Successful therapy with tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) does not guarantee amelioration of liver damage assessing by transient elastography. A retrospective - prospective multicenter study.

BACKGROUND: Preventing disease progression and viral suppression are the main goals of antiviral therapy in chronic hepatitis B (CHB). Liver stiffness measurement (LSM) by transient elastography is a reliable non-invasive method to assess liver fibrosis in patients with CHB. Our aim was to explore factors that may affect changes in LSMs during long term tenofovir (TDF) monotherapy in a well characterized cohort of patients with compensated CHB. METHODS: We analyzed serial LSMs in 103 adult patients with CHB who were on TDF monotherapy and had at least three LSMs over a period of 90 months. RESULTS: Twenty-five (24%) patients had advanced fibrosis at baseline. A significant decline in mean LSM between baseline and last visit (8.7 ± 6.2 kPa vs. 6.7 ± 3.3, p = 10- 3) was observed. Twenty-four (23%) patients had progression of liver fibrosis with mean increase in liver stiffness of 2.8 kPa (range: 0.2-10.2 kPa). Multivariate analysis showed that BMI ≥ 25 (OR, 0.014; 95% CI, 0.001-0.157; p = 0.001) and advanced fibrosis (OR, 5.169; 95% CI, 1.240-21.540; p = 0.024) were independently associated with a fibrosis regression of > 30% of liver stiffness compared to baseline value. CONCLUSIONS: In CHB patients TDF monotherapy resulted in liver fibrosis regression, especially in patients with advanced fibrosis. Despite the successful antiviral effect of TDF, 1 out of 4 patients had liver fibrosis progression. Obesity and advanced fibrosis at baseline were independently associated with significant liver fibrosis regression.

HERACLIS-HDV cohort for the factors of underdiagnosis and prevalence of hepatitis D virus infection in HBsAg-positive patients.

BACKGROUND AND AIMS: Hepatitis D virus (HDV) underdiagnosis remains common. We assessed the HDV screening and prevalence rates in HBsAg-positive patients seen at tertiary liver centres throughout Greece as well as factors affecting HDV diagnosis. METHODS: All adult HBsAg-positive patients seen within the last 5 years were included. Non-screened patients who visited or could be recalled to the clinics over a 6-month period were prospectively tested for anti-HDV. RESULTS: Of 5079 HBsAg-positive patients, 53% had anti-HDV screening (41% before and 12% after study initiation). Pre-study (8%-88%) and total screening rates (14%-100%) varied widely among centres. Screening rates were associated with older age, known risk group, elevated ALT, centre location and size and period of first visit. Anti-HDV prevalence was 5.8% without significant difference in patients screened before (6.1%) or after study initiation (4.7%, p = 0.240). Anti-HDV positivity was associated with younger age, parenteral drug use, born abroad, advanced liver disease and centre location. Overall, HDV RNA detectability rate was 71.6% being more frequent in anti-HDV-positive patients with elevated ALT, advanced liver disease and hepatitis B therapy. CONCLUSIONS: Anti-HDV screening rates and recall capabilities vary widely among Greek liver clinics being higher in HBsAg-positive patients of known risk group with active/advanced liver disease seen at smaller centres, while non-medical factors are also important. Anti-HDV prevalence varies throughout Greece being higher in patients born abroad with younger age, parenteral drug use and advanced liver disease. Viremia is more frequently but not exclusively detected in anti-HDV-positive patients with elevated ALT and advanced liver disease.

Anticoagulation in Patients with Liver Cirrhosis: Friend or Foe?

Concepts regarding the status of the coagulation process in cirrhosis are rapidly changing. Instead of a disease defined by excessive bleeding risk, recent studies have shown cirrhosis to be associated with a fragile state of rebalanced hemostasis, easily swayed in either direction, thrombosis, or bleeding. These findings, combined with the ever-growing population of patients with cirrhosis with an indication for anticoagulation (AC) and the emergence of the non-alcoholic fatty liver disease epidemic, have prompted a reexamination of the use of AC in patients with cirrhosis, either as a treatment for a concurrent thrombotic disorder or even as a possible therapeutic option that could influence the natural course of the disease and its complications. In recent years, a significant number of studies have been formulated to evaluate these possibilities. These studies evaluated, among others, the efficacy and safety of AC in thrombotic disorders or thrombotic complications of cirrhosis, its effect on survival, and the class of anticoagulants which is more suitable for patients with cirrhosis, depending on disease severity. This review examines recent studies investigating the use of AC in patients with cirrhosis and attempts to provide a simple guide for clinicians regarding the use of AC in patients with cirrhosis and its potential risks and benefits.

Peripheral endothelial and microvascular damage in liver cirrhosis: A systematic review and meta-analysis.

OBJECTIVE: This is the first systematic review and meta-analysis of studies using any available functional method to examine differences in peripheral endothelial function between cirrhotic and non-cirrhotic individuals. METHODS: Literature search involved PubMed, Web-of-Science, and Scopus databases, as well as gray literature sources. We included studies in adult subjects evaluating endothelial function with any semi-invasive or non-invasive functional method in patients with and without liver cirrhosis. RESULTS: From 3378 records initially retrieved, 15 studies with a total of 570 participants were included in the final quantitative meta-analysis. In six studies examining endothelial function with flow-mediated-dilatation, no differences between patients with cirrhosis and controls were evident (WMD: 1.33, 95%CI [-2.87, 5.53], I2  = 97%, p < .00001). Among studies assessing differences in endothelial-dependent or endothelial-independent vasodilation with venous-occlusion-plethysmography, there were no significant differences between the two groups. When pooling all studies together, regardless of the technique used, no significant difference in endothelial function between cirrhotic patients and controls was observed(SMD: 0.79, 95%CI[-0.04, 1.63], I2  = 94%, p < .00001). CONCLUSIONS: No differences in peripheral endothelial function assessed with semi-invasive or non-invasive functional methods exist between cirrhotic and non-cirrhotic subjects. The increasing co-existence of cardiovascular risk factors leading to impaired vascular reactivity in cirrhotic patients may partly explain these findings.

Randomized clinical trials towards a single-visit cure for chronic hepatitis C: Oral GSK2878175 and injectable RG-101 in chronic hepatitis C patients and long-acting injectable GSK2878175 in healthy participants.

Single-visit cures for chronic hepatitis C are lacking. We conducted two clinical studies towards the goal of developing a regimen for single-visit cure. In a randomized, open-label, Phase 2 study (RG101-04), investigators enrolled 26 adult chronic hepatitis C patients to evaluate safety and efficacy of single subcutaneous injection of RG-101 (4 mg/kg) and daily oral tablets of GSK2878175 (20 mg) for 6, 9 or 12 weeks. In another randomized, double-blind, single dose Phase 1 study (RG101-06), investigators enrolled 18 healthy men to assess safety and PK of GSK2878175 long-acting injectable at 100, 200 or 400 mg. In RG101-04, SVR48 rates were 50%, 56% and 89%, for the 6, 9 and 12 weeks treatment arms, respectively. All AEs were mild or moderate in severity (≤Grade 2). In RG101-06 at 400 mg, the mean duration of GSK2878175 plasma levels above in vitro therapeutic concentrations for GT1b was 41 days. All AEs were Grade 2 or less. In conclusion, single injection of RG-101 combined with 12 weeks of GSK2878175 oral tablets was generally well tolerated and resulted in high SVR rates in chronic hepatitis C patients. Single injections of GSK2878175 long-acting injectable were also well tolerated; however, higher doses would be required if used in combination with RG-101 to achieve the SVR rates observed in the oral combination study to enable a single-visit curative regimen.

Treatment of chronic hepatitis C with direct-acting antivirals in patients with ß-thalassaemia major and advanced liver disease.

Interferon-based regimens for chronic hepatitis C (CHC) were often deferred in patients with ß-thalasaemia major (ß-TM) due to poor efficacy and tolerance. Current guidelines recommend direct-acting antivirals (DAAs) for these patients. The aim of this study was to assess the safety and efficacy of DAAs in patients with ß-TM and advanced liver disease due to CHC. Patients were recruited from eight liver units in Greece. The stage of liver disease was assessed using transient elastography and/or liver histology. Five regimens were used: sofosbuvir (SOF) + ribavirin (RBV); SOF + simeprevir ± RBV; SOF + daclatasvir ± RBV; ledipasvir/SOF ± RBV and ombitasvir/paritaprevir-ritonavir + dasabuvir ± RBV. Sixty-one patients (median age 43 years) were included. The majority of patients was previously treated for hepatitis C (75%) and had cirrhosis (79%). Viral genotype distribution was: G1a: n = 10 (16%); G1b: n = 22 (36%); G2: n = 2 (3%); G3: n = 14 (23%); G4: n = 13 (22%). The predominant chelation therapy was a combination of deferoxamine and deferiprone (35%). Overall sustained virological response rates were 90%. All treatment regimens were well tolerated and no major adverse events or drug-drug interactions were observed. Approximately half of the patients who received RBV (7/16, 44%) had increased needs for blood transfusion. Treatment of CHC with DAAs in patients with ß-TM and advanced liver disease was highly effective and safe.

Comparison of creatinine and cystatin formulae with 51 Chromium-ethylenediaminetetraacetic acid glomerular filtration rate in patients with decompensated cirrhosis.

BACKGROUND AND AIM: Evaluation of renal function, that is, glomerular filtration rate (GFR), has become very important, but conventional mathematical formulae for GFR assessment are inaccurate in patients with cirrhosis. The aim of the present study was to compare serum creatinine (sCr)-based and serum cystatin C (cysC)-based estimated GFR (eGFR) formulae with 51 Chromium-ethylenediaminetetraacetic acid GFR (51 Chr-GFR) in patients with stable decompensated cirrhosis. METHODS: In 129 Caucasian patients with decompensated cirrhosis, we assessed sCr-based GFRs [Modification of Diet in Renal Disease and chronic kidney disease-epidemiology (CKD-EPI)-sCr formulae], cysC-based GFRs [Hoek, Larsson, and CKD-EPI-cysC equations], and the mathematical formulae, which combined both sCr and cysC [i.e. CKD-EPI-sCr-cysC and the specific for cirrhotics formula recently proposed by Mindikoglu et al. (Mindikoglu-eGFR)]. Multivariate linear regression analysis was used for GFR predictors in our cohort. RESULTS: The correlations between 51 Chr-GFR and all mathematical formulae were good (Spearman r2 > 0.68, P < 0.001). Modification of Diet in Renal Disease and CKD-EPI-sCr had lower bias (6.6 and -4.8, respectively), compared with the other eGFRs, while Mindikoglu-eGFR and CKD-EPI-sCr-cysC formulae had greater precision (17.1 and 17.3, respectively), compared with the other eGFRs. CKD-EPI-sCr and Mindikoglu-eGFR had higher accuracy (39% and 41%, respectively), compared with the other eGFRs. The factors independently associated with the 51 Chr-GFR were age, cysC, and sCr, and the new derived formula had lower bias (0.89) and similar precision (17.2) and accuracy (41%) with Mindikoglu-eGFR formula. CONCLUSION: The specific mathematical formulae derived from patients with cirrhosis seem to provide superior assessment of renal function, compared with the conventional used sCr-based and cysC-based formulae.

Relative Adrenal Insufficiency is Associated with the Clinical Outcome in Patients with Stable Decompensated Cirrhosis.

BACKGROUND: The clinical impact of relative adrenal insufficiency (AI) on patients with stable decompensated cirrhosis (DeCi) has not been yet elucidated. AIM: Explore the association between AI and outcome [death or liver transplantation (LT)] in patients with DeCi. MATERIAL AND METHODS: Patients with DeCi presenting no active complication have been included. Clinical and laboratory data, including serum levels of corticosteroid-binding globulin (CBG), interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNFα) were recorded in each participant. Salivary cortisol (SC) and serum total cortisol (STC) were assessed at (T0) and 1 h (T60) after intravenous injection of 250 µg corticotropin. RESULTS: 113 consecutive patients were totally tested. Median SC was 3.9 ng/mL and 15.5 ng/mL and median STC was 10.7 µg/dL and 22.7 µg/dL at T0 and T60 respectively. The patients with AI [group 1, n = 34 (30%)] had significantly lower systolic blood pressure (106 ± 12 vs. 113 ± 13 mmHg, p = 0.05), serum sodium (133 ± 7 vs. 137 ± 12 mEq/ L, p = 0.04), HDL (29.9 ± 14 vs. 38.6 ± 18 mg/dL, p = 0.034) and albumin (2.7 ± 0.5 vs. 3.1 ± 0.5 g/dL, p = 0.002), but higher direct bilirubin (median: 1.6 vs. 0.8 mg/dL, p = 0.029) compared to those without AI [group 2, n = 79 (70%)]. Moreover, group 1 patients presented more frequently past history of spontaneous bacterial peritonitis (SBP) [10/34 (29.4%) vs. 6/79 (7.5%), p = 0.002]. AI was significantly associated with death [HR = 2.65, 95% C.I.: 1.55 - 4.52, p = 0.003 over a follow up period of 12 (6-48) months.] Conclusions. The presence of AI in patients with stable DeCi predispose to obvious clinical implications since it is associated with circulatory dysfunction, previous history of SBP and worse survival.

Diastolic dysfunction is associated with low urinary sodium excretion in patients with decompensated cirrhosis.

BACKGROUND/AIM: The pathogenesis and the clinical impact of diastolic dysfunction (DD) in cirrhosis remain unclear. Our aim was to investigate the factors significantly associated with the presence of DD in patients with decompensated cirrhosis on the waiting list for liver transplantation. MATERIAL AND METHODS: consecutive patients with decompensated cirrhosis, who admitted for transplant assessment, were prospectively evaluated. We assessed the independent factors associated with the presence of DD, while their discriminative ability was evaluated by AUC curve. The diagnosis of DD was based on Doppler echocardiography and classified into three categories according to the current guidelines. RESULTS: we evaluated 115 consecutive patients. Sixty six patients (57.3%-group 1) had DD and 49 (42.7%-group 2) had not DD. The 2 groups had similar Child-Pugh/MELD scores and survival. In multivariable logistic regression analysis, pulse rate (OR: 1.082, 95% CI: 1.03-1.15, p = 0.004), and UNa24h (OR: 0.98, 95% CI: 0.97- 0.99, p = 0.004) were the only variables independently associated with the presence of DD. In the subgroup of consecutive patients (n = 31) with evaluation of cytokines, those (n = 22) with DD, compared to those (n = 9) without DD, had significantly higher levels of inteleukin-6 [145 (45-2000) vs. 56 (10-149)pg/mL, p = 0.043]. CONCLUSIONS: We found that DD was independently associated with lower 24-hour urine sodium. Although no correlation was found between DD and severity of liver disease or survival, further studies are needed for final conclusions.

On-treatment prediction of sustained response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B patients.

BACKGROUND & AIMS: We assessed predictors of response in HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a in routine clinical practice. METHODS: Ninety-five HBeAg-negative patients received peginterferonalfa-2a for 48 weeks and were followed-up for 48 weeks post-treatment. Serum HBsAg and HBV DNA levels were monitored during and after therapy with valid commercial assays. Sustained response (SR) was defined as HBV DNA <2000 IU/ml at study week 96. RESULTS: Twenty-two patients (23%) achieved SR and nine (9.5%) lost HBsAg. HBsAg decline was more profound in patients with SR. HBsAg decline ≥10% from baseline to week 24 was significantly associated with SR [81% (17/21) vs 37% (21/57); Odds ratio: 7.286 (2.162-24.552), P = 0.001]. The PARC rule (no decrease in HBsAg and <2 log drop in HBV DNA at week 12) was evaluated in a subset of 47 patients. Among eight patients who fulfilled the PARC rule, none achieved SR. Of the 39 patients who did not fulfil the PARC rule, 24 (62%) had HBsAg decline of ≥10% at week 24 (12 achieved SR) and 15 (38%) had HBsAg decline of <10% (1 achieved SR; negative predictive value: 93%). CONCLUSIONS: In HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a, HBsAg decline >10% at 24 weeks is significantly associated with SR. The combination of the PARC rule and week 24 decline in HBsAg can identify almost two-thirds of patients who are unlikely to achieve SR. Clinicaltrials.gov identifier: NCT01283074.

A global view of hepatitis C: physician knowledge, opinions, and perceived barriers to care.

UNLABELLED: Chronic infection with the hepatitis C virus (HCV) is a leading cause of global morbidity and mortality. Although recent advances in antiviral therapy have led to significant improvements in treatment response rates, only a minority of infected patients are treated. Multiple barriers may impede the delivery of HCV therapy. The aim of this study was to identify perceived barriers to care, knowledge, and opinions among a global sample of HCV treatment providers. An international, multidisciplinary survey of HCV treatment providers was conducted. Each physician responded to a series of 214 questions concerning his or her practice characteristics, opinions regarding the state of HCV care, knowledge regarding HCV treatment, and perception of treatment barriers. A total of 697 physicians from 29 countries completed the survey. Overall, physicians viewed patient-level barriers as most significant, including fear of side effects and concerns regarding treatment duration and cost. There were distinct regional variations, with Central and Eastern European physicians citing government barriers as most important. In Latin America, the Middle East, and Africa, payer-level barriers, including lack of treatment coverage, were prominent. Overall, the perception of barriers was strongly associated with physician knowledge, experience, and region of origin, with the fewest barriers reported by Nordic physicians and the most reported by Middle Eastern and African physicians. Globally, physicians demonstrated deficits in basic treatment principles, including the role of viral kinetics and the management of treatment nonresponders. Two thirds of surveyed physicians believed that patients do not have adequate access to providers in their community. CONCLUSION: Barriers to HCV treatment vary globally, though patient-level factors are viewed as most significant by treating physicians. Efforts to improve awareness, education, and specialist availability are needed.

New nucleos(t)ide analogue monoprophylaxis after cessation of hepatitis B immunoglobulin is effective against hepatitis B recurrence.

New nucleos(t)ide agents (NAs) [entecavir (ETV) and tenofovir (TDF)] have made hepatitis B immunoglobulin (HBIG)-sparing protocols an attractive approach against hepatitis B virus (HBV) recurrence after liver transplantation (LT). Twenty-eight patients transplanted for HBV cirrhosis in our centre were prospectively evaluated. After LT, each patient received HBIG (1000 IU IM/day for 7 days and then monthly for 6 months) plus ETV or TDF and then continued with ETV or TDF monoprophylaxis. All patients had undetectable HBV DNA at the time of LT, and they were followed up with laboratory tests including glomerular filtration rate (GFR) after LT. All patients (11 under ETV and 17 under TDF) remained HBsAg/HBV DNA negative during the follow-up period [median: 21 (range 9-43) months]. GFR was not different between TDF and ETV groups of patients at 6 and 12 months and last follow-up (P value >0.05 for all comparisons). The two groups of patients were similar regarding their ratio of maximum rate of tubular phosphate reabsorption to the GFR (TmP/GFR). In conclusion, in this prospective study, we showed for the first time that maintenance therapy with ETV or TDF monoprophylaxis after 6 months of low-dose HBIG plus ETV or TDF after LT is highly effective and safe.

Liver disease in patients with transfusion-dependent ß-thalassemia: The emerging role of metabolism dysfunction-associated steatotic liver disease.

In this Editorial, we highlight the possible role that metabolism dysfunction-associated steatotic liver disease (MASLD) may play in the future, regarding liver disease in patients with transfusion-dependent ß-thalassemia (TDBT). MASLD is characterized by excessive accumulation of fat in the liver (hepatic steatosis), in the presence of cardiometabolic factors. There is a strong correlation between the occurrence of MASLD and insulin resistance, while its increased prevalence parallels the global epidemic of diabetes mellitus (DM) and obesity. Patients with TDBT need regular transfusions for life to ensure their survival. Through these transfusions, a large amount of iron is accumulated, which causes saturation of transferrin and leads to the circulation of free iron molecules, which cause damage to vital organs (primarily the liver and myocardium). Over the past, the main mechanisms for the development of liver disease in these patients have been the toxic effect of iron on the liver and chronic hepatitis C, for which modern and effective treatments have been found, resulting in successful treatment. Additional advances in the treatment and monitoring of these patients have led to a reduction in deaths, and an increase in their life expectancy. This increased survival makes them vulnerable to the onset of diseases, which until recently were mainly related to the non-thalassemic general population, such as obesity and DM. There is insufficient data in the literature regarding the prevalence of MASLD in this population or on the risk factors for its occurrence. However, it was recently shown by a study of 45 heavily transfused patients with beta-thalassemia (Padeniya et al, BJH), that the presence of steatosis is a factor influencing the value of liver elastography and thus liver fibrosis. These findings suggest that future research in the field of liver disease in patients with TDBT should be focused on the occurrence, the risk factors, and the effect of MASLD on these patients.

Helicobacter pylori infection diagnosis and management: current practices of Greek gastroenterologists.

Background: The diagnosis and management of Helicobacter pylori (H. pylori) infection vary significantly, depending on country, area, and specialty. The aim of this study was to record the current practices of Greek gastroenterologists in the screening and treatment of H. pylori infection. Method: An anonymous questionnaire consisting of 19 questions about the management of H. pylori infection was sent with the aid of the Hellenic Society of Gastroenterology to all members of the Society. Results: The questionnaire was completed by 180 gastroenterologists, with a response rate of 31.4%. Diagnostic tests to confirm H. pylori infection are ordered by >90% of the gastroenterologists for patients with current peptic ulcer disease, gastric lymphoma, family history of gastric cancer, and an endoscopic appearance suggestive of gastritis. Most gastroenterologists (55.8%) also tested for H. pylori in patients with gastroesophageal reflux disease (GERD). Histopathology was the most preferred (60.6%) method when testing was decided during endoscopy, while urea breath test was the most preferred method (67.8%) regardless of endoscopy. Most gastroenterologists use quadruple eradication regimens supported by international guidelines (90%), while 65.6% of the physicians answered that they systematically recommend the addition of probiotics to standard therapy. Most physicians (82.8%) answered that they always confirm the eradication of the pathogen. Conclusions: The majority of Greek gastroenterologists conform to the recommendations of international guidelines regarding the diagnosis and management of H. pylori infection, except for the screening of patients with GERD. A considerable number of doctors use probiotics in addition to standard therapy.

Efficacy of Newer Nucleos(t)ide Analogs After Hepatitis B Immunoglobulin Discontinuation Against Hepatitis B and D Recurrence in Liver Transplant Recipients.

BACKGROUND: The use of nucleos(t)ide analogs (NAs) with a high genetic barrier to resistance, namely entecavir and tenofovir, has improved the efficacy of antiviral prophylaxis against hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, the optimal duration and dosage of hepatitis B immunoglobulin (HBIG) administration, particularly in patients transplanted for HBV and hepatitis D virus (HDV) coinfection, remains controversial. METHODS: We evaluated 28 patients transplanted for HBV/HDV cirrhosis. After LT, each patient received a fixed scheme of low-dose HBIG plus NA for 6 mo post-LT and then continued with long-term NA prophylaxis (entecavir: 8, tenofovir: 20 patients). RESULTS: During 72 mo of follow-up, reappearance of hepatitis B surface antigen at low titers was observed in 1 (3.6%) patient at 33 mo after HBIG discontinuation, which became negative after a single dose of HBIG 1000 IU/L, whereas both serum HBV DNA and HDV RNA remained persistently undetectable and without any clinical or biochemical evidence of HBV/HDV recurrence. CONCLUSIONS: We showed for the first time the efficacy of a short, fixed scheme of low-dose HBIG plus NA followed by long-term NA monoprophylaxis against HBV/HDV recurrence after LT, although careful follow-up is needed after HBIG discontinuation, whereas further larger studies are needed to confirm these findings.

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.

COVID-19 and liver injury: An ongoing challenge.

The new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019, in Wuhan, China. The virus was rapidly spread worldwide, causing coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is presented, usually, with typical respiratory symptoms (i.e., dyspnea, cough) and fever, extrapulmonary manifestations are also encountered. Liver injury is a common feature in patients with COVID-19 and ranges from mild and temporary elevation of liver enzymes to severe liver injury and, even, acute liver failure. The pathogenesis of liver damage is not clearly defined; multiple mechanisms contribute to liver disorder, including direct cytopathic viral effect, cytokine storm and immune-mediated hepatitis, hypoxic injury, and drug-induced liver toxicity. Patients with underlying chronic liver disease (i.e., cirrhosis, non-alcoholic fatty liver disease, alcohol-related liver disease, hepatocellular carcinoma, etc.) may have greater risk to develop both severe COVID-19 and further liver deterioration, and, as a consequence, certain issues should be considered during disease management. The aim of this review is to present the prevalence, clinical manifestation and pathophysiological mechanisms of liver injury in patients with SARS-CoV-2 infection. Moreover, we overview the association between chronic liver disease and SARS-CoV-2 infection and we briefly discuss the management of liver injury during COVID-19.

Aspartate aminotransferase-to-platelet ratio index can predict the outcome in patients with stable decompensated cirrhosis.

Background: Platelet (PLT)-based biomarkers have been studied for the evaluation of liver fibrosis and cirrhosis. There are no data regarding their prognostic significance in decompensated cirrhosis. Methods: We studied 525 stable decompensated patients from the 2 Greek transplant centers. We measured PLT values, mean PLT volume (MPV), red cell distribution width, γ-globulins, and calculated PLT-based scores: aspartate aminotransferase-to-PLT ratio index (APRI), γ-globulin-to-PLT model, and γ-glutamyl transpeptidase-to-PLT ratio (GPR). Results: We followed our cohort for 12 (range: 1-84) months. Baseline mean model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores were 15±6 and 8±2, respectively. On univariate analysis, MPV/PLT (hazard ratio [HR] 3.75, 95% confidence interval [CI] 1-14.5; P=0.05), APRI (HR 1.03, 95%CI 1.006-1.06; P=0.016), GPR (HR 1.096, 95%CI 1.016-1.182; P=0.017) were significantly associated with our patients' outcome (survival vs. death or liver transplantation). In a multivariate model without MELD and CTP scores, APRI was the only significant factor associated with the outcome (HR 1.054, 95%CI 1.009-1.101; P=0.018). APRI had good discriminative ability for the outcome (area under the curve 0.723 vs. 0.675 and 0.656 for MELD and CTP scores, respectively). The optimal cutoff point was 1.3 (sensitivity 71%, specificity 65%). There were 200 patients (38%) with APRI scores <1.3 who had better survival than patients with APRI >1.3 (log rank 22.4, P<0.001). Conclusions: This study found a prognostic role for APRI in stable decompensated cirrhosis, regardless of the underlying etiology of chronic liver disease. This suggests new perspectives for PLT-based noninvasive scores to discriminate patients' outcomes.

A new outbreak of HIV infection among people who inject drugs during the COVID-19 pandemic in Greece.

BACKGROUND: Multiple HIV outbreaks have been recorded among people who inject drugs (PWID) since 2010. During an intervention for PWID in 2019-2021 in Thessaloniki, Greece, an increasing number of HIV cases was documented. Here, we provide an analysis of this new outbreak. METHODS: ALEXANDROS was a community-based program and participation included interviewing, rapid HIV/HCV tests, counselling and linkage to care. PWID were recruited through Respondent-Driven Sampling (RDS) in five sampling rounds. Crude and RDS-weighted HIV prevalence estimates were obtained. HIV incidence was estimated from data on 380 initially seronegative PWID with at least two tests. Multivariable Cox proportional hazards model was used to assess risk factors for HIV seroconversion. RESULTS: In total, 1,101 PWID were recruited. At first participation, 53.7% were current PWID, 20.1% homeless, 20.3% on opioid substitution treatment and 4.8% had received syringes in the past 12 months. HIV prevalence (95% CI) was 7.0% (5.6-8.7%) and an increasing trend was observed over 2019-2021 (p = 0.002). Two-thirds of the cases (67.5%) were new diagnoses. HIV incidence was 7.0 new infections/100 person-years (95% CI:4.8-10.2). Homelessness in the past 12 months (HR:2.68; 95% CI:1.24-5.81) and receptive syringe sharing (HR:3.86; 95% CI:1.75-8.51) were independently associated with increased risk of seroconversion. By the end of the program, 67.3% of the newly diagnosed cases initiated antiretroviral treatment. CONCLUSIONS: A new HIV outbreak among PWID was documented in Greece during the COVID-19 pandemic with homelessness and syringe sharing being associated with increased risk of HIV acquisition. Peer-driven programs targeting the population of high-risk underserved PWID can be used to early identify emerging outbreaks and to improve linkage to HIV care.