Hepatitis C Virus Eradication Research Articles

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4weeks for new-onset LC and liver-related events. Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

Contemporary Insights into Hepatitis C Virus: A Comprehensive Review.

Hepatitis C virus (HCV) remains a significant global health challenge. Approximately 50 million people were living with chronic hepatitis C based on the World Health Organization as of 2024, contributing extensively to global morbidity and mortality. The advent and approval of several direct-acting antiviral (DAA) regimens significantly improved HCV treatment, offering potentially high rates of cure for chronic hepatitis C. However, the promising aim of eventual HCV eradication remains challenging. Key challenges include the variability in DAA access across different regions, slightly variable response rates to DAAs across diverse patient populations and HCV genotypes/subtypes, and the emergence of resistance-associated substitutions (RASs), potentially conferring resistance to DAAs. Therefore, periodic reassessment of current HCV knowledge is needed. An up-to-date review on HCV is also necessitated based on the observed shifts in HCV epidemiological trends, continuous development and approval of therapeutic strategies, and changes in public health policies. Thus, the current comprehensive review aimed to integrate the latest knowledge on the epidemiology, pathophysiology, diagnostic approaches, treatment options and preventive strategies for HCV, with a particular focus on the current challenges associated with RASs and ongoing efforts in vaccine development. This review sought to provide healthcare professionals, researchers, and policymakers with the necessary insights to address the HCV burden more effectively. We aimed to highlight the progress made in managing and preventing HCV infection and to highlight the persistent barriers challenging the prevention of HCV infection. The overarching goal was to align with global health objectives towards reducing the burden of chronic hepatitis, aiming for its eventual elimination as a public health threat by 2030.

Unmet needs in the post-DAA era: the risk and molecular mechanisms of hepatocellular carcinoma after HCV eradication.

Hepatitis C virus (HCV) is one of the major etiologies of hepatocellular carcinoma with approximately 30% of HCC being due to HCV infection worldwide. HCV eradication by antivirals greatly reduces the risk of HCC; nevertheless, HCC remains to occur in CHC patients who have achieved a sustained virological response (SVR). The proportion of post-SVR HCC among newly diagnosed HCC patients is increasing in the DAA era and might be due to preexisting inflammatory and fibrotic liver background, immune dysregulation between host and virus interaction, as well as host epigenetic scar, genetic predispositions and alternations. By means of applying surrogate markers and adopting risk stratification, HCC surveillance should be consistently performed in high-risk populations. In this review, we discuss the possible molecular mechanism, risk factors and surveillance strategy for HCC development after HCV eradication.

Reduction of the Risk of Hepatocellular Carcinoma over Time Using Direct-Acting Antivirals: A Propensity Score Analysis of a Real-Life Cohort (PITER HCV).

The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan-Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23-0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16-0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02-2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk.

The burden of HCV among prevalent hemodialysis patients after the National Egyptian HCV Eradication program

In the first phase of its treatment program, Egypt aimed to treat 250,000 people annually until 2020, thereby reducing the number of viremic patients and limiting hepatitis C virus (HCV) transmission. Egypt strives to eradicate HCV and HCV-associated morbidity by 2030. This study aimed to determine the prevalence of HCV infection among end-stage renal disease patients and the reasons for non-treatment among those offered free medication. This multi-center cross-sectional study was conducted during the period from November 2022 to April 2023. The study included 500 patients receiving hemodialysis (HD) sessions on a regular basis for more than three months in Dakahlia Governorate. According to patients` medical history, we found that 23.4% of patients had previous HCV infection. Of these, 12.6% received treatment, and 10.8% did not receive treatment due to a variety of reasons. For instance, some patients were unaware of the drug’s availability, five patients (1%) feared side effects, 43 patients (8.6%) did not require treatment, and five patients (1%) had other causes as contraindications of drugs, noncompliance and deterioration of health status. In addition, 20.4% of patients were reported to have fully recovered, while 0.8% had a recurrence. After investigations, 1% of patients had positive hepatitis B surface antigen (HbsAg), 23.4% positive HCV Ab, and 4.2% positive HCV by the polymerase chain reaction. In conclusion, the low prevalence of HCV among HD patients confirms that HCV infection is not currently a significant health concern among patients on maintenance HD.

Peripheral Neuropathy in Patients with Hepatitis C Infection-Reversibility after HCV Eradication: A Single Center Study.

Chronic hepatitis C virus (HCV) infection is characterized by a variety of extra-hepatic manifestations; peripheral neuropathy (PN) is one of the most common, especially when mixed cryoglobulinemia (MCG) is present. The prevalence and risk factors of HCV-related PN in the absence of MCG are largely unknown. We conducted a prospective, single-center study, examining the prevalence and reversibility of HCV-associated neuropathy in the absence of MCG. Nerve fiber density in the epidermis was evaluated through skin biopsy and electroneurography (ENG) before HCV-treatment initiation and 1 year post sustained virological remission (SVR). Forty HCV-infected individuals (nine HIV co-infected) with no other neuron-harming factors were included; four other HCV mono- and three HIV co-infected individuals were excluded due to presence of diabetes, B12 insufficiency, or neurotoxic drugs. Twelve consecutive controls with no neuron-harming conditions were also recruited; eight more were excluded due to meeting exclusion criteria. Four patients had ENG signs of polyneuropathy (two with HCV mono- and two with HIV co-infection), while seven more (five with HCV mono- and two with HIV co-infection) had signs of mono-neuropathy, leading to PN prevalences of 22.5% and 44% for mono- and co-infection, respectively (p value 0.179). The two patients with HCV mono-infection and polyneuropathy and the one with ulnar nerve damage showed ENG improvement 1 year post SVR. Regarding intraepidermal nerve density, HCV infection, irrespective of HIV co-infection, was correlated with a lower intraepidermal neuron density that improved 1 year post SVR (p value 0.0002 for HCV and 0.0326 for HCV/HIV co-infected patients). PN is common in HCV infection; successful eradication of HCV leads to PN improvement.

Lipid Profile and Cardiovascular Risk Modification after Hepatitis C Virus Eradication.

The eradication of the hepatitis C virus (HCV) has revolutionized the hepatology paradigm, halting the progression of advanced liver disease in patients with chronic infection and reducing the risk of hepatocarcinoma. In addition, treatment with direct-acting antivirals can reverse the lipid and carbohydrate abnormalities described in HCV patients. Although HCV eradication may reduce the overall risk of vascular events, it is uncertain whether altered lipid profiles increase the risk of cerebrovascular disease in certain patients. We have conducted a review on HCV and lipid and carbohydrate metabolism, as well as new scientific advances, following the advent of direct-acting antivirals.

Integration of Hepatitis C and Addiction Treatment in People Who Inject Drugs: The San Patrignano HCV-Free and Drug-Free Experience.

Injection drug use represents an important contributor to hepatitis C virus (HCV) transmission, hence therapeutic communities (TCs) are promising points of care for the identification and treatment of HCV-infected persons who inject drugs (PWIDs). We evaluated the effectiveness and efficacy of an HCV micro-elimination program targeting PWIDs in the context of a drug-free TC; we applied the cascade of care (CoC) evaluation by calculating frequencies of infection diagnosis, confirmation, treatment and achievement of a sustained virological response (SVR). We also evaluated the risk of reinfection of PWIDs achieving HCV eradication by collecting follow-up virologic information of previously recovered individuals and eventual relapse in drug use, assuming the latter as a potential source of reinfection. We considered 811 PWIDs (aged 18+ years) residing in San Patrignano TC at the beginning of the observation period (January 2018-March 2022) or admitted thereafter, assessing for HCV and HIV serology and viral load by standard laboratory procedures. Ongoing infections were treated with direct-acting antivirals (DAA), according to the current national guidelines. Out of the 792 individuals tested on admission, 503 (63.5%) were found to be seropositive for antibodies against HCV. A total of 481 of these 503 individuals (95.6%) underwent HCV RNA testing. Out of the 331 participants positive for HCV RNA, 225 were ultimately prescribed a DAA treatment with a sustained viral response (SVR), which was achieved by 222 PWIDs (98.7%). Of the 222 PWIDs, 186 (83.8%) with SVR remained HCV-free on follow-up (with a median follow-up of 2.73 years after SVR ascertainment). The CoC model in our TC proved efficient in implementing HCV micro-elimination, as well as in preventing reinfection and promoting retention in the care of individuals, which aligns with the therapeutic goals of addiction treatment.

Pregnancy as an Opportunity for Hepatitis C Virus Elimination and Eradication.

Since the development of highly effective direct-acting antivirals, the WHO has set a goal of hepatitis C virus (HCV) elimination by 2030. Key to this strategy is increased screening and treatment. Pregnancy and the postpartum period represent a unique time when underserved populations have increased contact with the healthcare system. We propose using antenatal care to maximize case identification, treatment, and prevention. Pregnant individuals are an ideal sentinel population for HCV surveillance. Universal screening in pregnancy can provide population-level data. Once cases are identified, pregnancy presents an opportunity for intervention. Although not currently WHO approved, clinical trials are examining treatment during pregnancy. In the interim, identification of infection during pregnancy allows for optimization of the treatment cascade postpartum. Pregnancy can be used as a time for prevention. Taking advantage of patient engagement and existing infrastructure, pregnancy presents an opportunity to intervene in the fight for HCV eradication.

Rising Lysophosphatidylcholine Levels Post-Hepatitis C Clearance.

Hepatitis C virus (HCV) infection alters lysophosphatidylcholine (LPC) metabolism, enhancing viral infectivity and replication. Direct-acting antivirals (DAAs) effectively treat HCV and rapidly normalize serum cholesterol. In serum, LPC species are primarily albumin-bound but are also present in lipoprotein particles. This study aims to assess the impact of HCV eradication on serum LPC species levels in patients infected with HCV. Therefore, 12 different LPC species were measured by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the sera of 178 patients with chronic HCV infections at baseline, and in 176 of these patients after therapy with DAAs. All LPC species increased at 4 and 12 weeks post-initiation of DAA therapy. The serum profiles of the LPC species were similar before and after the viral cure. Patients with HCV and liver cirrhosis exhibited lower serum levels of all LPC species, except LPC 16:1, both before and after DAA treatment. Percentages of LPC 18:1 (relative to the total LPC level) were higher, and % LPC 22:5 and 22:6 were lower in cirrhotic compared to non-cirrhotic patients at baseline and at the end of therapy. LPC species levels inversely correlated with the model of end-stage liver disease score and directly with baseline and post-therapy albumin levels. Receiver operating characteristic curve analysis indicated an area under the curve of 0.773 and 0.720 for % LPC 18:1 (relative to total LPC levels) for classifying fibrosis at baseline and post-therapy, respectively. In summary, HCV elimination was found to increase all LPC species and elevated LPC 18:1 relative to total LPC levels may have pathological significance in HCV-related liver cirrhosis.

The illness trap: The impact of disability benefits on willingness to receive HCV treatment

Health care is assumed to be a primary good, implying that patients should always demand or accept treatments that may enhance their life expectancy and quality of life, especially if the risks associated with the treatment are low. We argue that, especially in countries with a well-developed welfare state, treating an invalidating condition may lead to opportunity costs in terms of reduced disability allowances that may represent a barrier to treatment for low-income individuals. We test this hypothesis by applying a recursive bivariate probit approach to population data from an ad hoc administrative database for Liguria (an Italian administrative region). The dataset includes data for more than 8 thousand people affected by hepatitis C Virus (HCV) infection between 2013 and 2020. After the discovery of new direct-acting antivirals (DAAs) in 2014, HCV eradication may now be possible. However, despite the national and international efforts, several patients diagnosed with HCV choose not to undergo drug therapy despite the adverse consequences for their personal health and relevant costs to the national health system. We show that five years after the implementation of the new drugs, approximately 41 % of the diagnosed population in Liguria remains untreated. This percentage increases to 64 % within the subgroup entitled to disability benefits and characterized by lower income levels. The “illness trap” effect is more substantial for older people but also low-income patients. Moreover, we find that this effect is higher in patients with an intermediate range of comorbidities; indeed, these patients are at a higher risk of losing economic benefits if they recover from HCV. These results suggest the need for healthcare policies addressing this distorting effect when designing benefit programs and granting financial benefits to patients.

Effect of previous infection with hepatitis B virus on the incidence of hepatocellular carcinoma after sustained virologic response in patients with chronic hepatitis C virus infection.

Previous infection with hepatitis B virus (HBV), which is assessed by HBV core antibody (HBcAb) or surface antibody (HBsAb) titres, has reportedly been associated with an increased risk of developing hepatocellular carcinoma (HCC). We investigated the influence of previous HBV infection on the incidence of HCC in patients with hepatitis C virus (HCV) infection who achieved eradication of HCV, that is sustained virologic response (SVR). Both HBcAb and HBsAb were measured in a total of 1214 patients with HCV infection who had not been coinfected with HBV, as determined by both negative HBs antigen and HBV DNA, and in whom SVR was confirmed. Patients were followed up for a median of 5.7 years, and the incidence of post-SVR HCC was compared based on HBcAb and/or HBsAb. In both univariate and multivariate analyses, the incidence of post-SVR HCC did not differ based on the presence of HBcAb or HBsAb. In conclusion, previous HBV infection has no impact on the incidence of HCC in patients with HCV after SVR.

Liver Stiffness Measurement and Risk Prediction of Hepatocellular Carcinoma After HCV Eradication in Veterans With Cirrhosis

Background & AimsPatients with cirrhosis secondary to chronic hepatitis C virus (HCV) are at risk for hepatocellular carcinoma (HCC) despite a sustained virological response (SVR). We examined whether post-SVR liver stiffness measurement (LSM) could be used to stratify HCC risk. MethodsThis was a retrospective cohort study of 1850 participants identified from the Veterans Health Administration, with HCV cirrhosis and SVR, followed up over 5099 person-years, from the time of post-SVR elastography until death, HCC, or the end of the study. ResultsThe risk of HCC increased by 3% with every 1-kPa increase in LSM (adjusted hazard ratio [aHR], 1.03, 95% confidence interval [CI], 1.01–1.04; P < .001) and decreased with the number of years from SVR (aHR, 0.79; 95% CI, 0.70–0.90; P = .0003). The adjusted annual risk of HCC was 2.03% among participants with post-SVR LSM <10 kPa, 2.48% in LSM 10–14.9 kPa (aHR, 1.71; 95% CI, 1.01–2.88; P = .046), 3.22% for LSM 15–19.9 kPa (aHR, 1.59; 95% CI, 0.78–3.20; P = .20), 5.07% among LSM 20–24.9 kPa (aHR, 2.55; 95% CI, 1.30–5.01; P = .01), and 5.44% in LSM ≥25 kPa (aHR, 3.03; 95% CI, 1.74–5.26; P < .0001). The adjusted annual risk of HCC was < 0.4% in participants with LSM <5 kPa and without diabetes mellitus. ConclusionsLSM predicts rates of HCC in patients with HCV cirrhosis after SVR at multiple cutoff levels and offers a single test to predict portal hypertension–related complications and HCC. Patients with LSM <5 kPa in the absence of diabetes mellitus had a low risk of HCC in which surveillance could be discontinued.

Metabolic management after sustained virologic response in elderly patients with hepatitisC virus: A multicenter study.

Hepatocellular carcinoma (HCC) develops even in patients with hepatitisC virus (HCV) eradication by direct-acting antiviral agents. Fatty liver and metabolic dysfunction are becoming major etiologies of HCC. We aimed to evaluate the impact of metabolic dysfunction-associated steatotic liver disease (MASLD), a new definition of steatotic liver disease, on the development of HCC after HCV eradication. We enrolled 1280 elderly patients with HCV eradication and no history of HCC. We evaluated α-fetoprotein (AFP), Fibrosis-4 index and MASLD after 24weeks of sustained virological response. Decision tree analysis was used to investigate factors associated with HCC development after HCV eradication. A total of 86 patients (6.7%) developed HCC during the follow-up period (35.8±23.7months). On multivariate analysis, serum AFP level (HR 1.08, CI 1.04-1.11, P=0.0008), Fibrosis-4 index (HR 1.17, CI 1.08-1.26, P=0.0007), and MASLD (HR 3.04, CI 1.40-6.58, P=0.0125) at 24weeks of sustained virological response were independent factors associated with HCC development. In decision tree analysis, the initial classifier for HCC development was AFP ≥7ng/mL. However, in patients with AFP <7ng/mL, MASLD, rather than Fibrosis-4 index, was the classifier for HCC development. No significant difference was observed in the cumulative incidence of HCC between patients with AFP ≥7ng/mL and patients with AFP <7ng/mL and MASLD. MASLD at 24weeks of sustained virological response is a risk factor for HCC development in elderly patients with HCV eradication. Additionally, decision tree analysis revealed that MASLD was associated with HCC development, even in patients with serum AFP levels <7ng/mL.

Hepatitis C virus screening in Piemonte: an effective strategy to eliminate HCV chronic infections

Abstract In 2016, WHO set the goal of elimination of Hepatitis C Virus (HCV) by 2030. Globally, about 58 million people have chronic HCV, which causes cirrhosis, hepatocellular carcinoma and death (around 300000 in 2019), representing a heavy burden for public health. In Italy, the incidence of HCV acute infection is around 0.11 per 100000, and the estimated number of non-diagnosed chronic infections is 280000. In order to reach WHO's goal, the Istituto Superiore di Sanità (ISS) and the Ministry of Health implemented a strategy based on the detection of silent chronic infections and their treatment with direct-acting antivirals (DAAs), which cure around 95% of HCV infections. Therefore, in 2022, Regione Piemonte started a screening program contacting all residents born between 1969 and 1989. The screening was performed with rapid blood tests (antibodies detection, sensibility and specificity ca. 99%), and in case of a positive result, a HCV-RNA test was offered to confirm chronic infection and the need for treatment with DAAs. The Local Health Authority TO3, invited 36120 out of 158017 eligible residents (temporary and permanent), in the period March 2022 - April 2023 with invitation letters or catch-up strategies on other occasions; 6000 rapid blood tests were used (16.6% of invited population), and 11 (0.19%) tested positive. The RNA test confirmed 5 (0.08%) results. All the positive subjects were referred to 2 hospitals for DAAs treatment. As demonstrated by ISS, HCV screening could represent an effective mean to meet WHO's goal of HCV elimination by 2030 and also allow us to reduce HCV's burden on public health; although, with the current low adhesion rate, these results may not be reachable. Therefore, it is necessary to implement health promotion campaigns, to involve more stakeholders, including social and healthcare associations, General Practitioners and policy-makers, as the entire population's health would benefit from a successful HCV elimination program. Key messages • HCV and viral hepatitis represent a heavy burden for public health, high costs for Health Systems and severely affect the quality of life of subjects with un-diagnosed chronic infections. • The availability of reliable, non-invasive, tests and of extremely effective treatments should move policy-makers to allocate more resources in the implementation of HCV eradication strategies.

Serum inducible protein 10kDa/C-X-C motif chemokine10 levels predict regression of M2BPGi-based liver fibrosis after hepatitisC virus eradication by direct-acting antiviral agents.

It is desirable to identify predictors of regression of liver fibrosis after achieving sustained virological response by anti-hepatitisC virus (anti-HCV) therapy. We retrospectively investigated the serum interferon-γ inducible protein 10kDa (IP-10) level as a predictive indicator of regression of liver fibrosis after successful hepatitis C virus eradication by direct-acting antiviral agents (DAAs) therapy. The study participants were recruited from a historical cohort of 116 chronically hepatitisC virus-infected patients who had achieved sustained virological response by DAAs therapy and whose serum Mac-2 binding protein glycosylation isomer (M2BPGi) levels at baseline (before DAAs therapy) were ≥2.0 cut-off index. We defined patients with M2BPGi levels <1.76 and ≥1.76 cut-off index at 2years after the end of treatment (EOT) as the regression (n=71) and non-regression (n=45) groups, respectively. Multivariate analyses revealed that the albumin-bilirubin score at baseline, and albumin-bilirubin score, Fibrosis-4 index at 24weeks after the EOT, and serum IP-10 change from baseline to 24weeks after the EOT (IP-10 change) were significantly associated with regression of M2BPGi-based liver fibrosis. In addition, IP-10 change was significantly associated with regression of M2BPGi-based liver fibrosis by a multivariate analysis, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis: M2BPGi levels ≥3.3 cut-off index at baseline. Serum IP-10 change from baseline to 24weeks after the EOT is a feasible predictor of regression of M2BPGi-based liver fibrosis after achieving sustained virological response with DAA therapy.

IN HIV-INFECTED IMMUNOLOGICAL NON-RESPONDERS, HEPATITIS C VIRUS ERADICATION CONTRIBUTES TO INCOMPLETE NORMALIZATION OF SYSTEMIC INFLAMMATION INDEXES, BUT DOES NOT LEAD TO RAPID CD4&lt;sup&gt;+&lt;/sup&gt; T-CELL COUNT RECOVERY

In HIV-positive individuals taking antiretroviral therapy, coinfection with hepatitis C virus (HCV) increases the systemic inflammation, which interferes with the CD4+ T-cells regeneration. This study evaluated the effect of HCV eradication on systemic inflammation and CD4+ T-cell regeneration in patients who gave poor response to antiretroviral therapy, the so-called “immunological non-responders” (INRs). HIV-infected patients who received a course of direct-acting antiviral drugs for treating hepatitis C were examined. The control groups included HIV/HCV-coinfected individuals and relatively healthy volunteers. It has been established for the first time that HCV eradication is not accompanied by a complete suppression of systemic inflammation, but improves the T-cell pool composition: in INRs, the blood CD4+/CD8+ T-lymphocyte ratio increases and approaches those of healthy individuals. Apparently, in INRs treated for hepatitis C, the immune system recovery takes time and may be incomplete.

Hepatitis C Virus: Insights Into Its History, Treatment, Challenges, and Future Directions.

Hepatitis C virus (HCV) is a global public health concern with significant impacts. It primarily spreads through blood-to-blood contact, such as sharing needles among drug users. Given the wide prevalence of risk factors, HCV continues to pose a major threat. Hence, it is crucial to understand its characteristics, structure, and genotypes to prevent, treat, and potentially eradicate it. This narrative review aims to explore the history of HCV treatment, highlight the breakthroughs achieved with direct-acting antiviral(DAA) therapy, address potential barriers to HCV eradication, and discuss future treatment possibilities. For this article, relevant studies were identified using various databases, including PubMed, ClinicalTrials.gov, and Journal Storage. The literature search revealed that after identifying HCV and studying its characteristics, interferon alfa and ribavirin became primary treatment options. However, due to their limited coverage against different HCV genotypes, ethnic variations, and suboptimal sustained virological response, the development of DAAs became essential. Combining various DAAs, such as sofosbuvir and velpatasvir, for a duration of 12 weeks has become the standard HCV treatment, with effectiveness against most genotypes. Additionally, ongoing clinical trials have shown promising results for other drugs such as CDI31244/sofosbuvir/velpatasvir, sofosbuvir/coblopasvir, and daclatasvir/asunaprevir. Despite the success of DAAs and ongoing efforts to discover more effective treatments, the high costs of DAAs pose a significant challenge to eradicating HCV, as not all patients can afford these expensive therapies. Furthermore, the ability of HCV to mutate limits the potential for vaccine development. Therefore, it is crucial to focus on developing more cost-effective strategies to control the spread of HCV and create novel, highly effective, and affordable DAAs.

Persistence of monoclonal B-cell expansion and intraclonal diversification despite virus eradication in patients affected by hepatitis C virus-associated lymphoproliferative disorders.

We investigated 23 hepatitis C virus (HCV)-infected patients with overt lymphoproliferative diseases (15 cases) or monoclonal B lymphocytosis (8 cases) treated with direct agent antiviral (DAAs) per clinical practice. DAA therapy yielded undetectable HCV-RNA, the complete response of cryoglobulinemia vasculitis and related signs, whilst the presence of B-cell clones (evaluated by flow cytometry, IGHV, and BCL2-IGH rearrangements), detected in 19/23 cases at baseline, was maintained (17/19). Similarly, IGHV intraclonal diversification, supporting an antigen-driven selection mechanism, was identified in B-cell clones at baseline and end of follow-up. DAA therapy alone, despite HCV eradication and good immunological responses, was less effective on the pathological B-cell clones.

Hepatitis Virus-associated Non-hodgkin Lymphoma: Pathogenesis and Treatment Strategies.

Over the last decade, epidemiological studies have discovered a link between hepatitis C virus (HCV) and hepatitis B virus (HBV) infection and non-Hodgkin lymphoma (NHL). The regression of HCV-associated NHL after HCV eradication is the most compelling proof supporting HCV infection's role in lymphoproliferative diseases. HBV infection was found to significantly enhance the incidence of NHL, according to the epidemiological data. The exact mechanism of HCV leading to NHL has not been fully clarified, and there are mainly the following possible mechanisms: (1) Indirect mechanisms: stimulation of B lymphocytes by extracellular HCV and cytokines; (2) Direct mechanisms: oncogenic effects mediated by intracellular HCV proteins; (3) hit-and-run mechanism: permanent genetic B lymphocytes damage by the transitional entry of HCV. The specific role of HBV in the occurrence of NHL is still unclear, and the research on its mechanism is less extensively explored than HCV, and there are mainly the following possible mechanisms: (1) Indirect mechanisms: stimulation of B lymphocytes by extracellular HBV; (2) Direct mechanisms: oncogenic effects mediated by intracellular HBV DNA. In fact, it is reasonable to consider direct-acting antivirals (DAAs) as first-line therapy for indolent HCV-associated B-NHL patients who do not require immediate chemotherapy. Chemotherapy for NHL is affected by HBV infection and replication. At the same time, chemotherapy can also activate HBV replication. Following recent guidelines, all patients with HBsAg positive/HBV DNA≥2,000 IU/mL should be treated for HBV. The data on epidemiology, interventional studies, and molecular mechanisms of HCV and HBV-associated B-NHL are systematically summarized in this review.