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.

Antibiotic therapy in acute pancreatitis: From global overuse to evidence based recommendations.

BACKGROUND: Unwarranted administration of antibiotics in acute pancreatitis presents a global challenge. The clinical reasoning behind the misuse is poorly understood. Our aim was to investigate current clinical practices and develop recommendations that guide clinicians in prescribing antibiotic treatment in acute pancreatitis. METHODS: Four methods were used. 1) Systematic data collection was performed to summarize current evidence; 2) a retrospective questionnaire was developed to understand the current global clinical practice; 3) five years of prospectively collected data were analysed to identify the clinical parameters used by medical teams in the decision making process, and finally; 4) the UpToDate Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was applied to provide evidence based recommendations for healthcare professionals. RESULTS: The systematic literature search revealed no consensus on the start of AB therapy in patients with no bacterial culture test. Retrospective data collection on 9728 patients from 22 countries indicated a wide range (31-82%) of antibiotic use frequency in AP. Analysis of 56 variables from 962 patients showed that clinicians initiate antibiotic therapy based on increased WBC and/or elevated CRP, lipase and amylase levels. The above mentioned four laboratory parameters showed no association with infection in the early phase of acute pancreatitis. Instead, procalcitonin levels proved to be a better biomarker of early infection. Patients with suspected infection because of fever had no benefit from antibiotic therapy. CONCLUSIONS: The authors formulated four consensus statements to urge reduction of unjustified antibiotic treatment in acute pancreatitis and to use procalcitonin rather than WBC or CRP as biomarkers to guide decision-making.

Gender difference in the effects of interleukin-6 on grip strength - a systematic review and meta-analysis.

BACKGROUND: Aging sarcopenia characterized by low muscle mass with low muscle strength affects men and women differently. The contribution of interleukin-6 (IL-6) to sarcopenia has been suggested based on a negative correlation between plasma IL-6 and muscle function described by some studies. However, no consensus regarding clinically relevant cut-off criteria has been reached. Another question arises whether pooling male and female data is an accurate way to determine the predictive value of IL-6 in sarcopenia. The present meta-analysis was designed to assess: (1) whether plasma IL-6 in aged populations in fact correlates negatively to muscle strength; (2) whether such a correlation exists both in men and in women; and (3) whether plasma IL-6 shows a gender difference in old age. METHODS: We applied the preferred reporting items for systematic review and meta-analysis protocols (PRISMA). We searched PubMed and Embase for papers that reported data on individuals over 65 without inflammatory diseases. We extracted either separate male and female data on plasma IL-6 along with at least one muscle parameter or correlation coefficient between plasma IL-6 and these parameters. Random effect models calculated with DerSimonian and Laird weighting methods were applied to analyze correlation coefficients and gender difference in plasma IL-6. Egger's test was used to assess the small study effect. RESULTS: Twenty articles out of 468 records identified were suitable for analyses. Plasma IL-6 correlates negatively with grip strength in mixed populations and also separately in men [- 0.25 with 95% confidence interval (CI): - 0.48, - 0.02] and in women (- 0.14 with 95% CI: - 0.24, - 0.03). However, contrary to expectations, men with better muscle condition have higher plasma IL-6 than women of similar age with worse muscle condition (plasma IL-6 male-female difference: 0.25 pg/mL with 95% CI: 0.15, 0.35). CONCLUSION: This is the first study to demonstrate that a higher predictive IL-6 cut-off level should be determined for aging sarcopenia in men than in women.

[Three decades of the hepatitis C virus from the discovery to the potential global elimination: the success of translational researches]. / A hepatitis C-vírus (HCV) három évtizede a felfedezéstol a globális elimináció lehetoségéig: a transzlációs kutatás sikere.

More than 25 years after the discovery of hepatitis C virus, the development of the direct acting antivirals can lead to the regional or long-term global elimination of the virus with over 90% efficacy. This is the success of basic and clinical translational research. Yet, some unsolved challanges remain, such as the great number of unidentified patients who are not aware of their condition, the limited access to the therapy due to the high prices of the drugs, and the treatment of resistance-associated variants. In addition, the lack of vaccine is also an obstacle. In 2016, the World Health Organization (WHO) developed the first global health sector strategy for the elimination of viral hepatitis by 2030. Its evidence-based guidelines are primarily targeted at the national hepatitis programme managers who are responsible for the national testing and treatment plans. According to these recommendations, it is of basic importance to perform focused risk-based testing in higher-risk populations and after diagnosis to start treatment as "cure as prevention", furthermore, to limit the risk of reinfection. We review the events of the HCV story from the discovery to these days, including virology, epidemiology, pathogenesis, diagnosis and therapy. Orv Hetil. 2018; 159(12): 455-465.

Transpancreatic sphincterotomy has a higher cannulation success rate than needle-knife precut papillotomy - a meta-analysis.

Background and aim While many studies have discussed the different cannulation techniques used in patients with difficult biliary access, no previous meta-analyses have compared transpancreatic sphincterotomy (TPS) to other advanced techniques. Therefore, we aimed to identify all studies comparing the efficacy and adverse event rates of TPS with needle-knife precut papillotomy (NKPP), the most commonly used technique, and to perform a meta-analysis. Methods The Embase, PubMed, and Cochrane databases were searched for trials comparing the outcomes of TPS with NKPP up till December 2016. A meta-analysis focusing on outcome (cannulation success, post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP), post-procedural bleeding, and total adverse events) was performed. The population, intervention, comparison, outcome (PICO) format was used to compare these cannulation approaches. Five prospective and eight retrospective studies were included in our meta-analysis. Results NKPP has a significantly lower success rate (odds ratio [OR] 0.50, P = 0.046; relative risk [RR] 0.92, P = 0.03) and a higher rate of bleeding complications (OR 2.24, P = 0.02; RR 2.18, P = 0.02) than TPS. However, no significant differences were found in PEP (OR 0.79, P = 0.24; RR 0.80, P = 0.19), perforation (risk difference [RD] 0.01, P = 0.23), or total complication rates (OR 1.22, P = 0.44; RR 1.17, P = 0.47). Conclusion While TPS has a higher success rate in difficult biliary access and causes less bleeding than NKPP, there are no differences in PEP, perforation, or total complication rates between the two approaches. We conclude that TPS, in the hands of expert endoscopists, is a safe procedure, which should be used more widely in patients with difficult biliary access.

[Advances in the pathogenesis of non alcoholic fatty liver disease]. / Újabb adatok a nem alkoholos zsírmáj patogeneziséhez.

Non alcoholic fatty liver disease is the hepatic manifestation of metabolic syndrome, and the most common liver disease. Its more aggressive form is the non alcoholic steatohepatitis. Multiple genetic and environmental factors lead to the accumulation of triglicerides and the inflammatory cascade. High fat diet, obesity, adipocyte dysfunction with cytokine production, insulin resistance and increased lipolysis with free fatty acid flux into the liver - all are the drivers of liver cell injury. Activation of inflammasome by damage- or pathogen-associated molecular patterns results in "steril inflammation" and immune response, while the hepatic stellate cells and progenitor cells lead to fibrogenesis. Small intestinal bacterial overgrowth and gut dysbiosis are also of pivotal importance in the inflammation. Among the susceptible genetic factors, mutations of patatin-like phospholipase domain containing 3 and the transmembrane 6 superfamily 2 genes play a role in the development and progression of the disease, similarly as do epigenetic regulators such as microRNAs and extracellular vesicles. Better understanding of the pathogenesis of non alcoholic fatty liver disease may identify novel therapeutic agents that improve the outcome of the disease. Orv Hetil. 2017; 158(23): 882-894.

Meta-Analysis of Early Nutrition: The Benefits of Enteral Feeding Compared to a Nil Per Os Diet Not Only in Severe, but Also in Mild and Moderate Acute Pancreatitis.

The recently published guidelines for acute pancreatitis (AP) suggest that enteral nutrition (EN) should be the primary therapy in patients suffering from severe acute pancreatitis (SAP); however, none of the guidelines have recommendations on mild and moderate AP (MAP). A meta-analysis was performed using the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P). The following PICO (problem, intervention, comparison, outcome) was applied: P: nutrition in AP; I: enteral nutrition (EN); C: nil per os diet (NPO); and O: outcome. There were 717 articles found in Embase, 831 in PubMed, and 10 in the Cochrane database. Altogether, seven SAP and six MAP articles were suitable for analyses. In SAP, forest plots were used to illustrate three primary endpoints (mortality, multiorgan failure, and intervention). In MAP, 14 additional secondary endpoints were analyzed (such as CRP (C-reactive protein), WCC (white cell count), complications, etc.). After pooling the data, the Mann-Whitney U test was used to detect significant differences. Funnel plots were created for testing heterogeneity. All of the primary endpoints investigated showed that EN is beneficial vs. NPO in SAP. In MAP, all of the six articles found merit in EN. Analyses of the primary endpoints did not show significant differences between the groups; however, analyzing the 17 endpoints together showed a significant difference in favor of EN vs. NPO. EN is beneficial compared to a nil per os diet not only in severe, but also in mild and moderate AP.

[Non-alcoholic fatty liver disease and hepatocellular carcinoma - 2016]. / Nem alkoholos zsírmáj és hepatocellularis carcinoma - 2016.

In the past decade non-alcoholic liver disease became the most frequently diagnosed liver disease in developed countries. At the same time, the dramatic rise in the incidence of hepatocellular carcinoma is attributed to this common metabolic disorder, and mainly to its severe form, non-alcoholic steatohepatitis. The risk factors of these associated diseases are genetic predisposition, obesity and diabetes as well as chronic low grade necro-infammation, which often leads to liver fibrosis. Free fatty acids, cytokines, lipotoxicity, insulin resistance, microRNS dysregulation and alteration in intestinal microbiota play a pivotal role in the pathogenesis. Treatment of non-alcoholic fatty liver disease - weight reduction and physical exercise in obesity, metformin in diabetes, statins in dyslipidemia and, as a new option, obeticholic acid - may diminish the risk of the hepatocellular carcinoma related to this metabolic disease.

[Immune response and oxidative stress in hepatitis C virus infection]. / Immunválasz és oxidatív stressz hepatitis C-vírus-infekcióban.

This review summarizes our current knowledge of the innate and adaptive immune responses induced by hepatitis C virus, and of the genetic polymorphisms that may determine the outcome of the disease. In addition, the authors discuss the role of reactive oxygen species and oxidative stress in hepatitis C virus-related pathogenic processess, such as hepatitis, fibrosis, hepatocellular carcinoma, steatosis and insulin resistance.

[Non-invasive diagnostic methods of fibrosis in chronic hepatitis C virus infection: their role in treatment indication, follow-up and assessment of prognosis]. / Nem invazív fibrosisdiagnosztika hepatitis C-vírus-infekcióban: szerepe a kezelés indikációjában, követésében és a prognózis megítélésében.

Chronic hepatitis C virus infection associated with necroinflammation predisposes to liver fibrosis and cirrhosis, which lead to severe end-stage complications. Staging of fibrosis is of basic importance for the indication of antiviral treatment, for monitoring the response and predicting the prognosis of patients with hepatitis C virus related liver disease. Since liver biopsy, the "gold standard" diagnosis of fibrosis is invasive and it has some other limitations, non-invasive methods have been developed and widely used in the clinical practice. Serum biomarkers and physical approaches measuring liver stiffness by elastography as well as combination algorithms have been gradually been integrated into guidelines resulting in a reduction of the need for liver biopsy. The authors review these non-invasive fibrosis markers and discuss their role in the indication of treatment, follow-up, and assessment of prognosis of patients with chronic hepatitis C virus infection.

[Transient elastography as a predictor of oesophageal varices in patients with liver cirrhosis]. / Tranziens elasztográfia mint a nyelocso-varicositas prediktora májcirrhosisban szenvedo betegekben.

INTRODUCTION: One of the most serious complications of liver cirrhosis is variceal bleeding. Early recognition of the oesophageal varices is of primary importance in the prevention of variceal bleeding. Endoscopy is the only means to directly visualize varices and measure their size, as one of the most important predictor of the risk of bleeding. During the course of cirrhosis repeated oesophago-gastro-bulboscopic examinations are recommended. As these interventions are expensive and often poorly accepted by patients who may refuse further follow-up, there is a need for non-invasive methods to predict the progression of portal hypertension as well as the presence and the size of oesophageal varices. After several combinations of biological and ultrasonographical parameters proposed for the detection of advanced fibrosis, it was suggested that liver stiffness measured by transient elastography, a novel non-invasive technology may reflect not only fibrosis and portal pressure but it may even predict the presence or absence of large oesophageal varices in patients with cirrhosis. AIM: The aim of the authors was to study the diagnostic accuracy of transient elastography using FibroScan for selecting patients who are at risk of bearing large (Paquet-grade ≥ II) oesophageal varices and high risk of bleeding. METHOD: The authors performed upper tract endoscopy and transient elastography in 74 patients with chronic liver disease (27 patients with chronic hepatitis and 47 patients with liver cirrhosis). The relationships between the presence of oesophageal varices (Paquet-grade 0-IV) and liver stiffness (kPa), as well as the hematological and biochemical laboratory parameters (prothrombine international normalized ratio, platelet count, aspartate aminotransferase, alanine aminotransferase, albumin, and aspartate aminotransferase/platelet ratio index) were investigated. The predictive role of liver stiffness for screening patients with varices and those who are at high risk of variceal bleeding was also analysed. RESULTS: Liver stiffness values significantly correlated with the grade of oesophageal varices (Paquet-grade) (r = 0.67, p<0.0001). The liver stiffness value of 19.2 kPa was highly predictive for the presence of oesophageal varices (AUROC: 0.885, 95% CI: 0.81-0.96) and for the presence of high grade varices (P≥II) (AUROC: 0.850, 95% CI: 0.754-0.94). Using the cut-off value of 19.2 kPa, the sensitivity of transient elastography was 85%, specificity was 87%, positive predictive value was 85%, negative predictive value was 87% and validity was 86% for the detection of varices. Liver stiffness values less than 19.2 kPa were highly predicitive for the absence of large (P≥II) varices (sensitivity, 95%; specificity, 70%; positive predictive value, 54%; negative predictive value, 97%). CONCLUSIONS: Transient elastography may help to screen patients who are at high risk of bearing large (P≥II) oesophageal varices which predict variceal bleeding and, therefore, need endoscopic screening. Lives stiffness values higher than 19.2 kPa indicate the need for oesophageal-gastro-bulboscopy, while liver stiffness values lower than 19.2 kPa make the presence of large oesophageal varices unlikely.

[Non-alcoholic fatty liver disease and steatohepatitis]. / Nem alkoholos zsírmáj és zsírmájhepatitis.

Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, the hepatic manifestations of metabolic syndrome with close association with inzulin resistance and obesity, are the most common liver diseases, affecting up to a third of the population worldwide. They confer increased risk for hepatocellular carcinoma as well as cardiovascular diseases. The review aims to summarize advances in epidemiology, pathogenesis and clinical management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Besides liver biopsy and biomarkers, a novel non-invasive diagnostic tool the called "controlled attenuation parameter" measuring the attenuation of ultrasound generated by the transient elastography transducer, can quantitatively assess the hepatic fat content and differentiate between steatosis grades. At the same time, liver stiffness (fibrosis) can also be evaluated. The authors present their own results obtained with the latter procedure. In non-alcoholic fatty liver disease, the lifestyle intervention, weight loss, diet and exercise supported by cognitive behavioural therapy represent the basis of management. Components of metabolic syndrome (obesity, dyslipidaemia, diabetes and arterial hypertension) have to be treated. Although there is no approved pharmacological therapy for NASH, it seems that long lasting administration of vitamin E in association with high dose ursodeoxycholic acid may be beneficial. In addition, omega-3 polyunsaturated fatty acid substitution can also decrease liver fat, however, the optimal dose is not known yet. Further controlled clinical studies are warranted to establish the real value of any suggested treatment modalities for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, although these are in experimental phase yet.

[IL28B CC genotype: a protective factor and predictor of the response to interferon treatment in chronic hepatitis C virus infection]. / IL28B CC genotípus: védo tényezo és az interferonválasz prediktora krónikus hepatitis-C-vírus infekcióban.

INTRODUCTION: In chronic hepatitis C-virus infection the possible role of gene variants encoding cytokines has become the focus of interest. AIM: The aim of the study was to investigate the effect of IL28B polymorphisms on the outcome of chronic hepatitis C-virus genotype 1 infection in the Hungarian population. In addition, the association between IL28B genotypes and the Th1/Th2 cytokine production of activated peripheral blood monocytes and lymphocytes was evaluated. METHOD: Total of 748 chronic hepatitis C-virus genotype 1 positive patients (365 males and 383 females, aged between 18 and 82 years; mean age, 54±10 years) were enrolled, of which 420 patients were treated with pegylated interferon plus ribavirin for 24-72 weeks. Of the 420 patients, 195 patients (46.4%) achieved sustained virological response. The IL28B rs12979860 polymorphism was determined using Custom Taqman SNP Genotyping Assays (Applied Biosystems, Life Technologies, Foster, CA, USA). For cytokine studies, tumour necrosis factor-α, interleukin-2, interferon-γ, interleukin-2 and interleukin-4 production by LPS-stimulated monocytes and PMA-ionomycine activated lymphocytes were measured from the supernatant of the cells obtained from 40 hepatitis C-virus infected patients, using FACS-CBA Becton Dickinson test. The cytokine levels were compared in patients with different (CC, CT, TT) IL28B genotypes. RESULTS: The IL28B rs12979860 CC genotype occurred in lower frequency in hepatitis C-virus infected patients than in healthy controls (26.1% vs 51.4%, OR 0.333, p<0.001). Patients carried the T allele with higher frequency than controls (73.9%, vs 48.6%, OR 3.003, p<0.001). Pegylated interferon plus ribavirin treated patients with the IL28B CC genotype achieved higher sustained virological response rate than those with the CT genotype (58.6% vs 40.8%, OR 2.057, p = 0.002), and those who carried the T allele (41.8%, OR1.976, p = 0.002). LPS-induced TLR-4 activation of monocytes resulted in higher tumour necrosis factor-α production in patients with the IL28B CC genotype compared to non-CC individuals (p<0.01). Similarly, increased tumour necrosis factor-α, interleukin-2 and interferon-γ production by lymphocytes was found in the IL28B CC carriers (p<0.01) CONCLUSIONS: The IL28B CC genotype exerts protective effect against chronic hepatitis C-virus infection and may be a pretreatment predictor of sustained virological response during interferon-based antiviral therapy. The IL28B CC polymorphism is associated with increased Th1 cytokine production of activated peripheral blood monocytes and lymphocytes, which may play a role in interferon-induced rapid immune control and sustained virological response of pegylated interferon plus ribavirin treated patients.

[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.

[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.

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. 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.

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.