Concomitant Liver Research Articles

Study of Hypoglycemic Activity of Novel 9-N-alkyltetrahydroberberine Derivatives.

Novel 9-N-alkyltetrahydroberberine derivatives were synthesized, among which, based on the results of OGTT, one compound containing the longest aliphatic substituent was selected for study in mice C57BL/6Ay, which demonstrate obesity, impaired glucose tolerance, and concomitant liver non-alcoholic fatty disease. Administration of this substance at a dose of 15 mg/kg for four weeks improved the insulin sensitivity of mice, which resulted in a decrease in fasting glucose levels and improved the tolerance of mice to OGTT glucose loading. A decrease in the level of lactate in the blood and a decrease in the amount of glucokinase in the liver were also found. The introduction of compound 3c did not have a toxic effect on animals based on biochemical data, histological analysis, and measurements of general parameters such as body weight and feed intake. Thus, the 9-N-heptyltetrahydroberberine derivative showed prominent hypoglycemic effects, which makes it promising to obtain and study other derivatives with longer substituents.

Possibilities of cryosurgery in the treatment of the abdominal cavity diseases

Aim. To study the immediate results of the use of cryosurgical instruments and ultra-low temperature liquid nitrogen in diseases of abdominal organs.Materials and research methods. The article presents the results of surgical treatment using ultra-low temperature liquid nitrogen (196oC) for 308 patients with diseases of the abdominal organs in the Department of Liver and Pancreas Surgery of the Institute of Gastroenterology of the Republic of Tajikistan from 2016 to 2022.The results and discussion. The authors proposed an algorithm for the use of the ultra-low temperature of liquid nitrogen in the treatment of diseases of the abdominal organs after the development of the latest cryogenic equipment. It turned out that the resulting cryodestruction leads to the death of parasitic elements of alveococcosis, echinococcosis, and liver tuberculosis, as well as to cytolysis of atypical calls in hepatocellular carcinoma. The most important advantage of liver cryosurgery, especially in concomitant chronic viral hepatitis and liver cirrhosis, is a reliable parenchymal haemo-and cholestasis, a decrease in intraoperative blood loss, an increase in the radicality of an operation, and reliable prevention of intraoperative dissemination of malignant and parasitic diseasesConclusion. The accumulated experience of surgeries for various diseases of the abdominal organs using ultra-low temperature liquid nitrogen allows concluding that cryosurgery of the abdominal organs has an undoubted prospect. The positive characteristic of using cryotechnology in the treatment of severe diseases of abdominal organs suggests that it is advisable to introduce the method into clinical practice on a wide scale.

Geographical similarity and differences in the burden and genetic predisposition of NAFLD.

NAFLD has become a major public health problem for more than 2 decades with a growing prevalence in parallel with the epidemic of obesity and type 2 diabetes (T2D). The disease burden of NAFLD differs across geographical regions and ethnicities. Variations in prevalence of metabolic diseases, extent of urban-rural divide, dietary habits, lifestyles, and the prevalence of NAFLD risk and protective alleles can contribute to such differences. The rise in NAFLD has led to a remarkable increase in the number of cases of cirrhosis, hepatocellular carcinoma, hepatic decompensation, and liver-related mortality related to NAFLD. Moreover, NAFLD is associated with multiple extrahepatic manifestations. Most of them are risk factors for the progression of liver fibrosis and thus worsen the prognosis of NAFLD. All these comorbidities and complications affect the quality of life in subjects with NAFLD. Given the huge and growing size of the population with NAFLD, it is expected that patients, healthcare systems, and the economy will suffer from the ongoing burden related to NAFLD. In this review, we examine the disease burden of NAFLD across geographical areas and ethnicities, together with the distribution of some well-known genetic variants for NAFLD. We also describe some special populations including patients with T2D, lean patients, the pediatric population, and patients with concomitant liver diseases. We discuss extrahepatic outcomes, patient-reported outcomes, and economic burden related to NAFLD.

S1386 The National Trends and Hospitalizations of Patients with Hereditary Hemochromatosis in the United States: Insights From the National Inpatient Sample

Introduction: Hereditary hemochromatosis (HH) is a disorder of increased intestinal iron absorption leading to total body iron overload. Although it is among the most common genetic diseases globally, no large-scale nationwide data is available regarding HH-related hospitalizations in the United States. Our study aimed to find on a national level the demographics of the patients with HH, inpatient mortality, and resource utilization using the national inpatient database (NIS). Methods: We queried the nationwide inpatient (NIS) 2016-2019 databases using the ICD-10 CM codes to identify all the patients hospitalized with hereditary hemochromatosis (HH). We excluded patients under 18 years. The primary outcome of our study was to do an exploratory analysis and determine the baseline demographic characteristics of patients admitted with HH. The secondary outcomes included in-hospital mortality, length of stay (LOS), hospitalization cost, and outcomes. Results: A total of 196 adult patients with HH were admitted in the United States with a mean age of 59.3 years. The majority of the patients were males (55%) and Caucasians (97.2%). The mean length of stay was 6 days, and a total of 10 patients (0.5%) died in the hospital. Medicare (47.2%) was the most common insurance, and most of the patients were admitted to large tertiary care hospitals. Patients with concomitant Alcoholic Liver Disease (ALD) had greater LOS (7.5 days vs. 6 days) than patients without ALD. The rest of the demographics are shared in the Table. Conclusion: Our study demonstrated that most of the patients admitted with HH are Caucasians and males. The mean LOS is 6 days. The total mean cost of hospitalizations is $21,763.The HH patients with concomitant Hepatitis C and Alcoholic Liver Disease have higher healthcare utilization and worse outcomes than other patients. So, patients with HH should be screened for Hepatitis C and alcoholic Liver disease to improve the outcomes for these patients. Table 1. - Baseline patient and hospital characteristics and outcomes for HH-related hospitalizations Patient Characteristics Hereditary Hemochromatosis (HH) No. of patients 196 Male (%) 109 (55.7%) Mean age, (SD) years 59.38 Race [N, %] Caucasian 190 (97.04%) African American 0 Hispanic 0 Asian 6 (2.96%) Charlson Comorbidity Index Score [N, %] 0 56 (28.71%) 1 47 (24.07%) 2 19 (9.56%) 3 or more 74 (37.63%) Median Income (Zip Codes) [N, %] $1-$38,999 25 (12.97%) $39,000-$47,999 48 (24.29%) $48,000-$62,999 38 (19.17%) >$ 63,000 85 (43.54%) Insurance Provider [N, %] Medicare 93 (47.28%) Medicaid 14 (7.03%) Private 84 (42.94%) Others 2.7% Hospital Characteristics Hospital teaching Status [N, %] Non-Teaching 94 (48.05%) Teaching 102 (51.94%) Hospital Bed Size [N, %] Small 35 (17.79%) Medium 63 (32.07%) Large 98.2 (50.12%) Hospital Location [N, %] Rural 4 (1.8%) Urban 192 (98.11%) Outcomes HH HH & Hep C HH & ALD Mortality, no. % 10 (0.5%) 10(50%) 0 Length of Stay (SD) 6 5.9 7.5 Hospitalization cost (SD) $21,763 $38,161 $43,962

Porto-sinusoidal vascular disorder.

It is well established that portal hypertension can occur in the absence of cirrhosis, as reported in patients with immune disorders, infections and thrombophilia. However, similar histological abnormalities primarily affecting the hepatic sinusoidal and (peri)portal vasculature have also been observed in patients without portal hypertension. Thus, the term porto-sinusoidal vascular disorder (PSVD) has recently been introduced to describe a group of vascular diseases of the liver featuring lesions encompassing the portal venules and sinusoids, irrespective of the presence/absence of portal hypertension. Liver biopsy is fundamental for PSVD diagnosis. Specific histology findings include nodular regenerative hyperplasia, obliterative portal venopathy/portal vein stenosis and incomplete septal fibrosis/cirrhosis. Since other conditions including alcohol-related and non-alcoholic fatty liver disease, or viral hepatitis, or the presence of portal vein thrombosis may occur in patients with PSVD, their relative contribution to liver damage should be carefully assessed. In addition to histology and clinical diagnostic criteria, imaging and non-invasive tests such as liver and spleen stiffness measurements could aid in the diagnostic workup. The introduction of PSVD as a novel clinical entity will facilitate collaborative studies and investigations into the underlying molecular pathomechanisms encompassed by this term.

Combined stoma reversal and liver resection for rectal metastatic cancer: A single center retrospective analysis.

Concomitant liver metastases are discovered at the time of diagnosis in 25% of patients with colorectal cancers. The appropriate time to restore digestive continuity after stoma creation during rectal surgery has not yet been established. The objective of this study is to assess the morbidity of stoma reversal during the secondary hepatectomy procedure. This was a single-center retrospective case-control study including patients who underwent ileostomy or colostomy reversal by a direct approach (REVERSAL group) compared to those who did not undergo stoma reversal (NON-REVERSAL group) during hepatic resection of rectal cancer metastasis between 2004 and 2016. Peri-operative data were collected. The primary outcome measure was the comprehensive complication index (CCI). The secondary outcomes were overall mortality, liver-related morbidity, duration of hospital stay and occurrence of gastrointestinal leaks. Statistical analysis was carried out using SPSS 23.0 software. Thirty liver resections were included; 14 in the REVERSAL group (female/male=11/19, age=60 years). No statistically significant difference was observed in the CCI scores (15 vs. 20.8; P=0.6). Complications occurred in 9 (64%) and 8 (50%) patients in the REVERSAL and NON-REVERSAL groups, respectively (P=0.48). No gastro-intestinal leaks or post-operative mortality occurred. Stoma reversal during hepatectomy for liver metastasis from a primary rectal cancer represents a safe alternative since post-operative outcome was not associated with additional morbidity in this series.

Experience of treating patients with complicated forms of gallstone disease on the background of liver cirrhosis

Annotation. In recent years, further improvement of minimally invasive surgical interventions has been noted. Surgical treatment of complicated gallstone disease has become quite standardized all over the world. However, accompanying cirrhosis of the liver remains the most severe comorbid condition. The purpose of this study is to determine the optimal treatment strategy of this category of patients. We analyzed the results of surgical treatment of 79 patients with complicated forms of gallstone disease and concomitant liver cirrhosis. All patients were conditionally divided into 2 groups: a control group of patients who were treated according to the standard program – 38 patients and the main group of patients who were treated using an improved diagnostic and treatment program – 41 patients. The patients of the retrospective group underwent a standard diagnostic and treatment program according to the recommendations for diagnosis and treatment of patients with complicated forms of gastrointestinal tract with correction of hepatorenal insufficiency. Since 2016, an updated diagnostic and treatment algorithm has been introduced in patients with complicated forms of gastrointestinal tract against the background of liver cirrhosis. All patients underwent a balanced approach in the analysis of manifestations of liver cirrhosis, which manifested itself in the introduction of the principles of controlled antibacterial therapy according to the level of C-reactive protein; differentiated implementation of thromboprophylaxis: according to the standard scheme and early postoperative thromboprophylaxis based on the risks of hemorrhagic complications. The results of this research were statistically analyzed using chi-square test and statistical comparison of both groups. According to the results of a comparative analysis of the results of the treatment of patients in both groups was performed, it was established that postoperative complications occurred both in patients of the main group and in the comparison group. However, the frequency of occurrence of complications in the groups of studied patients has a significant difference. In the main group, complications were 14.6% versus 34.2% (in the comparison group) at p≤0.05 (χ2=4.14), which indicates that the improved diagnostic and treatment program made it possible to significantly reduce postoperative complications, and the outcome of treatment of patients with complicated forms of gallstone disease.

Relation of Liver Siderosis to Liver Fibrosis in Hemodialysis Patients With Severe Hyperferritinemia Secondary to High Doses of Intravenous Iron Supplementation

ObjectiveAggressive iron substitution in hemodialysis (HD) patients leads to iron overload. The association between liver siderosis and fibrosis is still debatable. We studied the association of liver siderosis with liver fibrosis in HD patients. Furthermore, we studied the performance of liver stiffness measurements (LSMs) in identifying advanced liver fibrosis. We investigated the performance of biochemical indicators of iron status in identifying advanced liver fibrosis. MethodsFifty-five HD patients (average HD duration 6 ± 2 years) with hyperferritinemia secondary to intravenous iron supplementation (weakly iron dose 252.7 ± 63 mg; median blood transfusions 3 [2-5]) were recruited. The liver fibrosis grade was determined with Fibroscan, aminotransferase-to-platelet ratio index (APRI), and Fib-4 index. Liver iron concentration (LIC) was estimated with magnetic resonance imaging (MRI). Iron parameters and liver function biochemical indicators were also assessed. ResultsThe median serum ferritin and transferrin saturation (TSAT) were 3531 μg/L and 77%, respectively. 34.5%, 20%, and 45.5% of the patients showed mild, moderate, or severe liver siderosis, respectively. All patients with severe liver siderosis showed advanced liver fibrosis. Patients with severe liver siderosis and advanced liver stiffness showed higher serum iron, TSAT, aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum bilirubin, APRI, and Fib-4 index scores than those with mild liver siderosis. Serum iron and TSAT showed good utility in identifying advanced liver fibrosis determined with Fibroscan, APRI, and Fib-4 index. Liver stiffness exhibited good utility in identifying advanced liver fibrosis diagnosed with APRI and Fib-4 index. ConclusionsHigh weekly intravenous iron dose associated with severe hyperferritinemia, high serum iron, and TSAT might lead to severe liver siderosis and concomitant liver fibrosis in HD patients. Serum iron, TSAT, Fibroscan, Fib-4, and APRI scores might offer noninvasive tools for identifying advanced liver fibrosis in those patients.

NAFLD VS MAFLD. The evidence-based debate has come. Time to change?

Non-alcoholic fatty liver disease (NAFLD) affects one-third of the world's adult population and is linked to metabolic syndrome. It can progress to steatohepatitis, cirrhosis and hepatocellular carcinoma. During the last four decades, it has been the subject of exhaustive research in multiple aspects to define its epidemiology, pathophysiological mechanisms and therapy.In 2020, a group of international experts proposed the change of name to metabolic-associated fatty liver disease (MAFLD) with the main objective of making it an inclusive diagnosis prioritizing metabolic abnormalities. However, the change in terminology included the modification of the diagnostic criteria allowing the non-exclusion of other concomitant liver diseases such as alcohol liver disease, and chronic hepatitis B or C.The proposal precipitated a wave of debates among experts based on theoretical opinions on the desirability of the rapid adoption of the new terminology. But it also precipitated a wave of epidemiological and clinical studies which, two years later, have provided clinical evidence on the differences and similarities of the two entities, specially, those that could be considered for future refinements of the diagnostic criteria of MAFLD. Likewise, this evidence may contribute to deciding the time of adoption of this terminology.In this text, we discuss, in general terms, important aspects of the clinical evidence that has been generated to date in cross-sectional and longitudinal studies focusing on clinical characteristics and outcomes, mainly on all-cause and specific mortality of MAFLD.

Systemic inflammation is linked to liver fibrogenesis in patients with advanced chronic liver disease.

Experimental evidence indicates that systemic inflammation (SI) promotes liver fibrogenesis. This study investigated the potential link between SI and fibrogenesis in patients with advanced chronic liver disease (ACLD). Serum biomarkers of SI (CRP, IL-6, procalcitonin [PCT]) and extracellular matrix (ECM) turnover (i.e., fibrogenesis/fibrolysis) were analysed in 215 prospectively recruited patients with ACLD (hepatic venous pressure gradient [HVPG] ≥6 mm Hg) undergoing hepatic vein catheterization. Patients with non-elective hospitalization or bacterial infection were excluded. Histological alpha-smooth muscle actin (α-SMA) area was quantified on full biopsy scans by automated morphometric quantification in a subset of 34 patients who underwent concomitant transjugular liver biopsy. Histological α-SMA proportionate area correlated with enhanced liver fibrosis (ELF) score (Spearman's ρ= 0.660, p< .001), markers of collagen formation (PRO-C3, ρ= 0.717, p< .001; PRO-C6, ρ= 0.526, p= .002) and tissue inhibitor of metalloproteinases-1 (TIMP1; ρ= 0.547, p< .001), indicating that these blood biomarkers are capable of reflecting the dynamic process of ECM turnover. CRP, IL-6 and PCT levels correlated with ELF, biomarkers of collagen synthesis/degradation and TIMP1, both in compensated and decompensated patients. Multivariate linear regression models (adjusted for HVPG) confirmed that CRP, IL-6 and PCT were independently linked to markers of liver fibrogenesis and ECM turnover. Systemic inflammation is linked to both liver fibrogenesis and ECM turnover in ACLD and this association is not confounded by the severity of liver disease, as evaluated by HVPG. Our study confirms experimental data on the detrimental impact of SI on ECM deposition and fibrosis progression in a thoroughly characterized cohort of patients with ACLD.

Long-term outcomes and trends in liver transplantation for hereditary hemochromatosis in the United States.

There have been conflicting data regarding liver transplantation (LT) outcomes for hereditary hemochromatosis (HH), with no recent data on LT outcomes in patients with HH in the past decade. Using the United Network for Organ Sharing registry, we evaluated waitlist and post-LT survival in all adult patients listed for HH without concomitant liver disease from 2003 to 2019. Post-LT survival for HH was compared with a propensity-matched (recipient and donor factors) cohort of recipients with chronic liver disease (CLD). From 2003 to 2019, 862 patients with HH were listed for LT, of which 55.6% ( n = 479) patients underwent LT. The 1- and 5-year post-LT survival rates in patients with HH were 88.7% (95% confidence interval [CI], 85.4%-91.4%) and 77.5% (95% CI, 72.8%-81.4%), respectively, and were comparable with those in the propensity-matched CLD cohort ( p value = 0.96). Post-LT survival for HH was lower than for Wilson's disease, another hereditary metabolic liver disease with similar LT volume ( n = 365). Predictors for long-term (5-year) post-LT mortality included presence of portal vein thrombosis (hazard ratio [HR], 1.96; 95% CI, 1.07-3.58), obesity measurements greater than Class II (HR, 1.98; 95% CI, 1.16-3.39), and Karnofsky performance status (HR, 0.98; 95% CI, 0.97-0.99) at the time of LT. The leading cause of post-LT death ( n = 145) was malignancy (25.5%), whereas cardiac disease was the cause in less than 10% of recipients. In conclusion, short- and long-term survival rates for HH are excellent and comparable with those of other LT recipients. Improving extrahepatic metabolic factors and functional status in patients with HH prior to LT may improve outcomes.

Hepatic granuloma-A diagnostic challenge

Hepatic granulomas can have various causes and their detection requires a systematic diagnostic evaluation. First, identification of risk factors for granulomatous diseases and the exclusion of extrahepatic organ manifestation are necessary. Laboratory investigations and serological screening for the most common underlying diseases of liver granulomas in Germany, such as primary biliary cholangitis (PBC), sarcoidosis and infectious causes (primarily tuberculosis and hepatitisC infections), are recommended. A liver biopsy is essential for confirming the diagnosis, whereby a minilaparoscopically guided tissue sampling offers many advantages, such as the macroscopic detection of granulomas on the liver surface, on the peritoneum or on the spleen. Whether the detection of hepatic granulomas results in atherapeutic consequence, depends decisively on the underlying primary disease. If hepatic granulomas are present without concomitant liver parenchymal damage or other manifestations that would make treatment necessary, awatch and wait approach under close clinical and laboratory monitoring is sufficient. If liver values increase or in cases of hepatic parenchymal damage, urgent treatment of the underlying disease is indicated.

Hypocomplementemia during tocilizumab treatment: Long-term follow-up results.

Hypocomplementemia has been reported in patients with rheumatoid arthritis treated with tocilizumab (TCZ), but its long-term consequences are unknown. We assessed the long-term outcome of patients treated with TCZ who developed hypocomplementemia regarding serious bacterial infections or autoimmune diseases (AID).The charts of patients treated with TCZ at two rheumatology centers were reviewed retrospectively. Data regarding patients’ age, gender, disease duration, autoantibodies status, previous or concomitant treatments, blood counts, liver enzymes, C3 and C4 levels at baseline and during TCZ treatment, episodes of infections, allergic reactions, and AID were analyzed. Univariate analysis was used to compare patients with low C3, C4 levels versus patients with normal C3, C4 levels. Variables that were statistically significant associated or tended to be associated with low C3 or C4 were included in multiple variable logistic regression.Of 132 patients treated with TCZ, 108 had serial measurements of serum complement concentration. Thirty-three (30%) patients developed low C4 levels and 23 (21%) had also low C3. Mean TCZ treatment period was 4.9 years (range, 1–14 years). All patients had normal complement levels at baseline. Leukopenia occurred in 18 (16.7%) patients, 14 of whom (77%) had low complement. Persistent leukopenia was observed in 8% and 5.3% of patients with normal C3 and C4 levels, respectively, as opposed to 47% and 42% of patients with low C3 or low C4, respectively. Low C3, C4 levels correlated with prolonged TCZ treatment retention time and effectiveness. There were no serious bacterial infections or new onset AID.Hypocomplementemia during TCZ treatment was accompanied by leukopenia that correlated with treatment duration. Hypocomplementemia was not associated with serious bacterial infections or new onset AID. Decreased complement levels were associated with treatment longevity. The role of monitoring complement level in predicting treatment response or assessing disease activity deserves further investigation.

Liver Injuries Associated with Coronavirus Disease 2019: View on the Problem

Introduction. Major cardiovascular and pulmonary comorbidities, as well as diabetes mellitus and certain cancers, are associated with worse clinical outcomes of coronavirus disease-2019 (COVID-19). Meanwhile, the impact of concomitant liver diseases on the COVID-19 natural course together with the influence of the COVID-19 on the hepatic tissues have been rarely investigated. The aim of the study was to analyse the available data regarding impact of liver pathologies on COVID-19 natural course and outcome, and, reciprocally, hepatic injuries development induced by COVID-19. Materials and methods. Content analysis, systematic and comparative analysis, bibliosemantic method of investigation of current scientific research results on liver damage associated with COVID-19 were used. Results. The potential mechanism of liver injury in COVID-19 is complex and includes direct cytopathic viral injury, proinflammatory cytokine outbreak, hypoxia/reperfusion damage and potential drug induced liver injury. Among the medications used for the treatment of COVID-19 patients, there are certain that could potentially cause drug-induced liver injury. Treatment of liver transplant patients can be challenging taking into consideration the possible necessity of immunosuppressive therapy correction combined with the needs to find a balance between the risk of graft rejection and effective elimination of the virus. Conclusions. Current review of the available database revealed that liver diseases are among substantive comorbidities in COVID-19 patients alongside with liver injuries which are rather frequent complications of COVID-19 treatment. Potential drug-induced liver injuries in patients subjected tocertain antiviral agents in combination with supportive therapy drugs should be taken into consideration. Special precautions are required to prevent potential drug-to-drug interactions in case of COVID-19 treatment in liver transplant patients.

Artificial Intelligence Improves Pathologist Agreement for Fibrosis Scores in Nonalcoholic Steatohepatitis Patients

Artificial Intelligence Improves Pathologist Agreement for Fibrosis Scores in Nonalcoholic Steatohepatitis Patients

Nationwide database analysis of insomnia, depression, and sleeping pill prescriptions in hepatocellular carcinoma patients

Objective To clarify the status of insomnia and depression and the prescription of sleeping pills in hepatocellular carcinoma (HCC) patients before and after HCC diagnosis and treatment. Methods Patients’ data from a Japanese health insurance claims database were analyzed retrospectively to determine the incidence of insomnia and depression and their association with sleeping pill prescriptions during the 6 months before and after HCC diagnosis and treatment. Results A total of 9,109 HCC patients (median age at diagnosis = 71.5 years, 68.1% male) were analyzed. The incidences of insomnia and depression increased significantly after HCC diagnosis. Insomnia was reported in 15.0% of patients before diagnosis, and it increased to 27.6% after diagnosis. Similarly, depression was reported in 6.3% and 11.3% before and after diagnosis, respectively. The incidences of insomnia and depression before diagnosis were higher in patients with concomitant liver diseases including hepatitis, cirrhosis, and hepatic encephalopathy. However, the rate of sleeping pill prescription was significantly lower in patients with concomitant liver diseases after diagnosis. The incidence of fracture was higher in insomnia or depression patients than others and in patients treated with sleeping pills than without before and after diagnosis. Conclusions HCC patients had increased risks of insomnia and depression after diagnosis. The high risk of fracture in HCC patients with insomnia and depression and treated with sleeping pills suggests that it is difficult to optimize the management of HCC patients, especially those with concomitant liver diseases.

Incidence of acute rejection and patient survival in combined heart-liver transplantation.

Combined heart-liver transplantation (CHLT) is indicated for patients with concomitant end-stage heart and liver disease or patients with amyloid heart disease where liver transplantation mitigates progression. Limited data suggest that the liver allograft provides immunoprotection for heart and kidney allografts in combined transplantation from the same donor. We hypothesized that CHLT reduces the incidence of acute cellular rejection (ACR) and the development of de novo donor-specific antibodies (DSAs) compared with heart-alone transplantation (HA). We conducted a retrospective analysis of 32 CHLT and 280 HA recipients in a single-center experience. The primary outcome was incidence of ACR based on protocol and for-cause myocardial biopsy. Rejection was graded by the International Society of Heart and Lung Transplantation guidelines with Grade 2R and higher considered significant. Secondary outcomes included the development of new DSAs, cardiac function, and patient and cardiac graft survival rates. Of CHLT patients, 9.7% had ACR compared with 45.3% of HA patients (p<0.01). Mean pretransplant calculated panel reactive antibody (cPRA) levels were similar between groups (CHLT 9.4% vs. HA 9.5%; p=0.97). Among patients who underwent testing, 26.9% of the CHLT and 16.7% of HA developed DSA (p=0.19). Despite the difference in ACR, patient and cardiac graft survival rates were similar at 5years (CHLT 82.1% vs. HA 80.9% [p=0.73]; CHLT 82.1% vs. HA 80.9% [p=0.73]). CHLT reduced the incidence of ACR in the cardiac allograft, suggesting that the liver offers immunoprotection against cellular mechanisms of rejection without significant impacts on patient and cardiac graft survival rates. CHLT did not reduce the incidence of de novo DSA, possibly portending similar long-term survival among cardiac allografts in CHLT and HA.

Non-alcoholic fatty liver disease association with structural heart, systolic and diastolic dysfunction: a meta-analysis.

Several studies have documented a relationship between non-alcoholic fatty liver disease (NAFLD) and structural heart disease, particularly diastolic function. This meta-analysis will be the first to examine the echocardiographic-derived cardiac function and structural characteristics in NAFLD patients, and its association with liver disease severity and metabolic profile. Medline and Embase were searched and pairwise meta-analysis was conducted in DerSimonian and Laird to obtain the odds ratio (OR) and mean difference (MD) for dichotomous and continuous variables, respectively, to compare the effects of NAFLD on the echocardiography parameters. Forty-one articles involving 33,891 patients underwent echocardiography. NAFLD patients had worse systolic indices with lower ejection fraction (EF, MD: -0.693; 95% CI: -1.112 to -0.274; p = 0.001), and worse diastolic indices with higher E/e' (MD: 1.575; 95% CI: 0.924 to 2.227; p < 0.001) compared to non-NAFLD patients. NAFLD patients displayed increased left ventricular mass (LVM, MD: 34.484; 95% CI: 26.236 to 42.732; p < 0.001) and epicardial adipose thickness (EAT, MD: 0.1343; 95% CI: 0.055 to 0.214; p = 0.001). An increased severity of NAFLD was associated with worse diastolic indices (decreased E/A ratio, p = 0.007), but not with systolic indices. NAFLD is associated with impaired systolic and diastolic function with changes in cardiac structure. Concomitant metabolic risk factors and liver disease severity are independently associated with worsening systolic and diastolic function.

Особливості структурно-функціональних порушень серця при коморбідності неалкогольної жирової хвороби печінки та гіпертонічної хвороби

The purpose of the study was to establish the features of structural and functional remodeling of the heart in patients with non-alcoholic fatty liver disease in combination with hypertension. Materials and methods. The study included 211 patients, of whom 121 had comorbidity of non-alcoholic fatty liver disease and hypertension, 60 patients had isolated non-alcoholic fatty liver disease, and 30 patients had isolated hypertensive disease. The control group consisted of 20 healthy individuals. To study the structural and functional properties of the myocardium, patients underwent ultrasound of the heart according to conventional methods. Results and discussion. Examination of patients showed that the mass of the left ventricular myocardium in both groups of patients with hypertension were significantly higher than in the control group and the non-alcoholic fatty liver disease group (p &lt; 0.001). The presence of comorbidity with non-alcoholic fatty liver disease did not lead to a further increase in left ventricular myocardial mass in patients with hypertension (p &gt; 0.05). It was found that patients with hypertension in the presence and absence of non-alcoholic fatty liver disease are characterized by an increase in the volume of the left and right atria, as well as the diameters of the left atrium and aorta, compared with the control and the non-alcoholic fatty liver disease groups. At the same time, there were no significant differences between the groups of patients with hypertension in terms of both the presence and absence of comorbidity (p &gt; 0.05). In addition, the main indicator of systolic function of the left ventricle – ejection fraction – was evaluated. This figure was significantly lower in the two groups of patients with hypertension than in the control group and the non-alcoholic fatty liver disease group (p &lt; 0.001). The presence of comorbidity with non-alcoholic fatty liver disease did not affect this indicator (p &gt; 0.05). Among the two groups of patients with hypertension, patients with concentric hypertrophy significantly prevailed. There was a significant increase in the value of a very important integral indicator of diastolic function E / e in patients of all groups, which significantly distinguished them from the control group (p &lt; 0.001). This indicated the presence of diastolic dysfunction in these patients. There is no significant difference in the geometry of the heart and the types of transmitral blood flow between patients with hypertension depending on the presence of concomitant non-alcoholic fatty liver disease. Conclusion. Thus, there is no significant difference between the indicators of left ventricle systolic function in the groups of patients with comorbidity and isolated hypertension. At the same time, there were signs of deterioration of diastolic function in the comorbidity group, which was manifested by an increase in E / e. Deterioration of diastolic function was recorded in the group of isolated non-alcoholic fatty liver disease. These facts may indicate the influence of non-alcoholic fatty liver disease itself on the formation of diastolic dysfunction, both in the presence of hypertension and in its absence. The presence of concomitant non-alcoholic fatty liver disease does not affect transmitral blood flow in patients with hypertension

Risk stratification of cirrhotic patients undergoing esophagectomy for esophageal cancer: A single-centre experience.

BackgroundConcomitant liver cirrhosis is a crucial risk factor for major surgeries. However, only few data are available concerning cirrhotic patients requiring esophagectomy for malignant disease.MethodsFrom a prospectively maintained database of esophageal cancer patients, who underwent curative esophagectomy between 01/2012 and 01/2016, patients with concomitant liver cirrhosis (liver-cirrhotic patients, LCP) were compared to non-liver-cirrhotic patients (NLCP).ResultsOf 170 patients, 14 cirrhotic patients with predominately low MELD scores (≤ 9, 64.3%) were identified. Perioperative outcome was significantly worse for LCP, as proofed by 30-day (57.1% vs. 7.7, p<0.001) and 90-day mortality (64.3% vs. 9.6%, p<0.001), anastomotic leakage rate (64.3 vs. 22.3%, p = 0.002) and sepsis (57.1 vs. 21.5%, p = 0.006). Even after adjustment for age, gender, comorbidities, and surgical approach, LCP revealed higher odds for 30-day and 90-day mortality compared to NLCP. Moreover, 5-year survival analysis showed a significantly poorer long-term outcome of LCP (p = 0.023). For risk stratification, none of the common cirrhosis scores proved prognostic impact, whereas components as Bilirubin (auROC 94.4%), INR (auROC = 90.0%), and preoperative ascites (p = 0.038) correlated significantly with the perioperative outcome.ConclusionCurative esophagectomy for cirrhotic patients is associated with a dismal prognosis and should be evaluated critically. While MELD and Child score failed to predict perioperative mortality, Bilirubin and INR proofed excellent prognostic capacity in this cohort.