PAGE-B incorporating moderate HBV DNA levels predicts risk of HCC among patients entering into HBeAg-positive chronic hepatitis B.

BACKGROUND & AIMS: Recent studies reported that moderate HBV DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed to develop and validate a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection. METHODS: This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in 23 tertiary university-affiliated hospitals of South Korea (2012-2020). A new HCC risk score (PAGED-B) was developed (training cohort, n = 2,367) based on multivariable Cox models. Internal validation using bootstrap sampling and external validation (validation cohort, n = 1,218) were performed. RESULTS: Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00-7.99 log10 IU/ml) were independently associated with HCC development; the PAGED-B score (based on these five predictors) showed a time-dependent AUROC of 0.81 for the prediction of HCC development at 5 years. In the validation cohort, the AUROC of PAGED-B was 0.85, significantly higher than for other risk scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio = 8.43 in the training and 11.59 in the validation cohorts, all p <0.001). CONCLUSIONS: The newly established PAGED-B score may enable risk stratification for HCC at the time of transition into HBeAg-positive CHB. IMPACT AND IMPLICATIONS: In this study, we developed and validated a new risk score to predict hepatocellular carcinoma (HCC) development in patients entering into hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) from chronic infection. The newly established PAGED-B score, which included baseline moderate HBV DNA levels (5-8 log10 IU/ml), improved on the predictive performance of prior risk scores. Based on a patient's age, gender, diabetic status, platelet count, and moderate DNA levels (5-8 log10 IU/ml) at the phase change into CHB from chronic infection, the PAGED-B score represents a reliable and easily available risk score to predict HCC development during the first 5 years of antiviral treatment in HBeAg-positive patients entering into CHB. With a scoring range from 0 to 12 points, the PAGED-B score significantly differentiated the 5-year HCC risk: low <7 points and high ≥7 points.

Incidence of primary hepatitis C infection among people who inject drugs during 2012-2020 in Athens, Greece.

One of the World Health Organization's targets for the 2030 viral hepatitis elimination strategy is to reduce new hepatitis C (HCV) infections. In Athens, Greece, people who inject drugs (PWID) have a high HCV prevalence, with increasing trends since the 2000s. This analysis aims to assess primary HCV incidence among PWID during 2012-2020. Two community-based interventions were implemented in 2012-2013 and 2018-2020 with repeated sero-behavioural surveys in each period. Participants enrolled in multiple surveys were identified through linkage. To assess trends in HCV transmission, three indicators were estimated: (i) anti-HCV prevalence among 'new' injectors (those injecting ≤2 years), (ii) indirect HCV incidence among 'new' injectors, assuming infection occurred at the midpoint between initiating injection and the first positive test, and (iii) HCV incidence from repeat participants. There were 431 and 125 'new' injectors, respectively, in 2012-2013 and 2018-2020. Αnti-HCV prevalence [95% CI] declined from 53.6% [48.8%, 58.3%] in 2012-2013 to 40.0% [31.3, 49.1%] in 2018-2020 (25.4% reduction, p = .007). The indirect estimate [95% CI] of HCV incidence among 'new' injectors decreased from 56.1 [49.3, 63.8] to 39.0/100 person-years (PYs) [29.6, 51.5] (30.5% reduction, p = .020). HCV incidence [95% CI] based on seroconversions in repeat participants (16/63 in 2012-2013 and 9/55 in 2018-2020) declined from 64.6 [39.6105.4] to 13.8/100 PYs [7.2, 26.5], respectively (78.6% reduction, p < .001). Primary HCV incidence remains high among PWID in Athens. Consistent implementation of combined interventions, including high-coverage harm reduction programs and initiatives tailored to increase access to HCV treatment, is essential to sustain the declining trends documented during 2012-2020.

Outbreaks of SARS-CoV-2 in naturally infected mink farms: Impact, transmission dynamics, genetic patterns, and environmental contamination.

SARS-CoV-2 infection outbreaks in minks have serious implications associated with animal health and welfare, and public health. In two naturally infected mink farms (A and B) located in Greece, we investigated the outbreaks and assessed parameters associated with virus transmission, immunity, pathology, and environmental contamination. Symptoms ranged from anorexia and mild depression to respiratory signs of varying intensity. Although the farms were at different breeding stages, mortality was similarly high (8.4% and 10.0%). The viral strains belonged to lineages B.1.1.218 and B.1.1.305, possessing the mink-specific S-Y453F substitution. Lung histopathology identified necrosis of smooth muscle and connective tissue elements of vascular walls, and vasculitis as the main early key events of the acute SARS-CoV-2-induced broncho-interstitial pneumonia. Molecular investigation in two dead minks indicated a consistently higher (0.3-1.3 log10 RNA copies/g) viral load in organs of the male mink compared to the female. In farm A, the infected farmers were responsible for the significant initial infection of 229 out of 1,000 handled minks, suggesting a very efficient human-to-mink transmission. Subsequent infections across the sheds wherein animals were being housed occurred due to airborne transmission. Based on a R0 of 2.90 and a growth rate equal to 0.293, the generation time was estimated to be 3.6 days, indicative of the massive SARS-CoV-2 dispersal among minks. After the end of the outbreaks, a similar percentage of animals were immune in the two farms (93.0% and 93.3%), preventing further virus transmission whereas, viral RNA was detected in samples collected from shed surfaces and air. Consequently, strict biosecurity is imperative during the occurrence of clinical signs. Environmental viral load monitoring, in conjunction with NGS should be adopted in mink farm surveillance. The minimum proportion of minks that need to be immunized to avoid outbreaks in farms was calculated at 65.5%, which is important for future vaccination campaigns.

Securing wider EU commitment to the elimination of hepatitis C virus.

In 2016, the Hepatitis B and C Public Policy Association (HepBCPPA), gathered all the main stakeholders in the field of hepatitis C virus (HCV) to launch the now landmark HCV Elimination Manifesto, calling for the elimination of HCV in the EU by 2030. Since then, many European countries have made progress towards HCV elimination. Multiple programmes-from the municipality level to the EU level-were launched, resulting in an overall decrease in viremic HCV infections and liver-related mortality. However, as of 2021, most countries are not on track to reach the 2030 HCV elimination targets set by the WHO. Moreover, the COVID-19 pandemic has resulted in a decrease in HCV diagnoses and fewer direct-acting antiviral treatment initiations in 2020. Diagnostic and therapeutic tools to easily diagnose and treat chronic HCV infection are now well established. Treating all patients with chronic HCV infection is more cost-saving than treating and caring for patients with liver-related complications, decompensated cirrhosis or hepatocellular carcinoma. It is more important than ever to reinforce and scale-up action towards HCV elimination. Yet, efforts urgently need the dedicated commitment of policymakers at all governmental and policy levels. Therefore, the third EU Policy Summit, held in March 2021, featured EU parliamentarians and other key decision makers to promote dialogue and take strides towards securing wider EU commitment to advance and achieve HCV elimination by 2030. We have summarized the key action points and reported the 'Call-to-Action' statement supported by all the major relevant European associations in the field.

Estimating the number of people who inject drugs using repeated respondent-driven sampling (RDS) in a community-based program: implications for the burden of hepatitis C and HIV infections and harm reduction coverage.

Estimates of the population size of people who inject drugs (PWID) are essential for efficient program planning and for monitoring key targets. Existing estimates in Greece are based on the capture-recapture method applied to drug treatment sources. We aimed to obtain estimates based on data collected from a community-based program addressing PWID in Athens, Greece. The program was implemented in 2012-2013 to increase diagnosis and treatment for HIV among PWID during an HIV outbreak. Five Responden-Driven Sampling (RDS) rounds were used to recruit participants. A unique code was used to identify participants among rounds. Capture-recapture was applied to estimate the population size in 2013 (PWID with injection in the past 12 months; active PWID with injection in the past 30 days). Log-linear models were applied. In 2013, the estimated number of active PWID in Athens was 4,117 [95% confidence interval (CI): 3,728-4,507] (vs. 1,956 [95% CI: 1,525-2,565] the existing population size estimate). Based on this estimate, the coverage of needle and syringe programs in 2013 was 103 syringes/PWID/year (vs. 216 based on the existing estimate). The population prevalence of injecting drug use in Athens (past 12 months) was 0.222% (95% CI: 0.200-0.245). The inclusion of data from community-based programs in the estimation of the PWID population size resulted in 2.1-fold higher estimates, compared to the official estimates obtained from drug treatment data, and indicates the need for re-evaluation of necessary resources for harm reduction and elimination of HIV and hepatitis C in PWID.

Incidence of liver- and non-liver-related outcomes in patients with HCV-cirrhosis after SVR.

BACKGROUND & AIMS: As the long-term benefits of a sustained virological response (SVR) in HCV-related cirrhosis following direct-acting antiviral (DAA) treatment remain undefined, we assessed the incidence and predictors of liver-related events (LREs), non-liver-related events (NLREs) and mortality in DAA-treated patients with cirrhosis. METHODS: Consecutive patients with cirrhosis and SVR were enrolled in a longitudinal, single-center study, and divided into 3 cohorts: Cohort A (Child-Pugh A without a previous LRE), Cohort B (Child-Pugh B or Child-Pugh A with prior non-hepatocellular carcinoma [HCC] LREs), Cohort C (previous HCC). RESULTS: A total of 636 patients with cirrhosis (median 65 years-old, 58% males, 89% Child-Pugh A) were followed for 51 (8-68) months (Cohort A n = 480, Cohort B n = 89, Cohort C n = 67). The 5-year estimated cumulative incidences of LREs were 10.4% in Cohort A vs. 32.0% in Cohort B (HCC 7.7% vs. 19.7%; ascites 1.4% vs. 8.6%; variceal bleeding 1.3% vs. 7.8%; encephalopathy 0 vs. 2.5%) vs. 71% in Cohort C (HCC only) (p <0.0001). The corresponding figures for NLREs were 11.7% in Cohort A vs. 17.9% in Cohort B vs. 17.5% in Cohort C (p = 0.32). The 5-year estimated probabilities of liver-related vs. non-liver-related deaths were 0.5% vs. 4.5% in Cohort A, 16.2% vs. 8.8% in Cohort B and 12.1% vs. 7.7% in Cohort C. The all-cause mortality rate in Cohort A was similar to the rate expected for the general population stratified by age, sex and calendar year according to the Human Mortality Database, while it was significantly higher in Cohort B. CONCLUSIONS: Patients with cirrhosis and an SVR on DAAs face risks of liver-related and non-liver-related events and mortality; however, their incidence is strongly influenced by pre-DAA patient history. LAY SUMMARY: In this large single-center study enrolling patients with hepatitis C virus (HCV)-related cirrhosis cured by direct-acting antivirals, pre-treatment liver disease history strongly influenced long-term outcomes. In patients with HCV-related cirrhosis, hepatocellular carcinoma was the most frequent liver-related complication after viral cure. Due to improved long-term outcomes, patients with cirrhosis after HCV cure are exposed to a significant proportion of non-liver-related events.

An artificial intelligence model to predict hepatocellular carcinoma risk in Korean and Caucasian patients with chronic hepatitis B.

BACKGROUND & AIMS: Several models have recently been developed to predict risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Our aims were to develop and validate an artificial intelligence-assisted prediction model of HCC risk. METHODS: Using a gradient-boosting machine (GBM) algorithm, a model was developed using 6,051 patients with CHB who received entecavir or tenofovir therapy from 4 hospitals in Korea. Two external validation cohorts were independently established: Korean (5,817 patients from 14 Korean centers) and Caucasian (1,640 from 11 Western centers) PAGE-B cohorts. The primary outcome was HCC development. RESULTS: In the derivation cohort and the 2 validation cohorts, cirrhosis was present in 26.9%-50.2% of patients at baseline. A model using 10 parameters at baseline was derived and showed good predictive performance (c-index 0.79). This model showed significantly better discrimination than previous models (PAGE-B, modified PAGE-B, REACH-B, and CU-HCC) in both the Korean (c-index 0.79 vs. 0.64-0.74; all p <0.001) and Caucasian validation cohorts (c-index 0.81 vs. 0.57-0.79; all p <0.05 except modified PAGE-B, p = 0.42). A calibration plot showed a satisfactory calibration function. When the patients were grouped into 4 risk groups, the minimal-risk group (11.2% of the Korean cohort and 8.8% of the Caucasian cohort) had a less than 0.5% risk of HCC during 8 years of follow-up. CONCLUSIONS: This GBM-based model provides the best predictive power for HCC risk in Korean and Caucasian patients with CHB treated with entecavir or tenofovir. LAY SUMMARY: Risk scores have been developed to predict the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. We developed and validated a new risk prediction model using machine learning algorithms in 13,508 antiviral-treated patients with chronic hepatitis B. Our new model, based on 10 common baseline characteristics, demonstrated superior performance in risk stratification compared with previous risk scores. This model also identified a group of patients at minimal risk of developing HCC, who could be indicated for less intensive HCC surveillance.

Impact of HBeAg on Hepatocellular Carcinoma Risk During Oral Antiviral Treatment in Patients With Chronic Hepatitis B.

BACKGROUND & AIMS: Antiviral treatment from hepatitis B envelope antigen (HBeAg)-positive status may attenuate the integration of hepatitis B virus DNA into the host genome causing hepatocellular carcinoma (HCC). We investigated the impact of HBeAg status at the onset of antiviral treatment on the risk of HCC. METHODS: The incidence of HCC was evaluated in Korean patients with chronic hepatitis B who started entecavir or tenofovir in either HBeAg-positive or HBeAg-negative phase. The results in the Korean cohort were validated in a Caucasian PAGE-B cohort. RESULTS: A total of 9143 Korean patients (mean age, 49.2 years) were included: 49.1% were HBeAg-positive and 49.2% had cirrhosis. During follow-up (median, 5.1 years), 916 patients (10.0%) developed HCC. Baseline HBeAg positivity was not associated with the risk of HCC in the entire cohort or cirrhotic subcohort. However, in the non-cirrhotic subcohort, HBeAg positivity was independently associated with a lower risk of HCC in multivariable (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.26-0.66), propensity score-matching (aHR, 0.46; 95% CI, 0.28-0.76), and inverse probability weighting analyses (aHR, 0.44; 95% CI, 0.28-0.70). In the Caucasian cohort (n = 719; mean age, 51.8 years; HBeAg-positive, 20.3%; cirrhosis, 34.8%), HBeAg-positivity was not associated with the risk of HCC either in the entire cohort or cirrhotic subcohort. In the non-cirrhotic subcohort, none of the HBeAg-positive group developed HCC, although the difference failed to reach statistical significance (aHR, 0.21; 95% CI, 0.00-1.67). CONCLUSIONS: This multinational cohort study implies that HBeAg positivity at the onset of antiviral treatment seems to be an independent factor associated with a lower risk of HCC in patients with chronic hepatitis B without cirrhosis, but not in those with cirrhosis.

Predictive score for patients with carbapenemase-producing enterobacterales colonization upon admission in a tertiary care hospital in an endemic area.

OBJECTIVES: Carbapenemase-producing Enterobacterales (CPE) comprise important nosocomial pathogens worldwide. Colonized patients are the source of further dissemination in healthcare settings. Considering that timely detection of CPE carriers is pivotal but universal screening is unfeasible, we aimed to develop and validate a prediction score to detect patients harbouring CPE on hospital admission. METHODS: The study was conducted in a tertiary care hospital located in a CPE endemic area. Rectal swabs were obtained from 2303 patients, screened shortly after hospital admission. The Enterobacterales isolated in cultures were examined for the presence of blaVIM, KPC, NDM, OXA-48 by PCR. Demographic data and patient history of the previous 6 months were recorded. Risk factors for CPE carriage were identified using a multivariable logistic regression model and a points-system risk score was developed. The discriminative ability of the risk score was assessed using the AUC and its predictive performance was validated in a second dataset of 1391 patients in a different time period. RESULTS: Seven predictors were identified: previous CPE colonization or infection, prior hospitalization, stay in a long-term health care facility, history of ≥2 interventions, renal replacement therapy, diabetes with end-organ damage and Karnofsky score. The developed risk score in the derivation dataset ranged between 0 and 79 points, with an AUC of 0.84 in the derivation and 0.85 in the validation dataset. CONCLUSIONS: This prediction tool may assist in identifying patients who are at risk of harbouring CPE on hospital admission in an endemic area and guide clinicians to implement prompt and appropriate infection control measures.

Pre-exposure Prophylaxis Persistence Among Greek Sexual Minority Men: Results from PrEP for Greece (P4G) Study.

Nearly half the new HIV infections in Greece occur in sexual minority men, yet pre-exposure prophylaxis is not currently supported in the national HIV program. We examined factors associated with PrEP persistence among Greek SMM in PrEP for Greece, the first PrEP study in Greece. Participants (n = 100) were recruited from 2016 to 2018 through respondent-driven sampling among SMM in Athens, receiving supplies for daily PrEP at interval visits over 12-months. PrEP persistence, operationalized as Total PrEP Time, was high, 74% of participants achieving perfect persistence. Higher alcohol risk scores (OR 1.27, 95% CI 1.08-1.49) and adherence to HIV testing guidelines (OR 1.23, 95% CI 1.00-1.51) were associated with persistence. Housing impermanence (OR 0.14, 95% CI 0.04-0.48) and serostatus disclosure concerns (OR 0.77, 95% CI 0.60-0.97) were associated with limited PrEP persistence. While PrEP persistence among Greek SMM is high, socioeconomic factors and societal attitudes may challenge prevention efforts.

A Network Approach to Determine Optimization of PrEP Uptake in Athens, Greece.

Although the HIV epidemic in Athens, Greece has reemerged and spread in men who have sex with men (MSM), state-supported PrEP programs have not been instituted. A PrEP intervention was implemented building upon an existing network cohort of MSM (308 participants; 1212 network members). A PrEP intervention cohort of 106 participants was selected based upon sex behaviors. Individual, partner, and network characteristics were compared between the cohorts. The PrEP cohort members were more highly connected and in more influential positions in the network than their peers. Further, their sexual network connections' behaviors increased their vulnerability to HIV infection relative to the rest of the network's sex partners. This included greater stimulant use (24.2% vs 7.0%; χ2 = 28.2; p < 0.001), greater rates of at least weekly condomless sex (OR = 2.7; 95% CI 2.1-3.5; χ2 = 59.2; p < 0.001) and at least weekly use of drugs or alcohol during sex (OR = 3.4; 95% CI 2.6-4.3; χ2 = 89.7; p < 0.001). Finally the PrEP cohort's social networks showed similarly increased vulnerability to seroconversion, including greater rates of injection drug use (4.1% vs 0.5%; χ2 = 3.9; p = 0.04), greater stimulant use (33.6% vs 14.6%; χ2 = 16.9, p < 0.001), and higher rates of recent STIs (21.6% vs 13.1%; χ2 = 4.4; p = 0.04). Thus, this PrEP intervention engaged individuals in vulnerable positions with vulnerable connections within an MSM community.

Hepatitis B, C and human immunodeficiency virus knowledge among the general greek population: results from the Hprolipsis nationwide survey.

BACKGROUND: Although several studies on hepatitis B (HBV), C (HCV) and human immunodeficiency virus (HIV) infection have been conducted in Greece, little is known on the knowledge level of the Greek population towards these three infections. Our aim was to assess the knowledge level of the adult Greek general population about the HBV, HCV and HIV. METHODS: Data were derived from the first general population health survey, Hprolipsis. The sample was selected by multistage stratified random sampling. A standardized questionnaire was administered by trained interviewers during home visits. A knowledge score was constructed based on responses to 17 per infection selected items and categorized in three levels; high (12-17 correct replies) medium (6-11) and low (0-5). Among 8,341 eligible individuals, 6,006 were recruited (response rate: 72%) and 5,878 adults (≥ 18 years) were included in the analysis. The statistical analysis accounted for the study design. RESULTS: Only 30.4%, 21.6%, and 29.6% of the participants had a high overall knowledge level of HBV, HCV and HIV, respectively. These low percentages were mainly attributed to the high levels of misconception about transmission modes (65.9%, 67.2%, and 67.9%, respectively). Results showed that increasing age and living out of the big metropolitan cities were associated with decreased odds of having higher knowledge. Female gender, higher education level, higher monthly family income, higher medical risk score, history of testing and being born in Greece or Cyprus, were associated with increased odds of having higher knowledge. CONCLUSIONS: There are significant knowledge gaps in the Greek general population regarding modes of transmission, preventive measures and treatment availability for HBV, HCV and HIV. There is an urgent need for large scale but also localized awareness activities targeted to less privileged populations, to fill the gaps in knowledge and increase population engagement in preventive measures.

Effects of Social Distancing Measures during the First Epidemic Wave of Severe Acute Respiratory Syndrome Infection, Greece.

Greece imposed a nationwide lockdown in March 2020 to mitigate transmission of severe acute respiratory syndrome coronavirus 2 during the first epidemic wave. We conducted a survey on age-specific social contact patterns to assess effects of physical distancing measures and used a susceptible-exposed-infectious-recovered model to simulate the epidemic. Because multiple distancing measures were implemented simultaneously, we assessed their overall effects and the contribution of each measure. Before measures were implemented, the estimated basic reproduction number (R0) was 2.38 (95% CI 2.01-2.80). During lockdown, daily contacts decreased by 86.9% and R0 decreased by 81.0% (95% credible interval [CrI] 71.8%-86.0%); each distancing measure decreased R0 by 10%-24%. By April 26, the attack rate in Greece was 0.12% (95% CrI 0.06%-0.26%), one of the lowest in Europe, and the infection fatality ratio was 1.12% (95% CrI 0.55%-2.31%). Multiple social distancing measures contained the first epidemic wave in Greece.

Sexual Mixing and HIV Transmission Potential Among Greek Men Who have Sex with Men: Results from SOPHOCLES.

HIV incidence among men who have sex with men (MSM) in Greece remains unchanged despite effective response to a recent outbreak among people who inject drugs (PWID). Network factors are increasingly understood to drive transmission in epidemics. The primary objective of the study was to characterize MSM in Greece, their sexual behaviors, and sexual network mixing patterns. We investigated the relationship between serostatus, sexual behaviors, and self-reported sex networks in a sample of MSM in Athens, Greece, generated using respondent driven sampling. We estimated mixing coefficients (r) based on survey-generated egonets. Additionally, multiple logistic regression was used to estimate adjusted odds ratios (AOR) and to assess relationships between serostatus, sexual behaviors, and sociodemographic indicators. A sample of 1,520 MSM participants included study respondents (n = 308) and their network members (n = 1,212). Mixing based on serostatus (r = 0.12, σr = 0.09-0.15) and condomless sex (r = 0.11, σr = 0.07-0.14) was random. However, mixing based on sex-drug use was highly assortative (r = 0.37, σr = 0.32-0.42). This study represents the first analysis of Greek MSM sexual networks. Our findings highlight protective behavior in two distinct network typologies. The first typology mixed assortatively based on serostatus and sex-drug use and was less likely to engage in condomless sex. The second typology mixed randomly based on condomless sex but was less likely to engage in sex-drug use. These findings support the potential benefit of HIV prevention program scale-up for this population including but not limited to PrEP.

Food insecurity among people who inject drugs in Athens, Greece: a study in the context of ARISTOTLE programme.

OBJECTIVE: To measure the prevalence of food insecurity and explore related characteristics and behaviours among people who inject drugs (PWID). DESIGN: Cross-sectional analysis of a community-based programme for HIV infection among PWID (ARISTOTLE programme). Food insecurity was measured by the Household Food Insecurity Access Scale. Computer-assisted interviews and blood samples were also collected. SETTING: A fixed location in Athens Metropolitan Area, Greece, during 2012-2013. PARTICIPANTS: In total, 2834 unique participants with history of injecting drug use in the past 12 months were recruited over four respondent-driven sampling rounds (approximately 1400/round). RESULTS: More than 50 % of PWID were severely or moderately food insecure across all rounds. PWID were more likely to be severely food insecure if they were older than 40 years [adjusted OR (aOR): 1·71, 95 % CI: 1·33-2·19], were women (aOR: 1·49, 95 % CI: 1·17-1·89), from Middle East countries (aOR v. from Greece: 1·80, 95 % CI: 1·04-3·11), had a lower educational level (primary or secondary school v. higher education; aOR: 1·54, 95 % CI: 1·29-1·84), had no current health insurance (aOR: 1·45, 95 % CI: 1·21-1·73), were homeless (aOR: 17·1, 95 % CI: 12·3-23·8) or were living with another drug user (aOR: 1·55, 95 % CI: 1·26-1·91) as compared with those living alone or with family/friends. HIV-infected PWID were more likely to be severely food insecure compared with uninfected (59·0 % v. 51·0 %, respectively, P = 0·002); however, this difference was attributed to the confounding effect of homelessness. CONCLUSIONS: Moderate/severe food insecurity was a significant problem, reaching > 50 % in this sample of PWID and closely related to socio-demographic characteristics and especially homelessness.

Univariable associations between a history of incarceration and HIV and HCV prevalence among people who inject drugs across 17 countries in Europe 2006 to 2020 - is the precautionary principle applicable?

BackgroundPeople who inject drugs (PWID) are frequently incarcerated, which is associated with multiple negative health outcomes.AimWe aimed to estimate the associations between a history of incarceration and prevalence of HIV and HCV infection among PWID in Europe.MethodsAggregate data from PWID recruited in drug services (excluding prison services) or elsewhere in the community were reported by 17 of 30 countries (16 per virus) collaborating in a European drug monitoring system (2006-2020; n = 52,368 HIV+/-; n = 47,268 HCV+/-). Country-specific odds ratios (OR) and prevalence ratios (PR) were calculated from country totals of HIV and HCV antibody status and self-reported life-time incarceration history, and pooled using meta-analyses. Country-specific and overall population attributable risk (PAR) were estimated using pooled PR.ResultsUnivariable HIV OR ranged between 0.73 and 6.37 (median: 2.1; pooled OR: 1.92; 95% CI: 1.52-2.42). Pooled PR was 1.66 (95% CI 1.38-1.98), giving a PAR of 25.8% (95% CI 16.7-34.0). Univariable anti-HCV OR ranged between 1.06 and 5.04 (median: 2.70; pooled OR: 2.51; 95% CI: 2.17-2.91). Pooled PR was 1.42 (95% CI: 1.28-1.58) and PAR 16.7% (95% CI: 11.8-21.7). Subgroup analyses showed differences in the OR for HCV by geographical region, with lower estimates in southern Europe.ConclusionIn univariable analysis, a history of incarceration was associated with positive HIV and HCV serostatus among PWID in Europe. Applying the precautionary principle would suggest finding alternatives to incarceration of PWID and strengthening health and social services in prison and after release ('throughcare').

Similar risk of hepatocellular carcinoma during long-term entecavir or tenofovir therapy in Caucasian patients with chronic hepatitis B.

BACKGROUND & AIMS: A recent study in Asian patients with chronic hepatitis B (CHB) reported that the incidence of hepatocellular carcinoma (HCC) was lower in patients treated with tenofovir disoproxil fumarate (TDF) than entecavir (ETV), but this finding remains controversial. We aimed to identify any differences in HCC incidence, or other patient outcomes, between patients receiving TDF or ETV in the well monitored, multicenter European PAGE-B cohort. METHODS: We included 1,935 Caucasians with CHB, with or without compensated cirrhosis, treated with ETV (n = 772) or TDF (n = 1,163) monotherapy. Mean follow-up was 7.1 ± 3.0 years from ETV/TDF onset. RESULTS: The 5-year cumulative HCC incidence was 5.4% in ETV- and 6.0% in TDF-treated patients (log-rank, p = 0.321), with no significant difference in any patient subgroup (with or without cirrhosis, naïve or experienced to oral antiviral(s) [total, with or without cirrhosis]). In multivariable Cox regression analyses, the hazard of HCC was similar between ETV- and TDF-treated patients after adjustment for several HCC risk factors. ETV- and TDF-treated patients had similar rates of on-therapy biochemical and virological remission, HBsAg loss, liver transplantation and/or death. Elastographic reversion of cirrhosis at year 5 (liver stiffness <12 kPa) was observed in 245/347 (70.6%) patients with pretreatment cirrhosis, being more frequent in TDF- than ETV- treated patients (73.8% vs. 61.5%, p = 0.038). CONCLUSION: In Caucasian patients with CHB, with or without cirrhosis, long-term ETV or TDF monotherapy is associated with similar HCC risk, rates of biochemical/virological remission, HBsAg loss and liver transplantation or death, but elastographic reversion of cirrhosis at year 5 was more frequent with TDF. LAY SUMMARY: In a large cohort of Caucasians with chronic hepatitis B treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) monotherapy, cumulative rates of hepatocellular carcinoma did not differ (up to 12 years). Nor did rates of biochemical/virological remission, HBsAg loss and liver transplantation or death. However, elastographic reversion of cirrhosis at year 5 was more frequent in TDF- than ETV-treated patients with pretreatment cirrhosis.

Hepatocellular carcinoma prediction beyond year 5 of oral therapy in a large cohort of Caucasian patients with chronic hepatitis B.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) may develop in patients with chronic hepatitis (CHB) even after 5 years of oral therapy and cannot be easily predicted. We assessed predictors of HCC development and the need for HCC surveillance in this setting. METHODS: Of 1,951 adult Caucasians with CHB included in the PAGE-B cohort, 1,427 (73%) had completed >5 years of follow-up under therapy without developing HCC by year 5. Median follow-up was 8.4 years from treatment onset. Points-based risk scores were developed to predict HCC risk after year 5. RESULTS: In years 5-12, HCC was diagnosed in 33/1,427 (2.3%) patients with cumulative incidences of 2.4%, 3.2% and 3.8% at 8, 10 and 12 years, respectively. Older age or age >50 years, baseline cirrhosis and liver stiffness (LSM) ≥12 kPa at year 5 were independently associated with increased HCC risk. The HCC incidence was lower in non-cirrhotics than cirrhotics at baseline with year-5 LSM <12; among cirrhotics at baseline, it was lower in those with year-5 LSM <12 than ≥12 kPa. CAGE-B score was based on age at year 5 and baseline cirrhosis in relation to LSM at year 5 and SAGE-B score was based only on age and LSM at year 5 (c-index = 0.809-0.814, 0.805-0.806 after bootstrap validation). Both scores offered 100% negative predictive values for HCC development in their low risk groups. CONCLUSIONS: In Caucasians with CHB, the HCC risk after the first 5 years of antiviral therapy depends on age, baseline cirrhosis status and LSM at year 5. CAGE-B and particularly SAGE-B represent simple and reliable risk scores for HCC prediction and surveillance beyond year 5 of therapy. LAY SUMMARY: In Caucasians with chronic hepatitis B, the risk of hepatocellular carcinoma after the first 5 years of entecavir or tenofovir therapy depends on age, baseline cirrhosis status and liver stiffness at year 5, which can provide simple and reliable risk scores for hepatocellular carcinoma prediction and surveillance beyond year 5. In patients with cirrhosis at baseline, liver stiffness <12 kPa at year 5 is associated with lower HCC risk, but surveillance may be still required.

aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is the leading cause of death in patients with chronic hepatitis. In this international collaboration, we sought to develop a global universal HCC risk score to predict the HCC development for patients with chronic hepatitis. METHODS: A total of 17,374 patients, comprising 10,578 treated Asian patients with chronic hepatitis B (CHB), 2,510 treated Caucasian patients with CHB, 3,566 treated patients with hepatitis C virus (including 2,489 patients with cirrhosis achieving a sustained virological response) and 720 patients with non-viral hepatitis (NVH) from 11 international prospective observational cohorts or randomised controlled trials, were divided into a training cohort (3,688 Asian patients with CHB) and 9 validation cohorts with different aetiologies and ethnicities (n = 13,686). RESULTS: We developed an HCC risk score, called the aMAP score (ranging from 0 to 100), that involves only age, male, albumin-bilirubin and platelets. This metric performed excellently in assessing HCC risk not only in patients with hepatitis of different aetiologies, but also in those with different ethnicities (C-index: 0.82-0.87). Cut-off values of 50 and 60 were best for discriminating HCC risk. The 3- or 5-year cumulative incidences of HCC were 0-0.8%, 1.5-4.8%, and 8.1-19.9% in the low- (n = 7,413, 43.6%), medium- (n = 6,529, 38.4%), and high-risk (n = 3,044, 17.9%) groups, respectively. The cut-off value of 50 was associated with a sensitivity of 85.7-100% and a negative predictive value of 99.3-100%. The cut-off value of 60 resulted in a specificity of 56.6-95.8% and a positive predictive value of 6.6-15.7%. CONCLUSIONS: This objective, simple, reliable risk score based on 5 common parameters accurately predicted HCC development, regardless of aetiology and ethnicity, which could help to establish a risk score-guided HCC surveillance strategy worldwide. LAY SUMMARY: In this international collaboration, we developed and externally validated a simple, objective and accurate prognostic tool (called the aMAP score), that involves only age, male, albumin-bilirubin and platelets. The aMAP score (ranged from 0 to 100) satisfactorily predicted the risk of hepatocellular carcinoma (HCC) development among over 17,000 patients with viral and non-viral hepatitis from 11 global prospective studies. Our findings show that the aMAP score had excellent discrimination and calibration in assessing the 5-year HCC risk among all the cohorts irrespective of aetiology and ethnicity.

High-risk behaviors and their association with awareness of HIV status among participants of a large-scale prevention intervention in Athens, Greece.

BACKGROUND: Aristotle was a seek-test-treat intervention during an outbreak of human immunodeficiency virus (HIV) infection among people who inject drugs (PWID) in Athens, Greece that started in 2011. The aims of this analysis were: (1) to study changes of drug injection-related and sexual behaviors over the course of Aristotle; and (2) to compare the likelihood of risky behaviors among PWID who were aware and unaware of their HIV status. METHODS: Aristotle (2012-2013) involved five successive respondent-driven sampling rounds of approximately 1400 PWID each; eligible PWID could participate in multiple rounds. Participants were interviewed using a questionnaire, were tested for HIV, and were classified as HIV-positive aware of their status (AHS), HIV-positive unaware of their status (UHS), and HIV-negative. Piecewise linear generalized estimating equation models were used to regress repeatedly measured binary outcomes (high-risk behaviors) against covariates. RESULTS: Aristotle recruited 3320 PWID (84.5% males, median age 34.2 years). Overall, 7110 interviews and blood samples were collected. The proportion of HIV-positive first-time participants who were aware of their HIV infection increased from 21.8% in round A to 36.4% in the last round. The odds of dividing drugs at least half of the time in the past 12 months with a syringe someone else had already used fell from round A to B by 90% [Odds Ratio (OR) (95% Confidence Interval-CI): 0.10 (0.04, 0.23)] among AHS and by 63% among UHS [OR (95% CI): 0.37 (0.19, 0.72)]. This drop was significantly larger (p = 0.02) among AHS. There were also decreases in frequency of injection and in receptive syringe sharing in the past 12 months but they were not significantly different between AHS (66 and 47%, respectively) and UHS (63 and 33%, respectively). Condom use increased only among male AHS from round B to the last round [OR (95% CI): 1.24 (1.01, 1.52)]. CONCLUSIONS: The prevalence of risky behaviors related to drug injection decreased in the context of Aristotle. Knowledge of HIV infection was associated with safer drug injection-related behaviors among PWID. This highlights the need for comprehensive interventions that scale-up HIV testing and help PWID become aware of their HIV status.