Course Of Liver Disease Research Articles

Notch signaling regulates macrophage-mediated inflammation in metabolic dysfunction-associated steatotic liver disease

The liver macrophage population comprises resident Kupffer cells (KCs) and monocyte-derived macrophages with distinct pro- or anti-inflammatory properties that affect the severity and course of liver diseases. The mechanisms underlying macrophage differentiation and functions in metabolic dysfunction-associated steatotic liver disease and/or steatohepatitis (MASLD/MASH) remain mostly unknown. Using single-cell RNA sequencing (scRNA-seq) and fate mapping of hepatic macrophage subpopulations, we unraveled the temporal and spatial dynamics of distinct monocyte and monocyte-derived macrophage subsets in MASH. We revealed a crucial role for the Notch-Recombination signal binding protein for immunoglobulin kappa J region (RBPJ) signaling pathway in controlling the monocyte-to-macrophage transition, with Rbpj deficiency blunting inflammatory macrophages and monocyte-derived KC differentiation and conversely promoting the emergence of protective Ly6Clo monocytes. Mechanistically, Rbpj deficiency promoted lipid uptake driven by elevated CD36 expression in Ly6Clo monocytes, enhancing their protective interactions with endothelial cells. Our findings uncover the crucial role of Notch-RBPJ signaling in monocyte-to-macrophage transition and will aid in the design of therapeutic strategies for MASH treatment.

Pharmacological considerations in pharmacotherapy of rheumatology patients with liver disease: a brief narrative review.

The presence of chronic liver diseases such as metabolic dysfunction-associated steatosis liver disease, viral hepatitis, and cirrhosis may affect the treatment plan in patients with rheumatologic disorders, with concern about the adverse effects of the rheumatic medications on the course of liver disease. Advanced liver disease can change the elimination and activation of many drugs. In addition, there are concerns about the risk of viral reactivation after using biologics and immunosuppressants in patients with chronic viral hepatitis. This narrative review will assess the considerations that should be made before starting the most frequently used drugs in all common rheumatic diseases and patients with chronic liver diseases including chronic viral hepatitis.

Outcomes of adolescent bariatric surgery: liver disease

The prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD) is increasing among children in the United States as pediatric obesity rates continue to rise. As such, metabolic and bariatric surgery (MBS) has become a more recognized option for treatment of obesity and has been recommended by the American Academy of Pediatrics. Although MBS is known to improve many obesity-associated comorbidities, such as hypertension and type 2 diabetes, less is known about its effect as a treatment for MASLD. This article reviewed the impact MBS has on the course of liver disease as measured by histopathology, serum markers, and radiographic imaging, among adolescents with severe obesity. Improvements were seen in alanine transaminase (ALT) liver enzymes, rates of hepatocyte steatosis, and degree of fibrosis on histopathology, and fat content in the liver on computed tomography and magnetic resonance imaging. Greater improvements in ALT were seen in patients with higher baseline values and/or a higher stage of biopsy-confirmed steatohepatitis. Biopsy-proven MASLD and metabolic dysfunction–associated steatohepatitis (MASH) have even been shown to disappear completely, but fibrosis does not completely resolve by 12 months post-MBS. To better understand the outcome of pediatric MASLD following MBS treatment, more longitudinal radiographic data and liver histology in patients with fibrosis would be informative beyond 12 months post-MBS.

Metabolic Profiles of the Gut Microbiota in Patients with Different Stages of Metabolism Dysfunction-Associated Fatty Liver Disease

Aim: to study the metabolic activity of the intestinal microbiota depending on the stage of metabolic dysfunction-associated fatty liver disease (MAFLD). Materials and methods. The study included 85 patients with MAFLD (27 patients with steatosis without steatohepatitis and fibrosis, 42 patients with steatohepatitis, 16 patients with cirrhosis as an outcome of MAFLD, Child — Pugh class A–B) and 20 healthy people who formed the control group. The level and spectrum of short-chain fatty acids (SCFA) were determined by gas-liquid chromatography. Results. It was found that patients with MAFLD at the stage of steatosis and cirrhosis of the liver have unidirectional changes in the metabolic activity of the intestinal microbiota. We established a decrease in the absolute concentrations of SCFA — their total content, the level of acetate, propionate, butyrate, a decrease in the level of isoacids. The SCFA profiles showed an increase in the proportion of acetate and a decrease in propionate and butyrate. Moreover, changes in the named parameters of SCFAs are aggravated with progression to liver cirrhosis. At the stage of steatohepatitis, we identified two subgroups of patients with different levels of metabolic activity of the microbiota. Patients whose microbiota metabolism for SCFA production was high had correspondingly elevated SCFA levels. And, on the contrary, patients in whom the metabolic activity of the microbiota was reduced were characterized by a steady decrease in SCFAs and disease progression to liver cirrhosis. In the study, we showed an inverse correlation between the calculated prognostic indices of NFS and FIB-4, elastography values with the total level of SCFA, the level of acetate, propionate, butyrate. Thus, a decrease in the content of SCFA for patients with MAFLD can be considered as a prognostic marker of an unfavorable course of liver disease.

Alcohol does not impact chronic hepatitis C treatment outcomes but increases risk for progressive liver disease: Findings from a prospective multicentre Australian study (OPERA-C).

Alcohol use is common in patients with chronic hepatitis C virus (HCV) infection. We examined the impact of alcohol use on direct-acting antiviral (DAA) therapy outcome and the clinical course of liver disease and 2-year survival for patients receiving HCV DAA therapy. Adults (n = 2624) recruited from 26 Australian hospital liver clinics during 2016-2021 were followed up for 2 years. Risky alcohol use was defined by a combination of self-report (≥40 g/day of ethanol), physician-reported history of problematic alcohol use, and anti-craving medication prescription via population-based database linkage. We examined factors associated with advanced liver fibrosis and survival using multivariable logistic and Cox regression. Among 1634 patients (62.3%) with risky alcohol use, 24.6% reported consuming ≥40 g/day of alcohol, 98.3% physician-reported problematic alcohol use; only 4.1% were dispensed naltrexone/acamprosate. One hundred and forty-three patients with cirrhosis reported ≥40 g/day of alcohol, 6 (4.3%) were prescribed naltrexone/acamprosate. Risky alcohol use was associated with advanced fibrosis (adjusted-odds ratio 1.69, 95% confidence interval 1.32-2.17) and patients were over-represented for cirrhosis (45.1% vs. 25.6% in no-risky alcohol use [p < 0.001]) and hepatocellular carcinoma (5.7% vs. 2.5% [p < 0.001]). Sustained viral response (p = 0.319) and 2-year survival (adjusted-hazard ratio 1.98, 95% confidence interval 0.84-4.63) after DAA therapy were not associated with risky alcohol use. Risky alcohol use in HCV patients was prevalent, but did not reduce HCV cure. Treatment for alcohol dependence was low. Risky alcohol use may be under-recognised in liver clinics. Better integration of addiction medicine into liver services and increased resourcing and addiction medicine training opportunities for hepatologists may help address this.

Τ cell-mediated adaptive immunity in the transition from metabolic dysfunction-associated steatohepatitis to hepatocellular carcinoma.

Metabolic dysfunction-associated steatohepatitis (MASH) is the progressed version of metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by inflammation and fibrosis, but also a pathophysiological "hub" that favors the emergence of liver malignancies. Current research efforts aim to identify risk factors, discover disease biomarkers, and aid patient stratification in the context of MASH-induced hepatocellular carcinoma (HCC), the most prevalent cancer among MASLD patients. To investigate the tumorigenic transition in MASH-induced HCC, researchers predominantly exploit preclinical animal-based MASH models and studies based on archived human biopsies and clinical trials. Recapitulating the immune response during tumor development and progression is vital to obtain mechanistic insights into MASH-induced HCC. Notably, the advanced complexity behind MASLD and MASH pathogenesis shifted the research focus towards innate immunity, a fundamental element of the hepatic immune niche that is usually altered robustly in the course of liver disease. During the last few years, however, there has been an increasing interest for deciphering the role of adaptive immunity in MASH-induced HCC, particularly regarding the functions of the various T cell populations. To effectively understand the specific role of T cells in MASH-induced HCC development, scientists should urgently fill the current knowledge gaps in this field. Pinpointing the metabolic signature, sketching the immune landscape, and characterizing the cellular interactions and dynamics of the specific T cells within the MASH-HCC liver are essential to unravel the mechanisms that adaptive immunity exploits to enable the emergence and progression of this cancer. To this end, our review aims to summarize the current state of research regarding the T cell functions linked to MASH-induced HCC.

Leukocyte indexes for liver lipidosis in cats

Chronic liver failure is characterized by significant impairment of liver function due to exposure to a damaging factor for a long time. In cats, one of the most common liver diseases is lipidosis, or fatty liver dystrophy – a condition in which there is an excessive accumulation of fats in hepatocytes caused by a complex of metabolic disorders (for example, obesity, impaired energy metabolism). Diagnosis and prognosis of the course of liver diseases in cats can cause difficulties due to a number of factors, therefore, it is relevant to search and evaluate available and minimally invasive diagnostic methods for early detection and treatment strategy planning. Leukocyte indices can be one of these mechanisms. They can be useful in the diagnosis of liver diseases, as they reflect the degree of neuro-humoral reactivity and the body's response to various stimuli, in particular, to a decrease in detoxification function of the liver. The purpose of the presented study was to evaluate and compare the indicators of leukocyte indices in cats with chronic degenerative liver disease using the example of liver lipidosis with the corresponding indicators of clinically healthy animals. significant deviations of leukocyte indices associated with the level of lymphocytes and neutrophils were revealed, which allow a comprehensive assessment of leukogram parameters. The introduction and use of these indicators in veterinary practice will make it possible to better predict the course of the disease and better develop a treatment strategy. It should be noted that in order to more accurately determine the diagnostic significance and the possibility of determining forecasts, it is necessary to increase the number of animal samples with an assessment of indicators in dynamics.

Liver involvement in presence of heart disease and heart involvement in presence of liver disease: a conundrum.

Data from literature show a cross-talk between the heart and liver during diseases which primarily involve one of the two organs, but data regarding this relationship are scant. Aim of this study was to investigate this relationship. In this narrative review we critically explored the most recent literature on this topic using PubMed and Medline and examining the most recent studies about liver involvement in heart failure and heart involvement in course of liver disease. Patients with acute and chronic heart failure and those who undergo heart transplatation (HT) manifest various signs of liver damage with a rate of incidence which is higher in candidates for left ventricular assist device. In presence of cardiogenic shock a very marked hepatocellular necrosis may occur while in the setting of chronic heart failure congestive hepatopathy and-or the so-called cardiac cirrhosis are observed. On the other side in presence of chronic liver disease and in case of liver transplantation (LT) heart functions may be altered and cirrhotic cardiomyopathy, which is a syndrome characterized by systolic, diastolic and electrophysiological abnormalities may occur. In this review we have analyzed the relationship between heart and liver disease, even in case of LT and HT. Furthermore we have underscored the effects of chronic alcoholism and of systemic disorders such as hemochromatosis and amyloidosis on both heart and liver.

Transjugular Intrahepatic Portosystemic Shunt Placement: Effects on Nutritional Status in Cirrhotic Patients.

Malnutrition is a tangible complication of cirrhosis with portal hypertension with a prevalence of up to 50%. In particular, sarcopenia and myosteatosis, defined as the alteration in muscle quantity and quality, have a negative impact on the main complications of liver disease and are associated with higher mortality in patients with cirrhosis. Recently, alterations in adipose tissue have also been described in cirrhotic patients and they seem to influence the course of liver disease. Several pieces of evidence indicate that a transjugular intrahepatic portosystemic shunt (TIPS), placed for the treatment of refractory portal hypertension, can lead to a modification of body composition consisting in the improvement of the skeletal muscle index, myosteatosis, and an increase in subcutaneous fat. These modifications of the nutritional status, even more pronounced in sarcopenic patients before TIPS, have been associated with an amelioration of cognitive impairment after TIPS as well as with an increase in the survival rate. The aim of this paper is to provide an overview of the effects of TIPS placement on nutritional status in cirrhosis focusing on its pathophysiological mechanisms and its relationship with liver-related outcomes.

Association Between Pre-Transplant Oral Health and Post-Liver Transplant Complications.

Oral disease is linked with systemic inflammation and various systemic conditions, including chronic liver disease. Liver transplantation (LT) candidates often need dental infection focus eradication, and after LT, there is high risk of many inflammation-related complications. We studied whether pre-LT dental status is associated with the occurrence of post-LT complications. This study included 225 adult LT recipients whose teeth were examined and treated before LT, and 40 adult LT recipients who did not have pre-LT dental data available. Data on post-LT complications were collected from the national liver transplant registry and followed up until the end of July 2020. Worse pre-LT dental status was associated with a higher risk of acute rejection post-LT compared to patients with good dental status. Worse dental status was also associated with higher 1-year-post-LT ALT levels and lower albumin levels. In conclusion, poor pre-LT oral health seems to associate with an increased risk of post-LT acute rejection and with elevated ALT levels and decreased albumin levels, suggesting an effect on post-LT liver health. Therefore, prevention and treatment of oral and dental diseases should be promoted early in the course of liver disease.

Lymphatic drainage dysfunction via narrowing of the lumen of cisterna chyli and thoracic duct after luminal dilation.

The chronological pattern of extrahepatic lymphatic vessel progression in the course of chronic liver disease has not been clarified. This study aimed to clarify the chronological changes in lymphatic vessels with liver disease progression. This was a prospective cross-sectional study that enrolled a total of 199 patients. The maximum diameter of the cisterna chyli (CC) or terminal thoracic duct (tTD) was measured using computed tomography or ultrasonography, respectively. Changes in the maximum diameters of the CC and tTD were evaluated with patients with chronic liver disease as the pilot set (n = 138). Subsequently, we examined whether CC/tTD could be used to re-allocate unclassified patients by the Baveno-VII criteria to appropriately diagnose clinically significant portal hypertension (CSPH) in the pilot and validation sets. In the pilot set, a scatter-plot showed that both CC and tTD were narrowed as terminal features in chronic liver disease after dilation. Because there was a significant correlation between the CC diameter and hepatic venous pressure gradient (r = 0.724) in unclassified patients, the diagnostic value of CC and tTD for CSPH was good (AUC: 0.961 and 0.913, respectively). After re-allocation, 68 and 27 unclassified patients were reduced to 4 and 5 in the pilot and validation sets, respectively. Both the CC and tTD narrow in the course of liver disease after dilation. Moreover, the maximum diameter of the CC and tTD can be used to re-allocate patients who are unclassified according to the Baveno-VII criteria. UMIN trial no. 000044857.

Integrative roles of sphingosine kinase in liver pathophysiology.

Bioactive sphingolipids and enzymes that metabolize sphingolipid-related substances have been considered as critical messengers in various signaling pathways. One such enzyme is the crucial lipid kinase, sphingosine kinase (SphK), which mediates the conversion of sphingosine to the potent signaling substance, sphingosine-1-phosphate. Several studies have demonstrated that SphK metabolism is strictly regulated to maintain the homeostatic balance of cells. Here, we summarize the role of SphK in the course of liver disease and illustrate its effects on both physiological and pathological conditions of the liver. SphK has been implicated in a variety of liver diseases, such assteatosis, liver fibrosis, hepatocellular carcinoma, and hepatic failure. This study may advance the understanding of the cellular and molecular foundations of liver disease and establish therapeutic approaches via SphK modulation.

Changes and influencing factors of liver volume after transjugular intrahepatic portosystemic shunt: a retrospective cohort study.

Liver volume is an important measure of liver reserve and helps to determine the course of liver disease. This study aimed to observe the dynamic changes of liver volume after transjugular intrahepatic portosystemic shunt (TIPS) and analyze the related factors. Clinical data of 168 patients who underwent TIPS procedures between February 2016 and December 2021 were collected and analyzed retrospectively. The changes in liver volume after TIPS in the patients were observed, and the independent predictors affecting increases in liver volume were analyzed using a multivariable logistic regression model. The mean liver volume was decreased by 12.9% at 2±1 months post TIPS and rebounded at 9±3 months post TIPS, but did not recover to its pre-TIPS level completely. Most patients (78.6%) had decreased liver volume at 2±1 months post TIPS, and in multivariable logistic regression, a lower albumin (ALB) level, a lower subcutaneous fat area at L3 (L3-SFA), and a higher degree of ascites were identified as independent factors predicting increased liver volume. The risk score model for predicting increased liver volume was Logit(P)=1.683-0.078 (ALB) -0.01 (pre TIPS L3-SFA) +0.996 (grade 3 ascites =1; non-grade 3 ascites =0). The area under the curve of the receiver operating characteristic curve was 0.729, and the cut-off value was 0.375. The rate of liver volume change at 2±1 months post TIPS was significantly correlated with that of spleen volume change (R2=0.378, P<0.001). The rate of subcutaneous fat change at 9±3 months post TIPS was significantly correlated with that of liver volume change (R2=0.782, P<0.001). In patients with a liver volume increase, the mean computed tomography value (Hounsfield units) decreased significantly after TIPS placement (65.9±17.7 vs. 57.8±18.2, P=0.009). Liver volume was decreased at 2±1 months post TIPS and slightly increased at 9±3 months post TIPS; however, it did not recover to its pre-TIPS level completely. A lower ALB level, a lower L3-SFA, and a higher degree of ascites were all predictors for increased liver volume post TIPS.

Correlation between individual autoantibodies and clinical features in primary biliary cholangitis: results of a retrospective longitudinal study.

Primary biliary cholangitis (PBC) is an immune-mediated liver disease. The immunological profile seems to relate to clinical prognosis. This study aims to determine the role of autoantibodies in the course of liver disease and in the response to ursodeoxycholic acid. Between January 2016 and December 2020, 143 patients with PBC who underwent immunological liver profile evaluation were enrolled. All data were extracted retrospectively from electronic clinical records. Chi-square test, Fisher's exact test and Mann-Whitney test were used to evaluate the relationship between autoantibodies and biochemical parameters, clinical outcomes and therapeutic response scores. A significance level of 0.05 was used. Antimitochondrial antibodies were present in 91.6%, antiglycoprotein-210 antibody (anti-gp210) in 18.2% and anti-Sp100 in 19.6% of patients. The incidence of liver-related death was higher in patients with autoimmune hepatitis variants. The occurrence of cirrhosis or portal hypertension was not linked to the presence of any of the autoantibodies tested. No relationship was found with the probability of dying or being transplanted. Patients with anti-Sp100 antibodies had higher baseline levels of aspartate aminotransferase and alanine aminotransferase and lower immunoglobulin M levels. Patients with anti-gp210 were more likely to have a lower median transplant-free survival rate and higher median risk of liver transplant or liver-related death using the GLOBE and UK-PBC scores. Our findings confirm a strong association between anti-gp210 antibodies and a worse outcome. The association between anti-Sp100 and hepatic lesions requires further elucidation.

Hepatitis C virus fitness can influence the extent of infection-mediated epigenetic modifications in the host cells.

Cellular epigenetic modifications occur in the course of viral infections. We previously documented that hepatitis C virus (HCV) infection of human hepatoma Huh-7.5 cells results in a core protein-mediated decrease of Aurora kinase B (AURKB) activity and phosphorylation of Serine 10 in histone H3 (H3Ser10ph) levels, with an affectation of inflammatory pathways. The possible role of HCV fitness in infection-derived cellular epigenetic modifications is not known. Here we approach this question using HCV populations that display a 2.3-fold increase in general fitness (infectious progeny production), and up to 45-fold increase of the exponential phase of intracellular viral growth rate, relative to the parental HCV population. We show that infection resulted in a HCV fitness-dependent, average decrease of the levels of H3Ser10ph, AURKB, and histone H4 tri-methylated at Lysine 20 (H4K20m3) in the infected cell population. Remarkably, the decrease of H4K20m3, which is a hallmark of cellular transformation, was significant upon infection with high fitness HCV but not upon infection with basal fitness virus. Here we propose two mechanisms ─which are not mutually exclusive─ to explain the effect of high viral fitness: an early advance in the number of infected cells, or larger number of replicating RNA molecules per cell. The implications of introducing HCV fitness as an influence in virus-host interactions, and for the course of liver disease, are warranted. Emphasis is made in the possibility that HCV-mediated hepatocellular carcinoma may be favoured by prolonged HCV infection of a human liver, a situation in which viral fitness is likely to increase.

What Do NAFLD, Liver Fibrosis, and Inflammatory Bowel Disease Have in Common? Review of the Current Literature

Liver disease is one of the most common extraintestinal manifestations of inflammatory bowel disease (IBD). Often the course of liver disease is associated with an exacerbation of the underlying disease (Crohn's Disease/Ulcerative Colitis). Nonalcoholic steatohepatitis encompasses a wide spectrum of liver damage. The most common form is nonalcoholic fatty liver disease (NAFLD) (75-80%), and the less common but more dangerous form is nonalcoholic steatohepatitis (NASH). NAFLD is now the most common cause of chronic liver disease in developed countries and the leading indication for liver transplantation in the United States. Genetic, demographic, clinical, and environmental factors can play a role in the pathogenesis of NAFLD. The increasing prevalence of NAFLD is associated with a widespread obesity epidemic, metabolic complications, including hypertension, type 2 diabetes, and dyslipidaemia. Some of the most common manifestations of IBD are liver, biliary tract, and gallbladder diseases. The liver fibrosis process has a complex pathophysiology and is often dependent on exogenous factors such as the treatment used and endogenous factors such as the gut microbiome. However, the factors that link IBD and liver fibrosis are not yet clear. The main purpose of the review is to try to find links between IBD and selected liver diseases and to identify knowledge gaps that will inform further research.

Features of clinical, biochemical, and sonographic parameters in patients with chronic viral hepatitis C with concomitant non-alcoholic fatty liver disease.

Introduction. Difficulties encountered in treating patients with chronic viral hepatitis C (CHC) are associated with the presence of concomitant liver pathology, namely fatty degeneration, which contributes to the progression of HCV infection. The above circumstances prompted the authorsled to thoroughly examine of this category of patients for further development of a new pathogenetically directed course of treatment. Objective. To study clinical, biochemical, and instrumental features of the course of liver disease in CHC patients with concomitant non-alcoholic fatty liver disease (NAFLD). Tested 339 patients with chronic hepatitis C with concomitant NAFLD; and 175 patients with СНС. Methodology: anamnestic, anthropometric and clinical, general clinical, biochemical, serological, and molecular genetic (markers of hepatitis C virus, HCV RNA PCR (qualitative and quantitative determination, genotyping), enzyme-linked immunosorbent assay, ultrasonographic examination of digestive organs, statistical methods. Conducted clinical, instrumental, and laboratory studies have shown that CHC patients with concomitant NAFLD are characterized by various disorders - a violation of the functional state of the liver, a violation of carbohydrate and lipid metabolism, an imbalance of the cytokine system, the presence of histological and non-inflammatory activity in the liver. The presence of concomitant NAFLD in patients with CHC aggravates the clinical picture, manifesting itself in a significant lipid metabolism disorder that provokes the rapid formation of liver fibrosis. An additional complicating factor is the development of insulin resistance, leading to persistent morphological changes in the liver parenchyma.

Right-sided heart failure as a first presentation of portopulmonary hypertension

Introduction. Pulmonary artery hypertension and right ventricular failure are potentially fatal complications that can develop in patients with portal hypertension. The objective of this case report was to report a patient with end-stage liver disease, and portal and pulmonary artery hypertension and right heart failure. Case outline. A 57-year-old man was admitted to the Cardiology Department of a tertiary referral hospital due to signs of right-sided heart failure, ascites, pleural effusions, and pretibial edema. The patient had the history of alcohol abuse, arterial hypertension, and gout. Just prior to the admission, abdominal ultrasound revealed granular liver structure, as well as ascites. Laboratory tests showed microcytic anemia, values of transaminases below referent, hypoalbuminemia, low creatinine clearance. Echocardiography revealed pulmonary hypertension, and right ventricle failure. Right heart catheterization unraveled precapillary pulmonary hypertension, but thoracic CT scan and thoracocentesis excluded underlying pulmonary illness. Treatment continued at the Gastroenterology Department of the tertiary hospital. Abdominal CT scan diagnosed cirrhotic liver, and signs of portal hypertension. The patient was treated with symptomatic therapy, but developed acute-on-chronic renal failure and eventually died. Conclusion. Multidisciplinary approach is very important to distinguish portopulmonary hypertension early in the course of liver disease, because evolution of right sided heart failure precludes these patients from adequate lifesaving therapy.

Sarcopenia in chronic liver disease, can we predict complications?

Introduction. Sarcopenia is a common complication of chronic liver disease. Today many studies are devoted to sarcopenia impact on the course of liver diseases. At the same time, many studies are being performed on the correlation of sarcopenia in patients with cirrhosis of the liver and the incidence of early complications after liver transplantation. In this regard, we conducted our own retrospective study of the correlation relationship of sarcopenia in patients with chronic liver diseases. Aim. To determine the correlation between the severity of sarcopenia and the incidence of complications of liver cirrhosis in patients on the waiting list for liver transplantation. Material and methods. In our own retrospective observational study, 87 patients suffering from chronic liver diseases and treated at the Minsk Scientific and Practical Center of Surgery, Transplantation and Hematology were included. The assessment of sarcopenia was carried out using the CT technique for assessing indexed parameters of the patient's muscle mass. Mathematical processing was performed using the FDA-approved Osirix TM software. The study was conducted within the framework of the project "ClinicalTrials: NCT04281797" Results. Body mass index was significantly correlated with the presence of sarcopenia (r pb =-0.48, 95% CI [-0.65;-0.27]). At the same time, the groups of patients with and without sarcopenia differed significantly (p&lt;0.0001), (Hedges g=-0.93, 95% CI [-1.37;-0.48]). In groups of patients with various etiological factors of chronic liver diseases, sarcopenia occurred most often among patients with autoimmune hepatitis, while the uneven distribution of the incidence of sarcopenia in different nosological groups was significant (p=0.028;  2 =14.1). Conclusion. Body mass index plays an important prognostic role in muscle mass loss among patients with clinically advanced liver disease. However, skeletal muscle index and Body Mass Index differ significantly between patients with and without sarcopenia. In addition, our study showed a significant difference in the occurrence of sarcopenia in patients on the waiting list of different etiological groups. Thus, further extensive randomized studies in this direction are needed today.

Favourable outcome of acute hepatitis E infection in patients with ANCA-associated vasculitis

BackgroundHepatitis E virus (HEV) infection is a frequent cause of acute viral hepatitis. Immunocompromised patients are at increased risk for viral infection and chronic courses of hepatitis. Whether patients with autoimmune diseases are at risk of developing clinically relevant hepatitis or even chronic liver disease after HEV infection is discussed controversially. ANCA-associated vasculitis is a rare autoimmune disease with potentially life-threatening organ involvement, thus requiring intensive immunosuppression with glucocorticoids, cyclophosphamide, or rituximab. As there are no reports available on the infection with HEV in patients with ANCA-associated vasculitis, clinical decision making in such cases is based on experiences from other disease entities. Therefore, in this study we analyzed the course of liver disease and the therapeutic management of autoimmune vasculitis in a retrospective cohort of five patients with ANCA-associated vasculitis and acute hepatitis E.ResultsFour patients were on immunosuppressive maintenance therapy and one patient was on remission induction therapy with cyclophosphamide and high dose glucocorticoids. All patients had at least one potentially hepatotoxic co-medication at the time of hepatitis. Hepatitis-associated clinical symptoms were recorded in four of five patients. The course of hepatitis was characterized by strongly elevated transaminases, a temporary liver failure was observed in one case. The management of hepatitis E included cessation of the immunosuppressants in all patients, whereas oral glucocorticoids were not discontinued. Under this regime, all patients cleared the virus without additional anti-viral treatment. Liver enzymes normalized one month after they peaked. In the follow-up period of at least 1.5 years (range 1.5–12 years), no chronic liver disease was observed, although one patient died of cholangiocarcinoma with liver metastases some years after HEV infection. Vasculitis was not active in our patient cohort at the time of HEV infection. However, inflammatory flares occured in three of five patients after discontinuation of the immunosuppressive therapy. Immunosuppressants were paused for a median time of 4 weeks and after their resumption vasculitic disease activity was controlled in all patients.ConclusionsAcute HEV infection in patients with ANCA-associated vasculitis shows a favorable outcome of liver disease but bears the risk of inflammatory flares due to cessation of immunosuppression.