HCC incidence changed by 1.17% (95% confidence interval (CI): 0.63-1.71, p < 0.001), 0.82% (95% CI: 0.45-1.18, p < 0.001), and 3.34% (95% CI: 2.44-4.25, p < 0.001) for every 1% change in the prevalence of HBV, HCV, and hepatitis D virus (HDV) respectively, per decade. The incidence of HBV-related HCC decreased by - 0.50% (95% CI: - 0.74 - - 0.25, p < 0.001) over the last 40 years, while HCV-related HCC increased. CONCLUSION: Overall, the incidence of viral hepatitis-associated HCC has not declined, mainly due to no decline in the prevalence of HCV, HDV, and the high number of chronic hepatitis B carriers on the African continent. There is an urgent need for the allocation of resources for the implementation of treatment and preventive programs for HBV, HCV, HDV, and HCC in Africa. This systematic review is registered with PROSPERO®, number CRD42020169723.

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RATIONALE & OBJECTIVE: Hemodialysis facilities are high-risk environments for the spread of hepatitis C virus (HCV). Eliminating HCV from all dialysis facilities in a community may be achieved more effectively under a collaborative care model. STUDY DESIGN: Quality improvement study of multidisciplinary collaborative care teams including nephrologists, gastroenterologists, and public health practitioners. SETTING & PARTICIPANTS: All dialysis patients in Changhua County, Taiwan were treated using an interdisciplinary collaborative care model implemented within a broader Changhua-Integrated Program to Stop HCV Infection (CHIPS-C). QUALITY IMPROVEMENT ACTIVITIES: Provision of an HCV care cascade to fill 3 gaps, including screening and testing, diagnosis, and universal direct-acting antiviral (DAA) treatment implemented by collaborating teams of dialysis practitioners and gastroenterologists working under auspices of Changhua Public Health Bureau. OUTCOME: Outcome measures included quality indicators pertaining to 6 steps in HCV care ranging from HCV screening to treatment completion to cure. ANALYTICAL APPROACH: A descriptive analysis. RESULTS: A total of 3,657 patients from 31 dialysis facilities were enrolled. All patients completed HCV screening. The DAA treatment initiation rate and completion rate were 88.9% and 94.0%, respectively. The collaborative care model achieved a cure rate of 166 (96.0%) of 173 patients. No virologic failure occurred. The cumulative treatment ratios for patients with chronic HCV infection increased from 5.3% before interferon-based therapy (2017) to 25.6% after restricted provision of DAA (2017-2018), and then to 89.1% after universal access to DAA (2019). LIMITATIONS: Unclear impact of this collaborative care program on incident dialysis patients entering dialysis facilities each year and on patients with earlier stages of chronic kidney disease. CONCLUSIONS: A collaborative care model in Taiwan increased the rates of diagnosis and treatment for HCV in dialysis facilities to levels near those established by the World Health Organization.

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BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality among patients with cirrhosis. The risk of HCC recurrence after a complete response among patients treated with direct-acting antivirals (DAAs) has not been fully elucidated yet. AIM: To assess the risk of HCC recurrence after DAA therapy for hepatitis C virus (HCV). METHODS: A systematic review across PubMed, Scopus and Scholar up to November 2020, including full-text studies that assessed the pattern of HCC recurrence after DAA therapy for HCV. Random-effect meta-analysis and univariable metaregression were applied to obtain pooled estimates for proportions and relative risk (RR) and variables influential for the outcome, respectively. RESULTS: Thirty-one studies with 2957 patients were included. Overall, 30% (CI, 26-34%) of the patients with a history of HCC experienced HCC recurrence after DAA therapy, at mean time intervals ranging from 4 to 21 months. This result increased when going from European studies (23%, CI, 17-28%) to US studies (34%, CI, 30-38%), to Egyptian studies (37%, CI, 27-47%), and to Asian studies (33%, CI, 27-40%). Sixty-eight percent (CI, 45-91%) of recurrent HCCs developed within 6 months of follow-up since DAA treatment, among the eight studies providing stratified data. Among the studies providing head-to-head comparisons, the HCC recurrence risk was significantly lower after DAA therapy than IFN (RR, 0.64; CI, 0.51-0.81), and after DAA therapy than no intervention (RR, 0.68; CI, 0.49-0.94). CONCLUSIONS: The recurrence of HCC after DAA is not negligible, being higher soon after the end of treatment and among non-European countries. DAA therapy seems to reduce the risk of HCC recurrence compared to an IFN regimen and no intervention.

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Hepatitis C virus (HCV) is a major cause of death and morbidity globally and is a leading cause of hepatocellular carcinoma (HCC). Incidence of HCV infections, as well as HCV-related liver diseases, are increasing. Although now, with new direct acting antivirals (DAAs) therapy available, HCV is a curable cancer-associated infectious agent, HCC prevalence is expected to continue to rise because HCC risk still persists after HCV cure. Understanding the factors that lead from HCV infection to HCC pre- and post-cure may open-up opportunities to novel strategies for HCC prevention. Herein, we provide an overview of the reported evidence for the induction of alterations in the transcriptome of host cells via epigenetic dysregulation by HCV infection and describe recent reports linking the residual risk for HCC post-cure with a persistent HCV-induced epigenetic signature. Specifically, we discuss the contribution of the epigenetic changes identified following HCV infection to HCC risk pre- and post-cure, the molecular pathways that are epigenetically altered, the downstream effects on expression of cancer-related genes, the identification of targets to prevent or revert this cancer-inducing epigenetic signature, and the potential contribution of these studies to early prognosis and prevention of HCC as an approach for reducing HCC-related mortality.