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Inflammatory bowel disease (IBD) represents heterogeneous and relapsing intestinal conditions with a severe impact on the quality of life of individuals and a continuously increasing prevalence. In recent years, the development of sequencing technology has provided new means of exploring the complex pathogenesis of IBD. An ideal solution is represented by the approach of precision medicine that investigates multiple cellular and molecular interactions, which are tools that perform a holistic, systematic, and impartial analysis of the genomic, transcriptomic, proteomic, metabolomic, and microbiomics sets. Hence, it has led to the orientation of current research towards the identification of new biomarkers that could be successfully used in the management of IBD patients. Multi-omics explores the dimension of variation in the characteristics of these diseases, offering the advantage of understanding the cellular and molecular mechanisms that affect intestinal homeostasis for a much better prediction of disease development and choice of treatment. This review focuses on the progress made in the field of prognostic and predictive biomarkers, highlighting the limitations, challenges, and also the opportunities associated with the application of genomics and epigenomics technologies in clinical practice.
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Biomarcadores , Epigénesis Genética , Enfermedades Inflamatorias del Intestino , Humanos , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/metabolismo , Pronóstico , Epigenómica/métodos , Genómica/métodos , Predisposición Genética a la EnfermedadRESUMEN
Portal hypertension from chronic liver disease leads to the formation of collateral blood vessels called spontaneous portosystemic shunts (SPSS). These shunts may form from existing vessels or through neo-angiogenesis. Their location affects clinical outcomes due to varying risks and complications. This review summarizes current knowledge on SPSS, covering their clinical impact and management strategies. Recent data suggest that SPSS increases the risk of variceal bleeding, regardless of shunt size. The size of the shunt is crucial in the rising incidence of hepatic encephalopathy (HE) linked to SPSS. It also increases the risk of portopulmonary hypertension and portal vein thrombosis. Detecting and assessing SPSS rely on computed tomography (CT) and magnetic resonance imaging. CT enables precise measurements and the prediction of cirrhosis progression. Management focuses on liver disease progression and SPSS-related complications, like HE, variceal bleeding, and portopulmonary hypertension. Interventional radiology techniques such as balloon-occluded, plug-assisted, and coil-assisted retrograde transvenous obliteration play a pivotal role. Surgical options are rare but are considered when other methods fail. Liver transplantation (LT) often resolves SPSS. Intraoperative SPSS ligation is still recommended in patients at high risk for developing HE or graft hypoperfusion.
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BACKGROUND AND AIMS: Increases in both the prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity are closely related. Type 2 diabetes (T2DM) has been associated with metabolic dysfunction-associated steatohepatitis (MASH)-related cirrhosis and hepatocellular carcinoma. Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of T2DM and has an important role in weight loss. Also, it may represent a new therapeutic option for the treatment of MASH in obese diabetic patients. The main outcomes were changes from baseline in liver steatosis and fibrosis at week 24. MATERIAL AND METHODS: A total of one hundred eighty-seven patients with T2DM were eligible for this prospective study; ninety-five subjects were treated with oral semaglutide, and ninety-two patients were treated with dapagliflozin as an add-on to metformin. All the subjects were evaluated using Vibration Controlled Transient Elastography (VCTE) from June to December 2022. RESULTS: From our cohort, 54% of the patients were females, with a mean age of 59.92 ± 11.89 years and a mean body mass index (BMI) of 29.53 ± 5.33 kg/m2. Following a six-month medication period, we observed a substantial reduction in anthropometric measurements, including the BMI, waist circumference (WC), and waist-to-hip ratio (WtHr), in both groups. Regarding HbA1c, a notable decrease was observed in the semaglutide group (p < 0.001) when compared to the dapagliflozin group (p = 0.011). In addition, the liver stiffness measurement (LSM) according to VCTE improved significantly in the semaglutide group participants from 8.07 ± 2.90 kPa at baseline to 6.51 ± 3.09 kPa after medication (p < 0.001). CONCLUSION: The superior metabolic effects of semaglutide, correlated to dapagliflozin, may contribute to a more efficient decrease in hepatic stress and injury, leading to a substantial enhancement of liver function in T2DM patients. Further investigations conducted over an ideal timeframe are necessary to confirm the evidence presented in this study.
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In this editorial we comment on the article titled "Inflammatory bowel diseases patients suffer from significant low levels and barriers to physical activity: The BE-FIT-IBD study" published in a recent issue of the World Journal of Gastroenterology 2023; 29 (41): 5668-5682. Inflammatory bowel diseases (IBD) are emerging as a significant global health concern as their incidence continues to rise on a global scale, with detrimental impacts on quality of life. While many advances have been made regarding the management of the disease, physical inactivity in these patients represents an underexplored issue that may hold the key for further and better understanding the ramifications of IBD. Chronic pain, fatigue, and fear of exacerbating symptoms promotes physical inactivity among IBD patients, while the lack of clear guidelines on safe exercise regimens contributes to a norm of physical inactivity. Physical activity (PA) is accepted to have a positive effect on disease outcomes and quality of life, while inactivity exacerbates comorbidities like cardiovascular disease and mental health disorders. The "BE-FIT-IBD" study, focusing on PA levels and barriers in IBD patients of Southern Italy, revealed that a significant proportion (42.9%) were physically inactive. This lack of PA is attributed to barriers such as fear of flare-ups and misconceptions about exercise exacerbating the disease. The study also highlighted the need for better communication between healthcare providers and patients regarding the benefits of PA and safe incorporation into lifestyles. Moreover, physical inactivity may also contribute to disability in IBD patients, having a great impact on employment status. Of note is the fact that IBD also comes with an important psychological burden with relevant evidence suggesting that regular PA can improve mood, reduce anxiety, and enhance mental health. The "BE-FIT-IBD" study advocated for the integration of PA into IBD management, emphasizing the bidirectional link between PA and IBD. Regular exercise can influence the course of IBD, potentially reducing symptom severity and prolonging remission periods. As such, it is mandatory that healthcare providers actively educate patients, dispel misconceptions, and tailor exercise recommendations to improve the quality of life and reduce IBD-related complications.
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Enfermedades Inflamatorias del Intestino , Calidad de Vida , Humanos , Conducta Sedentaria , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/psicología , Ejercicio FísicoRESUMEN
BACKGROUND AND AIMS: The burnout syndrome (BOS) is commonly seen in healthcare professionals, particularly in physicians who are exposed to a high level of stress at work and has a negative impact on the medical activity. Physicians with BOS manifest a negative attitude, a reduction in compassion at work, and suboptimal patient care experiences. These all can lead to absenteeism, poor performance and more frequent medical errors. We aimed to assess the level of BOS in a tertiary gastroenterology university center in Romania. METHODS: This observational study involved 40 physicians from a tertiary gastroenterology university center. An online questionnaire assessed the presence of BOS using the Maslach Burnout Inventory. RESULTS: A total of 40 physicians responded to the questionnaire. The prevalence of overall BOS of 87.5%. In terms of high burnout, 15 doctors (37.5%) had emotional exhaustion, 10 doctors (25%) had depersonalization, and 30 doctors (80%) scored low for personal achievement. Men presented more frequently emotional exhaustion and women lower personal achievement scores, but there was no significant statistical difference. No significant relationship was found between marital status or the number of children and BOS. We identified multiple risk factors associated to BOS, the most important one being strict internal regulations. CONCLUSIONS: Physicians presented an increased risk for BOS. The high rate of BOS among physicians found in our study requires careful attention. Further studies aiming to identify other factors that contribute to BOS and to identify measures to combat this syndrome are necessary.
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Agotamiento Profesional , Gastroenterología , Pruebas Psicológicas , Autoinforme , Femenino , Humanos , Masculino , Agotamiento Profesional/epidemiología , Agotamiento Profesional/psicología , Rumanía/epidemiología , Encuestas y Cuestionarios , UniversidadesRESUMEN
Background and Objectives: Alcoholic hepatitis (AH) poses a medical challenge, causing moderately severe to life-threatening episodes with high short- and long-term mortality. This study aimed to explore real-world corticosteroid utilization in severe AH, response predictors, and patient outcomes. Materials and Methods: We conducted a retrospective study on patients admitted for severe AH, defined as a Maddrey Discriminant Function score equal to or above 32, at a tertiary care center. We reviewed patients' medical observation charts to identify corticosteroid prescriptions, reasons for ineligibility, and response rates. Responders were defined based on the Lille score, and predictors of non-response were identified. Short-term (one-month) and long-term (one-year) mortality rates were calculated according to treatment and response. Results: Out of 310 patients enrolled with severe AH, 59% received corticosteroids, achieving a response rate of 75.4%. The reasons for not administering corticosteroids were as follows: uncontrolled infections (27.6%), renal dysfunction (20.4%), gastrointestinal bleeding (18.9%), acute pancreatitis (7.1%), uncontrolled diabetes (3.1%), and other or unknown causes (22.8%). The overall 1-month mortality rate was 12.2%, higher in non-responders (35.3%) and patients who did not receive corticosteroids (13.4%) compared to responders (3.6%). The overall 1-year mortality rate was 62.5%, similar between patients who did not receive corticosteroids (78.7%) and non-responders (77.7%) and higher compared to responders (42.8%). Predictive factors for non-response included older age (OR = 1.05, 95%CI: 1.01-1.08), concomitant cirrhosis (OR= 2.11, 95% CI: 1.064-4.20), MELD scores exceeding 30 (OR = 2.42, 95% CI: 1.21-4.80), severe hypoalbuminemia (OR = 2.46, 95%CI: 1.12-5.37), and increased serum creatinine (OR = 1.5, 95% CI: 1.1-2.03). Among the prognostic scores, MELD 3.0 score exhibited superior efficacy for short-term (AUC = 0.734, 95% CI 0.656-0.811) and long-term mortality (AUC = 0.777, 95% CI: 0.724-0.830) compared to alternative scoring systems. Conclusions: Low eligibility rate and poor prognosis underscore the need for effective therapies. Our findings contribute to refining risk stratification and early prediction of non-response, aiding clinicians in identifying more beneficial therapies.
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Hepatitis Alcohólica , Pancreatitis , Humanos , Hepatitis Alcohólica/complicaciones , Hepatitis Alcohólica/tratamiento farmacológico , Estudios Retrospectivos , Factores de Riesgo , Enfermedad Aguda , Pronóstico , Índice de Severidad de la Enfermedad , Corticoesteroides/uso terapéuticoRESUMEN
Traditional methods have their limitations when it comes to unraveling the mysteries of the small bowel, an area historically seen as the "black box" of the gastrointestinal tract. This is where capsule endoscopy and enteroscopy have stepped in, offering a remarkable synergy that transcends the sum of their individual capabilities. From their introduction, small bowel capsule endoscopy and device-assisted enteroscopy have consistently evolved and improved, both on their own and interdependently. Each technique's history may be told as a success story, and their interaction has revolutionized the approach to the small bowel. Both have advantages that could be ideally combined into a perfect technique: safe, non-invasive, and capable of examining the entire small bowel, taking biopsies, and applying therapeutical interventions. Until the realization of this perfect tool becomes a reality, the key for an optimal approach lies in the right selection of exploration method. In this article, we embark on a journey through the intertwined development of capsule endoscopy and enteroscopy, exploring the origins, technological advancements, clinical applications, and evolving inquiries that have continually reshaped the landscape of small bowel imaging.
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INTRODUCTION: Alcohol consumption (AC) represents a widespread cause of liver diseases affecting 10-20% of the population. The study aimed to evaluate the relationship between advanced liver fibrosis (ALF) measured by transient elastography (TE), laboratory parameters, and the amount of AC depending on non-modifiable risk factors such as age and gender. METHODS: We examined 689 patients with an average age of 49.32 ± 14.31 years, 72.9% males, without liver pathology, who admitted a moderate/high consumption (female ≤ 7 versus > 7 drinks/week; male ≤ 14 versus > 14 drinks/week) for at least five years. The fibrosis level was adjusted according to transaminase levels. Predictive factors were established using univariate regression analysis. RESULTS: ALF (≥F3) was detected in 19.30% of subjects, predominantly males (14.1%) and patients over 55 years (12.5%). Excessive consumption of distilled spirits is associated with ALF in females (OR = 4.5), males (OR = 6.43) and patients over 55 years (OR = 3.73). A particularity highlighted in both genders, regardless of the age group, was the negative correlation between the decrease in the number of platelets, the albumin concentration, and the appearance of AFL. CONCLUSIONS: Screening using TE represents an approach for early detection of ALF in asymptomatic populations and the development of a risk stratification scheme.
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Background and Objectives: Ulcerative colitis (UC) and Crohn's disease (CD) are idiopathic inflammatory bowel diseases (IBDs) without a unique, gold standard diagnostic test. UC and Crohn's colitis are impossible to distinguish in approximately 10% of cases. The term IBD type unclassified (IBD-U) is recommended for cases of chronic colitis showing overlapping endoscopic, radiological, and biopsy histological features between UC and CD, while indetermined colitis is reserved for colectomy specimens. Our aim was to assess the role of small-bowel capsule endoscopy (SBCE) in the diagnostic work-up of IBD-U. Materials and Methods: We retrospectively studied the cases of IBD-U explored by SBCE in a tertiary referral gastroenterology center. Patients were investigated using SBCE after contraindications were excluded. Diagnostic criteria for small bowel CD consisted in more than three ulcerations, irregular ulcers, or stenosis, and the Lewis score was used for the quantification of inflammation. The immediate impact of reclassification and outcome data was recorded over a follow-up period of more than one year. Results: Twenty-eight patients with IBD-U were examined using SBCE. Nine patients had small bowel lesions that met the diagnostic criteria for CD, resulting in a reclassification rate of 32.1%. In five of these cases, the treatment was subsequently changed. In the remaining nineteen examinations, no significant findings were observed. There were no complications associated with SBCE. Median follow-up time was 32.5 months (range 12-60). During follow-up, twelve patients were classified as having UC, and seven remained as having an unclassified type; one case of colectomy, for medically refractory UC, was recorded. Conclusions: SBCE is a useful safe tool in the work-up of IBD-U, allowing reclassification in about one third of cases, with subsequent treatment modifications. SBCE may provide a definite diagnosis, enhance the comprehension of the disease's progression, and optimize the short- and long-term management strategy.
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Endoscopía Capsular , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Endoscopía Capsular/métodos , Estudios Retrospectivos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/complicaciones , Colitis Ulcerosa/complicacionesRESUMEN
Background: Hepatic encephalopathy (HE) caused by cirrhosis has severe consequences on an individual's lifespan, leading to long-term liver complications and potentially life-threatening outcomes. Despite recent interest in this condition, the effectiveness of secondary prophylaxis involving rixafimin, lactulose, or L-ornithine L-aspartate (LOLA) may be hindered by the unique microbial profiles each patient possesses. Methods: Thus, in this manuscript, we aimed to search, identify, and gather all randomized controlled trials (RCTs) published between 2000-2023 (November) in four major academic databases such as PubMed, ISI Web of Science, Scopus, and ScienceDirect by using a controlled terminology and web strings that reunite six main keywords. We complementarily retrieved data on the ongoing RCTs. Results: Regardless of the relatively high number of results displayed (n = 75), 46.66% (n = 35) were initially deemed eligible after the first evaluation phase after removing duplicates, n = 40 (53.34%). At the second assessment stage, we eliminated 11.42% (n = 4) studies, of which n = 22 finally met the eligibility criteria to be included in the main body of the manuscript. In terms of RCTs, otherwise found in distinct stages of development, n = 3 target FMT and n = 1 probiotics. Conclusions: Although we benefit from the necessary information and technology to design novel strategies for microbiota, only probiotics and synbiotics have been extensively studied in the last decade compared to FMT.
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Encefalopatía Hepática , Probióticos , Humanos , Encefalopatía Hepática/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Lactulosa/uso terapéutico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Probióticos/uso terapéuticoRESUMEN
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. Its incidence is progressively rising and it is possibly becoming a worldwide epidemic. NAFLD encompasses a spectrum of diseases accounting for the chronic accumulation of fat within the hepatocytes due to various causes, excluding excessive alcohol consumption. In this study, we aimed to focus on finding evidence regarding the implications of oxidative stress and inflammatory processes that form the multifaceted pathophysiological tableau in relation to thrombotic events that co-occur in NAFLD and associated chronic liver diseases. Recent evidence on the pathophysiology of NAFLD suggests that a complex pattern of multidirectional components, such as prooxidative, proinflammatory, and prothrombotic components, better explains the multiple factors that promote the mechanisms underlying the fatty acid excess and subsequent processes. As there is extensive evidence on the multi-component nature of NAFLD pathophysiology, further studies could address the complex interactions that underlie the development and progression of the disease. Therefore, this study aimed to describe possible pathophysiological mechanisms connecting the molecular impairments with the various clinical manifestations, focusing especially on the interactions among oxidative stress, inflammation, and coagulation dysfunctions. Thus, we described the possible bidirectional modulation among coagulation homeostasis, oxidative stress, and inflammation that occurs in the various stages of NAFLD.
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Trastornos de la Coagulación Sanguínea , Enfermedad del Hígado Graso no Alcohólico , Enfermedades de la Piel , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Coagulación Sanguínea , Inflamación , Estrés OxidativoRESUMEN
BACKGROUND: Despite numerous advances that have aimed to increase the safety of endoscopic retrograde cholangiopancreatography (ERCP), post-ERCP pancreatitis (PEP) still remains a major issue. We aimed to assess the rate of PEP as well as the relation to the cannulation techniques in our unit, a high-volume center in north-eastern Romania. METHODS: ERCPs performed in our unit from March to August 2022 were retrospectively included. Data concerning demographic information, presence of difficult cannulation, the technique used for cannulation, as well as immediate complications, were gathered from the electronic database. RESULTS: 233 ERCPs were included. PEP was diagnosed in 23 (9.9%) of cases. Precut sphincterotomy (PS), transpancreatic sphincterotomy (TPBS), and a combination of TPBS and PS were performed in 6.4%, 10.3%, and 1.7% of cases, respectively, while an Erlangen precut papillotomy was performed in one case. Both in patients with PS and TPBS the rate of PEP was 20%. When the two techniques were associated, the rate of PEP was 25%. TPBS and PS represented risk factors for PEP (OR 1.211 for a CI of 0.946-1.551, p = 0.041, and OR 1.124 for a CI of 0.928-1.361, p = 0.088, respectively). No PEP-associated deaths were found. CONCLUSIONS: Both PS and TPBS presented a similar risk of PEP.
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Inflammatory bowel diseases (IBD) represent a global phenomenon, with a continuously rising prevalence. The strategies concerning IBD management are progressing from clinical monitorization to a targeted approach, and current therapies strive to reduce microscopic mucosal inflammation and stimulate repair of the epithelial barrier function. Intestinal permeability has recently been receiving increased attention, as evidence suggests that it could be related to disease activity in IBD. However, most investigations do not successfully provide adequate information regarding the morphological integrity of the intestinal barrier. In this review, we discuss the advantages of confocal laser endomicroscopy (CLE), which allows in vivo visualization of histological abnormalities and targeted optical biopsies in the setting of IBD. Additionally, CLE has been used to assess vascular permeability and epithelial barrier function that could correlate with prolonged clinical remission, increased resection-free survival, and lower hospitalization rates. Moreover, the dynamic evaluation of the functional characteristics of the intestinal barrier presents an advantage over the endoscopic examination as it has the potential to select patients at risk of relapses. Along with mucosal healing, histological or transmural remission, the recovery of the intestinal barrier function emerges as a possible target that could be included in the future therapeutic strategies for IBD.
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Atrial fibrillation is frequently diagnosed in patients with liver cirrhosis, especially in those with non-alcoholic steatohepatitis or alcoholic etiology. Anticoagulant treatment is recommended for thromboembolic protection in patients with atrial fibrillation. Considering the impaired coagulation balance in liver cirrhosis, predisposing patients to bleed or thrombotic events, the anticoagulant treatment is still a matter of debate. Although patients with liver cirrhosis were excluded from the pivotal studies that confirmed the efficacy and safety of the anticoagulant treatment in patients with atrial fibrillation, data from real-life cohorts demonstrated that the anticoagulant treatment in patients with liver cirrhosis could be safe. This review aimed to evaluate the recent data regarding the safety and efficacy of anticoagulant treatment in patients with decompensated liver cirrhosis. Direct oral anticoagulants are safer than warfarin in patients with compensated liver cirrhosis. In Child-Pugh class C liver cirrhosis, direct oral anticoagulants are contraindicated. New bleeding and ischemic risk scores should be developed especially for patients with liver cirrhosis, and biomarkers for bleeding complications should be implemented in clinical practice to personalize this treatment in a very difficult population represented by decompensated liver cirrhosis patients.
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Chronic hepatitis C infection is a systemic disease that affects over 71 million patients all over the world and it is to be considered nowadays as a new cardiometabolic risk factor. This study aimed to evaluate the weight and metabolic changes after viral eradication in patients with hepatitis C virus (HCV) infection. We conducted a prospective study between October 2017 to December 2021, in a tertiary care center, in which we included 132 patients with HCV or cirrhosis. All patients received treatment with direct antivirals (DAAs) and achieved sustained viral response at 12 weeks (SVR12). During the study, clinical laboratory data and Fibroscan examinations were recorded in all patients. The study group was evaluated at the initiation of antiviral treatment, at SVR12, and within an average follow-up period of 6 months to 12 months after the previous evaluation. Evaluation at SVR12 and the data recorded in the post-SVR surveillance period show a further increase in BMI compared with baseline measurements with a statistically significant difference (27.11 ± 3.22 vs. 27.415 ± 3.03 vs. 28.04 ± 1.11 kg/m2, p = 0.012). The same observation was noticed for waist circumference (WC) at post-SVR evaluation (87.6 ± 13.1 vs. 88.4 ± 13.6 cm, p = 0.031). Moreover, the study population registered an increase in the average total cholesterol (TC) values at post-SVR evaluation (177.01 ± 42.2 mg/dL, p = 0.014) compared to baseline. In addition, the serum level of triglycerides had been modified after viral clearance, with a minimal decrease in the mean values of triglycerides (TGD) at SVR-12 assessment (133.48 ± 41.8 mg/dL, p = 0.78), followed by a significant increase to the mean value of 145.4 ± 47.2 mg/dL (p = 0.026) in the third evaluation. Our study highlights that HCV eradication does not improve the lipid profile in the short term, and these patients still have an additional cardiovascular risk factor due to high levels of TC, TGD, and weight gain.
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BACKGROUND: Cirrhosis can be present undected for years prior to a symptomatic presentation. Early detection may result in improved outcomes. Data are lacking, however, regarding the yield of screening in many populations. We aimed to determined prevalence of significant liver fibrosis diagnosed by vibration-controlled transient elastography (VCTE) in apparently healthy Romanians. METHODS: Between December 2021 and March 2022, we prospectively screened 1,027 subjects from different counties of Northeastern Romania using VCTE and B-mode ultrasonagraphy after a comprehensive medical history questionnaire. Participants with abnormal liver stiffness measurement values were further evaluated by laboratory tests to identify the severity and etiology of chronic liver disease. RESULTS: Overall, 17.9% of subjects had liver stiffness measurments (LSM) ≥8 kpa, including 55 with LSM ≥13.0 kpa. Among these subjects, 26.1% had a history of heavy alcohol intake, 22.3% tested positive for hepatitis B and/or C infection, and 49.5% were diagnosed with NAFLD. The prevalence of elevated LSM was highest among older subjects (>60 y old) and those with diabetes. Among those with LSM ≥13 kPa and ≥9.6 kpa, FIB-4 was <2.67 in 46.9% and 87.5% respectively. CONCLUSION: There is high prevalence of significant liver fibrosis in the Romanian general population. VCTE is a usefool tool for early detection of liver disease and appears more sensitive than FIB-4.
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Enfermedad del Hígado Graso no Alcohólico , Calidad de Vida , Femenino , Humanos , Persona de Mediana Edad , Anciano , Masculino , Rumanía , Estudios Prospectivos , Prevalencia , Cirrosis Hepática/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/complicacionesRESUMEN
INTRODUCTION: Recent research points to a link between chronic hepatitis C virus (HCV) infection and cardiovascular disease, especially carotid atherosclerosis, and suggests that HCV clearance may impact cardiovascular outcomes. AIM: To determine if viral eradication by the new oral direct-acting antiviral (DAA) agents has benefit regarding carotid atherosclerosis, peripheral artery disease (PAD), steatosis, and liver fibrosis. PATIENTS, MATERIALS AND METHODS: We conducted a prospective study on 168 patients diagnosed with chronic HCV infection or HCV-related cirrhosis. They were all treated with DAAs, with sustained virological response (SVR). Laboratory data, vibration-controlled transient elastography (VCTE), carotid intima-media thickness (IMT) measurement, and ankle-brachial index (ABI) were recorded in all patients. RESULTS: We found an average IMT of 1.22±0.2 mm, with a variance range from 1.14±0.19 mm in the mild and moderate fibrosis (≤F2) group to 1.29±0.25 mm in the severe fibrosis (≥F3) group. Also, patients with severe fibrosis (≥F3) present a more critical decrease of IMT values, with the carotid thickness affecting only 18.2% of individuals in the follow-up period. At the baseline, the best values of ABI were recorded in patients having F1-F2 fibrosis stage (mean value 1.02±0.19). Instead, in the group with severe fibrosis, the average value of ABI was lower (0.91±0.16) at the baseline, with a significant increase at SVR evaluation (p<0.001). CONCLUSIONS: Our research highlights the beneficial effect of viral eradication on both carotid atherosclerosis and PAD, especially in those with advanced fibrosis and cirrhosis.
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Enfermedades de las Arterias Carótidas , Hepatitis C Crónica , Hepatitis C , Enfermedad Arterial Periférica , Humanos , Hepacivirus , Antivirales/farmacología , Antivirales/uso terapéutico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Grosor Intima-Media Carotídeo , Estudios Prospectivos , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/tratamiento farmacológico , Enfermedades de las Arterias Carótidas/complicaciones , Enfermedades de las Arterias Carótidas/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológicoRESUMEN
Alcoholic liver cirrhosis (ALC) is a disease with multiple complications and is associated with poor prognosis and significant mortality. Identifying risk factors associated with a poor outcome is important to ensure effective treatment and increase life expectancy. We aimed to evaluate the predictive values of complications regarding mortality in ALC. We retrospectively analyzed 1429 patients with ALC hospitalized between January 2019 and April 2022 at the Institute of Gastroenterology and Hepatology Iasi. The electronic medical records were interrogated to obtain information about demographic data, complications, comorbidities, and prognostic scores: MELD-Na (model for end-stage liver disease-sodium) and CTP (Child−Turcotte−Pugh). Based on uni- and multivariate analysis, independent predictors of mortality were identified. The mean age at diagnosis was 56.15 ± 11.49 years with a ratio of 2:1 in favor of males. There were 296 deaths (20.8%), most of them during the first hospitalization (208/14.6%). It was observed during the univariate analysis that complications of the disease negatively affected the survival rate, significant values being related to infections (sepsis; OR = 21.98; p < 0.001; spontaneous bacterial peritonitis (SBP) (OR = 11.94; p < 0.001) and hepatorenal syndrome (HRS) (OR = 9.35; p < 0.001). The independent predictors, confirmed by multivariate analysis, were the association of variceal bleeding, infections, and hepatic encephalopathy or ascites, each combination being responsible for two out of 10 of the deaths during the first admission. The prognosis of the disease was negatively influenced by the worsening of liver dysfunction and the appearance of complications. The main predictors of mortality were infections, hepatic encephalopathy, variceal bleeding, and hepatorenal syndrome. Improving compliance and strict application of specific follow-up and treatment strategies could contribute to a better prognosis of patients with alcoholic liver cirrhosis.
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Enfermedad Hepática en Estado Terminal , Várices Esofágicas y Gástricas , Encefalopatía Hepática , Síndrome Hepatorrenal , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Cirrosis Hepática Alcohólica/complicaciones , Cirrosis Hepática/complicaciones , Encefalopatía Hepática/complicaciones , Síndrome Hepatorrenal/etiología , Síndrome Hepatorrenal/complicaciones , Várices Esofágicas y Gástricas/complicaciones , Estudios Retrospectivos , Enfermedad Hepática en Estado Terminal/complicaciones , Hemorragia Gastrointestinal/etiología , Índice de Severidad de la Enfermedad , PronósticoRESUMEN
BACKGROUND AND AIMS: The sofosbuvir (SOF) / velpatasvir (VEL) / voxilaprevir (VOX) combination has been evaluated in more than 800 patients enrolled in phase II and phase III studies, where it demonstrated excellent safety and efficacy, achieving overall sustained viral response (SVR) rates of more than 95%. We aimed to assess the efficacy and safety of SOF/VEL/VOX in a real-world study, including patients previously treated for genotype 1b hepatitis C virus (HCV) infection that did not obtain a sustained viral response with previous direct-acting antivirals (DAAs) therapy. METHODS: In Romania, through a nationwide government-funded program in 2019-2020, 213 patients with chronic hepatitis C non-responders to previous DAAs therapy, received treatment with SOF/VEL/ VOX 400/100/100 mg/day for 12 weeks. We performed a retrospective longitudinal study that included 143 individuals who were treated in Bucharest, IaÈi, Craiova and ConstanÈa clinics, all with genotype 1b HCV infection. Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). Serious adverse events (SAE) were registered. RESULTS: Our cohort comprised 53% males with a median age of 60 years (27÷77); 47% were pre-treated with ombitasvir/paritaprevir/ritonavir+dasabuvir ± ribavirin, 40% with ledipasvir/SOF, 13% with elbasvir/ grazoprevir. 42% of patients associated co-morbidities, 45% had compensated liver cirrhosis, 2% had treated hepatocellular carcinoma (HCC) and 1% had hepatitis B virus co-infection. SVR by intention to treat was reported in 139/143 (97.2%) and per protocol in 141/143 (98.6%). No predictive factors for SVR were identified. Rate of liver decompensation in patients with cirrhosis was 6% and was statistically associated in multivariate analysis with Child-Pugh score (p<0.01) and with severe steatosis (p=0.004). Occurrence of new HCC was reported in 3.6% of all patients with cirrhosis and was associated with poor liver function [higher Child-Pugh score (p=0.001) and low albumin levels (p=0.02)]. Serious adverse events related to therapy were reported in 1/143(0.7%). CONCLUSIONS: SOF/VEL/VOX was highly efficient in our population of patients with a 97.2% SVR. Liver decompensation occurred in 6% of cirrhotic patients at SVR, related to hepatic dysfunction.
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Carcinoma Hepatocelular , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Masculino , Humanos , Persona de Mediana Edad , Femenino , Sofosbuvir/uso terapéutico , Antivirales/uso terapéutico , Rumanía , Hepatitis C Crónica/tratamiento farmacológico , Hepacivirus/genética , Estudios Retrospectivos , Carcinoma Hepatocelular/tratamiento farmacológico , Estudios Longitudinales , Resultado del Tratamiento , Neoplasias Hepáticas/tratamiento farmacológico , Hepatitis C/tratamiento farmacológico , Genotipo , Quimioterapia Combinada , Respuesta Virológica SostenidaRESUMEN
Parkinson's disease (PD) is an enigmatic neurodegenerative disorder that is currently the subject of extensive research approaches aiming at deepening the understanding of its etiopathophysiology. Recent data suggest that distinct compounds used either as anticonvulsants or agents usually used as dopaminergic agonists or supplements consisting of live active lactic acid bacteria strains might alleviate and improve PD-related phenotypes. This is why we aimed to elucidate how the administration of rotenone (ROT) disrupts homeostasis and the possible neuroactive potential of valproic acid (VPA), antiparkinsonian agents (levodopa and carbidopa - LEV+CARB), and a mixture of six Lactobacillus and three Bifidobacterium species (PROBIO) might re-establish the optimal internal parameters. ROT causes significant changes in the central nervous system (CNS), notably reduced neurogenesis and angiogenesis, by triggering apoptosis, reflected by the increased expression of PARKIN and PINK1 gene(s), low brain dopamine (DA) levels, and as opposed to LRRK2 and SNCA compared with healthy zebrafish. VPA, LEV/CARB, and PROBIO sustain neurogenesis and angiogenesis, manifesting a neuroprotective role in diminishing the effect of ROT in zebrafish. Interestingly, none of the tested compounds influenced oxidative stress (OS), as reflected by the level of malondialdehyde (MDA) level and superoxide dismutase (SOD) enzymatic activity revealed in non-ROT-exposed zebrafish. Overall, the selected concentrations were enough to trigger particular behavioral patterns as reflected by our parameters of interest (swimming distance (mm), velocity (mm/s), and freezing episodes (s)), but sequential testing is mandatory to decipher whether they exert an inhibitory role following ROT exposure. In this way, we further offer data into how ROT may trigger a PD-related phenotype and the possible beneficial role of VPA, LEV+CARB, and PROBIO in re-establishing homeostasis in Danio rerio.