[Alcoholic liver disease - 2023]. / Alkoholos májbetegség ­ 2023.

Alcoholic liver disease represents a spectrum of liver injuries from fatty liver, steatohepatitis, fibrosis and cirrhosis to hepatocellular carcinoma. Progression of the disease depends on the amount of alcohol consumption and risk factors or comorbidities, e.g., genetic predisposition, female susceptibility, diet, smoking, obesity, viral infection. Patients with alcoholic liver disease have two pathologies to be diagnosed and treated: the liver disease per se, and the harmful, excessive alcohol consumption (alcohol use disorder) or even dependence. The early diagnosis is important for both conditions and for achieving abstinence. For the diagnosis, there are several biomarkers and non-invasive tests, including psychological tools. To maintain abstinence, pharmacological and non pharmacological interventions can be applied. Concerning the liver disease, the main aims of treatment are to decrease inflammation and oxidative stress, to inhibit cell injury and fibrosis, to modulate liver-gut axis and to support regeneration. Management of patients with alcoholic hepatitis and cirrhosis often needs a psychological support, delivered by a multidisciplinary integrated care model, a close cooperation between addiction experts and hepatologists. Patients with severe alcoholic hepatitis not responding to medical (corticosteroid) therapy should be carefully selected and considered for early liver transplantation. Orv Hetil. 2023; 164(47): 1846-1864.

[Non-invasive tests for evaluation of the severity and prognosis of liver diseases]. / A májbetegségek súlyosságának és prognózisának nem invazív vizsgálómódszerei.

Liver fibrosis is part of the structural and functional alterations in chronic liver diseases, and it is the most important prognostic factor of the risk of developing cirrhosis, liver-related complications and mortality. Although liver biopsy has traditionally been considered as the (gold standard) reference method for evaluation of fibrosis, owing to its invasiveness, sampling variability, and the static nature of information it yields, non-invasive fibrosis markers became alternatives for assessment of the severity and outcome of liver diseases during the last two decades. Serum biochemical tests, elastographies and imaging methods are available for the diagnosis and staging of fibrosis. The present paper reviews the advantages and disadvantages of these tests in hepatopathy of different etiologies, and in compensated advanced chronic liver disease, on the ground of clinical experiences and the newest international guidelines. Orv Hetil. 2023; 164(22): 847-858.

Improved body composition decreases the fat content in non-alcoholic fatty liver disease, a meta-analysis and systematic review of longitudinal studies.

Background: Based on cross-sectional studies, there is a link between body composition parameters and steatosis in non-alcoholic fatty liver disease (NAFLD). However, whether long-term changes in different body composition parameters will result in NAFLD resolution is unclear. Therefore, we aimed to summarize the literature on longitudinal studies evaluating the association between NAFLD resolution and body composition change. Methods: Based on the recommendations of the Cochrane Handbook, we performed a systematic search on September 26th, 2021, in three databases: Embase, MEDLINE (via PubMed), and Cochrane Central Register of Controlled Trials (CENTRAL). Eligible studies reported on patients with NAFLD (liver fat >5%) and examined the correlation between body composition improvement and decrease in steatosis. We did not have pre-defined body composition or steatosis measurement criteria. Next, we calculated pooled correlation coefficient (r) with a 95% confidence interval (CI). Furthermore, we narratively summarized articles with other statistical methods. Results: We included 15 studies in our narrative review and five in our quantitative synthesis. Based on two studies with 85 patients, we found a pooled correlation coefficient of r = 0.49 (CI: 0.22-0.69, Spearman's correlation) between the change of visceral adipose tissue and liver steatosis. Similarly, based on three studies with 175 patients, the correlation was r = 0.33 (CI: 0.19-0.46, Pearson's correlation). On the other hand, based on two studies with 163 patients, the correlation between subcutaneous adipose tissue change and liver steatosis change was r = 0.42 (CI: 0.29-0.54, Pearson's correlation). Furthermore, based on the studies in the narrative synthesis, body composition improvement was associated with steatosis resolution. Conclusions: Based on the included studies, body composition improvement may be associated with a decrease in liver fat content in NAFLD. Systematic review registration: Identifier: CRD42021278584.

Metabolic-associated fatty liver disease is associated with acute pancreatitis with more severe course: Post hoc analysis of a prospectively collected international registry.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a proven risk factor for acute pancreatitis (AP). However, NAFLD has recently been redefined as metabolic-associated fatty liver disease (MAFLD). In this post hoc analysis, we quantified the effect of MAFLD on the outcomes of AP. METHODS: We identified our patients from the multicentric, prospective International Acute Pancreatitis Registry of the Hungarian Pancreatic Study Group. Next, we compared AP patients with and without MAFLD and the individual components of MAFLD regarding in-hospital mortality and AP severity based on the revised Atlanta classification. Lastly, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) using multivariate logistic regression analysis. RESULTS: MAFLD had a high prevalence in AP, 39% (801/2053). MAFLD increased the odds of moderate-to-severe AP (OR = 1.43, CI: 1.09-1.89). However, the odds of in-hospital mortality (OR = 0.89, CI: 0.42-1.89) and severe AP (OR = 1.70, CI: 0.97-3.01) were not higher in the MAFLD group. Out of the three diagnostic criteria of MAFLD, the highest odds of severe AP was in the group based on metabolic risk abnormalities (OR = 2.68, CI: 1.39-5.09). In addition, the presence of one, two, and three diagnostic criteria dose-dependently increased the odds of moderate-to-severe AP (OR = 1.23, CI: 0.88-1.70, OR = 1.38, CI: 0.93-2.04, and OR = 3.04, CI: 1.63-5.70, respectively) and severe AP (OR = 1.13, CI: 0.54-2.27, OR = 2.08, CI: 0.97-4.35, and OR = 4.76, CI: 1.50-15.4, respectively). Furthermore, in patients with alcohol abuse and aged ≥60 years, the effect of MAFLD became insignificant. CONCLUSIONS: MAFLD is associated with AP severity, which varies based on the components of its diagnostic criteria. Furthermore, MAFLD shows a dose-dependent effect on the outcomes of AP.

Non-alcoholic fatty liver disease and type 2 diabetes mellitus. II. Treatment / A nem alkoholos zsírmájbetegség és a 2-es típusú cukorbetegség. II. Kezelés

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. Non-alcoholic steatohepatitis (NASH), the aggressive form of NAFLD can progress to cirrhosis, and is becoming the leading cause of end-stage liver disease. NAFLD and NASH are prevalent in obese individuals and frequently coexist with type 2 diabetes mellitus as well as cardiovascular and renal complications. There is no approved therapy for the treatment of NAFLD and NASH. Their current management focuses on controlling risk factors, and lifestyle modification, weight reduction, caloric restriction, diet and exercise, but these can be difficult to achieve and maintain. Thus, there is an urgent need for effective pharmacotherapy. This review summarizes pharmacological agents available to treat diabetes mellitus, the main risk factor of NAFLD, drugs that could potentially be useful also for the therapy of NASH. Furthermore, we describe novel therapies targeting different pathogenic pathways of NAFLD, several agents that are under development specifically for the treatment of NASH. These new classes of medications may target hepatic fat accumulation, de novo lipogenesis, farnesoid X receptor-bile acid axis, oxidative stress, inflammation, gut microbiome and fibrogenesis. Until now, the use of pioglitazone and vitamin E has only been recommended by guidelines for selected patient groups with biopsy-proven NASH. It is likely that in the future, the combination of different types of targeted pharmacotherapies will provide an effective treatment for NASH. Since NAFLD is a systemic metabolic disease, cooperation between diabetologists, nephrologists, cardiologists and hepatologists is also highly advised in the management of these patients.

EASY-APP: An artificial intelligence model and application for early and easy prediction of severity in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a potentially severe or even fatal inflammation of the pancreas. Early identification of patients at high risk for developing a severe course of the disease is crucial for preventing organ failure and death. Most of the former predictive scores require many parameters or at least 24 h to predict the severity; therefore, the early therapeutic window is often missed. METHODS: The early achievable severity index (EASY) is a multicentre, multinational, prospective and observational study (ISRCTN10525246). The predictions were made using machine learning models. We used the scikit-learn, xgboost and catboost Python packages for modelling. We evaluated our models using fourfold cross-validation, and the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and accuracy metrics were calculated on the union of the test sets of the cross-validation. The most critical factors and their contribution to the prediction were identified using a modern tool of explainable artificial intelligence called SHapley Additive exPlanations (SHAP). RESULTS: The prediction model was based on an international cohort of 1184 patients and a validation cohort of 3543 patients. The best performing model was an XGBoost classifier with an average AUC score of 0.81 ± 0.033 and an accuracy of 89.1%, and the model improved with experience. The six most influential features were the respiratory rate, body temperature, abdominal muscular reflex, gender, age and glucose level. Using the XGBoost machine learning algorithm for prediction, the SHAP values for the explanation and the bootstrapping method to estimate confidence, we developed a free and easy-to-use web application in the Streamlit Python-based framework (http://easy-app.org/). CONCLUSIONS: The EASY prediction score is a practical tool for identifying patients at high risk for severe AP within hours of hospital admission. The web application is available for clinicians and contributes to the improvement of the model.

Non-alcoholic fatty liver disease and type 2 diabetes mellitus. I. Pathogenesis / A nem alkoholos zsírmájbetegség és a 2-es típusú cukorbetegség. I. Patogenezis

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease, affecting 25% of world population. NAFLD and its progressive subphenotype, non-alcoholic steatohepatitis (NASH) are prevalent in obese individuals, and also frequently coexist with type 2 diabetes mellitus (DM). NAFLD is associated with a 2- to 3-fold increased risk of developing DM, that parallels with the severity of liver disease. NAFLD and diabetes act synergistically increasing the risk of adverse clinical outcomes. Patients with diabetes frequently have fatty liver, and diabetes is a strong predictor of the progression of NAFLD to NASH or to fibrosis and cirrhosis. Genetic factors, and increased caloric intake, dysfunctional adipose tissue, insulin resistance, free fatty acids, proinflammatory cytokines, lipotoxicity and glucotoxicity play a pivotal role in the development of NAFLD and diabetes. In this review we describe the pathogenetic mechanisms that mirror the complex causal link between these two metabolic diseases.

Diabetes Mellitus Increases the Risk of Hepatocellular Carcinoma After Direct-Acting Antiviral Therapy: Systematic Review and Meta-Analysis.

Background: Hepatitis C virus (HCV)-infected patients treated with direct-acting antivirals (DAAs) are still at risk of developing hepatocellular carcinoma (HCC) after sustained virologic response (SVR). This study aimed to investigate the role of diabetes mellitus (DM) as a potential predictive risk factor in developing de novo HCC in HCV-infected patients after DAA treatment. Methods: This study was registered on PROSPERO under registration number CRD42021230457. We performed a systematic search in four medical databases from inception through November 3rd, 2020. Studies were eligible if they reported on HCV-infected patients treated with DAAs and compared the frequency of de novo HCC in patients with and without DM. We calculated pooled odds ratios, unadjusted (UHR), and adjusted hazard ratios (AHR) with 95% confidence intervals (CIs) in meta-analysis. Results: We included 30 articles in our systematic review and meta-analysis. DM proved to be a significant risk factor of HCC in DAA-treated HCV patients in unadjusted (UHR = 1.44, CI: 1.15-1.79) and adjusted analyses (AHR = 1.31, CI: 1.06-1.62). In the group of patients achieving SVR after DAA therapy, DM increased the risk of HCC in unadjusted (UHR = 1.3, CI: 1.09-1.51) analysis; however, in adjusted results, the risk was non-significant (AHR = 1.07, CI: 0.89-1.28). In patients with advanced liver fibrosis, DM was a risk factor for HCC in adjusted (AHR = 1.36, CI: 1.03-1.8), but not in unadjusted analysis (UHR = 1.11, CI: 0.8-1.42). Conclusions: DM is an independent risk factor of de novo HCC after DAA treatment in HCV-infected patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=230457, identifier: CRD42021230457.

Association of Nonalcoholic Hepatic Fibrosis with Body Composition in Female and Male Psoriasis Patients.

Psoriasis has been associated with increased frequency of hepatic diseases. Psoriasis severity, obesity, insulin resistance, aspartate aminotransferase level, platelet count, and alcohol use are significant predictors for advanced fibrosis in psoriasis patients. Although psoriasis patients also present body composition changes (e.g., higher overall body fat, visceral fat and sarcopenia), and these have recently been reported as risk factors for hepatic fibrosis, to date, body composition has not been prospectively investigated in psoriasis in the context of liver fibrosis. In this study anthropometric assessment (body weight and body mass index (BMI)), body composition analysis (body fat%, visceral fat scores and muscle mass%), and liver stiffness measurements (using transient elastography [TE]) were done in 52 psoriasis patients undergoing methotrexate therapy. Fourteen patients (26.9%) had advanced (F3-F4) liver fibrosis. There was no correlation between the patients' liver stiffness values and the cumulative MTX doses. On the other hand, patients with higher BMI values, total body fat% and visceral fat scores were significantly more likely to present with higher hepatic stiffness values. BMI was a significant predictor of hepatic fibrosis in both genders. In males, body fat% (R = 0.578, p = 0.002) and, especially, visceral fat scores (R = 0.716, p < 0.001) had statistically significant correlation with stiffness scores, while in females only visceral fat scores were statistically significant predictors of the liver stiffness values (R = 0.452, p = 0.023), and body fat% was not (R = 0.187, p = 0.382). Our results suggest that anthropometric data should be assessed differently in female and male psoriasis patients when evaluating liver fibrosis risk.

Metabolic Associated Fatty Liver Disease Is Associated With an Increased Risk of Severe COVID-19: A Systematic Review With Meta-Analysis.

Background: The most common pre-existing liver disease, the metabolic dysfunction-associated fatty liver disease (MAFLD) formerly named as non-alcoholic fatty liver disease (NAFLD), may have a negative impact on the severity of COVID-19. This meta-analysis aimed to evaluate if MAFLD or NAFLD are associated with a more severe disease course of COVID-19. Methods: A systematic search was performed in five databases for studies comparing severity, the rate of intensive care unit (ICU) admission, and mortality of COVID-19 patients with and without MAFLD or NAFLD. In meta-analysis, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: Altogether, we included nine studies in our quantitative and qualitative synthesis. MAFLD was associated with an increased risk of severe COVID-19 compared to the non-MAFLD group (28 vs. 13%, respectively; OR = 2.61, CI: 1.75-3.91). Similarly, in the NAFLD vs. non-NAFLD comparison, NAFLD proved to be a risk factor as well (36 vs. 12%, respectively; OR = 5.22, CI: 1.94-14.03). On the other hand, NAFLD was not associated with an increased risk of ICU admission (24 vs. 7%, respectively; OR = 2.29, CI: 0.79-6.63). We were unable to perform meta-analysis to investigate the association of MAFLD with the rate of ICU admission and with mortality. Conclusion: In conclusion, patients with MAFLD and NAFLD showed a more severe clinical picture in COVID-19. Our results support the importance of close monitoring of COVID-19 patients with MAFLD. Further research is needed to explore the cause of increased severity of COVID-19 in MAFLD.

Uncertainty in the impact of liver support systems in acute-on-chronic liver failure: a systematic review and network meta-analysis.

BACKGROUND: The role of artificial and bioartificial liver support systems in acute-on-chronic liver failure (ACLF) is still controversial. We aimed to perform the first network meta-analysis comparing and ranking different liver support systems and standard medical therapy (SMT) in patients with ACLF. METHODS: The study protocol was registered with PROSPERO (CRD42020155850). A systematic search was conducted in five databases. We conducted a Bayesian network meta-analysis of randomized controlled trials assessing the effect of artificial or bioartificial liver support systems on survival in patients with ACLF. Ranking was performed by calculating the surface under cumulative ranking (SUCRA) curve values. The RoB2 tool and a modified GRADE approach were used for the assessment of the risk of bias and quality of evidence (QE). RESULTS: In the quantitative synthesis 16 trials were included, using MARS®, Prometheus®, ELAD®, plasma exchange (PE) and BioLogic-DT®. Overall (OS) and transplant-free (TFS) survival were assessed at 1 and 3 months. PE significantly improved 3-month OS compared to SMT (RR 0.74, CrI: 0.6-0.94) and ranked first on the cumulative ranking curves for both OS outcomes (SUCRA: 86% at 3 months; 77% at 1 month) and 3-month TFS (SUCRA: 87%) and second after ELAD for 1-month TFS (SUCRA: 76%). Other comparisons did not reach statistical significance. QE was moderate for PE concerning 1-month OS and both TFS outcomes. Other results were of very low certainty. CONCLUSION: PE seems to be the best currently available liver support therapy in ACLF regarding 3-month OS. Based on the low QE, randomized trials are needed to confirm our findings for already existing options and to introduce new devices.

Sarcopenia - 2021: Pathophysiology, diagnosis, therapy / Sarcopenia - 2021: Patofiziológia, diagnózis, terápia

Összefoglaló. A sarcopenia progresszív, generalizált vázizombetegség az izomtömeg fogyásával és az izomfunkció romlásával, számos szövodménnyel, rossz prognózissal. A sarcopeniát eredetileg életkorfüggo, idosekben jelentkezo kórképnek írták le (primaer sarcopenia). Késobb derült ki, hogy fiatal- és középkorú személyeknél is elofordul, különbözo betegségekhez társulva (secundaer sarcopenia). A közlemény áttekintést ad a betegség patofiziológiájáról, a fizikai inaktivitás, az inzulinrezisztencia, a krónikus gyulladás, a citokinek, hepatokinek és miokinek szerepérol az izomkárosodásban, valamint az izom, a zsírszövet és a máj funkcionális kapcsolatairól nem alkoholos zsírmájban és cirrhosisban. A diagnózis felállítását számos funkcionális próba, illetve vizsgálóeljárás teszi lehetové. Az izomero-csökkenés igazolása a legfontosabb paraméter (kézszorító ero). Az izomtömegvesztést kettos energiájú röntgenabszorpciometria, bioelektromosimpedancia-analízis, komputertomográfia vagy mágneses rezonanciás képalkotó vizsgálat mutathatja ki, megerosítve a kórismét, a fizikai teljesítmény csökkenése pedig a sarcopenia súlyosságát jelzi. A sarcopenia kezelése és a progresszió prevenciója a fiatalkorban elkezdett és élethosszig tartó rendszeres fizikai aktivitáson, a protein-kalória túltápláláson és a gyógyszeres terápián alapul, beleértve a D-vitamin és a tesztoszteron pótlását, az elágazó láncú aminosavak és az L-karnitin adását. Másodlagos sarcopeniában az alapbetegség kezelése is szükséges. Orv Hetil. 2021; 162(1): 3-12. Summary. Sarcopenia is a progressive, generalized skeletal muscle disease with the loss of muscle mass and function, associated with adverse outcomes and poor prognosis. Sarcopenia first was regarded as an age-related disorder of older people (primary sarcopenia). Later it turned out that it can also occur in young age due to a range of chronic disorders such as cancer, anorexia or malnutrition (secondary sarcopenia). This paper overviews the pathophysiology of sarcopenia and the factors involved in the muscle mass loss, i.e., physical inactivity, insulin resistance, low-grade chronic inflammation, hepatokines and myokines. The basic feature is the imbalance between proteolysis and protein synthesis that leads to muscle atrophy. We discuss the relationship between liver, muscle and adipose tissue in non-alcoholic fatty liver disease and cirrhosis. To diagnose sarcopenia, there are a range of tests and tools that measure muscle strength and muscle mass as well as physical performance. The low muscle strength (hand grip strength) is the primary parameter of the diagnosis, the best measure of muscle function. The loss of skeletal muscle mass assessed by dual-energy X-ray absorptiometry, bioelectric impedance analysis, computer tomography, or magnetic resonance imaging confirms diagnosis, while the decrease in physical performance reflects severe sarcopenia. For the treatment and prevention of progression, the most important is the regular physical activity started from early adulthood, and healthy diet containing protein-calorie hyperalimentation. In addition, a pharmacotherapy with the supplementation of vitamin D and testosterone, furthermore, the administration of L-carnitine and branched-chain amino acids can be recommended. In the case of secondary sarcopenia, the underlying disease also requires treatment. Orv Hetil. 2021; 162(1): 3-12.

Early changes in laboratory parameters are predictors of mortality and ICU admission in patients with COVID-19: a systematic review and meta-analysis.

Despite the growing knowledge of the clinicopathological features of COVID-19, the correlation between early changes in the laboratory parameters and the clinical outcomes of patients is not entirely understood. In this study, we aimed to assess the prognostic value of early laboratory parameters in COVID-19. We conducted a systematic review and meta-analysis based on the available literature in five databases. The last search was on July 26, 2020, with key terms related to COVID-19. Eligible studies contained original data of at least ten infected patients and reported on baseline laboratory parameters of patients. We calculated weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) with 95% confidence intervals. 93 and 78 studies were included in quantitative and qualitative syntheses, respectively. Higher baseline total white blood cell count (WBC), C-reactive protein (CRP), lactate-dehydrogenase (LDH), creatine kinase (CK), D-dimer and lower absolute lymphocyte count (ALC) (WMDALC = - 0.35 × 109/L [CI - 0.43, - 0.27], p < 0.001, I2 = 94.2%; < 0.8 × 109/L, ORALC = 3.74 [CI 1.77, 7.92], p = 0.001, I2 = 65.5%) were all associated with higher mortality rate. On admission WBC, ALC, D-dimer, CRP, LDH, and CK changes could serve as alarming prognostic factors. The correct interpretation of laboratory abnormalities can guide therapeutic decisions, especially in early identification of potentially critical cases. This meta-analysis should help to allocate resources and save lives by enabling timely intervention.

Pre-existing Liver Diseases and On-Admission Liver-Related Laboratory Tests in COVID-19: A Prognostic Accuracy Meta-Analysis With Systematic Review.

Background: We aimed to perform a systematic search and meta-analysis to evaluate the prognostic value of on-admission liver function tests and pre-existing liver diseases on the clinical course of coronavirus disease 2019 (COVID-19). Methods: The study was registered on PROSPERO (CRD42020182902). We searched five databases between 01/01/2020 and 04/23/2020. Studies that reported on liver-related comorbidities and/or laboratory parameters in patients with COVID-19 were included. The main outcomes were COVID-19 severity, intensive care unit (ICU) admission, and in-hospital mortality. Analysis of predictive models hierarchical summary receiver-operating characteristic (HSROC) was conducted with a 95% confidence interval (CI). Results: Fifty studies were included in the meta-analysis. High specificity was reached by acute liver failure associated by COVID-19 (0.94, 95% CI: 0.71-0.99) and platelet count (0.94, 95% CI: 0.71-0.99) in the case of mortality; chronic liver disease (CLD) (0.98, 95% CI: 0.96-0.99) and platelet count (0.82, 95% CI: 0.72-0.89) in the case of ICU requirement; and CLD (0.97, 95% CI: 0.95-0.98), chronic hepatitis B infection (0.97, 95% CI: 0.95-0.98), platelet count (0.86, 95% CI: 0.77-0.91), and alanine aminotransferase (ALT) (0.80, 95% CI: 0.66-0.89) and aspartate aminotransferase (AST) (0.84, 95% CI: 0.77-0.88) activities considering severe COVID-19. High sensitivity was found in the case of C-reactive protein (CRP) for ICU requirement (0.92, 95% CI: 0.80-0.97) and severe COVID-19 (0.91, 95% CI: 0.82-0.96). Conclusion: On-admission platelet count, ALT and AST activities, CRP concentration, and the presence of acute and CLDs predicted the severe course of COVID-19. To highlight, pre-existing liver diseases or acute liver injury associated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection plays an important role in the prediction of mortality.

Fatty Liver Disease and Non-Alcoholic Fatty Liver Disease Worsen the Outcome in Acute Pancreatitis: A Systematic Review and Meta-Analysis.

The prevalence of fatty liver disease (FLD) and that of non-alcoholic fatty liver disease (NAFLD) share some risk factors known to exacerbate the course of acute pancreatitis (AP). This meta-analysis aimed to investigate whether FLD or NAFLD carry a higher risk of untoward outcomes in AP. In accordance with PRISMA guidelines, we performed a systematic search in seven medical databases for cohort studies that compared the outcomes of AP for the presence of FLD or NAFLD, and we calculated pooled odds ratio (OR) or weighted mean difference (WMD) with 95% confidence interval (CI). We included 13 articles in our meta-analysis. AP patients with FLD were more likely to die (5.09% vs 1.89%, OR = 3.56, CI = 1.75-7.22), develop severe AP (16.33% vs 7.87%, OR = 2.67, CI = 2.01-3.56), necrotizing pancreatitis (34.83% vs 15.75%, OR = 3.08, CI = 2.44-3.90) and had longer in-hospital stay (10.8 vs 9.2 days, WMD = 1.46, OR = 0.54-2.39). Patients with NAFLD were more likely to have severe AP and longer hospital stay. Both FLD and NAFLD proved to be independent risk factors of a more severe disease course (OR = 3.68, CI = 2.16-6.29 and OR = 3.39, CI = 1.52-7.56 for moderate/ severe vs. mild AP, respectively). FLD and NAFLD worsen the outcomes of AP, which suggests that incorporating FLD or NAFLD into prognostic scoring systems of AP outcomes might improve the prediction of severity and contribute to a more individualized patient care.

Obesity is a risk factor for developing critical condition in COVID-19 patients: A systematic review and meta-analysis.

The disease course of COVID-19 varies from asymptomatic infection to critical condition leading to mortality. Identification of prognostic factors is important for prevention and early treatment. We aimed to examine whether obesity is a risk factor for the critical condition in COVID-19 patients by performing a meta-analysis. The review protocol was registered onto PROSPERO (CRD42020185980). A systematic search was performed in five scientific databases between 1 January and 11 May 2020. After selection, 24 retrospective cohort studies were included in the qualitative and quantitative analyses. We calculated pooled odds ratios (OR) with 95% confidence intervals (CIs) in meta-analysis. Obesity was a significant risk factor for intensive care unit (ICU) admission in a homogenous dataset (OR = 1.21, CI: 1.002-1.46; I2 = 0.0%) as well as for invasive mechanical ventilation (IMV) (OR = 2.05, CI: 1.16-3.64; I2 = 34.86%) in COVID-19. Comparing body mass index (BMI) classes with each other, we found that a higher BMI always carries a higher risk. Obesity may serve as a clinical predictor for adverse outcomes; therefore, the inclusion of BMI in prognostic scores and improvement of guidelines for the intensive care of patients with elevated BMI are highly recommended.

Four-year long (2014-2017) clinical and laboratory surveillance of hepatitis E virus infections using combined antibody, molecular, antigen and avidity detection methods: Increasing incidence and chronic HEV case in Hungary.

BACKGROUND: Hepatitis E virus (HEV) is a pathogen of viral hepatitis. Since 2006, the number of reported HEV cases has ten-fold increase in Hungary. OBJECTIVES: The aim of this clinical and laboratory surveillance study was to analyse and confirm HEV IgM-positive sera with different methods in four consecutive years (2014-2017) in Hungary. STUDY DESIGN: Between 2014 and 2017, a total of 1439 sera samples were tested for HEV from in/out-patients with unknown hepatitis from university and county hospitals and general practitioners from three counties in Southwest Hungary (covered population: Σ894.000 persons) using combined antibody (serology), various molecular (RT-PCR and RT-qPCR), novel antigen (Ag) and avidity detection methods. RESULTS: Total of 162 (11.3%) of the 1439 sera were HEV IgM-positive including 13 (8%) HEV RT-PCR-positive (confirmed as HEV genotype 3 sub-genotypes 3a/c/e/f/i in genus Orthohepevirus A) with up to 1.1383 × 108 RNA copy/ml, 30 (18.5%) HEV Ag-positive and 16 with low avidity index for HEV, respectively. Total of 6 samples were positive simultaneously with the combined four methods and 31 with three methods. If the quotient of serum sample's OD/cut-off of anti-HEV ELISA IgM and IgG scores is higher than ≥1 it predisposes for acute HEV infection. No rat or ferret HEV RNA (genus Orthohepevirus C) were identified from these specimens by RT-PCR. During our surveillance period a 68-year-old professional (meat-packing) hunter with kidney transplantation and immunosuppressive therapy was confirmed and treated as the first documented case of chronic HEV infection in Hungary. CONCLUSION: This four-year-long clinical and laboratory surveillance highlights the increasing importance of acute and chronic HEV infections in Hungary and supports the use of confirmatory assays for laboratory diagnosis of HEV in human.

Direct-acting antiviral treatment downregulates immune checkpoint inhibitor expression in patients with chronic hepatitis C.

Chronic hepatitis C (CHC) infection is associated with increased TIM-3, PD-1 immune checkpoint receptors expression that inhibits adaptive T cells and increases NK cell cytotoxicity against T helper cells, both resulting T cell exhaustion. Elimination of the virus with direct-acting antivirals (DAAs) may modify host immune response via altering these immune checkpoint receptors' expression. We conducted a prospective study to analyze changes in TIM-3, PD-1 and their ligands galectin-9, PD-L1 expression by peripheral blood T cell subpopulations, NK cell subpopulations, and monocytes by multicolor flow cytometry in 14 CHC patients successfully treated with 12 weeks of dasabuvir, ombitasvir, and paritaprevir/ritonavir plus ribavirin. Blood samples were collected before, at the end of treatment, and 12 and 24 weeks later. Sustained virological response (SVR) was associated with increased percentage of peripheral blood CD3+ T and CD8+ cytotoxic T lymphocytes and decreased percentage of NKbright cells. After DAA treatment, decreased TIM-3 expression by CD4+ T cells, by NKbright, and by NKT cells was found. Expression of immune checkpoint molecules' ligand PD-L1 by NK cells and by regulatory T cells and galectin-9 by NK cells and monocytes also decreased significantly at SVR. Our data suggest that DAA treatment not only inhibits viral replication but may alter host adaptive and innate immune responses. A decrease in immune checkpoint molecules and their ligands expression both on adaptive and on innate immune cells may contribute to the recovery of exhausted adaptive immune responses and to sustained virological response.

Pre-transplant Sarcopenic Obesity Worsens the Survival After Liver Transplantation: A Meta-Analysis and a Systematic Review.

Background: The rising prevalence of cirrhotic cases related to non-alcoholic steatohepatitis has led to an increased number of cirrhotic patients with coexistence of obesity and muscle mass loss, known as sarcopenic obesity (SO). In patients undergoing liver transplantation (LT), the presence of SO may worsen prognosis, and increase morbidity and mortality. Objective: We aimed to evaluate the effect of the presence of pre-transplant SO on the outcomes of LT. Methods: A comprehensive search was performed in seven medical databases for studies comparing morbidity and mortality of patients with and without SO after LT. The primary outcome was overall mortality in the short- (1 year), intermediate- (3 years), and long- (5 years) term. We calculated pooled relative risks (RRs) with 95% confidence intervals (CIs). Heterogeneity was quantified with I2-statistics. Results: Based on the analysis of 1,515 patients from three articles, SO increased overall mortality compared to non-SO at short-, intermediate-, and long-term follow-up (RR = 2.06, 95% CI: 1.28-3.33; RR = 1.67, 95% CI: 1.10-2.51; and RR = 2.08, 95% CI: 1.10-3.93, respectively) without significant between-study heterogeneity for the short- and intermediate- term (I2 = 0.0% for both) and considerable heterogeneity for long-term follow-up (I2 = 81.1%). Conclusion: Pre-transplant SO proved to be a risk factor after LT and was associated with two times higher mortality at short- and long- term follow-up. Since SO worsens the prognosis of patients after LT, the inclusion of body composition assessment before LT may help to plan a more individualized nutritional treatment, physiotherapy, and postoperative care and may improve morbidity and mortality.

Baveno Criteria Safely Identify Patients With Compensated Advanced Chronic Liver Disease Who Can Avoid Variceal Screening Endoscopy: A Diagnostic Test Accuracy Meta-Analysis.

Background: The Baveno VI Consensus Workshop defined criteria (liver stiffness measured by transient elastography <20 kPa and platelet count >150 × 109 cells/L) to identify those patients with compensated advanced chronic liver diseases (cACLD) who are unlikely to have varices needing treatment (VNTs) and can safely avoid variceal screening endoscopy. This meta-analysis aimed to quantify the safety and efficacy of these criteria in suspected cACLD with liver stiffness >10 kPa and in compensated chronic liver diseases (cCLD) irrespective of liver stiffness. Methods: A systematic search was conducted in nine databases for studies discussed cACLD or cCLD and tested Baveno criteria against variceal screening endoscopy. The main safety and efficacy endpoints were missed VNT rate and spared endoscopy rate (SER), respectively; calculated with the random effect model. Pooled sensitivity, specificity, and area under the curve (AUC) were calculated with the hierarchical summary receiver operating characteristic model. For all outcome measures, 95% confidence intervals were computed. Heterogeneity was tested with I 2-statistics. Results: The search yielded 13 studies including 4,464 patients which reported on suspected cACLD. Pooled missed VNT rate was 0.3% (0.1-0.6%; I 2 = 45.5%), pooled SER was 32.8% (24.8-41.4%; I 2 = 97.0%). Sensitivity, specificity, and AUC of Baveno criteria were 97% (95-98%), 41% (27-57%), and 96% (94-97%), respectively. In the subgroups of cACLD from hepatitis C and B viruses, non-alcoholic fatty liver disease/steatohepatitis, or alcohol, missed VNT rates were 0.0% (0.0-0.3%), 1.2% (0.4-2.2%), 0.0% (0.0-1.3%), or 0.0% (0.0-0.4%), while SERs were 24.2% (20.5-28.1%), 24.9% (21.7-28.4%), 38.6% (10.9-70.8%), or 27.0% (16.9-38.4%), respectively. If we expanded the study population to cCLD, 27 studies included 7,534 patients. Missed VNT rate was 0.2% (0.1-0.5%; I 2 = 39.8%) with a SER of 30.5% (25.2-36.2%; I 2 = 96.1%) while Se, Sp, and AUC were 97% (93-99%), 35% (27-44%), and 80% (77-84%), respectively. Conclusions: The application of Baveno criteria significantly reduces the number of unnecessary variceal screening endoscopies while being safe: cACLD patients with liver stiffness <20 kPa and platelet count > 150 × 109 cells/L carry a very low chance (i.e., 0.3%) of having VNTs. The criteria preserve low missed VNT rate with lower diagnostic performance among cCLD patients.