Determinants of worse liver-related outcome according to HDV infection among HBsAg positive persons living with HIV: Data from the ICONA cohort.

OBJECTIVES: We aimed to study hepatitis D virus (HDV) prevalence and risk of progression to severe liver-related events (SLRE) in HBsAg positive people living with HIV (PLWH) in Italy; role of HDV-RNA copy levels, HCV coinfection and nadir CD4 counts were also investigated. METHODS: People living with HIV (PLWH) from Italian Foundation cohort Naïve antiretrovirals (ICONA) with available HBsAg and HDV Ab were enrolled. HBsAg, HDV Ab, HDV-RNA and HDV genotypes were tested. PRIMARY END-POINT: time from first HDV screening to Severe Liver Related Events (SLRE: decompensated cirrhosis, liver transplantation, HCC). Fine-grey regression models were used to evaluate the association of HDV Ab, HDV-RNA, HDV/HCV coinfection, CD4 nadir and outcome. Secondary end-points: time to SLRE or death; HDV Ab and HDV-RNA prevalence. RESULTS: A total of 152/809 (18.8%) HBsAg positive PLWH showed HDV Ab reactivity; 63/93 (67.7%) were HDV-RNA positive. Being male, persons who inject drugs (PWID), HCV Ab positive, with FIB-4 > 3.25 were independent factors of HDV Ab positivity. In a median follow-up of 5 years, 37 PLWH (4.1% at 5-year) developed SLRE and 97 (12.0%) reached the SLRE or death end-point. HDV-RNA positive (independently from HDV-RNA copy level) PLWH had a 4.6-fold (95%CI 2.0-10.5) higher risk of SLRE than HDV negatives. PLWH positive for both HCV Ab and HDV Ab showed the highest independent risk of SLRE (ASHR: 11.9, 95%CI: 4.6-30.9 vs. HCV neg/HDV neg). Nadir CD4 < 200/mL was associated with SLRE (ASHR: 3.9, 95% 1.0-14.5). CONCLUSIONS: One-fifth of the HBsAg positive PLWH harbour HDV infection, and are at high risk of progression to advanced liver disease. HCV contributes to worse outcomes. This population needs urgently effective treatments.

Assessment of eligibility criteria in renal cell carcinoma trials evaluating systemic therapy.

OBJECTIVES: To characterise the restrictiveness of eligibility criteria in contemporary renal cell carcinoma (RCC) trials, using recommendations from the American Society of Clinical Oncology (ASCO)-Friends of Cancer Research (FCR) initiative. METHODS: vPhase I-III trials assessing systemic therapies in patients with RCC starting between 30 June 2012 and 30 June 2022 were identified. Eligibility criteria regarding brain metastases, prior or concurrent malignancies, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and human immunodeficiency virus (HIV) infection were identified and stratified into three groups: exclusion, conditional inclusion, and not reported. Descriptive statistics were used to determine the frequency of eligibility criteria. Fisher's exact test or chi-square test were used to calculate their associations with certain trial characteristics. RESULTS: A total of 423 RCC trials were initially identified of which 112 (26.5%) had sufficient accessible information. Exclusion of patients with HIV infection, HBV/HCV infection, brain metastases, and prior or concurrent malignancies were reported in 74.1%, 53.6%, 33.0%, and 8.0% of trials, respectively. In the context of HIV and HBV/HCV infection, patients were largely excluded from trials evaluating immunotherapy (94.4% and 77.8%, respectively). In addition, brain metastases were excluded in trials assessing targeted therapy (36.4%), combined therapy (33.3%), and immunotherapy (22.2%). Exclusion of patients with prior or concurrent malignancies was less frequently reported, accounting for 9.1%, 8.3%, and 5.6% targeted therapy, combined therapy and immunotherapy trials, respectively. CONCLUSION: A substantial proportion of RCC trials utilise restrictive eligibility criteria, excluding patients with fairly prevalent comorbidities. Implementing the ASCO-FCR recommendations will ensure resulting data are more inclusive and aligned with patient populations in the real-world.

Hepatitis C (HCV) prevalence in citizens of the Métis Nation of Ontario.

BACKGROUND: Hepatitis C virus (HCV) infection is a major global concern, with Indigenous Peoples bearing the highest burden. Previous studies exploring HCV prevalence within Indigenous populations have predominantly used a pan-Indigenous approach, consequently resulting in limited availability of Métis-specific HCV data. The Métis are one of the three recognized groups of Indigenous Peoples in Canada with a distinct history and language. The Métis Nation of Ontario (MNO) is the only recognized Métis government in Ontario. This study aims to examine the prevalence of self-reported HCV testing and positive results among citizens of the MNO, as well as to explore the association between sociodemographic variables and HCV testing and positive results. METHODS: A population-based online survey was implemented by the MNO using their citizenship registry between May 6 and June 13, 2022. The survey included questions about hepatitis C testing and results, socio-demographics, and other health related outcomes. Census sampling was used, and 3,206 MNO citizens responded to the hepatitis C-related questions. Descriptive statistics and bivariate analysis were used to analyze the survey data. RESULTS: Among the respondents, 827 (25.8%, CI: 24.3-27.3) reported having undergone HCV testing and 58 indicated testing positive, resulting in a prevalence of 1.8% (CI: 1.3-2.3). Respondents with a strong sense of community belonging, higher education levels, and lower household income were more likely to report having undergone HCV testing. Among those who had undergone testing, older age groups, individuals with lower education levels, and retired individuals were more likely to test positive for HCV. CONCLUSION: This study is the first Métis-led and Métis-specific study to report on HCV prevalence among Métis citizens. This research contributes to the knowledge base for Métis health and will support the MNO's health promotion program and resources for HCV. Future research will examine the actual HCV incidence and prevalence among MNO citizens.

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: A total of 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.

Risk Factors of Hepatitis Associated With Time to Adopting a New Cancer Screening Model Under Diffusion of Innovation Theory-A 10-Year Cohort Study in Taiwan.

BACKGROUND: Hepatitis is a serious global health issue. To reduce mortality, early screening for liver disease has been recommended in community health policies, particularly for asymptomatic individuals. AIM: This study explored the link between liver function biomarkers and how quickly people adopt a new multiple cancer screening program, using the diffusion of innovation (DOI) Theory. METHODS: The study included 57,939 participants from a community-based screening program in Keelung, Taiwan, between January 1, 2001, and December 31, 2010. Data on demographics and lifestyle habits were collected through questionnaires, and blood samples were analyzed to measure biomarkers related to liver function. RESULTS: On average, participants took 3.48 years to accept the new screening program. People with healthier lifestyles, such as those who drank alcohol less often, were more likely to adopt the screening early. Additionally, those with higher levels of liver-related biomarkers like albumin, total protein, and ALT joined even sooner. In conclusion, using DOI theory, the study found that personal lifestyle and liver function play a role in how quickly individuals adopt a new screening system. CONCLUSION: These insights can help healthcare providers improve early screening efforts, particularly for people at risk of hepatitis and liver cancer, potentially reducing related deaths.

Policy and Strategy for Hepatitis C Virus Elimination at the National Level: Experience in Taiwan.

The estimated prevalence of anti-HCV was 3.1% in Taiwan. Studies have shown iatrogenic behavior was the major transmission route. It is highest in specific populations including patients with end stage renal disease (ESRD), human immunodeficiency virus infection, who inject drug (PWID), and under opioid substitution treatment. Approximately 405,160 patients were seropositive for HCV RNA and in need of treatment. Taiwan government claims to reach WHO's 2030 goal of HCV elimination by 2025 and works hard to resolve several barriers of HCV elimination including political commitment, sustainable financing, minimize reimbursement restrictions, instituted monitoring, and perform micro-elimination of specific populations. The last stage of HCV elimination is to accelerate the universal HCV screening program of populations aged 45-79 years and resolve the unawareness issue of HCV infection. Hopefully, we can achieve the targets of HCV elimination set by WHO and reach the goal earlier in 2025.

Estimated Prevalence and Awareness of Hepatitis C Virus Infection Among US Adults: National Health and Nutrition Examination Survey, January 2017-March 2020.

During January 2017-March 2020, approximately 2.2 million noninstitutionalized civilian US adults had hepatitis C; one-third were unaware of their infection. Prevalence was substantially higher among persons who were uninsured or experiencing poverty. Unrestricted access to testing and curative treatment is needed to reduce disparities and achieve 2030 elimination goals.

Targeting ER stress/PKA/GSK-3ß/ß-catenin pathway as a potential novel strategy for hepatitis C virus-infected patients.

BACKGROUND: Chronic hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC). The HCC risk, while decreased compared with active HCV infection, persists in HCV-cured patients by direct-acting antiviral agents (DAA). We previously demonstrated that Wnt/ß-catenin signaling remained activated after DAA-mediated HCV eradication. Developing therapeutic strategies to both eradicate HCV and reverse Wnt/ß-catenin signaling is needed. METHODS: Cell-based HCV long term infection was established. Chronically HCV infected cells were treated with DAA, protein kinase A (PKA) inhibitor H89 and endoplasmic reticulum (ER) stress inhibitor tauroursodeoxycholic acid (TUDCA). Western blotting analysis and fluorescence microscopy were performed to determine HCV levels and component levels involved in ER stress/PKA/glycogen synthase kinase-3ß (GSK-3ß)/ß-catenin pathway. Meanwhile, the effects of H89 and TUDCA were determined on HCV infection. RESULTS: Both chronic HCV infection and replicon-induced Wnt/ß-catenin signaling remained activated after HCV and replicon eradication by DAA. HCV infection activated PKA activity and PKA/GSK-3ß-mediated Wnt/ß-catenin signaling. Inhibition of PKA with H89 both repressed HCV and replicon replication and reversed PKA/GSK-3ß-mediated Wnt/ß-catenin signaling in both chronic HCV infection and replicon. Both chronic HCV infection and replicon induced ER stress. Inhibition of ER stress with TUDCA both repressed HCV and replicon replication and reversed ER stress/PKA/GSK-3ß-dependent Wnt/ß-catenin signaling. Inhibition of either PKA or ER stress both inhibited extracellular HCV infection. CONCLUSION: Targeting ER stress/PKA/GSK-3ß-dependent Wnt/ß-catenin signaling with PKA inhibitor could be a novel therapeutic strategy for HCV-infected patients to overcomes the issue of remaining activated Wnt/ß-catenin signaling by DAA treatment. Video Abstract.

Natural flavonoids effectively block the CD81 receptor of hepatocytes and inhibit HCV infection: a computational drug development approach.

Hepatitis C virus (HCV) infection is a major public health concern, and almost two million people are infected per year globally. This is occurred by the diverse spectrum of viral genotypes, which are directly associated with chronic liver disease (fibrosis, and cirrhosis). Indeed, the viral genome encodes three principal proteins as sequentially core, E1, and E2. Both E1 and E2 proteins play a crucial role in the attachment of the host system, but E2 plays a more fundamental role in attachment. The researchers have found the "E2-CD81 complex" at the entry site, and therefore, CD81 is the key receptor for HCV entrance in both humans, and chimpanzees. So, the researchers are trying to block the host CD81 receptor and halt the virus entry within the cellular system via plant-derived compounds. Perhaps that is why the current research protocol is designed to perform an in silico analysis of the flavonoid compounds for targeting the tetraspanin CD81 receptor of hepatocytes. To find out the best flavonoid compounds from our library, web-based tools (Swiss ADME, pKCSM), as well as computerized tools like the PyRx, PyMOL, BIOVIA Discovery Studio Visualizer, Ligplot+ V2.2, and YASARA were employed. For molecular docking studies, the flavonoid compounds docked with the targeted CD81 protein, and herein, the best-outperformed compounds are Taxifolin, Myricetin, Puerarin, Quercetin, and (-)-Epicatechin, and outstanding binding affinities are sequentially - 7.5, - 7.9, - 8.2, - 8.4, and - 8.5 kcal/mol, respectively. These compounds have possessed more interactions with the targeted protein. To validate the post docking data, we analyzed both 100 ns molecular dynamic simulation, and MM-PBSA via the YASARA simulator, and finally finds the more significant outcomes. It is concluded that in the future, these compounds may become one of the most important alternative antiviral agents in the fight against HCV infection. It is suggested that further in vivo, and in vitro research studies should be done to support the conclusions of this in silico research workflow.

Metabolic disorders induced by PNPLA3 and TM6SF2 gene variants affect chronic kidney disease in patients infected with non-genotype 3 hepatitis C virus.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) infections differ in their risk for metabolic disorders and chronic kidney disease (CKD). The aim of this study was to investigate the effect of metabolic disorders induced by genetic factors on CKD in HCV-infected patients. METHODS: Patients with chronic non-genotype 3 HCV infection with or without CKD were examined. PNPLA3 and TM6SF2 variants were determined using high-throughput sequencing. The relationships of variants and different combinations with metabolic disorders were analyzed in CKD patients. Univariate and multivariate analyses were used to identify factors associated with CKD. RESULTS: There were 1022 patients with chronic HCV infection, 226 with CKD and 796 without CKD. The CKD group had more severe metabolic disorders, and also had higher prevalences of liver steatosis, the PNPLA3 rs738409 non-CC genotype, and the TM6SF2 rs58542926 CC genotype (all P < 0.05). Relative to patients with the PNPLA3 rs738409 CC genotype, patients with the non-CC genotype had a significantly decreased eGFR and a greater prevalence of advanced CKD (CKD G4-5). Patients with the TM6SF2 rs58542926 CC genotype had a lower eGFR and a higher prevalence of CKD G4-5 than those with the non-CC genotype. Multivariable analysis indicated that multiple metabolic abnormalities, including liver steatosis and the PNPLA3 rs738409 C > G variant, increased the risk of CKD, but the TM6SF2 rs58542926 C > T variant decreased the risk of CKD. CONCLUSION: Specific PNPLA3 rs738409 and TM6SF2 rs58542926 variants are independent risk factors for CKD in patients with chronic HCV infections and are associated with the severity of renal injury.

Telemonitoring of the Continuum of Care of Hepatitis C During the COVID-19 Pandemic in Brazil.

Introduction: To accomplish elimination of hepatitis C virus (HCV) by 2030, as proposed by the World Health Organization, the Brazilian Ministry of Health outlined the Hepatitis C Elimination Plan, which provides coverage of all critical steps in the continuum of care (CoC) of hepatitis C. As expected, the advent of COVID-19 pandemic has disrupted the CoC of hepatitis C worldwide. The Brazilian Liver Institute launched a remote patient monitoring (RPM) program to assist the general population at risk in HCV testing and to provide linkage and retention to care for HCV-positive subjects. The RPM program was also designed to relink HCV-positive patients lost to follow-up during the COVID-19 pandemic due to their limited access to the health care system. Methods: The HCV telemonitoring number was highly advertised in Brazilian media. The RPM program was conducted by dedicated health care personnel trained to follow a predefined script designed to provide awareness, ensure consistent information for educational purposes, and recruit eligible participants to be tested for HCV. Results: From August 2020 to December 2021, 3,738 subjects entered in contact with RPM. There were 26,884 interactions (mean 7.2 interactions per participant), mostly by WhatsApp (78%). Twenty out of those 221 subjects (9%) who tested were HCV positive. Those subjects altogether with 128 other patients with HCV, tested elsewhere, were followed in the HCV CoC. Up to now, 94% of them were linked to care, 24% are undergoing treatment and 8% achieved sustained virological response (SVR). Conclusions: Our preliminary results showed that HCV CoC telemonitoring was a feasible and useful strategy to follow HCV at-risk subjects through all cascade of care until SVR during the COVID-19 health care disruption. It could be used beyond the defervescence of SARS-CoV-2 pandemic to ensure linkage to care of those HCV-positive patients.

Development of a Patient Activation Toolkit for Hepatitis C Virus Testing.

We evaluated the acceptability of a patient activation toolkit for hepatitis C virus (HCV) testing amidst universal adult guidelines. We developed a patient-facing toolkit that included a letter to the patient from their healthcare provider, HCV factsheet, and question prompt list, which contained questions for their provider about HCV infection and testing. We conducted qualitative interviews with patients ages 18-78 (n = 17), using a semi-structured interview guide based on learner verification. We assessed attraction, comprehension, cultural-linguistic acceptability, self-efficacy, and persuasiveness of toolkit materials using direct content analysis. Participants reported materials were attractive, offering suggestions to improve readability. They reported some understanding of materials but requested use of less medical jargon, particularly for the factsheet. Participants discussed cultural acceptability and suggested ways to improve language inclusiveness and comfort with content, given stigma surrounding HCV risk factors. Participants reported that including a letter, factsheet, and QPL improved the persuasiveness of materials, and they conveyed their motivation to be tested for HCV. Results indicate preliminary acceptability for use of the patient activation toolkit, which will be refined based on participants' recommendations. Overall, this patient activation toolkit holds promise for increasing HCV testing rates.

Patients with severe mental illness and hepatitis C virus infection benefit from new pangenotypic direct-acting antivirals: Results of a literature review.

INTRODUCTION: Hepatitis C virus (HCV) infection is a global health problem that can results in cirrhosis, hepatocellular carcinoma and even death. HCV infection is 3-20-fold more prevalent among patients with versus without severe mental illness (SMI), such as major depressive disorder, personality disorder, bipolar disorder and schizophrenia. Treatment options for HCV were formerly based on pegylated interferon alpha, which is associated with neuropsychiatric adverse events, and this contributed to the exclusion of patients with SMI from HCV treatment, elimination programmes, and clinical trials. Moreover, the assumption of poor adherence, scant access to healthcare and the stigma and vulnerability of this population emerged as barriers and contributed to the low rates of treatment and efficacy. METHODS: This paper reviews the literature published between December 2010 and December 2020 exploring the epidemiology of HCV in patients with SMI, and vice versa, the effect of HCV infection, barriers to the management of illness in these patients, and benefits of new therapeutic options with pangenotypic direct antiviral agents (DAAs). RESULTS: The approval of DAAs has changed the paradigm of HCV infection treatment. DAAs have proven to be an equally efficacious and safe option that improves quality of life (QoL) in patients SMI. CONCLUSIONS: Knowledge of the consequences of the HCV infection and the benefits of treatment with new pangenotypic DAAs among psychiatrists can increase screening, referral and treatment of HCV infection in patients with SMI.

Usefulness Of Sofosbuvir And Daclatasvir Combination In The Treatment Of HCV Infection In Childhood Cancer Patients: Experience From A Tertiary Care Hospital.

Objectives: To determine the usefulness of Sofosbuvir-Daclatasvir combination in the treatment of hepatitis c virus infection in paediatric cancer.. METHODS: The retrospective study was conducted at the Oncology Department of the National Institute of Child Health, Karachi, and comprised medical charts of patients who received sofosbuvir and daclatasvir from January 2018 to January 2022. Efficacy was documented by clearance of hepatitis C virus ribonucleic acid as rapid viral response, early viral response and sustained viral response at weeks 4, 12 and 24, respectively. Drug efficacy was determined by monitoring and recording adverse effects. Chemotherapy protocol for the treatment of patients concomitantly receiving direct acting antivirals was modified while looking at drug-drug interactions. The total duration of direct acting antiviral therapy was 12 weeks. Data was analysed using SPSS 24. RESULTS: Of the 804 patients with different malignancies, 132(16.4%) were found positive for hepatitis C virus. Of them, 28(21.21%) patients were started on direct acting antivirals; 17(60.71%) boys and 11(39.28%) girls. The overall mean age was 9.93±6.12 years. The diagnosis was pre-B acute lymphoblastic leukaemia in 18(64.28%) cases, 16 (57.14%) were on maintenance chemotherapy, and 18(64.28%) had genotype 1. Pre- and post-treatment mean alanine transaminase levels were 328.00±324.00IU and 36.00±29.00IU, respectively (p=0.003). Pre- and post- treatment mean serum bilirubin levels were 3.13±3.95mg/dl and 0.61±0.21mg/dl (p=0.022). Rapid viral response was achieved in 26(92.85%) children, while early viral response and sustained viral response were achieved in all 28(100%) patients. Minor side effects were noted in 4(14.28%) patients and chemotherapy was continued in all 28(100%) cases as per the designed protocol. CONCLUSIONS: The sofosbuvir-daclatasvir combination was found to be effective in hepatitis C virus treatment in paediatric cancer patients.

LncRNA NEAT1 regulates HCV-induced Hepatocellular carcinoma by modulating the miR-9-BGH3 axis.

Chronic hepatitis C virus (HCV) infection is a leading cause of end-stage liver diseases, such as fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Several cellular entities, including paraspeckles and their related components, are involved in viral pathogenesis and cancer progression. NEAT1 lncRNA is a major component of paraspeckles that has been linked to several malignancies. In this study, analysis of the Cancer Genome Atlas (TCGA) database and validation in HCV-induced HCC tissue and serum samples showed significantly high expression of NEAT1 in patients with liver cancer. Moreover, we found that NEAT1 levels increased upon HCV infection. To further understand the mechanism of NEAT1-induced HCC progression, we selected one of its targets, miR-9-5 p, which regulates BGH3 mRNA levels. Interestingly, miR-9-5 p levels were downregulated upon HCV infection, whereas BGH3 levels were upregulated. Additionally, partial NEAT1 knockdown increased miR-9-5 p levels and decreased BGH3 levels, corroborating our initial results. BGH3 levels were also upregulated in HCV-induced HCC and TCGA tissue samples, which could be directly correlated with NEAT1 levels. As a known oncogene, BGH3 is directly linked to HCC progression mediated by NEAT1. We also found that NEAT1 levels remained upregulated in serum samples from patients treated with direct-acting antivirals (DAA), indicating that NEAT1 might be a molecular trigger that promotes HCC development. Collectively, these findings provide molecular insights into HCV-induced HCC progression via the NEAT1-miR-9-BGH3 axis.

Hepatitis C virus (HCV) infection among patients with sickle cell disease at the Korle-Bu teaching hospital.

BACKGROUND: Hepatitis C virus (HCV) infection is a blood borne infection that remains potentially transmissible through blood transfusions. Sickle cell disease (SCD) is a common inheritable haemoglobinopathy in Ghana that requires multiple blood transfusions as part of its management. The SCD patient is therefore at a high risk of HCV infection; however, data on the occurrence of HCV in SCD patients has not been documented in Ghana. This study sought to determine the prevalence and genotypes of HCV infection in SCD patients. MATERIALS AND METHODS: This was a cross-sectional study which enrolled 141 sickle-cell disease patients from the Ghana Institute for Clinical Genetics, Korle-Bu Teaching Hospital (KBTH). Patient information was obtained through a structured questionnaire. Aliquots of the plasma obtained was used for both serology with Advanced Quality Rapid Anti-HCV Test Strip and molecular testing by RT-PCR with primers targeting the HCV core gene. The amplified DNA were purified and subjected to phylogenetic analysis to characterize HCV genotypes. RESULTS: Twelve (9%) out of the 141 patients were sero-positive for HCV total antibodies. HCV RNA was amplified from 8 (6%) out of the total number of patients' samples. One of the 12 sero-positives was HCV RNA positive. Five (63%) out of the 8 HCV RNA positive samples were successfully sequenced. The phylogenetic tree constructed with the study and GenBank reference sequences, clustered all five study sequences into HCV genotype 1. CONCLUSION: The HCV seroprevalence of 9% among sickle cell disease patients is higher than reported for the general Ghanaian population which is 3%. Genotype 1 is the common HCV genotype infecting SCD patients. Sickle cell disease is likely to be a high-risk group for HCV inapparent infections in Ghana as seroprevalence does not correlate with viremia. However, even with higher seroprevalence, the group must be given priority in resource allocation for preventive, diagnostic and therapeutic strategies.

SARS-CoV-2 infection: a hurricane that does not ignore chronic hepatitis.

BACKGROUND: The COVID-19 pandemic significantly compromised screening, laboratory controls, clinical surveillance and treatment of chronic hepatitis patients and worsened their outcome, as evidenced by its significant correlation with advanced cirrhosis, liver decompensation and mortality. RESULTS: This pandemic significantly impaired also the sector of liver transplantation, whose wards, operating rooms, outpatients' facilities, and healthcare personnel have been dedicated to patients with COVID-19. In addition, screening and treatment for HBV infection have been delayed or suspended in in most countries, with an increased risk of viral reactivation. Similar delay or suspension have also occurred for universal hepatitis B vaccination programs in many countries. Likewise, COVID-19 pandemic has made unreachable the goal of elimination of HCV infection as a worldwide public-health issue predicted for 2030 by the WHO. CONCLUSION: This review article demonstrates how COVID-19 pandemic is causing serious damage to the sector of liver disease, which has quickly lost the beneficial effects of years of study, research, and clinical and technological application, as well as considerable financial investments.

Hepatitis C seroprevalence among people living with HIV/AIDS and pregnant women in four provinces in Cambodia: an integrated bio-behavioral survey.

BACKGROUND: Understanding the extent of viral hepatitis burden in specific subgroups, such as pregnant women and people living with HIV/AIDS (PLWHA), and their geographic distribution is essential for evidence-informed policy and mobilizing resources for targeted treatment and prevention efforts. However, in Cambodia, the epidemiology of hepatitis C remains uncertain. We estimated the hepatitis C virus (HCV) burden and transmission risk factors among PLWHA and pregnant women attending antenatal care (ANC) in Cambodia. METHODS: Between March and April 2016, we conducted a cross-sectional survey in four diverse geographical areas: the capital city of Phnom Penh and three provinces. We collected information on demographic characteristics and risk behaviors and performed HCV antibody (Anti-HCV) testing among pregnant women attending public ANC clinics and among those receiving HIV care at the hospitals. We computed the prevalence of HCV among the two population subsets and performed logistic regression analyses to identify risk factors associated with HCV antibody positivity. RESULTS: Of 935 participants enrolled, 510 (54.6%) were pregnant women and 425 (45.4%) were PLWHA. Anti-HCV prevalence was significantly higher in PLWHA than in pregnant women (29/425, 6.8% vs 5/510, 0.9%, P < 0.001). Of the geographic regions, Preah Sihanouk province (Southwest) had the highest anti-HCV prevalence among PLWHA (12.0%, P = 0.031). There was no significant geographic difference in anti-HCV prevalence among pregnant women. In multivariable analyses (data subset to PLWHA), HCV infection was significantly associated with having a family member positive for HCV (OR = 7.6 [95% CI: 1.01-57.84], P = 0.048) and a history of intravenous medication injection in the last 5 years (OR = 7.1 [95% CI: 2.79-18.10], P < 0.001). CONCLUSIONS: HCV infection is relatively common among Cambodian PLWHA, likely related to intravenous medication injection and intra-familial viral transmission. Systematic HCV testing and care among PLWHA (and possibly their family members) might be necessary. Setting up a surveillance system for HCV might also be beneficial for some geographical regions and populations.

Dual hepatitis B and C-associated hepatocellular carcinoma: clinical characteristics, outcome, and prognostic role of albumin-bilirubin grade.

BACKGROUND: Albumin-bilirubin (ALBI) grade is used to evaluate the outcome of patients with hepatocellular carcinoma (HCC) which is often associated with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. This study aimed to investigate the clinical characteristics, outcome, and prognostic role of ALBI grade in dual HBV/HCV-related HCC. METHODS: A total 3341 HCC patients with viral etiology were prospectively enrolled and retrospectively analyzed. Multivariate Cox proportional hazards model was used to identify independent prognostic predictors. RESULTS: Of all patients, 2083 (62%), 1068 (32%), and 190 (6%) patients had HBV, HCV, and dual HBV/HCV infection, respectively. The mean age of HBV, HCV, and dual virus group was 60, 68, and 64 years (p < 0.001), respectively. There was no significant survival difference between HBV, HCV, and dual HBV/HCV-related HCC group (p = 0.712). Multivariate Cox analysis in dual HBV/HCV-related HCC showed that multiple tumors [hazard ratio (HR): 1.537, p = 0.044], tumor size >3 cm (HR 2.014, p = 0.044), total tumor volume (TTV) >50 cm3 (HR 3.050, p < 0.001), vascular invasion (HR 3.258, p < 0.001), performance status 2-4 (HR 2.232, p < 0.001), ALBI grade 2-3 (HR 2.177, p < 0.001), and BCLC stage B-D (HR 2.479, p < 0.001) were independent predictors of poor survival. CONCLUSIONS: Dual viral infection does not accelerate the development of HCC in HBV carriers. Patient survival is similar between dual HBV/HCV-related HCC and single HBV- or HCV-related HCC group. The ALBI grade is a robust prognostic model in dual virus-related HCC to discriminate patient long-term survival.

The P2X7R-NLRP3 and AIM2 Inflammasome Platforms Mark the Complexity/Severity of Viral or Metabolic Liver Damage.

P2X7R-NLRP3 and AIM2 inflammasomes activate caspase-1 and the release of cytokines involved in viral-related liver disease. Little is known about their role in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steato-hepatitis (NASH). We characterized the role of inflammasomes in NAFLD, NASH, and HCV. Gene expression and subcellular localization of P2X7R/P2X4R-NLRP3 and AIM2 inflammasome components were examined in histopathological preparations of 46 patients with biopsy-proven viral and metabolic liver disease using real-time PCR and immunofluorescence. P2X7R, P2X4R, and Caspase-1 are two- to five-fold more expressed in patients with NAFLD/NASH associated with chronic HCV infection than those with metabolic damage only (p ≤ 0.01 for all comparisons). The AIM2 inflammasome is 4.4 times more expressed in patients with chronic HCV infection, regardless of coexistent metabolic abnormalities (p = 0.0006). IL-2, a cytokine playing a pivotal role during chronic HCV infection, showed a similar expression in HCV and NASH patients (p = 0.77) but was virtually absent in NAFLD. The P2X7R-NLRP3 complex prevailed in infiltrating macrophages, while AIM2 was localized in Kupffer cells. Caspase-1 expression correlated with elastography-based liver fibrosis (r = 0.35, p = 0.02), whereas P2X7R, P2X4R, NRLP3, Caspase-1, and IL-2 expression correlated with circulating markers of disease severity. P2X7R and P2X4R play a major role in liver inflammation accompanying chronic HCV infection, especially when combined with metabolic damage, while AIM2 is specifically expressed in chronic viral hepatitis. We describe for the first time the hepatic expression of IL-2 in NASH, so far considered a peculiarity of HCV-related liver damage.