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Hypothesis: Chronic viral liver disease is often associated with other conditions. Diabetes mellitus (DM) is frequently reported in this context and may play a role in the progression of the liver disease to hepatocellular carcinoma (HCC). Renal disease is also an important extrahepatic manifestation of hepatitis viral infection and its presence is associated with poor prognosis and management issues. Objectives: Our study had multiple purposes: to determine the frequency of the association between chronic viral liver disease and diabetes mellitus, evaluate the potential of diabetes mellitus as a risk factor for HCC and assess an eventual renal involvement. Methods and results: We included in our study a number of 246 patients with chronic liver disease, from whom 136 were diagnosed with chronic viral hepatitis and 110 with viral liver cirrhosis. These patients were assessed by using a clinical examination and a series of tests, including serum transaminase levels, serum bilirubin, serum albumin, markers of cholestasis, fasting plasma glucose levels, serum creatinine, urea, albuminuria, Addis-Hamburger test, electrophoresis of urinary proteins, abdominal ultrasound and, in some cases, CT examination. We obtained the following results: diabetes mellitus is often associated with chronic liver disease of viral etiology, having been identified in 18.29% of the patients in our study. Age above 60 in patients with chronic hepatitis (p=0.013<0.05) and presence of hepatitis C virus were particularly correlated with the presence of diabetes mellitus. Renal disease was present in 13.4% of the patients with chronic liver disease and it was especially associated with liver cirrhosis and hepatitis C virus. The most common form of renal injury was glomerulonephritis. Acute kidney injury was diagnosed only in cirrhotic patients as hepatorenal syndrome, occurring in 7.27% of the subjects, while chronic kidney disease was identified only in two cases of chronic viral hepatitis. Four patients in our study were diagnosed with HCC and none of them presented diabetes mellitus. Discussion: Our study revealed that there is a significant association between diabetes mellitus and chronic viral liver disease induced by hepatitis C virus. Glomerulonephritis was the most common type of renal disease in both hepatitis patients and in those with cirrhosis. Glomerular injury was strongly correlated with the presence of hepatitis C virus than with hepatitis B virus. A connection between diabetes mellitus and hepatocellular carcinoma could not be established. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBD), which enclose Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing inflammatory ailments. Their specific pathogenesis is not completely clarified, the worldwide incidence and prevalence of IBD has been steadily growing, and there is still not a definitive cure. The management of IBD has become more and more targeted, with specific immune mediators identified to be involved in its pathogenesis. Vedolizumab, a humanised monoclonal antibody binding specifically to the α4β7 integrin, is a gut-selective immunosuppressive biologic drug administered for both CD and UC. With the same indications as vedolizumab, ustekinumab is a fully human IgG1κ monoclonal antibody binding with specificity to the shared p40 protein subunit of human cytokines interleukin (IL)-12 and IL-23. Several selective IL-23p19 monoclonal antibodies (risankizumab, mirikizumab, and guselkumab) have also revealed admirable efficacy and safety in IBD patients. Nutrition is a very important environmental factor associated with the onset and progression of IBD, and the Western diet is considered to contribute to the development of IBD. In this narrative review, our aim is to present an overview of the main results from recent clinical studies on IBD regarding diet, new drug treatments, and also vaccination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gheonea, Bogdan, Meca, Rogoveanu and Oancea.)

Background: Hepatitis B Virus (HBV) remains a major global health challenge, with significant morbidity and mortality associated with chronic infections. Methods: This study examines the epidemiology, screening, and risk factors associated with HBV in Romania, focusing on a comprehensive national screening program, LIVE(RO)2, involving 320,000 individuals (majority of them considered vulnerable population). A questionnaire was used to collect information on the potential risk factors for HBV transmission. Results: The overall prevalence rate of HBV chronic infection among all the participants tested was 1.67% (confidence interval: 1.63-1.72%), with significant differences ( p = 0.0001) between participants from the main geographical regions of residence (North-East 1.89%, South 1.38%, South-East 2.06%, and South-West 1.54%). Male persons aged 30-49 or 60-69 years old, from the rural and Eastern parts of Romania and non-Romanian ethnia, with a low level of education, unvaccinated, not married, unemployed, with family members with hepatitis, with personal histories of blood or blood product transfusion, surgical interventions, tattooing, hospitalizations, imprisonment, haemodialysis, unsafe sexual contacts, or with sexual transmitted infectious diseases were risk factors associated with HBsAg seropositivity. Conclusions: Our findings highlight significant demographic and epidemiological patterns of reduced HBV prevalence even in vulnerable persons, as well as modified risk factors and the impact of socio-economic factors.

Purpose: Non-alcoholic fatty liver disease (NAFLD) represents a heterogeneous spectrum of liver diseases that encompass simple steatosis, non-alcoholic steatohepatitis (NASH), and advanced fibrosis or cirrhosis. Periodontitis is a chronic infectious disease with multiple causal factors that presents a complex interaction between the microbial biofilm and the host's immune response. The aim of this study was to investigate the concentrations of Vascular Adhesion Protein-1 (VAP-1) and Thrombospondin-1 (TSP-1) in patients with coexisting periodontitis and NAFLD., Patients and Methods: This study included 48 patients, who were dental and periodontal assessed. Of these patients, 25 were diagnosed with NAFLD. After performing the periodontal clinical examination, gingival crevicular fluid (GCF) samples were collected. Enzyme-linked immunosorbent assay (ELISA) dedicated kits tests were used for the detection and quantitative determination of VAP-1 and TSP-1 in GCF samples. Statistical methods were applied for the comparison and correlation of data., Results: VAP-1 and TSP-1 levels showed significant differences between all test and control groups (p<0.0001). Statistically significant correlations (p<0.05) between VAP-1 and periodontal and liver parameters were found in patients with NAFLD and periodontitis., Conclusion: Periodontal inflammation is more marked in patients with periodontitis-NAFLD association. Vascular adhesion and angiogenesis could be affected in patients with periodontitis and NAFLD. These findings could suggest that addressing periodontal inflammation in individuals with the periodontitis-NAFLD association may have a broader impact on vascular adhesion and angiogenesis, highlighting the interplay between oral health and liver conditions for comprehensive patient care., Competing Interests: The author reports no conflicts of interest in this work., (© 2024 Pitru et al.)

Background: The incidence of peptic ulcers has decreased during the last decades; the COVID-19 pandemic may have influenced the peptic ulcer hospitalizations. The study aimed to assess the admissions and mortality for complicated and uncomplicated peptic ulcers and the influence of the pandemic period. Material and Methods: We performed an observational study at a tertiary academic center, including all patients admitted for peptic ulcers between 2017-2021. We evaluated the admissions for complicated and uncomplicated ulcers and risk factors for mortality. Results: 1416 peptic ulcers were admitted, with an equal proportion of gastric and duodenal ulcers; most patients were admitted for bleeding (66.7%), and perforation (17.3%). We noted a decreasing trend for peptic bleeding ulcer (PUB) and uncomplicated ulcer admissions during 2020-2021, while for perforation no significant variation was recorded; a decreasing mortality in PUB was noted from 2017 to 2020. Admissions for bleeding peptic ulcer have decreased by 36.6% during the pandemic period; the mortality rate was similar. Admissions for perforated peptic ulcer have decreased by 14.4%, with a higher mortality rate during the pandemic period (16.83 versus 6.73%). Conclusion: A decreasing trend for PUB admissions but not for perforated ulcers was noted. Admissions for PUB have decreased by more than 1/3 during the pandemic period, with a similar mortality rate. Admissions for perforated peptic ulcers have decreased by 1/7, with significantly higher mortality rates during the pandemic period., (Celsius.)

Background and Aims: Hepatocellular carcinoma (HCC) is a significant public health issue, with an increasing incidence and prevalence and a high incidence-to-mortality ratio. The prognosis of HCC depends on two competing factors, tumor burden and underlying liver disease severity, encompassed in the Barcelona Clinic Liver Cancer (BCLC) classification. To assess HCC staging and the way staging affects eligibility for treatment at the time of the first diagnosis in Romania in the setting of opportunistic diagnosis, in the absence of a national HCC screening policy., Methods: Data regarding HCC staging, underlying liver disease, and eligibility for treatment at the time of diagnosis was analyzed using a prospectively maintained multicentric database, which included patients from the five largest tertiary care hepatology units in the country between June 2016 and February 2020., Results: A consecutive series of 477 patients was included. The distribution within BCLC classes was as follows: very early (0) 7.1%, early (A) 34.3%, intermediate (B) 19.4%, advanced (C) 14.2%, terminal (D) 24.7%. At the time of the diagnosis, 198 (41.5%) were eligible for a curative intent treatment, while 359 (75.2%) were eligible for a disease-modifying therapy. 228 patients (47.8%) had decompensated liver disease at the time of diagnosis, the most common decompensating event being ascites (78.1%)., Conclusions: A large proportion of HCC cases are diagnosed at the time of a decompensating event, severely restricting the therapeutic potential. Proactive diagnostic strategies should be implemented to improve the rate of actionable diagnosis.

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., Competing Interests: Conflict-of-interest statement: Medical writing support was provided by Joe Jones, PhD, of PharmaGenesis London, London, United Kingdom, with funding provided by Gilead Sciences Europe Ltd., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Periodontitis is a common condition affecting the tissues surrounding and supporting teeth. In addition to oral health concerns, periodontal disease increases the chance of developing systemic illnesses including type 2 diabetes mellitus. Porphyromonas gingivalis, a key-stone pathogen that has been linked to the pathophysiology of periodontal disease, can generate a series of dipeptide producing exopeptidases, dipeptidyl peptidases (DPP). DPP-4 levels in gingival crevicular fluid have been shown to increase during active periodontal disease, which may lead to their association with the disease's progression. Following oral glucose administration, mice injected with DPP-4 had higher blood glucose than the control group. DPP-4 inhibitors are used to treat patients with type 2 diabetes mellitus in order to extend the half-life of incretins. Elevated glucagon-like peptide-1 (GLP-1) levels following periodontal therapy could be considered new and applicable real-world evidence confirming the experimental findings of a beneficial interaction between oral microbiota and incretin axis. GLP-1 receptor agonist exendin-4 enhanced the osteoblast proliferation and development of these stem cells and inhibited the effects of glucose on the cells. In addition to lowering blood sugar, liraglutide, a GLP-1 receptor agonist, also possesses anti-inflammatory and bone-protective properties. These findings support the use of GLP-1 in the management and prevention of diabetic periodontitis.

Quality of life, well-being, and psycho-emotional balance are closely related to the quality of the diet, the level of physical activity, the quality of rest, but also the absence of the consumption of narcotic substances and tobacco, or alcohol abuse. Based on the distribution of a questionnaire that included 30 questions, we aimed to statistically evaluate several factors that influence mental health and vices. It recorded a total of 1719 valid responses, which came from 78.3% female respondents and 21.7% male respondents. After processing the anthropometric data, it was observed that the majority of respondents are of normal weight (63.87%) and come from women in particular (36.13%). Based on the answers recorded, although over 60% of the respondents participating in the study are up to 40 years old, there is an increased tendency towards sedentarism (over 58% of the respondents declaring that they do sports very rarely or not at all), a low tendency regarding optimal consumption of vegetables and fruits, many respondents do not hydrate properly, which is why approximately 60% of respondents feel frequently tired, and over 32% are frequently nervous. The increased level of stress among the respondents and emotional eating are also generated by inadequate rest, reduced physical activity, and a diet that does not help the efficient detoxification of the body.

Introduction: The neutrophil-lymphocyte ratio (NLR) has been suggested as a reliable marker for predicting inflammation progression and severity of acute pancreatitis, although the role of the NLR stratified by etiology is still insufficiently studied. However, the NLR's role in mortality prediction was poorly evaluated in the literature., Patients and Methods: We performed a retrospective, cross-sectional study to analyze the role of NLR0 (at admission) and NLR48 (at 48 hours) in acute pancreatitis as compared with CRP, BISAP, SOFA, and modified CTSI (mCTSI) for the prediction of mortality and severe acute pancreatitis (SAP) in patients admitted into the Emergency Clinical County Hospital of Craiova during 48 months. The primary assessed outcomes were the rate of in-hospital mortality, the rate of persistent organ failure, and ICU admissions. We analyzed mortality prediction for all acute pancreatitis, for biliary, alcoholic, and hypertriglyceridemic acute pancreatitis, for severe forms, and for patients admitted to the ICU., Results: A total of 725 patients were selected; 42.4% had biliary acute pancreatitis, 27.7% had alcoholic acute pancreatitis, and 8.7% had hypertriglyceridemia-induced acute pancreatitis. A total of 13.6% had POF during admission. The AUC for NLR48 in predicting mortality risk and SAP was 0.81 and 0.785, superior to NLR0, CRP48, and mCTSI but inferior to BISAP and SOFA scores. The NLR48/NLR0 ratio did not add significantly to the accuracy. NLR0 and NLR48 performed poorly for mortality prediction in severe forms and in patients admitted to the ICU. NLR48 has good accuracy in our study for predicting death risk in biliary and alcoholic acute pancreatitis but not in hypertriglyceridemic acute pancreatitis., Conclusion: NLR48 was a good indicator in predicting mortality risk and severe forms in all patients with acute pancreatitis, but not of death in SAP and in patients admitted to ICU, with good accuracy for predicting death risk in biliary and alcoholic acute pancreatitis but not in hypertriglyceridemic acute pancreatitis., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Cazacu et al.)

The range of non-alcoholic drinks is very varied both from a compositional point of view and from a caloric and nutritional point of view. The excessive consumption of sweetened non-alcoholic beverages represents an important risk factor for health, especially when it is accompanied by an unbalanced diet and a disordered lifestyle. In order to evaluate the consumption of non-alcoholic beverages correlated with the evaluation of the main lifestyle factors that can affect the state of health among Romanians, a cross-sectional observational study was carried out based on a questionnaire. The results of the study indicate that among the most consumed non-alcoholic drinks are coffee and sweetened carbonated and non-carbonated drinks, which are indicated as being responsible for the development of consumption addictions: 44% for coffee, 16.5% for sweetened or tonic carbonated drinks and 12% for sweetened non-carbonated drinks. Considering that the consumption of coffee is usually associated with sweeteners, there is a risk of excessive caffeine and caloric intake in a context where a lack of exercise predominates (59.98%) among respondents declaring that they do sports rarely or not at all, which can lead, in the long term, to the appearance of imbalances either of a psycho-emotional nature or of a metabolic nature. A significant link was found between sports activity and the environment in which they work (χ 2 = 51.33, p = 0.05). Respondents with a daily activity that involves movement (working outdoors, working on a construction site) are also those who usually do sports, while 60.67% of the respondents who work a lot in front of the computer declared that they do sports very rarely or not at all. Reducing the excessive consumption of sweetened drinks can be achieved through an appropriate consumption of water and fruits and by intensifying physical activity as a way of counterbalancing the excess caloric intake.

Premature aging and degradative processes are mainly generated by unhealthy habits and an unbalanced diet. Quality of food and lifestyle are important factors in sano-genesis. Many imbalances and ailments have their origin in the adoption of an unbalanced diet and a disordered lifestyle. With the help of a transversal study carried out on the basis of a questionnaire, the consumption of junk food products among the population of Romania was evaluated; at the same time, an evaluation of the characteristics of the associated diet, as well as a series of lifestyle components (quality of rest, physical activity, evaluation of the state of health) was carried out. The data collected and processed indicate an increased tendency to consume junk food products in the 18-23 age group, and especially among obese respondents. Female respondents show a lower tendency toward an increased consumption of junk food products (OR = 0.703, 95% CI)-0.19-0.95, p = 0.011) compared to male respondents. The most consumed junk food products are fried potatoes (46.2%) and pastries (41.4%). Junk food products that show an increased tendency toward consumption addiction are fried potatoes (13.8%), sweets (12.4%), pastry products (11.1%), and sweetened drinks (11.2%). The poor quality of food from a nutritional point of view, and reduced physical activity, are reflected in the varied range of problems faced by the respondents: states of fatigue (62.4%), nervousness (37.5%), depression, anxiety, emotional eating, etc.

Introduction: In some cases, there may be a discrepancy between the symptomatology alleged by Crohn's disease (CD) patients and the results of laboratory tests or imaging investigations. Ileocolonoscopy with biopsy is the primary investigation for diagnosing and monitoring CD patients. Cross-sectional imaging techniques such as CT or MR enterography (MRE) and intestinal ultrasonography (IUS) have been proposed as complementary methods to colonoscopy for a complete evaluation of this category of patients. This study aims to identify the role of IUS, contrast-enhanced ultrasound (CEUS) and MRE in evaluating ileal CD activity, using clinical severity scores (Crohn's disease activity index-CDAI, Harvey-Bradshaw index-HBI) and faecal calprotectin or C-reactive protein (CRP) levels as reference methods., Materials and Methods: A total of 44 adult patients with ileal CD confirmed using an ileocolonoscopy with biopsy and histopathological examination were assessed by IUS, CEUS and MRE. The evaluation of the disease activity based on the results obtained from the cross-sectional imaging tests was carried out by using some severity scores available in the literature. The sensitivity and specificity of IUS + CEUS and MRE for differentiating active from inactive forms of CD were determined using CDAI, HBI, faecal calprotectin and CRP as reference methods. The accuracy of the results was assessed by the receiver operating characteristics method. The Pearson correlation coefficient was used to determine the types of correlation. A p -value less than 0.05 suggested a statistically significant relationship., Results: Compared to CDAI, the best correlation was identified for Limberg score (r = 0.667, 95% confidence interval (CI) [0.46, 0.8], p < 0.001), followed by MaRIAs score (r = 0.614, 95% CI [0.39, 0.77], p < 0.001). A sensitivity of 93.33% and a specificity of 71.43% (AUC = 0.98) were demonstrated in the case of Limberg score for differentiating patients with active disease from those in remission and for MaRIAs score a sensitivity of 100.00% and a specificity of 57.14% (AUC = 0.97). Regarding HBI, the best correlation was observed for MaRIAs score (r = 0.594, 95% CI [0.36, 0.76], p < 0.001). Also, faecal calprotectin showed the best correlation with MaRIAs score (r = 0.697, 95% CI [0.46, 0.84], p < 0.001), but in the case of CRP, there was only a weak correlation for all evaluated scores., Conclusions: Although magnetic resonance imaging does not appear to be superior to ultrasonography in terms of accuracy for differentiating active forms of CD from those in remission, the results of our study suggest that MRE associates a better correlation with clinical severity scores and faecal calprotectin levels compared to ultrasonography. More studies are needed to validate these results.

This observational study included all patients undergoing HCV treatment with direct-acting antiviral (DAA)-based therapy between May 2020 and September 2023 at the Dolj County Hospital, Romania. The aim was to investigate adherence to DAAs among HCV patients and the effect of this treatment on their health-related quality of life (HRQoL). Chronic HCV-infected patients were prospectively evaluated at baseline (T0), before the beginning of treatment, and 12 weeks after completing DAAs treatment (T1). The HCV-AD10 questionnaire was used to measure DAAs adherence, and HRQoL was assessed with the 15D instrument. The 15D questionnaire was administered at two time points: T0 and T1, during which the Sustained Virologic Response (SVR) was also measured. The primary outcome was DAAs adherence, with secondary outcomes including quality of life (QoL), and sustained virologic response (SVR). DAAs based therapy was initiated for 368 patients, all of whom were health insured. HRQoL and psychological state of HCV patients clinically improved. The DAAs adherence was very good (mean±SD, 91.51±8.34), being influenced by age (younger patients were much adherent, rho=-0.112, p-value=0.031) and the severity of the disease (patients with more severe hepatitis were less adherent, rho=-0.167, p-value=0.001). DAAs had a significant effect on improving HRQoL of HCV patients, but did not influence medication adherence., Competing Interests: None to declare., (Copyright © 2023, Medical University Publishing House Craiova.)

Background: Non-endoscopic risk scores, Glasgow Blatchford (GBS) and admission Rockall (Rock), are limited by poor specificity. The aim of this study was to develop an Artificial Neural Network (ANN) for the non-endoscopic triage of nonvariceal upper gastrointestinal bleeding (NVUGIB), with mortality as a primary outcome., Methods: Four machine learning algorithms, namely, Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA), logistic regression (LR), K-Nearest Neighbor (K-NN), were performed with GBS, Rock, Beylor Bleeding score (BBS), AIM65, and T-score., Results: A total of 1,096 NVUGIB hospitalized in the Gastroenterology Department of the County Clinical Emergency Hospital of Craiova, Romania, randomly divided into training and testing groups, were included retrospectively in our study. The machine learning models were more accurate at identifying patients who met the endpoint of mortality than any of the existing risk scores. AIM65 was the most important score in the detection of whether a NVUGIB would die or not, whereas BBS had no influence on this. Also, the greater AIM65 and GBS, and the lower Rock and T-score, the higher mortality will be., Conclusion: The best accuracy was obtained by the hyperparameter-tuned K-NN classifier (98%), giving the highest precision and recall on the training and testing datasets among all developed models, showing that machine learning can accurately predict mortality in patients with NVUGIB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ungureanu, Gheonea, Florescu, Iordache, Cazacu, Iovanescu, Rogoveanu and Turcu-Stiolica.)

The diagnosis of inflammatory bowel disease (IBD) can sometimes be challenging. By corroborating clinical, imaging and histological data, the two main entities of IBD, ulcerative colitis and Crohn's disease (CD), can be differentiated in most cases. However, there remains 10-20% of patients where the diagnosis cannot be accurately established, in which case the term "IBD unclassified" is used. The imaging techniques most used to evaluate patients with IBD include colonoscopy, ultrasonography and magnetic resonance imaging. Endoscopic ultrasonography is mainly recommended for the evaluation of perianal CD. Through this work, we aim to identify other uses of this method in the case of patients with IBD.

Osteopenic bone disease occurs frequently in patients with chronic liver cirrhosis, which most frequently presents with hepatic osteodystrophy. Thus, the relationship between nutritional status and bone mineral density has been poorly measured in liver cirrhosis. This single-center study consisted of a group of 70 patients diagnosed with liver cirrhosis. The nutritional status was evaluated with the Controlling Nutritional Status index, and volumetric vertebral bone mineral density was measured with quantitative computed tomography. Among the 70 patients included, osteopenia and osteoporosis were found in 71% and 24.3%, respectively. Malnutrition assessed with the Controlling Nutritional Status index was observed in 56 (80%) patients and was more frequent in alcoholic cirrhosis patients than viral cirrhosis patients (87.24% vs. 65.22%). Significant positive correlation with Controlling Nutritional Status score was found with Model for End-Stage Liver Disease (rho = 0.576, p-value < 0.0001), Child−Pugh score (rho = 0.670, p-value < 0.0001), International Normalized Ratio (rho = 0.517, p-value = 0.001), aspartate aminotransferase (rho = 0.293, p-value = 0.045), and bilirubin (rho =0.395, p-value = 0.02). Among the liver cirrhosis patients, 15 had osteoporosis and 49 had osteopenia at the lumbar spine (L1-L4 vertebrae), as determined by bone mass density via quantitative computed tomography. A non-significant relationship between Controlling Nutritional Status index-assessed nutritional status and bone mass density was documented. Regarding osteoporosis, no differences were found between the viral and alcohol types of liver cirrhosis patients (p-value = 0.870). Age, obesity, grade of varices, Child−Pugh score, and Model for End-Stage Liver Disease score were associated with osteoporosis in patients with liver cirrhosis.

The treatment of acute life-threatening events in patients suffering from chronic pathologies is problematic, as physicians need to consider multisystemic drug effects. Regarding Cerebrolysin, a Sonic Hedgehog signaling pathway amplifier and one of the few approved neurotrophic treatments for stroke patients, concerns of excessive Hedgehog pathway activation that could accelerate NAFLD progression to cirrhosis seem valid. We investigated stroke patients treated with Cerebrolysin that presented elevated levels of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT). We also investigated the efficiency of Cerebrolysin in reversing the neurogenesis inhibition within the hippocampus in a mouse model of NAFLD by evaluating behavior and histological outcomes. NeuN, BrdU and Iba1 positive signals in the cortex and hippocampus of the animals were also observed. Clinically, Cerebrolysin improved AST levels in a majority of stroke patients with hepatic damage. The same treatment in an experimental setup was able to reverse anxiety-like behavior in MCD mice, reducing their freezing time from 333.61 ± 21.81 s in MCD animals to 229.17 ± 26.28 in treated ones. The use of Cerebrolysin did not improve short-term memory nor rescued cell multiplication in the hippocampus after MCD food intake. Understanding the neuroprotective and neurotrophic effects that drugs have on NAFLD patients can significantly contribute to a suitable therapeutic approach., Competing Interests: The authors declare no conflict of interest.

Periodontitis is characterized by low-grade inflammation of the periodontal tissues, the structures that support and connect the teeth to the maxilla and mandible. This inflammation is caused by the accumulation of subgingival bacterial biofilm and gradually leads to the extensive damage of these tissues and the consequent loss of teeth. Hepatitis B is a major global health concern; infection with the hepatitis B virus causes significant inflammation of the liver and the possibility of its gradual evolution to cirrhosis. Hepatitis D, caused by infection with the delta hepatitis virus, is manifest only in patients already infected with the type B virus in a simultaneous (co-infected) or superimposed (superinfected) manner. The dental and periodontal status of patients with hepatitis B/D could exhibit significant changes, increasing the risk of periodontitis onset. Moreover, the progression of liver changes in these patients could be linked to periodontitis; therefore, motivating good oral and periodontal health could result in the prevention and limitation of pathological effects. Given that both types of diseases have a significant inflammatory component, common pro-inflammatory mediators could drive and augment the local inflammation at both a periodontal and hepatic level. This suggests that integrated management of these patients should be proposed, as therapeutical means could deliver an improvement to both periodontal and hepatic statuses. The aim of this review is to gather existing information on the proposed subject and to organize significant data in order to improve scientific accuracy and comprehension on this topic while generating future perspectives for research.

Cerebral ischemia is a major health problem worldwide, that affects millions of people, leaving a major percentage of them with major disabilities, therefore becoming one of the most resource consuming pathology. Beside the blockage of blood supply of the brain that leads to loss of cellular function and neuronal necrosis, metabolic processes are modified in the whole body through mechanisms that are not fully explained yet. The results in the analysis of the 2 groups, one with 70 patients with stroke and another with 68 patients with no cerebral infarction, revealed that brain ischemia is more often found in patients with atrial fibrillation and higher blood pressure values. The metabolic changes, found in the stroke group, are represented by increased values of blood glucose, serum urea and lower levels of creatinine levels. Also, the value of leucocytes count and the erythrocyte sedimentation rate were shown to be increased in stroke patients, indicating that inflammation is highly present in cerebral infarction. In the regard of these findings, cerebral ischemia is associated with major systemic disruptions that could be significant pathogenic factors and also effects of the complex processes that take place in the affected brain region, but further investigation should be done in order to explain all the mechanisms involved and also the possible impact in prophylaxis and acute management of stroke., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2022, Medical University Publishing House Craiova.)

Patients with cirrhosis often develop malnutrition and micronutrient deficiencies, leading to a worse prognosis and increased mortality. Our purpose was to assess the prevalence of micronutrient deficiencies especially calcium and phosphorus in patients with decompensated liver cirrhosis (LC). This was a retrospective study including 143 consecutive patients hospitalized for acute decompensation of cirrhosis, most of them with alcoholic etiology along with viral B or viral C and autoimmune induced cirrhosis. A blood test including minerals was performed on admission. Lower serum calcium levels were found in patients with a more severe forms of LC and also the ones diagnosed with viral and alcoholic LC rather than autoimmune induced LC. Peritoneal ascitic fluid was observed in 51 patients with hypocalcemia and only 24 patients with normal calcium levels had fluid accumulation. Low levels of phosphorus were noted in patients with a more severe form of LC (chi-square: 20.2504; p-value 0.000446). Ascitic fluid was found in patients with low values of phosphorus as well as in those with hypocalcemia (chi-square 5.235; p-value 0.022137). In conclusion, this study confirmed that patients with advanced liver disease had lower values of calcium and phosphorus and a more severe form of LC can be associated with hypocalcemia and hypophosphatemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest, (Copyright © 2022, Medical University Publishing House Craiova.)

Data about the association between primary sclerosing cholangitis (PSC) and metabolic bone disease are still unclear. PSC is a chronic cholestatic liver disease (CCLD) which affects the biliary tract, and it has a highly variable natural history. We systematically searched until 28 February 2022 MEDLINE, Cochrane Central Register of Controlled Trials, the ISI Web of Science, and SCOPUS, for studies in patients with PSC. We identified 343 references to potential studies. After screening them, we included eight studies (893 PSC patients, 398 primary biliary cirrhosis (PBC) patients, and 673 healthy controls) for the present meta-analysis. Pooled analyses found no difference in BMD-LS (Z = 0.02, p -value = 0.98) between PSC patients and healthy controls. BMD-LS was statistically lower in PBC patients than in PSC patients (Mean Difference, MD, 0.06, 95% CI 0.03 to 0.09, p -value = 0.0007). The lumbar spine T-score was higher in the PSC patients compared with PBC patients (MD 0.23, 95% CI 0.04 to 0.42, p -value = 0.02). Given the limited literature available, better designed, and larger scale primary studies will be required to confirm our conclusion.

The liver is a key organ in the pharmacokinetics of iron oxide nanoparticles (IONPs). This paper examined how the intravenous (IV) or intragastric (IG) route of administration influenced the intrahepatic distribution or therapeutic effects of IONPs. Wistar rats, some with bleeding-induced anemia, and iron oxide nanoparticles functionalized with salicylic acid (SaIONPs), with an average hydrodynamic diameter of 73 nm, compatible with rat sinusoid fenestrations, were used in this study. Light microscopy and multispectral camera analysis of Prussian blue labeled SaIONPs allowed mapping of intrahepatic nanoparticle deposits and revealed intrahepatic distribution patterns specific to each route of administration: loading of Kupffer cells and periportal hepatocytes when the IV route was used and predominant loading of hepatocytes when the IG route was used. Reducing the time to return to baseline values for hemoglobin (HGB) in rats with bleeding-induced anemia with IV or IG therapy has proven the therapeutic potential of SaIONPs in such anemias. The long-term follow-up showed that IV therapy resulted in higher HGB values. Proper use of the administration routes may modulate intrahepatic distribution and therapeutic effects of nanoparticles. These results may be beneficial in theragnosis of liver disease.

The Hepatitis C Virus (HCV) infection often associates medical and mental health conditions which lead to increased levels of distress. Our study aimed at assessing the level of perceived stress on a sample of 90 HCV infected patients treated with Direct-Acting Antiviral (DAA) agents for 12 weeks, and its possible correlations with clinical and evolutionary elements. The evaluation was conducted in three phases: before administration of the DAAs (BSL), at the End of the Treatment (EOT), and 24 weeks after the BSL (Sustained Viral Response—SVR). The perceived stress was measured using the Perceived Stress Scale (PSS). The efficiency of the DAA treatment reduced the levels of stress (98.99% moderate and high stress at BSL to 70.00% at SVR). It was observed, for the entire study period (BSL to SVR), that the decrease in the perceived stress severity was significantly associated with demographic items such as gender (p < 0.01), urban environment (p < 0.001), the age of the subjects (p < 0.05), and clinical data such as F4 degree of fibrosis (p = 0.001) and overweight or obesity class II (p < 0.01). The perceived stress is directly associated with the severity of the HCV infection, and it could be significantly lowered by an efficient therapeutic approach, as DAAs are nowadays.

With a simple synthesis and easy engineering of physicochemical properties, iron oxide nanoparticles (IONPs) have become widely used in multiple biomedical applications. The study of IONPs toxicity has become an important issue, especially as the results reported so far are contradictory and range from lack of toxicity to cellular toxicity. The aim of this study was to evaluate the histopathological changes induced in mouse liver by long-term intraperitoneal injection of low doses of IONPs functionalized with salicylic acid (SaIONPs). The study was performed on C57BL/6 mice that received by intraperitoneal injection (IP), every two days, 0.6ml of SaIONPs aqueous suspension (35mg/kg body weight SaIONPs that contained 20mg/kg body weight of Fe3O4) for 28 days. The results of this study showed that the cumulative dose of 105mg/kg body weight SaIONPs (62mg/kg body weight of Fe3O4) induced histopathological changes in the subcapsular region of the mouse liver, possible by the release of salicylic acid into the peritoneal cavity. The cumulative dose of 244mg/kg body weight SaIONPs (145mg/kg body weight of Fe3O4) induced liver centrilobular necrosis, which requires the use of lower doses in biological applications. However, this may prove to be beneficial in the case of targeted accumulation of SaIONPs., Competing Interests: None to declare., (Copyright © 2014, Medical University Publishing House Craiova.)

Liver damage can lead to secondary organ damage by toxic substances and catabolic products accumulation which can increase the permeability of blood-brain barrier, leading to cognitive impairment. The only real treatment for end stage liver failure is grafting. With some, but not all, neurological symptoms subsiding after transplantation, the presence of brain damage can impair both the short and long-term outcome. We tested if Cerebrolysin can prevent brain injury in an experimental model of non-viral liver damage in mice. Behavior, abdominal ultrasound evaluation and immunohistochemistry were used to evaluate the animals. No ultrasound or behavior differences were found between the control and treated animals, with both groups displaying more anxiety and no short-term memory benefit compared to sham mice. Cerebrolysin treatment was able to maintain a normal level of cortical NeuN + cells and induced an increase in the area occupied by BrdU + cells. Surprisingly, no difference was observed when investigating Iba1 + cells. With neurological complications of end-stage liver disease impacting the rehabilitation of patients receiving liver grafts, a neuroprotective treatment of patients on the waiting lists might improve their rehabilitation outcome by ensuring a minimal cerebral damage.

Hepatitis C virus (HCV) represents the most important etiologic factor for advanced fibrosis/cirrhosis and hepatocellular carcinoma associated with a psychological dimension. Our study aims to assess, on a sample comprising of 90 HCV-infected subjects (96.67% F3-F4 METAVIR), the relationship between Direct-Acting Antiviral (DAA) therapies and the psychological effects of the liver disease, focused on the anxious and depressive symptoms. The comprehensive evaluation was done before starting the DAA treatment (BSL), after 12 weeks (End of Treatment-EOT), respectively after another 12 weeks (Sustained Viral Response-SVR). Presumable depressive and/or anxious symptoms were evaluated by Hospital Anxiety and Depression Scale (HADS). The reported depressive symptoms decreased from 21.11% (BSL) to 1.11% (SVR) ( p < 0.00001), while the anxious ones dropped from 43.34% (BSL) to 4.44% (SVR) ( p < 0.00001), without a clear evolutionary pattern. We identified no statistically significant interaction between comorbidities (anemia, CKD, obesity) over HADS scores evolution ( p > 0.05), while the DAAs side-effects (fatigue, headache, pruritus) significantly influenced the anxious and depressive symptoms ( p < 0.05). During and after the DAA-based therapy, patients with HCV infection presented a significantly reduced rate of the associated depressive and anxious relevant symptoms.

The study is aimed at assessing the impact that periodontal disease and chronic hepatitis C could have on gingival crevicular fluid levels of the NLRP3 inflammasome, caspase-1 (CASP-1), and interleukin-18 (IL-18) and at evaluating whether the increased local inflammatory reaction with clinical periodontal consequences is correlated to their upregulation. Patients were divided into four groups, according to their periodontal status and previously diagnosed hepatitis C, as follows: (i) CHC group, chronic hepatitis C patients; (ii) P group, periodontal disease patients, systemically healthy; (iii) CHC + P group, patients suffering from both conditions; and (iv) H group, systemically and periodontally healthy controls. Gingival crevicular samples were collected for quantitative analysis of the NLRP3 inflammasome, CASP-1, and IL-18. CHC + P patients expressed the worse periodontal status and the highest NLRP3, CASP-1, and IL-18 levels, the difference being statistically significant ( p < 0.05). The P group patients also expressed significantly more elevated NLRP3, CASP-1, and IL-18 levels, as compared to nonperiodontal patients (CHC and H groups). Chronic hepatitis C and periodontal disease could have a significant influence on the upregulation of NLRP3 inflammasome and its components, possibly contributing to an increased local inflammatory reaction and clinical periodontal consequences., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Petra Surlin et al.)

Non-surgical periodontal therapy (NSPT) is the first essential step for the management of any periodontitis patient. This study aims to evaluate the impact of NSPT on pro-inflammatory mediators' regulation and on clinical parameters in periodontitis patients who suffer from chronic hepatitis C. At baseline, selected patients were clinically evaluated for their periodontal status. A subsequent quantitative assessment of C-reactive protein and pentraxin-3 in samples of gingival fluid was performed by Enzyme-Linked Immunosorbent Assay (ELISA). Afterwards, NSPT was performed. Three months after NSPT, the clinical and ELISA assessments were repeated. The results show an improvement of the clinical parameters in periodontitis patients at the three-month recall. In chronic hepatitis C patients with periodontitis, the gingival fluid levels of pro-inflammatory markers reduced significantly. The targeted markers also expressed significant correlations with the clinical parameters used for the assessment of periodontitis' severity. The results suggest that, while chronic hepatitis C patients exhibited a more negative periodontal status at baseline as compared to non-hepatitis ones, NSPT is effective in decreasing the local periodontal inflammatory reaction and in proving the periodontal status of this type of patients. Given the limitation of the study, periodontal screening and NSPT should be included in the integrated therapeutical approach of chronic hepatitis C patients, for its impact on the local inflammatory response.

Telomeres, the protective caps of chromosomes, shorten with age, as telomerase, the enzyme responsible for the compensation of telomere erosion, is inactive in the majority of cells. Telomere shortening and subsequent cell senescence lead to tissue aging and age‑related diseases. Neurodegenerative disorders, characterized by the progressive loss of neurons among other hallmarks of aged tissue, and poor cognitive function, have been associated with a short telomere length. Thus, telomerase activity has emerged as a therapeutic target, with novel agents being under investigation. The present study aimed to examine the effects of a novel natural telomerase activator, 'Reverse™', containing Centella asiatica extract, vitamin C, zinc and vitamin D3 on the brains of 18‑month‑old rats. The administration of the 'Reverse™' supplement for 3 months restored telomerase reverse transcriptase (TERT) expression in the brains of rats, as revealed by ELISA and immunohistochemistry. In addition, the findings from PCR‑ELISA demonstrated an enhanced telomerase activity in the cerebellum and cortex cells in the brains of rats treated with the 'Reverse™' supplement. The histopathological findings confirmed a structural reversibility effect close to the differentiation observed in the young control group of rats treated with two capsules/kg body weight of the 'Reverse™' supplement. On the whole, the findings of the present study provide a strong indication that an increased telomerase activity and TERT expression may be achieved not only in the postnatal or embryonic period, but also in the brains of middle‑aged rats through nutraceutical supplementation. The use of the 'Reverse™' supplement may thus contribute to the potential alleviation of a number of central nervous system diseases.

Background: In response to the goal of the World Health Organisation to eliminate hepatitis C virus infections by 2030, Romania is striving for national elimination. An already successful micro-elimination project was expanded to test-and-treat specific populations and at-risk groups. The aim of this project was to identify the individuals with HCV infection in disadvantaged regions who do not have proper medical care access., Materials and Methods: Our two-arm interventional cross-sectional study used rapid anti-HCV antibody testing on two population groups from the Romanian southwestern region of Oltenia, approached between September 2020 and May 2021. The first group consisted of predominantly over 40 years old individuals, recruited through five family doctors from two medium-sized towns (community lot-CL). We approached a second group, aged 18-65, through 11 medical offices of five large factories in the same region (industry lot, IL). A 12-items questionnaire was given to each participant, to determine risk factors and record demographic data. Eligible patients initiated antiviral therapy using direct-acting antivirals (DAAs)., Results: We enrolled 15,383 individuals between all 16 locations. The overall prevalence by antibody testing was 0.77% (119 cases). Of these, 57 subsequently received treatment with DAAs. We identified blood transfusions as a risk factor within the CL. Participants in the IL reported a relatively high risk for the following situations: sharing of personal hygiene belongings with another person, performing previous blood transfusions, dental interventions and previous surgery., Conclusions: In this global context, the use of micro-elimination allows interventions to be faster and more efficient. This is possible by targeting smaller and specific HCV risk groups.

This study aims to develop a new self-report tool (HCV-AD) measuring adherence factors, intentional or unintentional, during Hepatitis C Virus (HCV) treatment with direct-acting antivirals (DAA) aiming to achieve high efficacy, otherwise resulting in drug resistance and treatment failure. Two phases were conducted: in the first phase, items were generated based on an extensive literature review, and, in the second phase, a prospective cohort study was conducted using HCV patients from Gastroenterology Department from University County Hospital of Craiova, Romania (n = 222), to evaluate the validity and reliability of the questionnaire. A number of 19 items were generated following a systematic review and through expert opinion. The internal consistency reliability was evaluated using Cronbach's alpha. The construct validity was assessed using correlations with two other instruments: visual analog scale (VAS) and medication possession ratio (MPR). The final questionnaire (HCV-AD10) was derived through exploratory factor analysis, with 82% of total variance explained. This instrument appeared as a reliable and valid measure for medication adherence, with Cronbach's alpha (0.867) and significant high positive correlations between adherence scores calculated with HCV-AD10 and VAS (ρ = 0.61, p < 0.001) or with HCV-AD10 and MPR (ρ = 0.75, p < 0.001). This research would make a worthwhile contribution to HCV management.

Hepatitis C virus represents one of the most important public health problems nowadays. Several epidemiological studies have shown a continuous increasing rate of prevalence and incidence with severe consequences in terms of mortality. During the last decades, the treatment of the liver infection has evolved, and now there are available new therapies with better side-effect' profiles and bigger efficiency. The needs for more therapeutically efficacy also stand behind the numerous comorbidities associated to the liver disease, and also for assuring better quality of life for patients and their families., Competing Interests: None to declare., (Copyright © 2014, Medical University Publishing House Craiova.)

Purpose: The purpose of this ex vivo study is to exhibit the inflammatory changes that occur within the gingival tissue by using optical coherence tomography (OCT) in periodontal patients with non-alcoholic fatty liver disease (NAFLD) and if NAFLD could influence the local periodontal inflammation., Patients and Methods: Gingival tissue samples obtained from patients were divided into three groups - P (periodontitis), NAFLD+P (NAFLD+periodontitis) and H (healthy) groups - and were scanned using an OCT light beam, in order to perform a qualitative and quantitative analysis of images. The value of average pixel density has been associated with the degree of inflammation., Results: The highest average pixel density was found in patients from the H group, while the lowest value of average pixel density was recorded in gingival tissue samples collected from patients with NAFLD+P. The image assessments from NAFLD+P group delivered lower values of average pixel density than those of P group, suggesting a possible influence of this disease on the inflammatory tissular changes produced by periodontal disease., Conclusion: After comparing the OCT analysis results obtained for the three groups of patients, we can consider that NAFLD may be an aggravating factor for the inflammation of periodontal disease., Competing Interests: The authors declared no conflicts of interest for this work., (© 2021 Surlin et al.)

Clostridioides difficile infection (CDI) stands as the leading cause of nosocomial infection with high morbidity and mortality rates, causing a major burden on the healthcare system. Driven by antibiotics, it usually affects older patients with chronic disease or immunosuppressed or oncologic management. Variceal bleeding secondary to cirrhosis requires antibiotics to prevent bacterial translocation, and thus patients become susceptible to CDI. We aimed to investigate the risk factors for CDI in cirrhotic patients with variceal bleeding following ceftriaxone and the mortality risk in this patient's population. We retrospectively screened 367 cirrhotic patients with variceal bleeding, from which 25 patients were confirmed with CDI, from 1 January 2017 to 31 December 2019. We found MELD to be the only multivariate predictor for mortality (odds ratio, OR = 1.281, 95% confidence interval, CI: 0.098-1.643, p = 0.042). A model of four predictors (age, days of admission, Charlson index, Child-Pugh score) was generated (area under the receiver operating characteristics curve, AUC = 0.840, 95% CI: 0.758-0.921, p < 0.0001) to assess the risk of CDI exposure. Determining the probability of getting CDI for cirrhotic patients with variceal bleeding could be a tool for doctors in taking decisions, which could be integrated in sustainable public health programs.

Non-alcoholic fatty liver disease affects about 30% of the population and it has a growing tendecy with the increasing incidence of obesity. Currently, a large amount of clinical evidence has shown that cardiovascular disease represents the main cause of mortality in patients suffering from non-alcoholic fatty liver disease., Objective: In this study we investigated the structural and functional changes of the left ventricle in young adults with hepatic steatosis using modern echocardiographic techniques., Methods: By using tissue Doppler imaging and also Speckle tracking echocardiography the left ventricle systolic function was assessed., Results: All patients included in the study had a normal left ventricular ejection fraction but, when the longitudinal function of the left ventricle was assessed using the tissue Doppler technique (maximum systolic velocity S) statistically significant differences were found in both the group of patients with non-alcoholic fatty liver as well as in the group of patients associated with diabetes. Using speckle tracking echocardiography, we found a statistically significant decrease of the global longitudinal strain in the endocardium, in the group of patients with non-alcoholic liver disease but also in the group of those with diabetes. The overall longitudinal strain at the myocardium was significantly reduced only in the group of patients with non-alcoholic fatty liver disease and diabetes, while the overall longitudinal strain at the epicardium showed no changes in any of the groups studied. Also, no changes were observed at the circumferential strain., Conclusion: Non-alcoholic fatty liver disease, diagnosed in asymptomatic young adults may be a risk factor for remodeling the left ventricle over time, being associated with subclinical myocardial dysfunction, regardless of the presence of other cardiovascular risk factors., Competing Interests: None to declare., (Copyright © 2014, Medical University Publishing House Craiova.)