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.

High levels of all-cause mortality among people who inject drugs from 2018 to 2022.

BACKGROUND: Mortality among people who inject drugs (PWID) is high, with overdose and HIV infection being the main causes of death. In Greece, there have been no data on mortality, and two HIV outbreaks have been recorded in this population in the past decade. In this study, we aim to estimate the all-cause crude mortality rate and the standardised mortality ratio in this population during 2018-2022. METHODS: PWID recruited from two community-based programs in Athens and Thessaloniki during 2018-2021 were interviewed and tested for HIV/HCV. Data on vital status (deceased/alive) and date of death were obtained from death registries through December 31, 2022. All-cause crude mortality rates (CMR) and standardised mortality ratios (SMR) were estimated. Determinants of mortality were assessed using Cox proportional-hazards model. RESULTS: Of 2,530 participants, 301 died over 8,543 person-years (PYs) of follow-up. The CMR (95 % CI) was 3.52 (3.15-3.94) deaths per 100 PYs; 3.10 per 100 PYs (2.68-3.58) in Athens and 4.48 per 100 PYs (3.74-5.37) in Thessaloniki. An increasing trend in CMR was identified over 2018-2022 in Athens (from 2.90 to 4.11 per 100 PYs, 41.5 % increase, p = 0.018). The pooled SMR (95 % CI) was 15.86 (14.17-17.76) for both cities and was particularly increased in younger individuals, females, those injecting daily, not enrolled to opioid agonist treatment and HIV-infected individuals. Older age, living in Thessaloniki, Greek origin, homelessness, history of injection in the past 12 months, and HIV infection were independently associated with higher risk of death. CONCLUSION: Mortality among PWID in the two largest cities (Athens and Thessaloniki) in Greece in 2018-2022 was high, with the population in Thessaloniki being particularly affected. The increasing trend in mortality in Athens may reflect the long-term impact of the COVID-19 pandemic. Preventive programs such as take-home naloxone, screening and treatment for HIV, are urgently needed.

A cost of illness analysis of hepatocellular carcinoma for the Greek healthcare setting.

AIM: To estimate the cost per patient for hepatocellular carcinoma in Greece, a setting that is currently facing financial constraints. BACKGROUND: Hepatocellular carcinoma patient management strategies are associated with significant costs. Despite this, patient level data on healthcare resource use and cost-of-illness analyses of hepatocellular carcinoma remain rather scarce in the international literature. METHODS: 123 patients diagnosed with hepatocellular carcinoma and followed in a specialised clinic of a tertiary hospital in Greece formed the basis of the analysis. Detailed resource use data were derived from the medical records of each patient. Data were recorded from the first encounter of the patient with the facility until a fatal endpoint or until the last day of follow up. Patients that were lost to follow-up were excluded from the analysis. Calculations follow a third-party payer perspective, according to official prices and tariffs. RESULTS: The average cost per patient was estimated at 12,119.1 Euros (SD: 14,670.3) (21,375.1 PPP USD) for the average follow-up period and 10,241.5 Euros (18,063.5 PPP USD) per year. Median costs per month of follow-up according to underlying disease were 1,218.1, 1,376.8, 1,521.3 and 686.9 Euros (2,148.4, 2,428.3, 2,683.2 and 1,211.5 PPP USD) for patients with alcoholic steatohepatitis, hepatitis B, hepatitis C and non-alcoholic fatty liver disease, respectively. CONCLUSION: Hepatocellular carcinoma represents a heavy toll, both from the clinical as well as from the economic perspective, especially for a setting in "dire straits". Interventions towards reducing the incidence and, subsequently, the cost of HCC are imperative.

Sfrp5 associates with beta-cell function in humans.

BACKGROUND: Secreted frizzled-related protein (Sfrp)5 improves insulin sensitivity, but impairs beta-cell function in rodents. However, the relationship between Sfrp5, insulin sensitivity and secretion in humans is currently unclear. Therefore, the aim of the study was to characterize the associations between serum Sfrp5 and indices of insulin sensitivity and beta-cell function from dynamic measurements using oral glucose tolerance tests (OGTT) in humans. MATERIAL AND METHODS: This study enrolled 194 individuals with nonalcoholic fatty liver disease (NAFLD), who were diagnosed based on ultrasound and liver transaminases and underwent a frequent sampling 75-g OGTT. Fasting serum Sfrp5 was measured by ELISA. Associations were assessed with several indices of insulin sensitivity and beta-cell function derived from glucose, insulin and C-peptide concentrations during the OGTT. RESULTS: Circulating Sfrp5 associated inversely with the insulinogenic index based on C-peptide (rs = -0·244, P = 0·001), but not with the insulinogenic index based on insulin levels (rs = -0·007, P = 0·926) after adjustment for age, sex and body mass index. Sfrp5 inversely correlated only with QUICKI as a marker of insulin sensitivity in the model adjusted for age and sex (rs = -0·149, P = 0·039). These associations were not influenced by the additional adjustment for hepatic steatosis index. CONCLUSIONS: The inverse association of serum Sfrp5 with beta-cell function suggests a detrimental role of Sfrp5 for insulin secretion also in humans. The severity of NAFLD does not appear to affect this relationship. The weak association between serum Sfrp5 and insulin sensitivity was partially explained by body mass.

Serum Chemerin Concentrations Associate with Beta-Cell Function, but Not with Insulin Resistance in Individuals with Non-Alcoholic Fatty Liver Disease (NAFLD).

The novel adipokine chemerin has been related to insulin-resistant states such as obesity and non alcoholic fatty liver disease (NAFLD). However, its association with insulin resistance and beta cell function remains controversial. The main objective was to examine whether serum chemerin levels associate with insulin sensitivity and beta cell function independently of body mass index (BMI), by studying consecutive outpatients of the hepatology clinics of a European university hospital. Individuals (n=196) with NAFLD were stratified into persons with normal glucose tolerance (NGT; n=110), impaired glucose tolerance (IGT; n=51) and type 2 diabetes (T2D; n=35) and the association between serum chemerin and measures of insulin sensitivity and beta cell function as assessed during fasting and during oral glucose tolerance test (OGTT) was measured. Our results showed that serum chemerin positively associated with BMI (P=0.0007) and C peptide during OGTT (P<0.004), but not with circulating glucose, insulin, lipids or liver enzymes (all P>0.18). No BMI independent relationships of chemerin with fasting and OGTT derived measures of insulin sensitivity were found (P>0.5). Chemerin associated positively with fasting beta cell function as well as the OGTT derived insulinogenic index IGI_cp and the adaptation index after adjustment for age, sex and BMI (P=0.002-0.007), and inversely with the insulin/C peptide ratio (P=0.007). Serum chemerin neither related to the insulinogenic index IGI_ins nor the disposition index. In conclusion, circulating chemerin is likely linked to enhanced beta cell function but not to insulin sensitivity in patients with NAFLD.

Serum soluble urokinase plasminogen activator receptor as a screening test for the early diagnosis of hepatocellular carcinoma.

BACKGROUND & AIMS: Early detection of hepatocellular carcinoma (HCC) before imaging signs appear remains an unmet medical need. Former publications suggest that soluble urokinase plasminogen activator receptor (suPAR) is a non-specific cancer marker. suPAR was validated for the detection of patients at risk for HCC. METHODS: After an initial training set in 23 patients with extreme disease phenotypes, a prospective test set was conducted in which 267 patients without any imaging signs of HCC were followed up for 7 years. Patients were divided into low risk and high risk for the development of HCC by the EASL criteria. suPAR was measured at the beginning of follow-up. All patients underwent liver biopsy to define staging of fibrosis. The primary study endpoint was to define a cut-off among high-risk patients by the EASL criteria that can early discriminate those at real risk for HCC. RESULTS: The training set showed that suPAR was significantly greater in patients with HCC even in the absence of underlying cirrhosis compared with patients with minimal liver inflammation because of fatty deposition. The test set showed that among the high-risk EASL subgroup, suPAR more than 9.56 ng/ml had sensitivity 76.0%, specificity 90.4%, positive predictive value 54.3% and negative predictive value 96.2% for the development of HCC (odds ratio: 29.88, P < 0.0001). In survival analysis, patients with suPAR above 9.56 ng/ml at baseline progressed earlier to HCC. CONCLUSIONS: The specificity and negative predictive value make serum suPAR a potential screening tool for the early detection of HCC in patients with chronic liver disorders.

Predictors of impaired glucose regulation in patients with non-alcoholic fatty liver disease.

INTRODUCTION. Many patients with non-alcoholic fatty liver disease (NAFLD) have impaired glucose regulation or type 2 diabetes mellitus (DM). We investigated characteristics of NAFLD patients associated with hyperglycemia. METHODS. During a 2-hour oral glucose tolerance test (OGTT), serum glucose and insulin were measured in 152 NAFLD patients. RESULTS. 48.7% of NAFLD patients had hyperglycemia. Age (odds ratio (OR) = 1.08, 95% confidence interval (CI): 1.03-1.13), body mass index (BMI) (OR = 1.12, 95% CI: 1.01-1.25), and lower high-density lipoprotein cholesterol (HDL-C) (OR = 0.95, 95% CI: 0.92-0.98) proved to be independent predictors of hyperglycemia. After OGTT, 30 min insulin was lower in hyperglycemic patients (74.2 ± 49.7 versus 94.5 ± 53.9 µIU/mL, P = 0.02), while 90 min insulin (170.1 ± 84.6 versus 122.9 ± 97.7 µU/mL, P = 0.01) and 120 min insulin (164.0 ± 101.2 versus 85.3 ± 61.9 µIU/mL, P < 0.01) were higher. CONCLUSIONS. NAFLD patients with higher BMI, lower HDL-C, or older age were more likely to have impaired glucose metabolism. An OGTT could be of value for early diagnosis of DM among this population.

Female sexual dysfunction in essential hypertension: a common problem being uncovered.

OBJECTIVES: Female sexual dysfunction (FSD) is increasingly attracting more scientific and public interest, and represents a poorly investigated issue in patients with essential hypertension. We evaluated the prevalence of sexual dysfunction in hypertensive women compared with normotensive women according to age, hypertension severity, hypertension duration, and antihypertensive treatment. METHODS: The study population consisted of consecutive, sexually active women attending an outpatient hypertension clinic. The Female Sexual Function Index (FSFI questionnaire) was used to evaluate FSD. Univariate and multivariate analyses were used to evaluate predictors of FSD. RESULTS: Four hundred and seventeen women were studied. From them, 216 women had arterial hypertension (136 treated, 80 untreated) and 201 were normotensive. Sexual dysfunction was found in 42.1% of hypertensive women compared with 19.4% of normotensive women (odds ratio, 3.2; 95% confidence interval, 1.9-4.7; P < 0.001). Systolic blood pressure levels were significantly related to FSFI score (r = -0.67, P < 0.001). Successful control of hypertension was related to lower prevalence of FSD. Increasing age (beta = -0.187, P = 0.001), increasing systolic blood pressure (beta = -0.687, P < 0.001), and beta-blocker administration (beta = -0.162, P = 0.001) were significant predictors of sexual dysfunction in this patient population. CONCLUSIONS: FSD is more prevalent in women with essential hypertension compared with women with normal blood pressure, and its prevalence declines with adequate blood pressure control. Adequate control of hypertension with medication not affecting sexual function can have a great impact on the quality of life of hypertensive patients. Physicians should recognize and properly manage FSD in hypertensive women.

Cholestatic liver injury after glimepiride therapy.

Drug induced hepatotoxicity has been reported infrequently with sulfonylureas. For glimepiride, a second-generation sulfonylurea there is no report of hepatotoxicity in English literature. A patient with non-insulin-dependent diabetes mellitus who developed cholestatic liver injury soon after initiation of glimepiride therapy is presented. Complete work-up disclosed no other cause for hepatotoxicity including negative serological results for viral hepatitis. Liver biopsy was consistent with drug-induced cholestasis. The patient recovered 50 days after stopping glimepiride with no further recurrences.