Estimating the Allocation of the Economic Value Generated by Utilization of All-Oral Direct-Acting Antivirals for Hepatitis C in the United States, 2015-2019.

OBJECTIVES: Between 2013-2019, several all-oral direct-acting antivirals (DAAs) were launched with the potential to cure patients with hepatitis C virus (HCV). They generated economic value in terms of the health gains for patients and cost-savings for the US healthcare system. We estimated the share of this value allocated to four manufacturers vs society. METHODS: For 2015-2019, we estimated the incremental impact of DAAs on HCV health outcomes and costs. We used the CDAF Polaris Observatory database to estimate utilization. Per-patient projections of lifetime quality-adjusted life-years (QALYs) gained and medical costs avoided were based on a standard 9-state HCV disease-progression model for DAA treatment vs alternatives. Annual QALY gains were valued at $114,000 per QALY. Outcomes and costs were discounted at 3%. Estimated revenues were based on reported sales. RESULTS: An estimated 1,080,000 patients received DAAs: 81.5% would not have received the pre-DAA standard of care. On average, these patients were projected to gain 4.4 QALYs and save $104,400 in lifetime healthcare costs, generating $531.8 billion in value. Those who would have received treatment gained 1.7 QALYs and saved $41,500 in lifetime costs, generating $47.4 billion in economic value. As treatment costs fell nearly 75%, the four manufacturers reported $37.4 billion from DAA sales-an allocation of 6.5% of the total value. CONCLUSIONS: The great majority (∼90%) of the economic value of curing HCV with DAAs were health benefits to patients and net cost-savings to society. DAA manufacturers received a minority share (6.5%) of the aggregate economic value generated.

Development and validation of a nomogram for assessing hepatocellular carcinoma risk after SVR in hepatitis C patients with advanced fibrosis and cirrhosis.

BACKGROUND: Hepatitis C patients with advanced fibrosis or cirrhosis are at high risk of developing hepatocellular carcinoma (HCC), even after sustained virological response (SVR). Clinical recommendations impose a significant burden on patients by recommending lifelong screening for HCC every six months. The goals of this study were to develop a nomogram that accurately stratifies risk of HCC and improve the screening approach that is currently in use. METHOD: Risk factors for HCC were identified using univariate and multivariate analyses in this prospective study. We developed and validated a nomogram for assessing hepatocellular carcinoma risk after SVR in patients with advanced fibrosis and cirrhosis. RESULTS: During the median follow-up period of 61.00 (57.00-66.00) months in the derivation cohort, 37 patients (9.61%) developed HCC. Older age (HR = 1.08, 95% CI 1.02-1.14, p = 0.009), male gender (HR = 2.38, 95% CI 1.10-5.13, p = 0.027), low serum albumin levels (HR = 0.92, 95% CI 0.86-1.00, p = 0.037), and high liver stiffness measurement (LSM) (HR = 1.03, 95% CI 1.01-1.06, p = 0.001) were found to be independent predictors of HCC development. Harrell's C-index for the derivation cohort was 0.81. The nomogram's 3-, 5- and 7-years time-dependent AUROCSs were 0.84 (95% CI 0.80-0.88), 0.83 (95% CI 0.79-0.87), and 0.81 (95% CI 0.77-0.85), respectively (all p > 0.05). According to the nomogram, patients are categorized as having low, intermediate, or high risk. The annual incidence rates of HCC in the three groups were 0.18%, 1.29%, and 4.45%, respectively (all p < 0.05). CONCLUSIONS: Older age, male gender, low serum albumin levels, and high LSM were risk factors for HCC after SVR in hepatitis C patients with advanced fibrosis and cirrhosis. We used these risk factors to establish a nomogram. The nomogram can identify a suitable screening plan by classifying hepatitis C patients according to their risk of HCC.

Cost effectiveness of hepatitis C direct acting agents.

INTRODUCTION: Introduction of direct acting antivirals (DAA) has transformed treatment of chronic hepatitis C (HCV) and made elimination of HCV an achievable goal set forward by World Health Organization by 2030. Multiple barriers need to be overcome for successful eradication of HCV. Availability of pan-genotypic HCV regimens has decreased the need for genotype testing, but maintained high efficacy associated with DAAs. AREAS COVERED: In this review, we will assess the cost-effectiveness of DAA treatment in patients with chronic HCV disease, with emphasis on general, cirrhosis, and vulnerable populations. EXPERT OPINION: Multiple barriers exist limiting eradication of HCV, including cost to treatment, access, simplified testing, and implementing policy to foster treatment for all groups of HCV patients. Clinically, DAAs have drastically changed the landscape of HCV, but focused targeting of vulnerable groups is needed. Public policy will continue to play a strong role in eliminating HCV. While we will focus on the cost-effectiveness of DAA, several other factors regarding HCV require on going attention, such as increasing public awareness and decreasing social stigma associated with HCV, offering universal screening followed by linkage to treatment and improving preventive interventions to decrease spread of HCV.

Hepatitis C screening in Lithuania: first-year results and scenarios for achieving WHO elimination targets.

BACKGROUND: The World Health Organization (WHO) has outlined a set of targets to achieve eliminating hepatitis C by 2030. In May 2022, Lithuanian health authorities initiated a hepatitis C virus (HCV) screening program to start working towards elimination. In the program, bonus was given to general practitioners (GPs) to promote and conduct anti-HCV tests for two situations: (1) one time testing for individuals born in 1945-1994 and (2) annual HCV testing for persons who inject drugs or are living with human immunodeficiency virus (HIV) regardless of age. This study aimed to model the current viral hepatitis C epidemiological status in Lithuania and to outline the requirements for WHO elimination targets using the first-year HCV screening results. METHODS: Individuals were invited to participate in the anti-HCV screening by GPs during routine visits. Patients who tested positive were then referred to a gastroenterologist or infectious disease doctor for further confirmatory testing. If a patient received a positive RNA test and a fibrosis staging result of ≥ F2, the doctor prescribed direct-acting antivirals. Information on the patients screened, diagnosed, and treated was obtained from the National Health Insurance Fund. The Markov disease progression model, developed by the CDA Foundation, was used to evaluate the screening program results and HCV elimination progress in Lithuania. RESULTS: Between May 2022 and April 2023, 790,070 individuals underwent anti-HCV testing, with 11,943 individuals (1.5%) receiving positive results. Anti-HCV seroprevalence was found to be higher among males than females, 1.9% and 1.2%, respectively. Within the risk population tested, 2087 (31.1%) seropositive individuals were identified. When comparing the screening program results to WHO elimination targets through modelling, 2180 patients still need to be treated annually until 2030, along with expanding fibrosis restrictions. If an elimination approach was implemented, 1000 new infections would be prevented, while saving 150 lives and averting 90 decompensated cirrhosis cases and 110 hepatocellular carcinoma cases. CONCLUSIONS: During the first year of the Lithuanian screening program, GPs were able to screen 44% of the target population. However, the country will not meet elimination targets as it currently stands without increasing treatment levels and lifting fibrosis restrictions.

Kidney Histopathology of Patients with Hepatitis C Infection and Diabetes Mellitus before and after Availability of Direct-Acting Antiviral Therapy.

Introduction: Type 2 diabetes mellitus (DM) and diabetic kidney disease are increasing. Hepatitis C infection (HCV) occurs in 1% of the world population and can induce several kidney diseases. DM prevalence is increased in individuals with HCV; however, kidney diseases in those with both DM and HCV have not been assessed. Direct-acting antiviral agents (DAAs) became available for HCV treatment in 2014; it is unknown if DAAs altered the spectrum of kidney disease in patients with DM and HCV. Methods: Case review identifying patients with kidney biopsy and clinical history of DM and HCV between 2009-2013 (pre-DAA) and 2016-2020 (post-DAA), excluding kidney transplant, hepatitis B, HIV, and inadequate biopsy, identified 245 biopsies. Biopsies were evaluated for diabetic glomerulosclerosis (DGS) class, global and focal segmental glomerulosclerosis (FSGS), other glomerular diseases, interstitial fibrosis/tubular atrophy (IFTA), interstitial nephritis, acute tubular injury and degree of arterial and arteriolar sclerosis. Kidney disease differences in pre-DAA versus post-DAA eras and in mild versus severe DGS were assessed by χ2 and Fisher's exact tests. Results: The most common non-DGS lesions were non-collapsing FSGS (41%), HCV-related IgM dominant immune complex glomerulonephritis (IgM-ICGN, 18%), IgA nephropathy (9%), and membranoproliferative glomerulonephritis (MPGN, 7%). Collapsing FSGS was more common pre-DAA versus post-DAA (8% vs. 1%, p = 0.03). Biopsies from patients with HCV and DM were reduced in post-DAA (0.7%) versus pre-DAA (1.3%) (p < 0.0001). Post-DAA there were less MPGN (2% vs. 10%, p = 0.02) and more advanced DGS (85% vs. 61%, p = 0.0002), non-collapsing FSGS (57% vs. 31%, p < 0.0001), IFTA (2.0 vs. 1.6, p = 0.0002), and vascular sclerosis (2.1 vs. 1.6, p < 0.0001). Conclusion: Post-DAA there were reduced biopsies and MPGN, with more severe DGS class, non-collapsing FSGS, IFTA, and chronic vascular changes. This suggests a modulating effect of DAAs on HCV-related kidney pathology with DM and chronic changes driving indications for kidney biopsy.

Shared genetic factors and causal association between chronic hepatitis C infection and diffuse large B cell lymphoma.

BACKGROUND: Epidemiological research and systematic meta-analyses indicate a higher risk of B-cell lymphomas in patients with chronic hepatitis C virus (HCV) compared to non-infected individuals. However, the genetic links between HCV and these lymphomas remain under-researched. METHODS: Mendelian randomization analysis was employed to explore the association between chronic hepatitis C (CHC) and B-cell lymphomas as well as chronic lymphocytic leukemia (CLL). Approximate Bayes Factor (ABF) localization analysis was conducted to find shared genetic variants that might connect CHC with B-cell lymphomas and chronic lymphocytic leukemia (CLL). Furthermore, The Variant Effect Predictor (VEP) was utilized to annotate the functional effects of the identified genetic variants. RESULTS: Mendelian randomization revealed a significant association between CHC and increased diffuse large B cell lymphoma (DLBCL) risk (OR: 1.34; 95% CI: 1.01-1.78; P = 0.0397). Subsequent colocalization analysis pinpointed two noteworthy variants, rs17208853 (chr6:32408583) and rs482759 (chr6:32227240) between these two traits. The annotation of these variants through the VEP revealed their respective associations with the butyrophilin-like protein 2 (BTNL2) and notch receptor 4 (NOTCH4) genes, along with the long non-coding RNA (lncRNA) TSBP1-AS1. CONCLUSION: This research provides a refined genetic understanding of the CHC-DLBCL connection, opening avenues for targeted therapeutic research and intervention.

Risk factors for hepatocellular carcinoma associated with hepatitis C genotype 3 infection: A systematic review.

BACKGROUND: Hepatitis C virus (HCV) is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality. Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma (HCC) in people with cirrhosis. Of the 6 HCV genotypes (G1-G6), genotype-3 accounts for 17.9% of infections. HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis. AIM: To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings. Consequently, we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023. METHODS: This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations. We searched Web of Science, Medline, EMBASE, and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings, 1946-2023. RESULTS: Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates. Three thousand eight hundred and eighty-four records were screened with 3514 excluded. Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis. Of the seven studies, three studies were retrospective case-control trials, two retrospective cohort studies, one a prospective cohort study and one a cross-sectional study design. All were based in hospital settings with four in Pakistan, two in South Korea and one in the United States. The total number of participants were 9621 of which 167 developed HCC (1.7%). All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age (five-studies), with two studies each showing male sex, high alpha feto-protein, directly-acting antivirals treatment and achievement of sustained virologic response as risk factors for developing HCC. CONCLUSION: Although, studies have shown that HCV genotype-3 infection is an independent risk factor for end-stage liver disease, HCC, and liver-related death, there is a lack of evidence for specific risk factors for HCC secondary to HCV genotype-3. Only cirrhosis and age have demonstrated an association; however, the number of studies is very small, and more research is required to investigate risk factors for HCC secondary to HCV genotype-3.

Investigation of the effectiveness of a classification method based on improved DAE feature extraction for hepatitis C prediction.

Hepatitis C, a particularly dangerous form of viral hepatitis caused by hepatitis C virus (HCV) infection, is a major socio-economic and public health problem. Due to the rapid development of deep learning, it has become a common practice to apply deep learning to the healthcare industry to improve the effectiveness and accuracy of disease identification. In order to improve the effectiveness and accuracy of hepatitis C detection, this study proposes an improved denoising autoencoder (IDAE) and applies it to hepatitis C disease detection. Conventional denoising autoencoder introduces random noise at the input layer of the encoder. However, due to the presence of these features, encoders that directly add random noise may mask certain intrinsic properties of the data, making it challenging to learn deeper features. In this study, the problem of data information loss in traditional denoising autoencoding is addressed by incorporating the concept of residual neural networks into an enhanced denoising autoencoder. In our experimental study, we applied this enhanced denoising autoencoder to the open-source Hepatitis C dataset and the results showed significant results in feature extraction. While existing baseline machine learning methods have less than 90% accuracy and integrated algorithms and traditional autoencoders have only 95% correctness, the improved IDAE achieves 99% accuracy in the downstream hepatitis C classification task, which is a 9% improvement over a single algorithm, and a nearly 4% improvement over integrated algorithms and other autoencoders. The above results demonstrate that IDAE can effectively capture key disease features and improve the accuracy of disease prediction in hepatitis C data. This indicates that IDAE has the potential to be widely used in the detection and management of hepatitis C and similar diseases, especially in the development of early warning systems, progression prediction and personalised treatment strategies.

Neuropsychiatric and Laboratory Outcomes of Hepatitis C Treatment in an Early-Treated HIV Cohort in Thailand.

Background: Hepatitis C virus (HCV) coinfection may further compromise immunological and cognitive function in people with HIV (PWH). This study compared laboratory and neuropsychiatric measures across the periods of HCV seroconversion and direct-acting antiviral (DAA) therapy with sustained virologic response (SVR) among PWH who initiated antiretroviral therapy (ART) during acute HIV infection (AHI) and acquired HCV after 24 weeks of ART. Methods: Participants from the RV254 AHI cohort underwent paired laboratory and neuropsychiatric assessments during regular follow-up. The former included measurements of CD4 + and CD8 + T-cell counts, HIV RNA, liver enzymes, and lipid profiles. The latter included the Patient Health Questionnaire-9 (PHQ-9), Distress Thermometer (DT), and a 4-test cognitive battery that evaluated psychomotor speed, executive function, fine motor speed and dexterity. The raw scores in the battery were standardized and averaged to create an overall performance (NPZ-4) score. Parameters of HCV-coinfected participants were compared across HCV seroconversion and DAA treatment groups. Results: Between 2009 and 2022, 79 of 703 RV254 participants acquired HCV after ≥ 24 weeks of ART; 53 received DAA, and 50 (94%) achieved SVR. All participants were Thai males (median age: 30 years); 34 (68%) denied past intravenous drug use, and 41 (82%) had a history of other sexually transmitted infections during follow-up. Following SVR, aspartate transferase (AST) and alanine transaminase (ALT) decreased (p < 0.001), while total cholesterol, low-density lipoprotein, and triglycerides increased (p < 0.01). The median CD4+/CD8 + ratio increased from 0.91 to 0.97 (p = 0.012). NPZ-4 improved from 0.75 to 0.91 (p = 0.004). The median DT score increased from 1.7 to 2.7 (p = 0.045), but the PHQ-9 score remained unchanged. Conclusion: HCV coinfection is common in this group of high-risk PWH, highlighting the need for regular screening, early diagnosis, and treatment. There was a modest improvement in the CD4+/CD8 + T-cell ratio and cognitive performance after DAA therapy in patients who achieved SVR. Future studies should examine potential neuropsychiatric impacts during early HCV infection as well as the longer-term neuropsychiatric outcomes after DAA treatment with SVR.

Isolation of mucosa-associated microbiota dysbiosis in the ascending colon in hepatitis C virus post-sustained virologic response cirrhotic patients.

Background: Achieving sustained virologic response (SVR) in patients infected with hepatitis C virus (HCV) reduces all-cause mortality. However, the mechanisms and risk factors for liver fibrosis and portal hypertension post-SVR remain incompletely understood. In the gut-liver axis, mucosa-associated microbiota (MAM) substantially influence immune and metabolic functions, displaying spatial heterogeneity at the anatomical intestinal site. We analyzed MAM composition and function to isolate the locoregional MAM involved in chronic liver disease progression in HCV post-SVR patients. Methods: We collected MAM samples from three intestinal sites (terminal ileum, ascending colon, and sigmoid colon) via brushing during colonoscopy in 23 HCV post-SVR patients and 25 individuals without liver disease (controls). The 16S rRNA of bacterial DNA in specimens collected with a brush and in feces was sequenced. The molecular expression of intestinal tissues and hepatic tissues were evaluated by quantitative real-time PCR. Results: In the post-SVR group, the microbial ß-diversity of MAM, especially in the ascending colon, differed from the control group and was associated with liver fibrosis progression. In PICRUSt analysis, MAM in the ascending colon in the liver cirrhosis (LC) group showed compromised functions associated with the intestinal barrier and bile acid production, and FGF19 expression was markedly decreased in the terminal ileum biopsy tissue in the LC group. At the genus level, six short-chain fatty acid (SCFA)-producing bacterial genera, Blautia, Alistipes, Roseburia, Agathobaculum, Dorea, and Pseudoflavonifractor were reduced in the ascending colon of post-SVR LC patients. Conclusion: In patients of HCV post-SVR, we identified the association between the degree of liver fibrosis and dysbiosis of mucosa-associated SCFA-producing bacterial genera that may be related to intestinal barrier and bile acid production in the ascending colon.

The COVID-19 Pandemic Affected Hepatitis C Virus Circulation and Genotypic Frequencies-Implications for Hepatitis C Prevention, Treatment and Research.

Hepatitis C is regarded as a global health issue caused by hepatitis C virus (HCV) infection. HCV is targeted for elimination by 2030 as a global public health goal. However, the COVID-19 pandemic has changed human circulation and prevented access to diagnostics and treatment to many other diseases, including hepatitis C. COVID-19 impacted HCV global elimination efforts with implications not fully comprehended yet. The high genetic variability in HCV makes the development of vaccines and pan-genotypic drug therapies a difficult task. Changes in the dynamics of HCV impose new challenges for public health and opportunities for future research. Meta-analysis, the follow up of new cases and sampling of HCV patients compared with previously available data are options for investigating the possible changes. The determination of HCV genotypes and subtypes is important for understanding viral dynamics and treatment; therefore, the changes in genotype and subtype prevalences can directly affect such processes. Recent results in the literature already suggest changes in HCV dynamics during the COVID-19 pandemic, both considering viral circulation and differential genotypic frequencies in distinct geographic areas. In this context, we propose a further examination of these trends using different approaches to provide support for the hypothesis that the COVID-19 pandemic affected HCV circulation, since these findings would have important implications for hepatitis C prevention, treatment and research.

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.

Biomarkers in Detection of Hepatitis C Virus Infection.

The hepatitis C virus (HCV) infection affects 58 million people worldwide. In the United States, the incidence rate of acute hepatitis C has doubled since 2014; during 2021, this increased to 5% from 2020. Acute hepatitis C is defined by any symptom of acute viral hepatitis plus either jaundice or elevated serum alanine aminotransferase (ALT) activity with the detection of HCV RNA, the anti-HCV antibody, or hepatitis C virus antigen(s). However, most patients with acute infection are asymptomatic. In addition, ALT activity and HCV RNA levels can fluctuate, and a delayed detection of the anti-HCV antibody can occur among some immunocompromised persons with HCV infection. The detection of specific biomarkers can be of great value in the early detection of HCV infection at an asymptomatic stage. The high rate of HCV replication (which is approximately 1010 to 1012 virions per day) and the lack of proofreading by the viral RNA polymerase leads to enormous genetic diversity, creating a major challenge for the host immune response. This broad genetic diversity contributes to the likelihood of developing chronic infection, thus leading to the development of cirrhosis and liver cancer. Direct-acting antiviral (DAA) therapies for HCV infection are highly effective with a cure rate of up to 99%. At the same time, many patients with HCV infection are unaware of their infection status because of the mostly asymptomatic nature of hepatitis C, so they remain undiagnosed until the liver damage has advanced. Molecular mechanisms induced by HCV have been intensely investigated to find biomarkers for diagnosing the acute and chronic phases of the infection. However, there are no clinically verified biomarkers for patients with hepatitis C. In this review, we discuss the biomarkers that can differentiate acute from chronic hepatitis C, and we summarize the current state of the literature on the useful biomarkers that are detectable during acute and chronic HCV infection, liver fibrosis/cirrhosis, and hepatocellular carcinoma (HCC).

Chronic Hepatitis C Virus Infection, Extrahepatic Disease and the Impact of New Direct-Acting Antivirals.

Chronic hepatitis C virus infection is an important cause of liver cirrhosis, hepatocellular carcinoma and death. Furthermore, it is estimated that about 40-70% of patients develop non-hepatic alterations in the course of chronic infection. Such manifestations can be immune-related conditions, lymphoproliferative disorders and metabolic alterations with serious adverse events in the short and long term. The introduction of new Direct-Acting Antivirals has shown promising results, with current evidence indicating an improvement and remission of these conditions after a sustained virological response.

The Fixed Dose Combination of Sofosbuvir and Velpatasvir is Safe and Effective in Patients of Chronic Hepatitis C With End-stage Renal Disease.

Background: The burden of hepatitis C virus (HCV) in India is alarming, with a major share of this virus being witnessed in patients with end-stage renal disease (ESRD). A pan-genotypic combination of sofosbuvir and velpatasvir is found to be safe, effective, and economical in resource-constraint countries such as ours. However, there are scanty data on the efficacy and safety of sofosbuvir and velpatasvir combination in patients with ESRD. Hence, we performed this study to evaluate the safety and efficacy of the combination of sofosbuvir and velpatasvir in patients of chronic hepatitis C (CHC) with ESRD. Methods: This is an observational study comprising of 40 CHC patients with ESRD on maintenance hemodialysis. All patients were treated with a fixed-dose combination of sofosbuvir and velpatasvir for 12 weeks in case of non-cirrhotic or compensated cirrhosis and 24 weeks in case of decompensated cirrhosis. The efficacy was assessed by sustained virological response defined by negative HCV RNA at 12 weeks (sustained virological response [SVR] 12) post treatment, and safety was assessed by recording any side-effects of all patients. Results: Out of the 40 patients enrolled in our study, majority were non-cirrhotic (77%), and all were treatment-naive. The mean age was 49.87 ± 12.13 years, and 80% patients were male. The mean baseline HCV RNA was 2.61 ± 7.83 × 106 IU/ml. All the 40 patients (100%) achieved undetectable HCV RNA at the end of treatment; however, 39 patients (97.5%) achieved SVR 12. There was no significant deterioration of estimated glomerular filtration rate (eGFR) after completion of antiviral therapy as compared to the baseline eGFR (13.27 ± 10.32 vs13.54 ± 11.38, P = 0.54). None of the patients reported any serious adverse effects during treatment. Conclusion: The fixed-dose combination of sofosbuvir and velpatasvir is effective and has showed excellent safety profile in patients of CHC with ESRD.

Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy.

Backgrounds and Aim: Chronic hepatitis C (CHC) patients who fail antiviral therapy have a high risk of developing hepatocellular carcinoma (HCC). We investigated the effects of metformin and statins, commonly used to treat diabetes mellitus (DM) and hyperlipidemia (HLP), on HCC risk in CHC patients who failed antiviral therapy. Methods: CHC patients with failed interferon-based therapy were enrolled in a large-scale multicenter cohort study in Taiwan (T-COACH). HCC occurrence 1.5 years after the end of antiviral therapy was identified by linking to the cancer registry databases from 2003 to 2019. After considering death and liver transplantation as competing risks, Gray's cumulative incidence and Cox sub-distribution hazards for HCC development were used. Results: Among the 2,779 CHC patients, 480 (17.3%) developed new-onset HCC and 238 (8.6%) died after antiviral therapy. Metformin non-users with DM had a 51% higher risk of liver cancer than patients without DM, while statin users with HLP had a 50% lower risk of liver cancer than patients without HLP. The 5-year cumulative incidence of HCC was 16.5% in metformin non-users, significantly higher in metformin non-users than in patients without DM (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Conversely, HLP statin users had a significantly lower HCC risk than patients without HLP (3.8% vs. 12.5%; aSHR=0.50; P<0.001). Notably, the unfavorable effect of non-metformin use on increased HCC risk was mainly observed among patients without cirrhosis but not in patients with cirrhosis. In contrast, a favorable effect of statins reduced the risk of HCC in both cirrhotic and non-cirrhotic patients. Conclusion: Metformin for DM and statins for HLP have chemopreventive effects on HCC risk in CHC patients who failed antiviral therapy. These findings emphasize the importance of personalized preventive strategies for managing patients with these clinical profiles.

Trends in Mortality Related to Hepatitis B and C from 1990 to 2019 in the Western Pacific Region.

Background/Aims: : This study aimed to analyze the trends in mortality attributed to hepatitis B and C around the Western Pacific region from 1990 to 2019. Methods: : We used data from the Global Burden of Disease Study for a systematic analysis. The deaths related to hepatitis B and C were analyzed by age, sex, year, risk factors, geographical location, and Socio-demographic Index (SDI). Results: : From 1990 to 2019, the annual total deaths from hepatitis B decreased from 0.266 to 0.210 million and those from hepatitis C increased from 0.119 to 0.142 million in the Western Pacific region. The age-standardized mortality rate (ASMR) of hepatitis B and C decreased by 63.5% and 48.0%, respectively. The declines in the ASMR related to hepatitis B and C were only detected in 12 and two Western Pacific countries, respectively. As the major risk factors, the contribution of alcohol use to hepatitis B deaths was 52% and drug use to hepatitis C was 80%. In males and females, the ASMR attributed to hepatitis B decreased by 61% and 71%, respectively, and the ASMR attributed to hepatitis C decreased by 43% and 55%, respectively. The association between SDI and ASMRs suggested that hepatitis B and C, respectively, showed an overall decline and stable trends as the SDI improved in the Western Pacific region. Conclusions: : Although the mortality rate from hepatitis B and C decreased from 1990 to 2019, notable variation was observed among 27 Western Pacific countries. Efforts targeting hepatitis B and C prevention and treatment are still required in this region, especially for the pandemic countries.

Understanding current antenatal Hepatitis C testing and care in maternity services in England.

OBJECTIVES: Universal opt-out antenatal screening for Hepatitis C virus (HCV) is not currently recommened and it is recommended that maternity services offer risk-based testing. We aimed to investigate antenatal HCV testing and adherence to testing guidance. METHODS: A cross-sectional survey was circulated to maternity service providers between November-December 2020 which included testing policy, training for healthcare staff, and management of women found to be HCV positive. Descriptive data are presented. RESULTS: 75 questionnaires were returned, representing 48 % of English maternity service providers. 87 % of providers reported offering antenatal HCV risk-based testing. Risk factors used to identify pregnant women for testing varied. Less than 15 % of respondents considered women that were ever homeless or with history of incarceraton or from higher HCV prevalence areas as high risk. CONCLUSIONS: Current antenatal HCV testing practices are inadequate and HCV infection likely goes undiagnosed in pregnancy, especially among vulnerable population groups. In the absence of universal antenatal screening, re-framing antenatal HCV risk-based testing and management as a quality improvement initiative and developing HCV specific pathway guidance for maternity units is required.

The role and impact of viruses on cancer development.

This review focuses on three major aspects of oncoviruses' role in cancer development. To begin, we discuss their geographic distribution, revealing that seven oncoviruses cause 20% of all human cancers worldwide. Second, we investigate the primary carcinogenic mechanisms, looking at how these oncogenic viruses can induce cellular transformation, angiogenesis, and local and systemic inflammation. Finally, we investigate the possibility of SARS-CoV-2 infection reactivating latent oncoviruses, which could increase the risk of further disease. The development of oncovirus vaccines holds great promise for reducing cancer burden. Many unanswered questions about the host and environmental cofactors that contribute to cancer development and prevention remain, which ongoing research is attempting to address.