Numerous meta-analyses have identified various risk factors for hepatocellular carcinoma (HCC), prompting a comprehensive study to synthesize evidence quality and strength.

This umbrella review of meta-analyses was conducted throughout PubMed, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews. Evidence strength was evaluated according to the evidence categories criteria.

We identified 101 risk factors throughout 175 meta-analyses. 31 risk factors were classified as evidence levels of class I, II, or III. HBV and HCV infections increase HCC risk by 12.5-fold and 11.2-fold, respectively. These risks are moderated by antiviral treatments and virological responses but are exacerbated by higher HBsAg levels, anti-HBc positivity, and co-infection. Smoking, obesity, non-alcoholic fatty liver disease, diabetes, low platelet, elevated liver enzymes and liver fluke infection increase HCC risk, while coffee consumption, a healthy diet, and bariatric surgery lower it. Medications like metformin, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), aspirin, statins, and selective serotonin reuptake inhibitors reduce HCC risk, while acid suppressive agents, particularly proton pump inhibitors, elevate it. Blood type O reduces the risk of HCC, while male gender and older age increase the risk.

HBV and HCV are major HCC risk factors, with risk mitigation through antiviral treatments. Lifestyle habits such as smoking and alcohol use significantly increase HCC risk, highlighting the importance of cessation. Certain drugs like aspirin, statins, GLP-1 RAs, and metformin may reduce HCC occurrence, but further research is needed to confirm these effects.

The aim of the study was to determine how depression and cognitive dysfunction in patients with chronic hepatitis C virus (HCV) infection are affected by treatment with direct-acting antivirals (DAA). Fifty-two chronic hepatitis C patients underwent neurocognitive and psychological evaluation before therapy and 5-6 months later. Depression was measured by Beck Depression Inventory (BDI), anxiety by State-Trait Anxiety inventory (STAI), neuroticism by Eysenck Personality Inventory (N/EPO-R), while Ruff Figural Fluency Test (RFFT), Wisconsin Card Sorting Test (WCST), The Grooved Pegboard Test (GPT), and California Verbal Learning Test (CVLT) were used to assess neurocognitive function. There was significant positive change in BDI scores (8.8 ± 6.6 vs 6.1 ± 6.1; p < 0.0001) while the most striking improvement in cognitive tests was observed for CVLT sum of immediate recall from Trial-1 to Trial-5 (50.9 ± 10.0 to 54.1 ± 10.0; p = 0.0005) and RFFT, where the number of unique designs increased from 77.2 ± 21.0 to 86.1 ± 28.3 (p < 0.0001). These differences remained significant when patients with advanced (METAVIR grade F3/F4) and those with mild (grade F0/F1/F2) liver disease were analyzed separately, although in general the improvements were more pronounced in the former group. In conclusion, in chronic HCV infection the brain function is markedly improved by DAA treatment.

Hepatitis C virus (HCV) infection is a major public health burden in China, affecting more than 10 million individuals. We aimed to evaluate the effectiveness of a hospital-based intervention programme for HCV Surveillance with linkage to care (HEAL) in a prospective cohort. The HEAL programme was carried out targeting inpatients from non-infectious departments of two tertiary hospitals in Jiangsu, China. It consisted of an educational campaign to raise awareness of physicians from non-IDs to promote HCV surveillance, a patient-navigator-centred clinical algorithm responsible for the efficient follow-up of patients with positive HCV antibody, including comprehensive testing, diagnosis and treatment. We characterised the rate of linkage to HCV diagnosis, care and treatment during the pre-intervention period (from 1 July 2016 and June 30, 2018) and after the intervention (from March 2019 to May 2021). During the pre-intervention period, 89,303 (45.3%) out of 196,780 non-ID inpatients were screened for anti-HCV, and 631 patients were tested positive. One hundred and fifty-six (24.7%) patients was followed up for HCV RNA confirmatory testing, and 58 (37.1%) of patients further were diagnosed with chronic HCV infection (CHC). Only 18 (31.3%) of the diagnosed patients with CHC were linked to hepatitis C clinics for treatment, 10 (55.6%) patients received antiviral regimen. Among them, two (11.1%) received DAA treatment, while eight (44.4%) adopted peginterferon/ribavirin regimen. During the intervention period, 232,275 patients were hospitalised in non-infectious department and 151,203 (65.1%) were screened for anti-HCV. Of these, 960 patients tested positive for HCV antibodies, resulting in a prevalence of anti-HCV positivity of 0.63%. Six hundred and seventy (69.8%) patients were enrolled, and 100% were followed up for HCV RNA confirmatory testing. Two hundred and ninety-one (43.4%) individuals with active HCV were identified. Two hundred and thirty-eight (81.8%) of HCV-infected individuals were linked to HCV care, and 157 (65.9%) were linked to treatment. Compared to the pre-intervention period, there was a 2.61-fold increase in the percentage of patients linked to care and a 5.94-fold increase in the proportion of patients who started DAAs therapy. This HEAL programme achieved enhanced HCV Surveillance with linkage to care, which has been demonstrated as an effective strategy in the hospital setting to improve the hepatitis C care continuum by identifying inpatients unaware of their HCV status and facilitating their access to HCV treatment.

More accurate stratification of patients with chronic hepatitis C after permanent hepatitis C virus (HCV) clearance by direct-acting antivirals (DAAs) is important for improving long-term surveillance and treatment. The aim of this study was to stratify patients with chronic hepatitis C who are at risk of developing hepatocellular carcinoma (HCC) after HCV cure.

This multicenter, retrospective cohort study included 3177 consecutive adult chronic hepatitis C patients without decompensated cirrhosis who were treated with all-oral DAAs. The primary study endpoints were long-term cumulative de novo HCC incidence, HCC recurrence rates, and survival. Additionally, we analyzed the development of HCC by patients without cirrhosis, stratified by age and fibrosis status according to the FIB-4 index.

After exclusions, data from 3024 patients were available for analysis. The overall median follow-up period was 6.5 years. None of the patients with non-cirrhosis/FIB-4 < 1.45 (n = 475) developed HCC regardless of background factors. For patients with non-cirrhosis/FIB-4 ≥ 3.25, older age had a greater impact on HCC incidence (log-rank test: p = 0.038). In addition, metabolic factors, including body mass index and diabetes mellitus, were not related to HCC incidence. HCC recurrence commonly occurred within 5 years after HCV cure; nevertheless, HCV cure contributed to an improvement of survival rates.

Age is a pivotal factor in predicting de novo HCC development following HCV cure in patients with moderate to advanced fibrosis. Conversely, patients with mild fibrosis (FIB-4 < 1.45) may be eligible for discharge from specialized care after achieving HCV elimination.

Disrupted linkage to care is a major barrier to hepatitis C virus (HCV) elimination leading to high attrition rates. This study aimed to describe (1) flow through the HCV care-cascade (2009-2020), and (2) monthly patterns in HCV care during the coronavirus disease 2019 (COVID-19) pandemic (2020) in Israel.

Data were obtained from Maccabi Healthcare Services, a 2.6-million-member healthcare provider in Israel. Flow through the HCV care-cascade in 2009-2020 was described from individuals' first positive HCV antibody (Ab+) test to sustained virological response (SVR), and monthly data were obtained on individuals newly attaining a given stage in the HCV care-cascade in 2020.

Among 2809 new patients who were Ab+, 2651 (94.4%) had an HCV polymerase chain reaction (PCR) test, and 1417 (50.4%) were PCR+ during the study. Median time from Ab+ to PCR+ was 3.9 years, with 39.7% PCR+ within 12 months. Median time from PCR+ to HCV treatment was 3.3 years, with 639 (55.5%) of patients who were PCR+ purchasing direct-acting anti-viral agents (DAAs), and 413/416 patients attained SVR. A significant reduction was observed in the time from first HCV detection (Ab+) to HCV confirmation (PCR+) and from PCR+ test to HCV treatment purchase in the pre-DAA era compared to the post-DAA. Monthly data during 2020 (Part B) indicates a decline in the numbers of patients receiving HCV care during the first pandemic-related closure.

Real-world data from a nationally representative healthcare provider database suggest that HCV linkage to care improved over time alongside increased access to DAAs, despite observed declines in access to care in 2020.

As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles in metabolism, detoxification, and immune response. Various factors including viruses, alcohol, metabolites, toxins, and other pathogenic agents can compromise liver function, leading to acute or chronic injury that may progress to end-stage liver diseases. While sharing common features, liver diseases exhibit distinct pathophysiological, clinical, and therapeutic profiles. Currently, liver diseases contribute to approximately 2 million deaths globally each year, imposing significant economic and social burdens worldwide. However, there is no cure for many kinds of liver diseases, partly due to a lack of thorough understanding of the development of these liver diseases. Therefore, this review provides a comprehensive examination of the epidemiology and characteristics of liver diseases, covering a spectrum from acute and chronic conditions to end-stage manifestations. We also highlight the multifaceted mechanisms underlying the initiation and progression of liver diseases, spanning molecular and cellular levels to organ networks. Additionally, this review offers updates on innovative diagnostic techniques, current treatments, and potential therapeutic targets presently under clinical evaluation. Recent advances in understanding the pathogenesis of liver diseases hold critical implications and translational value for the development of novel therapeutic strategies.

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic and complex autoimmune conditions. Despite the advancements in biologics and small molecules, the therapeutic ceiling persists, posing significant treatment challenges and contributing to the concept of difficult-to-treat IBD. Dual-targeted therapy (DTT), combining two biologic agents or biologics with small molecules, has emerged as a novel approach to address this unmet need by targeting multiple inflammatory pathways simultaneously. Evidence suggests that DTT holds promise in improving clinical and endoscopic outcomes, especially in patients with refractory disease or extraintestinal manifestations. Safety data, while consistent with monotherapy profiles, highlight the importance of vigilant monitoring for infections and other adverse events. Continued research and high-quality trials are crucial to defining optimal DTT regimens and broadening its clinical applicability. This review explores the efficacy and safety of DTT in IBD, reporting data from clinical trials, systematic reviews, and real-world studies.

The study aimed to gather information about the target population's knowledge, attitudes, and behaviors regarding HCV screening to develop effective communication strategies and improve service offerings.

This was a Cross-Sectional study.

A target population random sample was submitted a phone questionnaire based on the Health Belief Model (HBF), containing 4 sections on perceived HCV susceptibility and severity, screening benefits and barriers. Each person interviewed was finally invited to adhere to the screening. Prevalence was estimated using a 95 % C.I., and association between sociodemographic characteristics, HBF attitudes, and screening adherence following the interview was assessed.

Survey involved 641 participants. HCV susceptibility was perceived by 4.8 % (95 % CI 3.23-6.57) and HCV severity by 69.4 % (95 % CI 65.83-72.97), 95 % (95 % CI 93.3-96.6) acknowledged screening benefits and 88 % (95 % CI 85.4-90.5) perceived no barriers. Insufficient or no information about HCV or the screening was received by the 49.0 % (95 % CI 45.1-52.8) of people interviewed. Among these people, in the 2 months aftermath, 17.6 % carried out the HCV screening. Perception of screening barriers was associated with low education level (OR 1.83, P = 0.02).

Low adherence to the HCV screening could be explained with a poor perception of HCV susceptibility and gravity by the target population particularly with socioeconomic hurdles. Forthcoming communication campaign would need to focus on those factors to improve adherence.

The epidemiology of hepatocellular carcinoma (HCC) has shifted significantly in the last 2 decades with non-viral etiologies such as metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease on the rise. Key factors include the global obesity epidemic and the resurgence of alcohol use disorder, both of which were exacerbated by the coronavirus disease 2019 pandemic. While these non-viral etiologies of HCC are becoming the leading cause in developed countries, the potential impact of immigration patterns on Hepatitis B virus epidemiology cannot be ignored. The risk of HCC remains significant in individuals with cirrhosis and viral hepatitis after curative treatments.

With Direct Acting Antivirals for Hepatitis C virus (HCV), cure is possible in > 95% including those with HIV/HCV co-infection. Achieving strategic targets for cure requires addressing barriers including suboptimal care engagement. We adapted Data to Care (D2C), a public health strategy designed to identify and link persons out of care (OOC) for HIV, for persons with HIV/HCV co-infection untreated for HCV.

In partnership with Connecticut Department of Public Health (DPH), persons OOC for HIV (defined as no HIV surveillance laboratory tests from 10/1/2018-10/1/2019) were matched to a list of persons co-infected with HIV/HCV (through 12/31/2019). We used a three-phase follow-up approach (pre-work, case conferencing, and Disease Intervention Specialist (DIS) follow-up) to track outreach outcomes and re-engagement/HCV cure success.

There were 90 HIV/HCV co-infected persons who were OOC for HIV. The pre-work and case conferencing phases determined that 33 (36.7%) had previous HCV cure or were in treatment. There were 41 eligible for DIS-follow-up of which 21 (51%) were successfully contacted and 7 (33%) successfully re-engaged (kept appointment with HCV provider). No new HCV treatment initiations were recorded.

Using a D2C approach, we identified and conducted outreach to persons who were OOC for HIV to promote HCV treatment. This approach resulted in intensive data clean-up and outreach efforts which produced modest re-engagement and no HCV treatment initiations. Future studies should develop alternative and complementary interventions to promote effective re-engagement and HCV treatment.

The introduction of Direct-Acting Antivirals (DAAs) transformed Hepatitis C (HCV) treatment, despite this uptake of DAAs remains lower than required to meet the WHO Sustainable Development Goal (3.3). Treatment with interferon was suggested to be able to deliver important outcomes for people who use drugs in addition to a viral cure, such as social redemption, and shift from a stigmatised identity. There is a lack of understanding if DAAs can deliver these transformative outcomes.

This recurrent cross-sectional study combines qualitative semi-structured interviews and demographic data of 15 participants receiving DAAs in Tayside, Scotland. A thematic analysis explored the non-clinical outcomes of DAA treatment viewed through the lens of the Social Identity Model of Recovery (SIMOR) to build understanding of the influence DAAs have in a recovery journey from drug use.

Three key themes emerged: identity, relationships and social networks; building recovery capital; and reflecting on re-infection and the shift to DAAs. Concern about the transmission of HCV resulted in self-imposed isolation which weakened support structures. Cure provides a mechanism to strengthen family bonds, however social networks in the wider community remain limited. Participants gained opportunities to undertake activities that build health and wellbeing providing a shift in identity, future plans and aspirations. Social isolation remained for some, revealing unmet need in post-cure support.

DAAs may support recovery journeys through the SIMOR, individuals reduced the number of active users within their social network and reconnected with family members, building recovery capital. Individuals, however, remained socially isolated in the context of the wider community. HCV services should support links to community resources to deliver the social inclusion people desire.

Gastrointestinal (GI) cancers account for over a quarter of all cancer-related deaths in the United States; however, the latest trends in their prevalence remain unclear.

Data on GI cancers were obtained from the Global Burden of Disease Study 2021. Age-standardized incidence rates (ASIR) and age-standardized mortality rates (ASMR) were estimated across various states, sexes, ages, and risk factors, and annual percentage changes were calculated.

From 2000 to 2021, liver cancer exhibited the greatest increase in both the ASIR and the ASMR, followed by pancreatic cancer. In contrast, stomach cancer showed the greatest decline, followed by colorectal cancer, esophageal cancer, and biliary tract cancer. Most GI cancers predominantly affect men and tend toward a younger age of onset. Geographic disparities exist in the burden of GI cancers and their risk factors. For esophageal, stomach, and colorectal cancers, mortality rates linked to diet and smoking decreased, whereas alcohol-related mortality increased in several states, especially West Virginia. Hepatitis C remains the leading cause of liver cancer, with intravenous drug use as the primary risk factor. Non-alcoholic steatohepatitis (NASH) is the fastest-growing cause of liver cancer, followed by excessive alcohol use. Mortality rates for pancreatic cancer due to high body-mass index and high fasting plasma glucose have increased across states and age groups.

The epidemiological trends of GI cancers in the U.S. have shifted substantially. States need to implement targeted policies that address specific populations and risk factors for each cancer type.

In regions with a high prevalence of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, coinfected patients face a heightened risk of developing hepatocellular carcinoma (HCC), termed HBV/HCV-related HCC (HBCV-HCC). We aimed to investigate the contribution of preexisting chronic hepatitis B (CHB) and subsequent chronic hepatitis C (CHC) to the development of HBCV-HCC.

We examined HBV's involvement in 93 HBCV-HCC cases by analyzing HBV DNA integration as an indicator of HCC originating from HBV-infected hepatocytes, compared with 164 HBV-HCCs and 56 HCV-HCCs as controls.

Next generation sequencing revealed that 55% of HBCV-HCCs exhibited clonal HBV integration, which falls between the rates observed in HBV-HCCs (88%) and HCV-HCCs (7%), with similar integration patterns to HBV-HCCs. Common HCC somatic mutation analysis indicated HCV superinfection in HBCV-HCCs correlated with increased mutation rates in the telomerase reverse transcriptase (TERT) promoter and beta-catenin genes. Transcriptome analysis showed a prevalence of replicating HCV over HBV in HBCV-HCCs, with preexisting HBV exerting a proliferative role. The comparison of clinical characteristics revealed similarities between HBCV-HCC and HCV-HCC patients, including later onset for HBCV-HCC, possibly due to HCV superinfection slowing carcinogenesis. Notably, HBCV-HCCs with the same driver mutation, HBV integration at the TERT promoter, tended to develop later and showed a better prognosis post-tumor resection than HBV-HCCs.

Our findings shed light on the interplay between preexisting CHB and subsequent CHC in elevating the risk of HBCV-HCC. These insights are crucial for understanding viral etiology-specific carcinogenesis and guiding surveillance policies for HBCV-HCC post-antiviral therapy.

Little is known about the effect of hepatitis C virus (HCV) treatment on sexual risk behavior among men who have sex with men (MSM) with HIV by treatment type (interferon [IFN]-based vs direct-acting antiviral [DAA]-based).

MSM with HIV and recently acquired HCV infection enrolled in the MSM Observational Study of Acute Infection with hepatitis C (MOSAIC) cohort.

Using data from 2009 to 2018, we evaluated risk behavior through a validated HCV risk score (where ≥2 indicated high risk) and its individual risk behaviors. Levels of risk behavior before, during, and after treatment were modeled for each treatment episode using linear and logistic regression with Generalized Estimating Equations adjusting for DAA availability and number of reinfections.

One hundred forty MSM with a median age of 45 years (interquartile range = 40-49) yielded 180 treatment episodes (n = 131 IFN-based, n = 49 DAA-based). Adjusted mean risk score before, during, and after treatment was 2.4 (95% confidence interval [CI] = 2.1 to 2.6), 0.9 (95% CI = 0.8 to 1.0), and 1.7 (95% CI = 1.5 to 1.8), respectively. Before treatment, no differences in mean HCV risk score or proportion of specific behaviors were found between the regimen groups. During treatment, MSM treated with DAAs had a higher average risk score and proportion of receptive condomless anal sex, sharing toys and unprotected fisting than those treated with IFN. After treatment, the proportion sharing straws were significantly higher in MSM treated with DAAs than in MSM treated with IFN.

MSM treated with DAAs, compared with MSM treated with IFN, had higher levels of HCV-related risk behavior during treatment. The higher risk of HCV reinfection in the DAA-era underscores the need for ongoing HCV testing and behavioral interventions against HCV.

Hepatitis C virus (HCV) is predominantly transmitted through parenteral exposures to infectious blood or body fluids. In 2019, approximately 58 million people worldwide were infected with HCV, and 290,000 deaths occurred due to hepatitis C-related conditions, despite hepatitis C being curable. There are substantial barriers to elimination, including the lack of widespread point-of-care diagnostics, cost of treatment, stigma associated with hepatitis C, and challenges in reaching marginalized populations, such as people who inject drugs. The World Health Organization (WHO) has set goals to eliminate hepatitis C by 2030. Several countries, including Australia, Egypt, Georgia, and Rwanda, have made remarkable progress toward hepatitis C elimination. In the United States, the Biden-Harris administration recently issued a plan for the national elimination of hepatitis C. Global progress has been uneven, however, and will need to accelerate considerably to reach the WHO's 2030 goals. Nevertheless, the global elimination of hepatitis C is within reach and should remain a high public health priority.

The World Health Organization (WHO) has established objectives for eradicating the hepatitis C virus (HCV). People who inject drugs (PWID), a major driver of HCV transmission, are an essential part of China's hepatitis C elimination program. This study aimed to estimate the requisite screening and antiviral treatment levels to achieve these goals among people who inject drugs in China and identify the most cost-effective strategy.

This study utilized models based on dynamic social networks to simulate HCV transmission and disease progression among people who inject drugs in China, incorporating a cost-effectiveness analysis from a healthcare perspective.

To achieve the WHO targets, a minimum screening and treatment rate of 10% is required to meet the mortality goal, while a 25% rate is necessary for the incidence goal. The most cost-effective strategy includes a 25% screening rate and a 95% treatment rate. Compared to no intervention, this approach significantly reduces costs by - $85,873.38 (95% CI  - $94,311.16 to  - $77,435.59) and adds 24.66 (95% CI 23.68 to - 25.64) quality-adjusted life years. The intervention is dominant, with a cost-effectiveness ratio of - $3482.29 (95% CI  - $3982.73 to  - $3020.11) per quality-adjusted life year.

Achieving the WHO's hepatitis C virus elimination targets among people who inject drugs in China is feasible and cost-saving.

Although therapies based on direct-acting antivirals (DAAs) effectively eradicate hepatitis C virus (HCV) in patients, there is still a high risk of liver fibrosis even after a sustained virological response. Therefore, it is of great clinical importance to understand the mechanism of potential factors that promote liver fibrosis after virological cure by treatment with DAAs. Here, we found that tubulointerstitial nephritis antigen-like 1 (TINAGL1) is significantly increased in HCV-infected hepatocytes and in the liver of patients with liver fibrosis, and that higher TINAGL1 expression persists in HCV-eradicated hepatocytes after treatment with DAAs. Overexpression of TINAGL1 in the liver triggers and exacerbates liver fibrosis, and xenotransplantation of HCV-eradicated Huh7.5 cells leads to a higher risk of hepatocellular carcinoma. Conversely, knockdown of TINAGL1 expression prevents and attenuates the progression of liver fibrosis in mice. TINAGL1 binds and stabilizes platelet-derived growth factor-BB (PDGF-BB) in hepatocytes, leading to an increase in intracellular and extracellular PDGF-BB, which sensitizes the PDGF-BB/PDGFRβ pathway to activate hepatic stellate cells. This study highlights that TINAGL1 is a new factor contributing to liver fibrosis after injury, including but not limited to HCV infection, even after virological cure by DAAs, and emphasizes the therapeutic potential of TINAGL1 as an innovative target for the treatment of liver fibrosis.

Hepatitis C virus (HCV) infection is a significant risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). Traditionally, the primary prevention strategy for HCV-associated HCC has focused on removing infection through antiviral regimes. Currently, highly effective direct-acting antivirals (DAAs) offer extraordinary success across all patient categories, including cirrhotics. Despite these advancements, recent studies have reported that even after sustained virologic response (SVR), individuals with advanced liver disease/cirrhosis at the time of DAA treatment may still face risks of HCC occurrence or recurrence. Based on this premise, this review tries to shed light on the multiple mechanisms that establish a tumorigenic environment, first, during chronic HCV infection and then, after eventual viral eradication by DAAs. Furthermore, it reviews evidence reported by recent observational studies stating that the use of DAAs is not associated with an increased risk of HCC development but rather, with a significantly lower chance of liver cancer compared with DAA-untreated patients. In addition, it seeks to provide some practical guidance for clinicians, helping them to manage HCC surveillance of patients who have achieved SVR with DAAs.

Advanced combination treatment (ACT), defined as a combination of at least 2 biologic agents, a biologic agent and an oral small molecule, 2 oral small molecules drug with different mechanisms of action is a proposed strategy to improve outcomes in patients with immune-mediated inflammatory disease (IMID). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing ACT with monotherapy in patients with select IMIDs.

Through a systematic literature search, we identified 10 RCTs (n = 1154) comparing ACT with single agent therapy (monotherapy). The primary outcome was induction of clinical remission. Secondary outcomes were adverse events, serious adverse events, infections, and serious infections. We performed random-effects meta-analysis and used GRADE to appraise certainty of evidence.

Eight out of 10 trials investigated an anti-TNF-α drug (e.g., etanercept, infliximab, golimumab, certolizumab) combined with another biologic (e.g anti-IL-23, anti-integrin, anti-IL-1) or an oral small molecule. There was no significant difference in the likelihood of achieving clinical remission with ACT vs. monotherapy in patients with rheumatoid arthritis (n = 7 RCTs) (RR, 1.75 [95 % CI 0.60-5.13]; moderate heterogeneity (I2 = 33 %)] and systemic lupus erythematosus (n = 1) (RR, 1.20 [0.53-2.72]) (GRADE; low certainty evidence). Patients with rheumatoid arthritis in the ACT arm were more likely to experience adverse events (RR, 1.07 [1.01-1.12]) compared to monotherapy. ACT led to higher rates of induction of clinical remission in patients with IBD (n = 2 RCTs) (RR, 1.68 [1.15-2.46]) with minimal heterogeneity (I2 = 15 %) (GRADE; low certainty evidence), and no differences in the likelihood of adverse events (RR 0.92 [0.80-1.05]). There were no differences in the risk of infections or serious infections in patients treated with ACT or monotherapy with rheumatological disease or IBD.

ACT did not offer clinical benefit in patients with rheumatological IMIDs and resulted in higher rate adverse events in rheumatoid arthritis. ACT may offer clinical benefit without a clear safety signal in patients with IBD, but further trials are warranted. The variability in ACT regimens across studies limits the generalizability of these findings.

Identification of people living with hepatitis C virus (HCV) via readily available laboratory records could be a key strategy for macro-elimination, aligning with the WHO elimination goal. Therefore, the ELIMINATE(ELIMINation of HCV in AusTria East) project aimed to systematically re-link people with a 'last-positive' HCV-RNA PCR record to care.

In 10 major liver centres in Eastern Austria, a systematic readout of 'last-positive' HCV-RNA PCR test records obtained between 2008 and 2020 were conducted and linked to available patient contact data. Between 2020 and 2023, individuals were contacted first by phone, then by letter, to inform them about the availability of effective direct-acting antiviral (DAA) treatment and invite them for pre-treatment evaluation.

The overall cohort of last-positive HCV+ individuals included 5695 subjects (62.5% males, mean age 57.3 ± 17.3 years); of note, 1931 (34%) of them had died and 759 (13%) individuals had no valid contact information. Of the remaining 3005 individuals, 1171 (40.0%) had already achieved sustained virological response (SVR) at the time of re-call. We successfully reached 617 (20.5%), of whom 417 (67.6%) attended their pre-treatment visit, and 397 (64.3%) commenced DAA-therapy. HCV cure has been confirmed in 326 individuals, corresponding to an SVR rate of 82.1%.

The ELIMINATE project identified 5695 people living with HCV who were 'lost to care' despite documented HCV viraemia. While invalid contact data were an evident barrier to HCV elimination, premature deaths among the cohort underscored the severity of untreated HCV. The implementation of a systematic HCV-RNA PCR recorded-based re-call workflow represents an effective strategy supporting the WHO goal of HCV elimination.

Background There is ongoing debate regarding the impact of direct-acting antiviral drugs (DAAs) on the occurrence of de novo hepatocellular carcinoma (HCC). Vascular endothelial growth factor (VEGF) plays a crucial role in the development and angiogenesis of HCC. Aim This study aims to evaluate dynamic changes in vascular endothelial growth factor (VEGF) levels at different point times during and after treatment of HCV to evaluate the risk of de novo HCC in DAAs-treated HCV patients. Methods This prospective cohort study was conducted on 60 HCV-infected patients; 30 patients had early fibrosis (F1-F2) and 30 patients had advanced fibrosis (F3-F4). HCV-RNA, aspartate aminotransferase (AST) to platelet ratio index (APRI), and fibrosis-4 index scores, liver function tests, serum VEGF, alpha-fetoprotein (AFP), and abdominal ultrasound were done at baseline, 4 weeks after starting treatment, at the end of treatment, and 12 weeks after treatment. Results VEGF was significantly decreased after completion of treatment (78.94± 10.03) compared to its baseline level (103.17 ± 33.89 pg/ml). Conclusion No de-novo hepatic focal lesion was detected during and up to 12 weeks after completion of treatment. The treatment of HCV by DAAs was associated with a significant decrease in VEGF and AFP levels and an improvement in liver enzymes and fibrosis scores.

Chronic hepatitis C virus infections can lead to liver fibrosis. Appropriate treatment of chronic hepatitis C may result in significant fibrosis reversal. The best method to assess liver fibrosis is an invasive hepatic biopsy. Among non-invasive options, one of the most recent methods is two-dimensional shearwave elastography, which allows real-time visualization of liver stiffness. The purpose of this study was to analyze changes in liver fibrosis among patients with hepatitis C virus receiving direct-acting antiviral therapy.

Five different elastographic measurements in kilopascals were performed in a group of 50 patients before direct-acting antiviral treatment, at the end of treatment, and 24 weeks after the end of treatment, using an Aixplorer® (Supersonic Imagine, France) ultrasound device. The results were correlated with biochemical serum tests, specifically the Fibrosis-4 and AspAT-to-platelet ratio indices.

Time-dependent alterations of all of the parameters were observed, including a significant decrease in liver stiffness in comparison to baseline values (before treatment). A moderate correlation between liver stiffness measurement values and both Fibrosis-4 and AspAT-to-platelet ratio indices was observed. Interestingly, only liver stiffness and blood platelet count changed over time, regardless of the sex and age of the patient.

Two-dimensional shear-wave elastography combined with non-invasive serologic tests like Fibrosis-4 and AspAT-to-platelet ratio indices is a sufficient tool for evaluating liver fibrosis regression during and after direct-acting antiviral therapy.

This study aimed to evaluate the effectiveness and safety of direct-acting antivirals (DAAs) for hepatitis C treatment by measuring sustained virologic response (SVR) and serious adverse events to help design effective interventions for reducing disease prevalence.

This was a retrospective, observational, real-life study of patients with chronic hepatitis C receiving DAA treatment in the state of Ceará, Brazil. Data were collected in REDCap and analyzed using R® software by the Student's t, chi-square, and Fisher's exact tests, with a significance level of 5%.

In this study, 1075 patients who were diagnosed with hepatitis C infection between October 2015 and October 2023 were included. The mean age of the participants was 56.6 ± 11 years and 60.2% were men. The sample included 51 HIV-infected patients (6.6%), 166 (15,4%) liver transplant recipients, 34 (3,1%) kidney transplant recipients, and 446 patients with cirrhosis (41.4%). The overall SVR rate was 96.4%. The sofosbuvir/daclatasvir/ribavirin regimen used in 354 (32.9%) patients achieved an SVR of 96%. The cure rate was 96.5%, with a lower SVR in patients with cirrhosis (93.4%) than in those with less severe fibrosis (97.9%) (p=0.0015). Serious adverse events associated with ribavirin use occurred in 3.5% of patients.

DAA treatment for hepatitis C achieved SVR in real life in all patient profiles, including transplant recipients, HIV carriers, and patients with cirrhosis. Although these drugs are safe, a few decompensated patients with cirrhosis died during treatment.

Limited data exists about treatment outcomes in nationwide hepatitis C virus (HCV) elimination programs where injection drug use (IDU) is the main mode of transmission. In 2016 Iceland initiated the HCV elimination program known as Treatment as Prevention for Hepatitis C (TraP HepC). Factors associated with HCV cure in this population are examined.

Unrestricted access was offered to direct acting antiviral agents (DAAs). Testing and harm reduction was scaled up and re-treatments were offered for those who did not attain cure. Cure rates for the first 36 months were assessed and factors associated with failure to achieve cure analysed using multivariable logistic regression.

Treatment was initiated for 718; 705 consented for the study. Median age was 44 years (IQR 35-56), history of IDU reported by 593 (84.1 %), recent IDU by 234 (33.2 %); 48 (6.8 %) were homeless. Of 705 patients, 635 achieved cure (90.1 %) during the first treatment. A total of 70 (9.9 %) patients initiated two or more treatments, resulting in 673 participants cured (95.5 %). By multivariable analysis, homelessness was the only statistically significant independent factor associated with not achieving cure (OR 2.67, 95 % CI 1.32-5.41) after first treatment attempt.

By reengagement in care and prompt retreatment when needed, a cure rate of 95.5 % was achieved. Unstable housing, a potentially actionable factor is associated with poor outcome.

A barrier to hepatitis C virus (HCV) cure is conventional testing. The aim of this study was to evaluate the effect of HCV antibody and RNA point-of-care testing (POCT) on testing rates, linkage to care, treatment, and acceptability of testing in 3 priority settings in Australia.

Participants were enrolled in an interventional cohort study at a reception prison, inpatient mental health service, and inpatient alcohol and other drug unit, between October 2020 and December 2021. HCV POCT was performed using SD Bioline HCV antibody fingerstick test and a reflexive Xpert HCV Viral Load Fingerstick test using capillary blood samples. A retrospective audit of HCV testing and treatment data was performed at each site for the preceding 12-month period to generate a historical control.

A total of 1549 participants received a HCV antibody test with 17% (264 of 1549) receiving a positive result, of whom 21% (55 of 264) tested HCV RNA positive. Across all settings the rate of testing per year significantly increased between the historical controls and the study intervention period by 2.57 fold (rate ratio, 2.57 [95% confidence interval, 2.32-2.85]) for HCV antibody testing and 1.62 (rate ratio, 1.62 [95% confidence interval, 1.31-2.01]) for RNA testing. Treatment uptake was higher during the POCT intervention (86% [47 of 55]; P = .01) compared to the historical controls (61% [27 of 44]).

This study demonstrated across 3 settings that the use of HCV antibody and RNA POCT increased testing rates, treatment uptake, and linkage to care. The testing model was highly acceptable for most participants.

ACTRN-12621001578897.

The benefits of HCV eradication on distinct recurrence patterns and long-term hepatic outcomes in patients with hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA) remain uncertain. This study aims to assess the impact of HCV eradication on HCC recurrence patterns and long-term hepatic outcomes after RFA and to identify predictors of recurrence in patients achieving sustained virological response (SVR).

We retrospectively enrolled 274 patients receiving RFA for HCV-related HCC, including 73 and 88 patients treated with interferon-based (IFN) and direct-acting antivirals (DAA) therapy, respectively. We analysed factors associated with local tumour progression (LTP), distant recurrence, overall survival, and hepatic decompensation.

SVR was achieved in 49.3% of patients undergoing IFN therapy and 93.2% of patients undergoing DAA therapy. HCV eradication was not associated with LTP but significantly correlated with reduced risk of distant recurrence (by DAA: hazard ratio (HR) = 0.449, p = 0.006), overall survival (by IFN: HR = 0.242, p < 0.001; by DAA: HR = 0.274, p < 0.001) and hepatic decompensation (by IFN: HR = 0.313, p = 0.004; by DAA: HR = 0.281, p < 0.001). The benefits of achieving SVR in terms of overall survival and hepatic decompensation remained significant in subgroups of patients with and without recurrence. Patients with SVR showed a significant decline in FIB-4 score and a higher proportion of ALBI grade improvement. Among SVR patients, the IMbrave050 criteria predicted LTP but not distant recurrence, whereas the FIB-4 score after SVR, rather than the baseline FIB-4, predicted distant recurrence.

HCV eradication was associated with a significant reduction in distant recurrence, mortality and hepatic decompensation following RFA in patients with HCV-related HCC.

Recent studies suggested that successful clearance of chronic Hepatitis C Virus (HCV) by using direct-acting antiviral (DAA) agents could improve glycemic control in patients with diabetes; however, some studies failed to identify this benefit. We conducted a systematic review and meta-analysis to assess the impact of sustained virologic response (SVR) after treatment with DAA agents on glycemic control. Embase, Scopus and PubMed were searched through March 26th, 2023, for all studies evaluating whether eradication of HCV infection with DAAs is associated with an impact on glycemic control. Only studies with data on glycemic control, including haemoglobin A1c (HbA1c), fasting glucose, or Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), at least 12-week post-SVR were included. Sixteen studies met our eligibility criteria and were included in qualitative analysis. The mean HbA1c was 8.05% (95% CI: 7.79%-8.31%) before treatment and 7.19% (95% CI: 6.98%-7.39%) after treatment. There was a significant mean absolute reduction in HbA1c of 0.72% (95% CI: 0.52%-0.93%) with high heterogeneity between studies (I2 = 91.7%). The reduction in HbA1c remained significant in the subgroup analysis at 3 months follow up post SVR [0.74% (95% CI: 0.57%-0.91%)] and at least 6 months follow up [0.66% (95% CI: 0.23%-1.10%)]. We found a significant reduction in HbA1C after SVR in patients with type 2 diabetes mellitus, reflecting better glycemic control with HCV eradication. This data highlights an important extrahepatic benefit of HCV eradication.

The Elecsys® HCV Duo immunoassay (Roche Diagnostics International Ltd., Rotkreuz, Switzerland) detects both antibodies to hepatitis C virus (anti-HCV) and HCV core antigen (HCV-Ag) and has shown excellent diagnostic performance in blood donor samples. We aim to validate its use for diagnosing chronic HCV infection and assessing sustained virological response (SVR) post-direct-acting antivirals (DAAs) in patients with or without HIV infection.

Blood samples from 100 healthy controls, as well as 64 HCV mono-infection and 136 HCV-HIV coinfections, were collected before and 12-24 weeks after DAAs. The assay performance for determining active infection at baseline and SVR was compared with HCV RNA.

Overall, 156 (78.0%) of HCV-infected patients had HCV genotype 1, and the SVR rate was 96.5%. The sensitivity, specificity, and area under the ROC curve (AUROC) for HCV diagnosis at baseline were 99.50% (95% confidence interval [CI], 96.82-99.97%), 100% (95%CI, 95.39-100%), and 0.998 (95%CI, 0.992-1.003), respectively. The corresponding results for HCV-Ag in determining SVR were 57.14% (95%CI, 20.24-88.19%), 97.41% (95%CI, 93.73-99.04%), and 0.773 (95%CI, 0.543-1.003), respectively. The assay also exhibited comparable sensitivity and specificity between HCV mono- and coinfection.

Our study showed that the Elecsys® HCV Duo immunoassay effectively diagnosed HCV infection, regardless of HIV status, making it suitable for managing high-risk populations in resource-limited settings.

Viral hepatitis is a major cause of liver illness worldwide. Despite advances in the understanding of these infections, the pathogenesis of hepatitis remains a complex process driven by intricate interactions between hepatitis viruses and host cells at the molecular level. This paper will examine in detail the dynamics of these host-pathogen interactions, highlighting the key mechanisms that regulate virus entry into the hepatocyte, their replication, evasion of immune responses, and induction of hepatocellular damage. The unique strategies employed by different hepatitis viruses, such as hepatitis B, C, D, and E viruses, to exploit metabolic and cell signaling pathways to their advantage will be discussed. At the same time, the innate and adaptive immune responses put in place by the host to counter viral infection will be analyzed. Special attention will be paid to genetic, epigenetic, and environmental factors that modulate individual susceptibility to different forms of viral hepatitis. In addition, this work will highlight the latest findings on the mechanisms of viral persistence leading to the chronic hepatitis state and the potential implications for the development of new therapeutic strategies. Fully understanding the complex host-pathogen interactions in viral hepatitis is crucial to identifying new therapeutic targets, developing more effective approaches for treatment, and shedding light on the mechanisms underlying progression to more advanced stages of liver damage.

Direct-acting antivirals (DAAs) share pharmacokinetic pathways with many comedications commonly administered to patients living with chronic hepatitis C virus (HCV) infection (PLWHCV). International guidelines recommend a thorough drug-drug interaction (DDI) risk assessment prior to starting DAA therapy and before starting comedications. This study aims to evaluate the impact of potential multiple DDIs in the real-life adverse event (AE) profile of PLWHCV treated with DAAs.

This is a retrospective, observational study using electronic medical records. Patients included were PLWHCV and were treated with either the protease inhibitor (PI) free DAA sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB) between 2017 and 2020. Potential (single and multiple) DDIs were identified using the Liverpool HEP Interaction Checker. AEs potentially associated to DDIs were identified during DAA treatment period.

1620 patients with DAA prescriptions (SOF/VEL or GLE/PIB) were included. Of these, 123 were predicted to have multiple DDIs (multi-DDI). About 10% (123/1256) of the patients receiving ≥2 comedications were at risk of multi-DDI with DAA. Most comedication-associated AEs were recorded in this multi-DDI population (88.9%, 16/18), meaning that 13% (16/123) of the multi-DDI population suffered AEs. According to DAA regimen, more comedication-associated AEs were reported in GLE/PIB-treated as compared with SOF/VEL-treated patients (18.3% [13/71] vs 5.8% [3/52] p<0.05). These AEs were mainly reported by primary care physicians (62.5%).

PLWHCV predicted to have multiple DDIs are at high risk of AEs. Moreover, fewer comedication-associated AEs were identified with the PI-free DAA SOF/VEL as compared with GLE/PIB.