Efficacy of current treatments against hepatitis C virus

It is estimated that currently, in the world, approximately 3% of the population has chronic hepatitis, the hepatitis C virus is the etiological agent most related to the development of this pathology. The diversity of genotypes (7) and quasi-species of HCV, due to its high mutation rate, interferes with an effective humoral immunity. The aim of this work is precisely to evoke those usual drugs used in HCV therapy, as well as cutting-edge drugs. The goal of treatment is the eradication of HCV infection. One strategy offered by the WHO is to eradicate the virus in at-risk populations. Alternatives to the previously used treatment with interferon and ribavirin are shown in this paper; protease inhibitors and other targets have now been developed to make eradication of the virus more effective.

Serum microRNA-122 Levels in Egyptian Patients with Chronic Hepatitis C virus Genotype 4 Infection before and after treatment with Direct Acting Antiviral Drugs

Background Viral hepatitis was estimated to be the 7th leading cause of mortality globally. About half of this mortality is attributed to HCV, a primary cause for liver fibrosis, cirrhosis and cancer. The recent development of highly efficacious oral DAAs provides opportunities for reducing HCV disease burden and its onward transmission, with the potential for eliminating this blood-borne virus as a public health concern. WHO has recently formulated the ‘Global Health Sector Strategy on Viral Hepatitis, 2016– 2021 with service coverage targets to eliminate HCV as a public health threat by 2030. Objective To asses the possible relation of miRNA 122 to HCC development after HCV therapy with direct antiviral drug. Patients and Methods Previous studies suspect that HCV therapy by DAAS may increase risk of HCC so the aim of our study is to evaluate miR-122level at end of HCV treatment by DAAS and compare the results with miR-122level in HCC patients. The study was performed as a case control study in Ain Shams University hospital and Suez Canal authority hospital (Outpatient Clinic), at Ismailia Egypt in the period between Augusts to October 2018. Results These results revealed an effect of treatment by DAAs in HCV infected patients leading to miRNA 122 reduction and this may be related to hepatocarcinogenesis. However, further studies on a large patients number are needed to clarify this point and determine the diagnostic and possible therapeutic value of miRNA 122 in HCV infected patients. Conclusion Baseline MiR-122 level at cutoff value ≤0.26 was significantly lower in HCC patients than chronic HCV patients and normal controls, with a sensitivity of 80%, a specificity of 70%. MiR-122 was significantly reduced at end of HCV therapy with DAAs and became similar to values in HCC patients. Whether this observed reduction is mechanistically related to hepatocarcinogenesis is still a possibility, to be clarified in furtur large scale studies. The reduction of MiR-122 at the end of HCV therapy with DAAs was significantly observed in (F3,F4) patients than those with early fibrosis stages(F1,F2).This again gives a possible explanation of HCC development in HCV patients with advanced fibrosis(cirrhosis)and raises the question about the diagnostic and therapeutic value of miRNA 122 (and possibly other miRNAs)in the management strategy of HCV infected patients.

Adherence to Hepatitis C Therapy in a Shelter-Based Education and Treatment Model among Persons Experiencing Homelessness

Background Medication adherence is a common reason for treatment deferment in persons experiencing homelessness. We evaluated adherence to HCV therapy following HCV education in a shelter-based care model. Methods Prospective study conducted at 4 homeless shelters in Minneapolis, MN and San Francisco, CA from 11/2018–1/2021. Sixty-three patients underwent HCV education and treatment. Multivariable modeling evaluated factors associated with (1) medication and (2) overall (composite score of medication, laboratory, and clinic visit) adherence. Results Median age was 56, 73% male, 43% Black, 52% had psychiatric illness, and 81% used illicit drugs and 60% used alcohol in the past year. Following education, 52% were extremely confident in their ability to be adherent to HCV therapy. Medication adherence by patient and provider report was 88% and 48% respectively and 81% achieved HCV cure. Active alcohol use was associated with less confidence in medication adherence (43% vs. 78%, P=0.04). Older age was positively (Coef=0.3) associated with overall adherence to HCV treatment while prior therapy was associated with both medication (OR=0.08) and overall treatment (Coef=-0.87) non-adherence. Conclusions Despite imperfect adherence, SVR rates were still high. Expanding opportunities to treat persons experiencing homelessness in a structured and supportive setting is critical to HCV elimination efforts.

A Genome-Wide Association Study on Liver Stiffness Changes during Hepatitis C Virus Infection Cure

Liver stiffness (LS) at sustained virological response (SVR) after direct-acting antivirals (DAA)-based therapy is a predictor of liver events in hepatitis C virus (HCV)-infected patients. The study aim was to identify genetic factors associated with LS changes from the moment of starting anti-HCV therapy to SVR. This prospective study included HCV-infected patients from the GEHEP-011 cohort who achieved SVR with DAA-based therapy, with LS pre-treatment ≥ 9.5 kPa and LS measurement available at SVR. Plink and Magma software were used to carry out genome-wide single-nucleotide polymorphism (SNP)-based and gene-based association analyses, respectively. The ShinyGO application was used for exploring enrichment in Gene Ontology (GO) categories for biological processes. Overall, 242 patients were included. Median (quartile 1, quartile 3) LS values at pre-treatment and at SVR were 16.8 (12, 28) kPa and 12.0 (8.5, 19.3) kPa, respectively. Thirty-five SNPs and three genes reached suggestive association with LS changes from the moment of starting anti-HCV therapy to SVR. GO categories related to DNA packaging complex, DNA conformation change, chromosome organization and chromatin organization were significantly enriched. Our study reports possible genetic factors associated with LS changes during HCV-infection cure. In addition, our results suggest that processes related to DNA conformation are also involved in these changes.

Pharmacotherapy Profiles in People with Opioid Use Disorders: Considerations for Relevant Drug–Drug Interactions with Antiviral Treatments for Hepatitis C

People who inject drugs (PWID) are often affected by physical and psychological diseases and prone to co-medication. In Germany, about 50% of PWID are on opioid substitution therapy (OST). Comprehensive data on pharmacotherapy in these patients may help to select antiviral therapy against hepatitis C virus (HCV) infections and avoid drug–drug interactions (DDIs). We compared co-medication profiles based on statutory health insurance prescriptions (IQVIA database) of PWID (n = 16,693), OST (n = 95,023) and treated HCV patients (n = 7886). Potential DDIs with the most widely used HCV direct-acting agents (Sofosbuvir/Velpatasvir, Glecaprevir/Pibrentasvir and Elbasvir/Grazoprevir) were evaluated based on the Liverpool DDI database. Co-medication was present in 57% of PWID, 57% of OST, 44% of patients on HCV therapy and 46% in a subgroup receiving OST+HCV therapy (n = 747 of 1613). For all groups, co-medication belonging to ATC-class N (nervous system) was most commonly prescribed (in 75%, 68%, 41% and 62% of patients, respectively). Contraindications (i.e., DDIs precluding HCV therapy) were infrequent (0.4–2.5% of co-medications); potential DDIs with HCV therapies were shown for 13–19% of co-medications, namely for specific substances including some analgesics, antipsychotics, anticoagulants, lipid lowering drugs and steroids. In conclusion, concomitant pharmacotherapy is common and clinically relevant when treating HCV infection in PWID.

Retrieval of lost patients in the system for hepatitis C microelimination: a single-center retrospective study

Background Hepatitis C virus (HCV) is one of the major causes of chronic liver disease, cirrhosis, and liver cancer. Most of the infected people have no clinical symptoms. The current strategy for HCV elimination includes test and treatment. In this study, we aimed to evaluate the campaign for retrieving patients who were lost to follow-up, for subsequent re-evaluation. Methods From January 2020 to October 2020, patients who had prior tests for positive anti-HCV antibody in 2010–2018 in our hospital were enrolled for our patient callback campaign. Patients who had unknown HCV RNA status or no documented successful antiviral therapy history were selected for anti-HCV therapy re-evaluation. To facilitate patient referral in the hospital, we developed an electronic reminding system and called the candidate patients via telephone during the study period. Results Through the hospital electronic system, 3783 patients with positive anti-HCV antibody documentation were identified. Among them, 1446 (38.22%) had tested negative for HCV RNA or had anti-HCV therapy, thereby excluded. Of the 2337 eligible patients, 1472 (62.99%) were successfully contacted and called back during the study period for subsequent HCV RNA testing and therapy. We found that 42.19% of the patients had positive HCV RNA and 88% received subsequent anti-HCV therapy. Conclusions A significant number of patients with positive HCV serology were lost for HCV confirmatory test or therapy in the hospital. Therefore, this targeted HCV callback approach in the hospital is feasible and effective in achieving microelimination.

Telemedicine Chronic Viral Hepatitis C Treatment during the Lockdown Period in Romania: A Pilot Study

The COVID-19 pandemic is currently delaying the process of chronic hepatitis C (HCV) eradication, since most of the chronic diseases are neglected. Thus, there is a need for alternative programs for HCV therapy implementation and disease monitoring. Our aim was to provide a multidisciplinary approach, so that HCV-infected patients from distant locations may benefit from HCV antivirals during the COVID-19 outbreak and within the lockdown period in Romania. Previously diagnosed HCV patients willing to participate in this telemedicine pilot study were included. Patient characteristics and medical adherence were assessed and compared to the year preceding the pandemic. We proposed a multidisciplinary approach by using a telemedicine program for HCV therapy monitoring. Patients also received a satisfaction questionnaire after delivering the sustained virologic response (SVR) result. A total of 41 patients agreed to participate in this study. The medication adherence was 100% for patients included in the telemedicine group, with a statistically significant difference from the medication adherence of the patients treated in 2019. The satisfaction item score was 4.92 out of 5 and our results (r = −0.94, p < 0.0001) suggested that older patients embraced the telemedicine program less, but with the same success in terms of SVR (100%) and medication adherence (100%). Our pilot study offers the first example of a telemedicine program in Romania for HCV therapeutic management. During the lockdown period, telemedicine has served as a reliable tool and novel alternative for conventional monitoring of patients treated with direct antiviral agents and should be further considered even following the pandemic.