Morphology of the papilla can predict procedural safety and efficacy of ERCP-a systematic review and meta-analysis.

Endoscopic Retrograde Cholangiopancreatography (ERCP) is the primary therapeutic procedure for pancreaticobiliary disorders, and studies highlighted the impact of papilla anatomy on its efficacy and safety. Our objective was to quantify the influence of papilla morphology on ERCP outcomes. We systematically searched three medical databases in September 2022, focusing on studies detailing the cannulation process or the rate of adverse events in the context of papilla morphology. The Haraldsson classification served as the primary system for papilla morphology, and a pooled event rate with a 95% confidence interval was calculated as the effect size measure. Out of 17 eligible studies, 14 were included in the quantitative synthesis. In studies using the Haraldsson classification, the rate of difficult cannulation was the lowest in type I papilla (26%), while the highest one was observed in the case of type IV papilla (41%). For post-ERCP pancreatitis, the event rate was the highest in type II papilla (11%) and the lowest in type I and III papilla (6-6%). No significant difference was observed in the cannulation failure and post-ERCP bleeding event rates between the papilla types. In conclusion, certain papilla morphologies are associated with a higher rate of difficult cannulation and post-ERCP pancreatitis.

The Calculation and Evaluation of an Ultrasound-Estimated Fat Fraction in Non-Alcoholic Fatty Liver Disease and Metabolic-Associated Fatty Liver Disease.

We aimed to develop a non-linear regression model that could predict the fat fraction of the liver (UEFF), similar to magnetic resonance imaging proton density fat fraction (MRI-PDFF), based on quantitative ultrasound (QUS) parameters. We measured and retrospectively collected the ultrasound attenuation coefficient (AC), backscatter-distribution coefficient (BSC-D), and liver stiffness (LS) using shear wave elastography (SWE) in 90 patients with clinically suspected non-alcoholic fatty liver disease (NAFLD), and 51 patients with clinically suspected metabolic-associated fatty liver disease (MAFLD). The MRI-PDFF was also measured in all patients within a month of the ultrasound scan. In the linear regression analysis, only AC and BSC-D showed a significant association with MRI-PDFF. Therefore, we developed prediction models using non-linear least squares analysis to estimate MRI-PDFF based on the AC and BSC-D parameters. We fitted the models on the NAFLD dataset and evaluated their performance in three-fold cross-validation repeated five times. We decided to use the model based on both parameters to calculate UEFF. The correlation between UEFF and MRI-PDFF was strong in NAFLD and very strong in MAFLD. According to a receiver operating characteristics (ROC) analysis, UEFF could differentiate between <5% vs. ≥5% and <10% vs. ≥10% MRI-PDFF steatosis with excellent, 0.97 and 0.91 area under the curve (AUC), accuracy in the NAFLD and with AUCs of 0.99 and 0.96 in the MAFLD groups. In conclusion, UEFF calculated from QUS parameters is an accurate method to quantify liver fat fraction and to diagnose ≥5% and ≥10% steatosis in both NAFLD and MAFLD. Therefore, UEFF can be an ideal non-invasive screening tool for patients with NAFLD and MAFLD risk factors.

[The significance of omega-3 fatty acids in the treatment of non-alcoholic fatty liver disease]. / Az ómega-3 zsírsavak jelentosége a nem alkoholos zsírmájbetegség kezelésében.

Today, non-alcoholic fatty liver disease is the most common chronic liver disease, yet there is no clearly accepted effective therapy. What is certain is that the number of people suffering from the disease is increasing, making prevention, treatment and recognition of co-morbidities of paramount importance. Current evidence suggests that the development of non-alcoholic fatty liver disease may be due to pathological factors of different origins. The main risk factors include genetic factors, acquired environmental influences and lifestyle. Lifestyle modification, i.e., the elimination or reduction of these harmful factors, can reverse liver damage, depending on the stage of the disease. In this summary statement, we review the pathophysiology of non-alcoholic fatty liver disease, risk factors and therapeutic options, within that in particular lifestyle modification (dietary changes, increasing physical activity, weight loss). Furthermore, we also show the importance of omega-3 fatty acids such as eicosapentaenoic acid and docosahexaenoic acid in detail. With our knowledge, the personalized treatment of non-alcoholic fatty liver disease can be elaborated. Orv Hetil. 2023; 164(33): 1294-1299.

Hypocalcemia on Admission Is a Predictor of Disease Progression in COVID-19 Patients with Cirrhosis: A Multicenter Study in Hungary.

Hypocalcemia is a common condition in liver cirrhosis and is associated with the severity of SARS-CoV-2 infection. However, there is a lack of data demonstrating the prognostic value of hypocalcemia in COVID-19 patients with cirrhosis. This study aimed to evaluate the prognostic value of hypocalcemia for COVID-19 severity, mortality and its associations with abnormal liver function parameters. We selected 451 COVID-19 patients in this retrospective study and compared the laboratory findings of 52 COVID-19 patients with cirrhosis to those of 399 COVID-19 patients without cirrhosis. Laboratory tests measuring albumin-corrected total serum calcium were performed on admission, and the levels were monitored during hospitalization. The total serum calcium levels were significantly lower in cirrhosis cases (2.16 mmol/L) compared to those without cirrhosis (2.32 mmol/L). Multivariate analysis showed that hypocalcemia in COVID-19 patients with cirrhosis was a significant predictor of in-hospital mortality, with an OR of 4.871 (p < 0.05; 95% CI 1.566-15.146). ROC analysis showed the AUC value of total serum calcium was 0.818 (95% CI 0.683-0.953, p < 0.05), with a sensitivity of 88.3% and a specificity of 75%. The total serum calcium levels showed a significant negative correlation with the Child-Turcette-Pugh score (r = -0.400, p < 0.05). Hypocalcemia on admission was a significant prognostic factor of disease progression in COVID-19 patients with cirrhosis.

Evaluation of Artificial Intelligence-Calculated Hepatorenal Index for Diagnosing Mild and Moderate Hepatic Steatosis in Non-Alcoholic Fatty Liver Disease.

Background and Objectives: This study aims to evaluate artificial intelligence-calculated hepatorenal index (AI-HRI) as a diagnostic method for hepatic steatosis. Materials and Methods: We prospectively enrolled 102 patients with clinically suspected non-alcoholic fatty liver disease (NAFLD). All patients had a quantitative ultrasound (QUS), including AI-HRI, ultrasound attenuation coefficient (AC,) and ultrasound backscatter-distribution coefficient (SC) measurements. The ultrasonographic fatty liver indicator (US-FLI) score was also calculated. The magnetic resonance imaging fat fraction (MRI-PDFF) was the reference to classify patients into four grades of steatosis: none < 5%, mild 5-10%, moderate 10-20%, and severe ≥ 20%. We compared AI-HRI between steatosis grades and calculated Spearman's correlation (rs) between the methods. We determined the agreement between AI-HRI by two examiners using the intraclass correlation coefficient (ICC) of 68 cases. We performed a receiver operating characteristics (ROC) analysis to estimate the area under the curve (AUC) for AI-HRI. Results: The mean AI-HRI was 2.27 (standard deviation, ±0.96) in the patient cohort. The AI-HRI was significantly different between groups without (1.480 ± 0.607, p < 0.003) and with mild steatosis (2.155 ± 0.776), as well as between mild and moderate steatosis (2.777 ± 0.923, p < 0.018). AI-HRI showed moderate correlation with AC (rs = 0.597), SC (rs = 0.473), US-FLI (rs = 0.5), and MRI-PDFF (rs = 0.528). The agreement in AI-HRI was good between the two examiners (ICC = 0.635, 95% confidence interval (CI) = 0.411-0.774, p < 0.001). The AI-HRI could detect mild steatosis (AUC = 0.758, 95% CI = 0.621-0.894) with fair and moderate/severe steatosis (AUC = 0.803, 95% CI = 0.721-0.885) with good accuracy. However, the performance of AI-HRI was not significantly different (p < 0.578) between the two diagnostic tasks. Conclusions: AI-HRI is an easy-to-use, reproducible, and accurate QUS method for diagnosing mild and moderate hepatic steatosis.

The Nobel prize in physiology and medicine - 2022.

The Nobel Assembly at Karolinska Institutet awarded the 2022 Nobel Prize in Physiology or Medicine to a Swedish geneticist, Svante Pääbo, for his discoveries concerning the genomes of extinct hominins and human evolution, for the sequencing of the genome of the Neanderthal, the discovery of a previously unknown hominin, Denisova, and the establishment of a new scientific discipline, paleogenomics.

Infection risk related to gastrointestinal endoscopic procedures during the SARS-CoV-2 pandemic / Tápcsatornai endoszkópos eljárásokkal összefüggo infekciós kockázat a SARS-CoV-2-járvány idején

Introduction: COVID­19 significantly affects endoscopic labs' workflow. Endoscopic examinations are considered high-risk for virus transmission. Objectives: To determine impact of COVID­19 pandemic on Hungarian endoscopic labs' workflow and on infection risk of endoscopic staff. Method: A nation-wide, cross-sectional online questionnaire was sent to heads of endoscopic labs in Hungary. The average number (with 95% confidence intervals) of upper and lower gastrointestinal endoscopies performed in 2020 was compared to that in 2019. The number of SARS-CoV-2-infected endoscopic staff members and the source of infection was also investigated. Results: Completion rate was 30% (33/111). Neither the number of upper (1.593 [743­1.514] vs. 1.129 [1.020­2.166], p = 0.053), nor that of lower gastrointestinal endoscopies (1.181 [823­1.538] vs. 871 [591­1.150], p = 0.072) decreased in 2020, but both upper and lower gastrointestinal endoscopies' number decreased by 80% during peak phases. Separate examination room was available in 12% of institutes. Appropriate quality personal protective equipment (PPE) was available during the first and second peak phase in 70% and 82%, respectively. Infection risk stratification by questionnaire and PCR testing was routinely performed in 85% and 42%, respectively. Employee number decreased by 33% and 26% for physicians, and by 19% and 21% for assistants during peak phases, mainly due to age restrictions and COVID care assignments. 32% of assistants and 41% of physicians were infected (associated with inappropriate PPE use in 16% and 18%, respectively). Conclusion: Peak phases' restrictions increase endoscopic workload afterwards. Despite PPE availability, 15% of employees' COVID infection resulted from inappropriate PPE use in pre-vaccination era.

The Elevated De Ritis Ratio on Admission Is Independently Associated with Mortality in COVID-19 Patients.

Liver damage in COVID-19 patients was documented as increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels or an elevated AST/ALT ratio, known as the De Ritis ratio. However, the prognostic value of the elevated De Ritis ratio in COVID-19 patients is still unknown. The aim of our study was to evaluate the prognostic value of the De Ritis ratio compared to other abnormal laboratory parameters and its relation to mortality. We selected 322 COVID-19 patients in this retrospective study conducted between November 2020 and March 2021. The laboratory parameters were measured on admission and followed till patient discharge or death. Of the 322 COVID-19 patients, 57 (17.7%) had gastrointestinal symptoms on admission. The multivariate analysis showed that the De Ritis ratio was an independent risk factor for mortality, with an OR of 29.967 (95% CI 5.266-170.514). In ROC analysis, the AUC value of the the De Ritis ratio was 0.85 (95% CI 0.777-0.923, p < 0.05) with sensitivity and specificity of 80.6% and 75.2%, respectively. A De Ritis ratio ≥1.218 was significantly associated with patient mortality, disease severity, higher AST and IL-6 levels, and a lower ALT level. An elevated De Ritis ratio on admission is independently associated with mortality in COVID-19 patients, indicating liver injury and cytokine release syndrome.

Tissue attenuation imaging and tissue scatter imaging for quantitative ultrasound evaluation of hepatic steatosis.

We aimed to assess the feasibility of ultrasound-based tissue attenuation imaging (TAI) and tissue scatter distribution imaging (TSI) for quantification of liver steatosis in patients with nonalcoholic fatty liver disease (NAFLD). We prospectively enrolled 101 participants with suspected NAFLD. The TAI and TSI measurements of the liver were performed with a Samsung RS85 Prestige ultrasound system. Based on the magnetic resonance imaging proton density fat fraction (MRI-PDFF), patients were divided into ≤5%, 5-10%, and ≥10% of MRI-PDFF groups. We determined the correlation between TAI, TSI, and MRI-PDFF and used multiple linear regression analysis to identify any association with clinical variables. The diagnostic performance of TAI, TSI was determined based on the area under the receiver operating characteristic curve (AUC). The intraclass correlation coefficient (ICC) was calculated to assess interobserver reliability. Both TAI (rs = 0.78, P < .001) and TSI (rs = 0.68, P < .001) showed significant correlation with MRI-PDFF. TAI overperformed TSI in the detection of both ≥5% MRI-PDFF (AUC = 0.89 vs 0.87) and ≥10% (AUC = 0.93 vs 0.86). MRI-PDFF proved to be an independent predictor of TAI (ß = 1.03; P < .001), while both MRI-PDFF (ß = 50.9; P < .001) and liver stiffness (ß = -0.86; P < .001) were independent predictors of TSI. Interobserver analysis showed excellent reproducibility of TAI (ICC = 0.95) and moderate reproducibility of TSI (ICC = 0.73). TAI and TSI could be used successfully to diagnose and estimate the severity of hepatic steatosis in routine clinical practice.

Effectiveness of COVID-19 Vaccination with mRNA Vaccines for Patients with Cirrhosis in Hungary: Multicentre Matched Cohort Study.

Patients with cirrhosis are vulnerable to hepatic decompensation events and death following COVID-19 infection. Therefore, primary vaccination with COVID-19 vaccines is fundamental to reducing the risk of COVID-19 related deaths in patients with cirrhosis. However, limited data are available about the effectiveness of mRNA vaccines compared to other vaccines. The aim of our study was to investigate the efficacy of mRNA vaccines versus other vaccines in cirrhosis. In this retrospective study, we compared clinical characteristics and vaccine effectiveness of 399 COVID-19 patients without cirrhosis (GROUP A) to 52 COVID-19 patients with cirrhosis (GROUP B). 54 hospitalised cirrhosis controls without COVID-19 (GROUP C) were randomly sampled 1:1 and matched by gender and age. Of the cirrhosis cases, we found no difference (p = 0.76) in mortality rates in controls without COVID-19 (11.8%) compared to those with COVID-19 (9.6%). However, COVID-19 patients with cirrhosis were associated with higher rates of worsening hepatic encephalopathy, ascites and esophageal varices. Patients with cirrhosis receiving mRNA vaccines had significantly better survival rates compared to viral vector or inactivated vaccines. Primary vaccination with the BNT162b2 vaccine was the most effective in preventing acute hepatic decompensating events, COVID-19 infection requiring hospital admission and in-hospital mortality.

The Nobel Prize in Physiology or Medicine-2020.

At the time of COVID-19 coronavirus pandemia, the Nobel Prize of Physiology or Medicine 2020 was awarded jointly to three researchers Harvey J. Alter, Charles M. Rice, and Michael Houghton for the discovery of Hepatitis C virus. Their works contributed to the isolation of the blood-borne virus, causing chronic hepatitis in 80% of infected person, resulting in cirrhosis, and in elevated risk of liver failure and hepatocellular carcinoma formation. Their results created the basis of HCV screening of blood, and blood products, achieving more than 95% cure of infected people without nearly side effects with direct-acting antiviral agents, supporting the goal of the WHO targeting the elimination of viral hepatitis by 2030.

Impact of milk thistle (Silybum marianum) on the mycotoxin caused redox-homeostasis imbalance of ducks liver.

The Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEA) frequently contaminate grain crops, especially maize, the basis of poultry's feed. Mycotoxins enter the food chain and induce pathological changes in edible tissues. Milk thistle (Silybum marianum) has been used for the treatment of liver disease in humans because of its antioxidant and hepatoprotective effects, but its utility in veterinary use is poorly examined. To investigate possible protective properties against mycotoxin caused oxidative stress in poultry, pressed form of milk thistle seed (0.5%) was tested in white, female, Hungarian ducks over a feeding period of 47 days. Ducks were separated into 3 groups. The first group was fed with normal diet. The second group was fed with normal diet contaminated with DON (4.9 mg/kg) and ZEA (0.66 mg/kg). The third group received mycotoxin contaminated feed with milk thistle supplementation. Histological examination, markers of the redox status and metal element concentration measurements were carried out. The results showed alterations in the histological examination and in the redox homeostasis markers as a short-term effect by strengthening the antioxidant system. Acute exposure of mycotoxins caused an oxidative stress, which induced an effective antioxidant defensive response of the organism indicated by the free sulfhydryl group content (from 0.72 ± 0.06 to 0.77 ± 0.11) and the reducing power (0.49 ± 0.06 to 0.52 ± 0.08) elevation. The short-term free radical injury may be compensated by the liver resulting in decreased lipid peroxidation markers (malondialdehyde concentration: from 16.86 ± 0.49 to 0.94 ± 0.15, conjugated diene concentration: from 0.21 ± 0.07 to 0.17 ± 0.03). Silymarin further strengthtened the antioxidant defense by the elevation of sulfhydryl groups concentration and reducing power property resulted in decreased total scavenger capacity. However the concentration of lipid peroxidation markers were further elevated by the used antioxidant treatment (MDA: 5.2 ± 0.35, DC: 0.26 ± 0.08). In conclusion, the mycotoxin-contamination activated effectively the antioxidant system. The milk thistle supplementation has cytoprotective effects according to the histological findings, activated the antioxidant system, however the elevation of lipid peroxidation products need further explanation.

Factors affecting liver disease progression, with emphasis on the role of free radical reactions / A májbetegségek progresszióját meghatározó tényezok, különös tekintettel a szabad gyökös reakciókra.

Chronic liver disorders are the main leading cause of morbidity and mortality data. Viral infection, toxic injury, metabolic, autoimmun, storage disorders, in the case of ongoing presence of the etiological factors, could result in fibrotic remodelling in the liver. The process is complex, not fully understood in details; cells, cytokines, chemokines release, altered secretion of hepatokines, lipotoxicity, innate immun system, gut microbiom, metal ions and free radical reactions all have a role in it. Chronic liver disorders are often symptomless, diagnosed in the stage of fibrotic tissue accumulation, liver failure or hepatocellular carcinoma formation, when the prognosis is poor, treatment options are narrow. Noninvasive, properly sensitive and specific biomarkers are the targets of studies, with them the necessity of liver biopsies can be decreased, through the follow-up of processes, progression and treatment efficacy. Authors review the processes taking part in the progression of the most frequent chronic liver disorders, emphasizing the parameters of pro/antioxidant balance, and the necessity of a combined reliable biomarker. Orv Hetil. 2020; 161(35): 1441-1448.

The potential role of organic and conventional yoghurt consumption in the treatment of non-alcoholic fatty liver disease / Az ökológiai és a konvencionális joghurtfogyasztás lehetséges szerepe a nem alkoholos zsírmájbetegség kezelésében.

INTRODUCTION: Health is an important motivation for the consumption of both organic and functional foods. Organic food contains fewer pesticide residues and statistically more selected health-related compounds such as polyphenols in plant products and polyunsaturated fatty acids in milk and meat products. Recent studies suggest that the gut-liver axis plays an important role in the pathogenesis of non-alcoholic fatty liver disease, so probiotics could be a therapeutic tool. Comparing the health effects of yoghurt from organic origin with so-called conventional yoghurt is difficult, because there is no biomarker that would signal the difference with good specificity and sensitivity. AIM: The aim of this study was to investigate numerous biomarkers to evaluate the difference between yoghurt from conventional and organic origin and their health effects in NAFLD. PATIENTS AND METHOD: We performed a prospective, cohort study consisting of 37 (age = 51.73 ± 11.82, male = 21, female = 16) patients with NAFLD at the 2nd Department of Internal Medicine of the Semmelweis University, Budapest. Diagnosis of NAFLD was based on ultrasonography and the exclusion of other etiololgy. The patients were examined also with shear wave elastography to evaluate the hepatic fibrosis stage. We divided the patients randomly into two groups. The patients consumed individually daily 300 grams of yoghurt from organic (n = 21) or conventional (n = 16) origin for 8 weeks. We collected 37 routine laboratory data, measured 4 cytokines, 3 markers of the redox-homeostasis and 14 body composition values before, after, and 12 weeks after the yoghurt consumption. RESULTS: We found a mild elevation of vitamin D and a minimal reduction of LDL after the yoghurt consumption, but in the other 35 routine laboratory data there was no statistical difference. Adiponectin and leptin levels were elevated after the yoghurt consumption in the "conventional group". In contrast, we found significant decrease of adiponectin levels in the "organic group" after the treatment. Only the adiponectin tendency was different in the two groups. The induced free radical content was also statistically lower after the yoghurt consumption. In the body composition measurements, there were no significant differences. CONCLUSION: These data suggest that adiponectin could be a possible biomarker to evaluate the effectiveness of probiotic treatment in non-alcoholic fatty liver disease. Our work can serve as a basis for future studies investigating relationships between organic yoghurt consumption and health outcomes. Orv Hetil. 2020; 161(35): 1466-1474.

Changes in endogenous metal element concentrations in various aetiologies of chronic liver disease. / Az endogén fémionok koncentrációinak változása különbözo kórokú, idült májbetegségekben.

Our body contains physiologically many metal ions used for its metabolic processes and function. Metal ion changes can start pathological processes, however, the pathological processes may also lead to changes in metal ion concentration. In this study, the authors summarize the physiologically present metal ions' change in liver diseases with various aetiologies, the consequences are discussed as well as the connections with the progression. Further, the authors point out the element concentration changes as diagnostic or prognostic values for the liver diseases as well. Orv Hetil. 2020; 161(22): 917-923.

[Hepatitis C virus infection and hepatocarcinogenesis]. / Hepatitis C-vírus-fertozés és hepatocarcinogenesis.

Hepatitis C virus infection causes approximately 4 million new infections worldwide, and 399 000 deaths due to its complications, cirrhosis and hepatocellular carcinoma (HCC). Microenvironmental changes, chronic inflammation, oxidative stress, endoplasmic reticulum stress caused by HCV infection, via genetic and epigenetic changes can result in primary liver cancer during decades. The direct oncogenic property of HCV is wellknown. The transforming effect of four HCV proteins (core, NS3, NS4B, NS5A) has been proven. Effective antiviral therapy, sustained viral response decreases the HCV-related general and liver-related mortality. Interferon-based therapy reduces the risk of HCC development. Shorter therapy with direct acting antiviral agents (DAA) has higher efficacy, fewer side-effects. Publications have reported the unexpected effects of DAA. The authors review the articles focusing on the occurrence of HCC in connection with DAA therapies. There is a need for prospective, multicentric studies with longer follow-up to examine the risk of HCC formation. After antiviral therapy, HCC surveillance is of high importance which means abdominal ultrasound every 3-6-12 months in sustained viral response patients as well. Orv Hetil. 2019; 160(22): 846-853.

[The role of gut microbiota in chronic liver diseases, and treatment possibilities]. / A bélflóra patofiziológai jelentosége és szerepe mint terápiás célpont májbetegségekben.

The community of microorganisms in the intestine, namely gut microbiome lives in symbiosis with the host, contributing to its homeostasis and influencing it simultaneously. It can be suspected that gut microbiome plays a central role in the pathophysiology of intestinal and extraintestinal diseases: determining their development, progress and complications. Recently, intestinal microbiome has become a highlighted field of interest and important topic in research, especially in hepatology. It is in the focus of relevant research as the liver is the organ which meets nutrients, bacterial components, toxins and metabolites at first, as a filter. The evolvement of different liver diseases - just like alcoholic and non-alcoholic fatty liver disease, steatohepatitis, cirrhosis or hepatocellular carcinoma - correlates with the changed composition and activity of gut microbiome. Thus, it can be hypothesized that pre-, pro- and antibiotics could have an impact on the treatment of these diseases. In our review article, the relationship between intestinal flora and liver diseases with different etiologies as well as therapeutic possibilities are discussed. Orv Hetil. 2018; 159(36): 1465-1474.

[Extrahepatic manifestations in chronic hepatitis C infected patients]. / Extrahepaticus manifesztációk idült hepatitis C-vírus-fertozöttekben.

The importance of chronic hepatitis C infection is significant. 3% of the World's population is infected. There is at least one extrahepatic manifestation in 50% of HCV patients, which makes the prognosis and mortality worse. The pathomechanisms included are cryoglobulin production, immunmechanisms, and direct viral effects. The authors summarize the main extrahepatic manifestations, as well as treatment possibilities. The aim is to draw attention to this colourful infection in order to improve the recognition in the era of the new effective direct antiviral agents. Orv. Hetil., 2017, 158(16), 603-612.

[Various pathways leading to the progression of chronic liver diseases]. / Az idült májbetegségek progressziójához vezeto folyamatok.

As the result of various effects (viruses, metabolic diseases, nutritional factors, toxic agents, autoimmune processes) abnormal liver function, liver steatosis and connective tissue remodeling may develop. Progression of this process is complex including various pathways and a number of factors. The authors summarize the factors involved in the progression of chronic liver disease. They describe the role of cells and the produced inflammatory mediators and cytokines, as well as the relationship between the disease and the intestinal flora. They emphasize the role of oxidative stress, mitochondrial dysfunction and cell death in disease progression. Insulin resistance and micro-elements (iron, copper) in relation to liver damage are also discussed, and genetic and epigenetic aspects underlying disease progression are summarized. Discovery of novel treatment options, assessment of the effectiveness of treatment, as well as the success and proper timing of liver transplantation may depend on a better understanding of the process of disease progression.

[Antioxidants--antioxidative stress: facts and questions, 2015]. / Antioxidánsok--antioxidánssokk: tények és kérdések, 2015.

In the past years great importance has been attributed to antioxidant therapy in the prevention and treatment of disorders developed in connection with oxidative stress. After initial success, undesirable effects, toxicities, and prooxidant effects of antioxidants were reported [CARET, ATBC study]. In addition, metaanalyses failed to confirm the role of antioxidant supplementation in the primary and secondary prevention. The authors review the prooxidant effects of antioxidants, and their role in cell signalling and cell process modulation. Finally, the authors summarize possible explanations why combined use of antiooxidants is more favourable.