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Abstract 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.

Background and Objectives: Specificity and reliability issues of the current cortisol assessment methods lead to limitations on the accurate assessment of relative adrenal insufficiency. Although free cortisol provides a more accurate evaluation of adrenal cortisol production, the expense and time-consuming nature of these assays make them impractical for routine use. Research has, thus, focused on alternative methods, such as indirectly measuring free cortisol using Coolens’ equation or directly assessing salivary cortisol concentration, which is considered a more favorable approach despite associated challenges like sampling issues and infection risks. The aim of this study was to explore correlations between 24 h urinary free cortisol (UFC), free plasma cortisol, serum total cortisol, and salivary cortisol as potential reliable indices of free cortisol in the setting of variceal bleeding. Additionally, we assessed the predictive value of UFC for 6-week mortality and 5-day treatment failure in patients with liver cirrhosis and variceal bleeding. Materials and Methods: A total of 40 outpatients with liver cirrhosis and variceal bleeding were enrolled. Free cortisol levels in serum, saliva, and urine were assessed using the electrochemiluminescence immunoassay method. For the measurement of plasma-free cortisol, a single quadrupole mass spectrometer was employed. The quantification of free cortisol was fulfilled by analyzing the signal response in the negative ESI-MS mode. Results: UFC was significantly correlated to free plasma cortisol. Negative correlations were demonstrated between UFC, the Child–Pugh (CP) score, and C reactive protein (CRP) levels. In the multivariate analysis, CP stage C was associated with 6-week mortality risk and portal vein thrombosis with 5-day treatment failure using Cox regression and binary logistic regression analyses, respectively. Patients who experienced rebleeding, infection, or death (or any combination of these events) presented with lower levels of UFC. Conclusions: This study suggests that low levels of UFC may impose a risk factor for patients with liver cirrhosis and variceal bleeding. The use of UFC as an index of adrenal cortisol production in variceal bleeding warrants further investigation.

Background: Vitamin D and its receptor (VDR) exert important immunoregulatory functions that contribute to liver homeostasis. The aim of this study was to investigate the influence of FokI, ApaI, BsmI and TaqI VDR polymorphisms on cirrhosis development and laboratory variables in patients with chronic hepatitis C (CHC)., Methods: A total of 48 patients were enrolled in this retrospective, observational study and underwent genotype analysis; their medical records were examined to obtain relevant data., Results: The cumulative rate of progression to cirrhosis during the course of CHC was 31.3% after a median period of 11 years from diagnosis. Importantly, in multivariate analysis, FokI ff (adjusted hazard ratio [aHR] 13.6, 95% confidence interval [CI] 2.51-73.73; P=0.002) and ApaI aa (aHR 4.69, 95%CI 1.13-19.43; P=0.033) genotypes were independently associated with progression to cirrhosis. The presence of the aa genotype was also associated with higher liver stiffness measurements measured by transient elastography compared to the AA/Aa genotype (12.3kPa interquartile range [IQR] 9.6-17.3 vs. 7.1kPa IQR 5.6-11.1; P=0.012). In addition, higher HCV RNA and lower serum albumin levels were observed in patients with the tt genotype of the TaqI polymorphism compared to TT/Tt carriers, and in patients with the aa genotype compared to AA/Aa carriers. In haplotype analysis, no association was found between any haplotype and disease progression., Conclusions: In patients with CHC, laboratory parameters are influenced by VDR polymorphisms and the development of cirrhosis is related to homozygosity for the dominant trait of ApaI and FokI variants., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Background: Long-term monotherapy with nucleos(t)ide analogs (NAs) represents the treatment option for the majority of patients with chronic hepatitis B (CHB), an aging population with a greater likelihood of comorbidities. We assessed the prevalence of concurrent non-hepatic diseases and the safety monitoring in a large cohort of CHB patients receiving NAs and their potential impact on disease outcomes., Methods: We included 500 consecutive CHB patients from 5 major tertiary Greek centers, under long-term therapy with an NA. Epidemiological/clinical characteristics and data on concomitant disease, drug use and investigations ordered were collected., Results: The mean age was 58 years and 66% were male. Most patients were receiving tenofovir disoproxil fumarate (TDF, 60%) or entecavir (ETV, 37%) monotherapy. Decompensated cirrhosis at baseline was present in 10%, while hepatocellular carcinoma (HCC) under therapy developed in 21 patients. The median duration of total NA therapy was 56 and of latest therapy 42 months. The most common (prevalence >10%) comorbidities were hypertension (28%), non-HCC cancer(s) (12%), and diabetes (11%). Patients with a longer duration of latest therapy (≥4 vs. <4 years) were older (mean age: 58 vs. 56 years, P=0.004), had more frequent history of prior use of NA(s) (53% vs. 35%, P<0.001), and less frequent liver decompensation (5% vs. 13%, P=0.008) and non-HCC cancers (8% vs. 15%, P=0.020). HCC developed more frequently in patients with than in those without diabetes (11% vs. 3%, P=0.022)., Conclusion: Greek CHB patients currently treated with NAs, almost exclusively ETV or TDF, are often older than 60 years, have several comorbidities, and thus require careful management., Competing Interests: Conflict of Interest: This study was supported by an unrestricted grant from Gilead Sciences Hellas, (Copyright: © 2021 Hellenic Society of Gastroenterology.)

Background: It is estimated that 17,000 people who inject drugs (PWID) in Greece have hepatitis C virus (HCV) viremia. The aim of our study was to explore the characteristics of the HCV-infected, direct acting antiviral (DAA)-naïve PWID., Methods: This is a retrospective analysis of PWID with HCV infection. We selected data from six liver clinics during the period from 1 st May 2014 to 31 st May 2017 in order to record the characteristics of infected PWID., Results: We included 800 PWID with HCV infection (78.5% male, mean age 42±10 years) who had not received DAAs before 1 st June 2017. One third of the patients had comorbidities (diabetes mellitus, arterial hypertension and psychological disorders); 70% were smokers, 27% alcohol users, 67% unemployed, 29% married, and 34% had education >12 years; 65% were attending addiction programs; 57% were receiving methadone and 36% buprenorphine. Sporadic or systemic drug use was reported by 37% while 1.4% and 2.9% had HIV and HBV coinfection, respectively. The genotype distribution was 20.5%, 4.6%, 3.3%, 61% and 10% for genotypes 1a, 1b, 2, 3 and 4, respectively. Mean (±SD) liver stiffness was 9±7 kPa and 21% of the patients had cirrhosis. Half of the patients were in the F0-F1 stage of liver disease, defined as stiffness ≤7 kPa., Conclusions: Our real-life data suggest that HCV genotype 3 remains the predominant genotype among PWID. One third of PWID had comorbidities and one-fifth cirrhosis. Half of PWID had early-stage liver disease and remained without access to DAAs according to the Greek prioritization criteria., Competing Interests: Conflict of Interest: Gilead Sciences

Background: We determined the proportions of patients with chronic hepatitis C (CHC) in association with possible prioritized indications for interferon-free regimens and the use of co-medications with potential drug-drug interactions (DDIs)., Methods: Five hundred consecutive mono-infected CHC patients seen in 2015 at 5 Greek centers were included. Priorities for interferon-free regimens were based on liver disease severity, contraindication(s) for interferon and prior interferon-treatment failure. All co-medications were classified into those with no DDIs/no clear data for DDIs, potential DDIs, and contraindication due to DDI for each agent, according to the HEP Drug Interaction Checker., Results: Of the 500 patients, 1% had undergone liver transplantation, whereas 6.6% had decompensated cirrhosis, 21.8% F4, 17.1% F3, 10.4% F2, and 34.8% F0-1 fibrosis. Contraindications for interferon were present in 38.5% of non-transplant patients with compensated liver disease. The probability of contraindications/potential DDIs was greater for boceprevir/telaprevir and ombitasvir/paritaprevir/ritonavir±dasabuvir, compared to all other agents (P<0.001), and least for sofosbuvir (P<0.05). Contraindications/potential DDIs were more frequently present in patients ≥50 than <50 years old (P≤0.034), and more common in F3-4 than F0-2, and F4 than F0-3 fibrosis (P≤0.019) for all direct-acting antivirals (DAAs)., Conclusions: The expansion of the criteria for prioritization of interferon-free regimens from cirrhosis to F3 and perhaps F2 fibrosis will increase the proportion of patients with DAA access by only 10-15% and 10%, respectively. A potential for DDIs is frequently present with protease inhibitors, but also exists with other DAAs. The probability of DDIs is higher in patients with priority for DAAs, including those who have advanced liver disease and are usually of older age., Competing Interests: Conflict of Interest: Μargarita Papatheodoridi has nothing to declare. George N. Dalekos has served as an advisor/lecturer for AbbVie, Bayer, Bristol-Myers Squibb, Gilead, Janssen, Novartis, Roche and has received grant support from Bristol-Myers Squibb, Gilead, Roche. John Goulis has served as an advisor/lecturer for Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck Sharp & Dohme, Roche and has received grant support from Bristol-Myers Squibb. Spilios Manolakopoulos has served as an advisor/lecturer for AbbVie, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Roche and has received grant support from Bristol-Myers Squibb. Christos Triantos has served as an advisor/lecturer for Bristol-Myers Squibb, Gilead, Merck Sharp & Dohme. Kalliopi Zachou has nothing to declare. Argyro Koukoufiki has nothing to declare. Αnastasia Κourikou has nothing to declare. Κonstantinos Ζisimopoulos has nothing to declare. Christos Τsoulas is an employee of Gilead Science Hellas, Greece. George V. Papatheodoridis has served as an advisor/lecturer for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Novartis, Roche, has received grant support from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Roche, has served as consultant for Roche and has served as a member of Data Safety Management Board for Gilead.