Prospective study of hepatitis B and D epidemiology and risk factors in Romania: A 10-year update.

BACKGROUND: The global burden of hepatitis D virus (HDV) infection represents a major medical challenge and a public health crisis worldwide. However, there is a lack of accurate data on the epidemiology and risk factors for HDV. Hepatitis B virus (HBV) and HDV coinfection causes the most severe form of viral hepatitis, leading to a higher cumulative incidence of liver-related events compared with HBV monoinfection, including the need for liver transplantation and death. AIM: To investigate the epidemiology, natural history, risk factors and clinical management of HBV and HDV coinfection in Romanian patients. METHODS: This prospective study was conducted between January and July 2022 in six tertiary gastroenterology and hepatology referral centres in Romania. All consecutive adults admitted for any gastroenterology diagnosis who were HBV-positive were enrolled. Patients with acute hepatitis or incomplete data were excluded. Of the 25390 individuals who presented with any type of gastroenterology diagnosis during the study period, 963 met the inclusion criteria. Testing for anti-HDV antibodies and HDV RNA was performed for all participants. Demographic and risk factor data were collected by investigators using medical charts and patient questionnaires. All data were stored in an anonymized online database during the study. RESULTS: The prevalence of HBV was 3.8%; among these patients, the prevalence of HBV/HDV coinfection was 33.1%. The median age of the study population was 54.0 years, and it consisted of 55.1% men. A higher prevalence of HBV/HDV coinfection was observed in patients 50-69 years old. Patients with HBV/HDV coinfection were significantly older than those with HBV monoinfection (P = 0.03). Multivariate multiple regression analysis identified female gender (P = 0.0006), imprisonment (P < 0.0001), older age at diagnosis (P = 0.01) and sexual contact with persons with known viral hepatitis (P = 0.0003) as significant risk factors for HDV. CONCLUSION: This study shows that HDV infection among those with HBV remains endemic in Romania and updates our understanding of HDV epidemiology and associated risk factors. It emphasizes the need for systematic screening for HDV infection and collaborative initiatives for controlling and preventing HBV and HDV infection.

Paraneoplastic Syndromes in Hepatocellular Carcinoma, Epidemiology, and Survival: A Retrospective Seven Years Study.

Background and Objectives: Liver cancer poses a significant global health threat, ranking among the top three causes of cancer-related deaths. Patients with hepatocellular carcinoma (HCC) often present with symptoms associated with neoplasms or unusual clinical features such as paraneoplastic syndromes (PNS), including hypoglycemia, hypercholesterolemia, thrombocytosis, and erythrocytosis. Our study aimed to investigate the prevalence, clinical characteristics, and survival outcomes associated with PNS in HCC patients and assess each PNS's impact on patient survival. Materials and Methods: We conducted a retrospective analysis of PNS clinical features and survival among consecutive HCC patients diagnosed at our department over seven years, comparing them with HCC patients without PNS. The study involved a retrospective data evaluation from 378 patients diagnosed with HCC between January 2016 and October 2023. Results: We obtained a PNS prevalence of 25.7%, with paraneoplastic hypercholesterolemia at 10.9%, hypoglycemia at 6.9%, erythrocytosis at 4.5%, and thrombocytosis at 3.4%. Patients with PNS tended to be younger and predominantly male. Multivariate analysis revealed a strong correlation between PNS and levels of alpha-fetoprotein and tumor size, with diabetes also showing a significant statistical association (p < 0.05). Subgroup analysis based on specific paraneoplastic syndromes demonstrated shorter survival in patients with PNS, albeit without significant statistical differences, except for hypoglycemia (p < 0.0001). Matched analysis indicated a shorter survival rate for patients with PNS, although no significant statistical differences were observed. Conclusions: PNS are frequently observed in HCC cases and are associated with unfavorable prognoses and decreased survival rates due to their correlation with increased tumor burdens. However, they do not independently predict poor survival. The impact of individual PNS on HCC prognosis varies.

Comparative Analysis of Microbial Species and Multidrug Resistance Patterns in Acute Cholangitis Patients with Cholecystectomy: A Single-Center Study.

This study aimed to compare microbial species and multidrug resistance patterns in acute cholangitis patients with and without a history of cholecystectomy, highlighting potential differences We hypothesized that post-cholecystectomy patients would exhibit distinct microbial spectra and resistance patterns. Conducted at a western Romanian hospital specializing in gastroenterology and hepatobiliary diseases from 2020 to 2023, this retrospective study included 488 acute cholangitis patients, divided into groups based on their cholecystectomy history. Bile and blood samples were analyzed for microbial identification and antibiotic susceptibility using VITEK®2. Positive biliary cultures were found in 66% of patients. The cholecystectomy group showed a higher prevalence of multidrug-resistant organisms, with 74.4% exhibiting resistance compared to 31.5% in the non-cholecystectomy group (p < 0.001). Notable microbial differences included higher occurrences of Escherichia coli (40.2%) and Enterococcus spp. (32.4%) in the cholecystectomy group. Resistance to Piperacillin/Tazobactam and Penems was significantly higher in this group, with odds ratios of 3.25 (p < 0.001) and 2.80 (p = 0.001), respectively, for the development of multidrug-resistant (MDR) bacterial species. The study confirmed our hypothesis, revealing distinct microbial profiles and a higher prevalence of multidrug resistance in acute cholangitis post-cholecystectomy patients. These findings underscore the need for tailored antibiotic strategies in managing acute cholangitis in this patient demographic.

Comparative Analysis of Antibiotic Resistance in Acute Cholangitis Patients with Stent Placement and Sphincterotomy Interventions.

In response to rising concerns over multidrug resistance patterns in acute cholangitis patients, this retrospective study was conducted at the Emergency County Hospital Timisoara, Romania, encompassing patients treated between August 2020 and August 2023. The study aimed to investigate the influence of prior interventions, specifically sphincterotomy (with or without stent placement), on the current clinical and microbiological profiles of acute cholangitis patients. By differentiating between patients with a history of sphincterotomy and the endoscopic retrograde cholangiopancreatography (ERCP)-naïve, we assessed the resistance of bacterial strains to antibiotics by the Tokyo Guidelines 2018, using bile cultures from 488 patients. The study identified various multidrug-resistant organisms, with a total multidrug resistance incidence of 19.9%. Significant variations were observed in the distribution of specific microorganisms and resistance patterns across different intervention groups. Patients with previous interventions, particularly those with both sphincterotomy and stent, exhibited elevated white blood cells (WBC) and C-reactive protein (CRP) levels in comparison to their ERCP-naïve counterparts. This group also presented a striking prevalence of two bacteria in their bile cultures at 50.0%, compared to 16.1% in ERCP-naïve individuals. Regarding multidrug resistance, the prior sphincterotomy with stent placement had a prevalence of 50.0%. The presence of ESBL bacteria was also significantly higher in the same group at 28.7%, contrasting with the 8.9% in ERCP-naïve patients. Additionally, the same group had a higher burden of Klebsiella spp. infections, at 37.2%, and Enterococcus spp. at 43.6%. On the antibiotic resistance front, disparities persisted. Piperacillin/Tazobactam resistance was notably more rampant in patients with a previous sphincterotomy and stent, registering at 25.5% against 11.1% in the ERCP-naïve group. This study underscores a substantial discrepancy in multidrug resistance patterns and antibiotic resistance among acute cholangitis patients with previous manipulation of the bile ducts, without expressing significant differences by the type of stent used.

Identification of Microbial Species and Analysis of Antimicrobial Resistance Patterns in Acute Cholangitis Patients with Malignant and Benign Biliary Obstructions: A Comparative Study.

Background and Objectives: Acute cholangitis (AC) is still lethal if not treated promptly and effectively. Biliary drainage, also known as source control, has been acknowledged as the backbone treatment for patients with AC; nonetheless, antimicrobial therapy allows these patients to undergo non-emergent drainage procedures. This retrospective study aims to observe the bacterial species involved in AC and analyze the antimicrobial resistance patterns. Materials and Methods: Data were collected for four years, comparing patients with benign and malignant bile duct obstruction as an etiology for AC. A total of 262 patients were included in the study, with 124 cases of malignant obstruction and 138 cases of benign obstruction. Results: Positive bile culture was obtained in 192 (73.3%) patients with AC, with a higher rate among the benign group compared with malignant etiologies (55.7%.vs 44.3%). There was no significant difference between the Tokyo severity scores in the two study groups, identifying 34.7% cases of malignant obstruction with Tokyo Grade 1 (TG1) and 43.5% cases of TG1 among patients with benign obstruction. Similarly, there were no significant differences between the number of bacteria types identified in bile, most of them being monobacterial infections (19% in the TG1 group, 17% in the TG2 group, and 10% in the TG3 group). The most commonly identified microorganism in blood and bile cultures among both study groups was E. coli (46.7%), followed by Klebsiella spp. (36.0%) and Pseudomonas spp. (8.0%). Regarding antimicrobial resistance, it was observed that significantly more patients with malignant bile duct obstruction had a higher percentage of bacterial resistance for cefepime (33.3% vs. 11.7%, p-value = 0.0003), ceftazidime (36.5% vs. 14.5%, p-value = 0.0006), meropenem (15.4% vs. 3.6%, p-value = 0.0047), and imipenem (20.2% vs. 2.6%, p-value < 0.0001). Conclusions: The positive rate of biliary cultures is higher among patients with benign biliary obstruction, while the malignant etiology correlates with increased resistance to cefepime, ceftazidime, meropenem, and imipenem.

A Statistical Approach to the Diagnosis and Prediction of HCC Using CK19 and Glypican 3 Biomarkers.

Various statistical models predict the probability of developing hepatocellular carcinoma (HCC) in patients with cirrhosis, with GALAD being one of the most extensively studied scores. Biomarkers like alpha-fetoprotein (AFP), AFP-L3, and des-g-carboxyprothrombin (DCP) are widely used alone or in conjunction with ultrasound to screen for HCC. Our study aimed to compare the effectiveness of Cytokeratin 19 (CK19) and Glypican-3 (GPC3) as standalone biomarkers and in a statistical model to predict the likelihood of HCC. We conducted a monocentric prospective study involving 154 participants with previously diagnosed liver cirrhosis, divided into two groups: 95 patients with confirmed HCC based on clinical, biological, and imaging features and 59 patients without HCC. We measured the levels of AFP, AFP-L3, DCP, GPC3, and CK19 in both groups. We used univariate and multivariate statistical analyses to evaluate the ability of GPC3 and CK19 to predict the presence of HCC and incorporated them into a statistical model-the GALKA score-which was then compared to the GALAD score. AFP performed better than AFP-F3, DCP, GPC3, and CK19 in predicting the presence of HCC in our cohort. Additionally, GPC3 outperformed CK19. We used multivariate analysis to compute the GALKA score to predict the presence of HCC. Using these predictors, the following score was formulated: 0.005*AFP-L3 + 0.00069*AFP + 0.000066*GPC3 + 0.01*CK19 + 0.235*Serum Albumin-0.277. The optimal cutoff was >0.32 (AUROC = 0.98, sensitivity: 96.8%, specificity: 93%, positive predictive value-95.8%, negative predictive value-94.8%). The GALKA score had a similar predictive value to the GALAD score for the presence of HCC. In conclusion, AFP, AFP-L3, and DCP were the best biomarkers for predicting the likelihood of HCC. Our score performed well overall and was comparable to the GALAD score.