Concomitant Liver Research Articles

Anti-inflammatory adipokines: chemerin, vaspin, omentin concentrations and SARS-CoV-2 outcomes

Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation. A wide range of adipokines activities suggests they influence pathogenesis and infection course. The aim was to assess concentrations of chemerin, omentin, and vaspin among COVID-19 patients with an emphasis on adipokines relationship with COVID-19 severity, concomitant metabolic abnormalities and liver dysfunction. Serum chemerin, omentin and vaspin concentrations were measured in serum collected from 70 COVID-19 patients at the moment of admission to hospital, before any treatment was applied and 20 healthy controls. Serum chemerin and omentin concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers (271.0 vs. 373.0 ng/ml; p < 0.001 and 482.1 vs. 814.3 ng/ml; p = 0.01, respectively). There were no correlations of analyzed adipokines with COVID-19 severity based on the presence of pneumonia, dyspnea, or necessity of Intensive Care Unit hospitalization (ICU). Liver test abnormalities did not influence adipokines levels. Elevated GGT activity was associated with ICU admission, presence of pneumonia and elevated concentrations of CRP, ferritin and interleukin 6. Chemerin and omentin depletion in COVID-19 patients suggests that this adipokines deficiency play influential role in disease pathogenesis. However, there was no relationship between lower adipokines level and frequency of COVID-19 symptoms as well as disease severity. The only predictive factor which could predispose to a more severe COVID-19 course, including the presence of pneumonia and ICU hospitalization, was GGT activity.

Single approach to pulmonary and liver hydatid cysts

Back groundHydatid cyst means cyst full of water. It is a parasitic disease caused by larval stage of small tape worm (Taenia Ecchinococcus), causing cyst formation in the liver and in the lung. It is endemic in Iraq. AimTo illustrate how to make use of single surgical approach for the removal of pulmonary and liver Hydatid cysts. Patients and methodsThis is a retrospective study of 75 patients with pulmonary and liver hydatid cysts admitted and surgically managed at the Thoracic and Vascular Department of the Surgical specialties Hospital of the Medical City Teaching Hospital during twenty –year's period from January 2001 to the end of December 2020. ResultsFifty-one patients were female (68%), the remaining 24-patients were male (32%). The youngest patient was two –years old female child, presented with bilateral pulmonary and liver hydatid cysts, while the oldest patient was a 70-years old female. The most common symptoms were cough and dyspnea though some patients are completely asymptomatic. Plain chest X-ray is mandatory in addition to U/S abdomen for accurate localization of the liver Hydatid cyst. CT scan is also used for accurate diagnosis ConclusionSurgery is the primary treatment for the concomitant right pulmonary hydatid cyst and liver, it should be approach by single right thoracotomy incision, and this will offers the best chance of cure.

The difference in prolonged continuous and intermittent Pringle maneuver during complex hepatectomy for hepatocellular carcinoma patients with chronic liver disease: A retrospective cohort study.

PurposeTo explore the differences between prolonged continuous Pringle maneuver (CPM) and prolonged intermittent Pringle maneuver (IPM) in patients with hepatocellular carcinoma (HCC), who underwent complex hepatectomy.MethodsThis retrospective cohort study performed between June 2014 and May 2016 included 142 patients who underwent complex hepatectomy for HCC and concomitant chronic liver disease but with good liver function. Patients were categorized into CPM (n = 69) and IPM groups (n = 73). The differences in these aspects were compared between the two groups which include operation time, intraoperative bleeding, perioperative transfusion, postoperative complications, liver function injury, postoperative overall survival (OS), and tumor recurrence.ResultsThe cumulative clamping time, operation time, intraoperative bleeding, and perioperative transfusion rates were 38.0, 132 min, 300 ml, and 17.4% in CPM and 40.0, 145 min, 400 ml, and 32.9% in IPM, respectively. There were significant intergroup differences in operation time (p = 0.018), intraoperative bleeding (p < 0.001), and perioperative transfusion rates (p = 0.034). Besides, the postoperative complications and postoperative liver function injury of the CPM group were better than those of IPM. There was no significant intergroup difference in OS (p = 0.908) and tumor recurrence (p = 0.671) between two groups.ConclusionCompared with IPM, CPM with a cumulative clamping time between 30 and 50 min can shorten operation time, reduce intraoperative bleeding and perioperative transfusion, and reduce postoperative complications and postoperative liver function injury in patients who underwent complex hepatectomy for HCC and concomitant liver disease but with good liver function. There was no significant difference in OS and tumor recurrence between two groups.

Outcomes of transfemoral-transcatheter aortic valve replacement with Sapien-3 valve in liver cirrhosis patients

Abstract Background Little is known about the outcomes of liver cirrhosis patients with severe aortic stenosis (AS) who undergo transcatheter aortic valve replacement (TAVR). Methods We undertook a retrospective analysis of consecutive patients with severe symptomatic AS who underwent transfemoral-TAVR with Sapien-3 valve at our Clinic between April 2015 and December 2018, yielding 32 patients with liver cirrhosis on imaging including ultrasound and/or computed tomography. Their baseline characteristics, procedural and long-term outcomes after TAVR with the non-cirrhotic group were compared, along with their management strategies as per the hepatology team. Results Among 1028 patients, 32 were assigned to the cirrhosis, and 996 were assigned to the non-cirrhosis (control) group. Compared with the control group cirrhotic patients were slightly younger in age (74.5 vs 81.2 years), had a slightly higher BMI (31.3 vs 29.3), and had a higher incidence of prior history of myocardial infarction (38% vs 33%). Baseline variables including the history of smoking, hypertension, diabetes, and atrial fibrillation were comparable in both groups. Among cirrhotic patients (n=32), the most common etiologies were non-alcoholic steatohepatitis (NASH) (37.5%), Alcoholism (18.75%), and Hepatitis C (12.5%). The mean MELD-NA score was 11.8 and 67% of patients were Child PUGH Class A and 33% were Child PUGH Class B and all patients had a Child PUGH score of ≥5. 53% of patients (n=17) in the cirrhosis group were evaluated by Hepatology and 12.5% (n=4) were evaluated for a liver transplant but only 1 patient had a liver transplant post-TAVR. Compared with the control group cirrhotic patients had similar 1-year mortality (12% vs 12%, p=1), had a lower rate of 30-day new pacemaker post tavr (6% vs 9% p=0.85), had a higher rate of 1-year readmission for heart failure (12% vs 5% p=0.12) and similar 1-year major adverse cardiac and cerebrovascular event (MACCE) rate (15% vs 14% p=0.98) Conclusion Patients with severe AS undergoing TAVR with concomitant liver cirrhosis demonstrate comparable outcomes compared with their non- cirrhotic counterparts. NASH followed by alcoholic cirrhosis was found to be most common etiology. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

One liver, two samples and two diagnoses-An example of how multiple samples by laparoscopically guided liver biopsy can be decisive.

Laparoscopically-guided liver biopsy was performed to make the diagnosis in a 54-year old female patient with clinical and serological signs of both non-alcoholic fatty liver disease and autoimmune hepatitis (AIH). Figure A shows a sample from the right liver lobe (HE, 20x) with a blue-boxed area (Figure B) (HE, 100x) demonstrating a total of eight portal tracts. Macrovesicular steatosis of about 50% of hepatocytes and mild lymphocyte infiltration were detected.

Voriconazole Pharmacokinetics Are Not Altered in Critically Ill Patients with Acute-on-Chronic Liver Failure and Continuous Renal Replacement Therapy: An Observational Study.

Infection and sepsis are a main cause of acute-on-chronic liver failure (ACLF). Besides bacteria, molds play a role. Voriconazole (VRC) is recommended but its pharmacokinetics (PK) may be altered by ACLF. Because ACLF patients often suffer from concomitant acute renal failure, we studied the PK of VRC in patients receiving continuous renal replacement therapy (RRT) with ACLF and compared it to PK of VRC in critically ill patients with RRT without concomitant liver failure (NLF). In this prospective cohort study, patients received weight-based VRC. Pre- and post-dialysis membrane, and dialysate samples obtained at different time points were analyzed by high-performance liquid chromatography. An integrated dialysis pharmacometric model was used to model the available PK data. The recommended, 50% lower, and 50% higher doses were analyzed by Monte-Carlo simulation (MCS) for day 1 and at steady-state with a target trough concentration (TC) of 0.5–3mg/L. Fifteen patients were included in this study. Of these, 6 patients suffered from ACLF. A two-compartment model with linear clearance described VRC PK. No difference for central (V1) or peripheral (V2) volumes of distribution or clearance could be demonstrated between the groups. V1 was 80.6L (95% confidence interval: 62.6–104) and V2 106L (65–166) with a body clearance of 4.7L/h (2.87–7.81) and RRT clearance of 1.46L/h (1.29–1.64). MCS showed TC below/within/above target of 10/74/16% on day 1 and 9/39/52% at steady-state for the recommended dose. A 50% lower dose resulted in 26/72/1% (day 1) and 17/64/19% at steady-state and 7/57/37% and 7/27/67% for a 50% higher dose. VRC pharmacokinetics are not significantly influenced by ACLF in critically ill patients who receive RRT. Maintenance dose should be adjusted in both groups. Due to the high interindividual variability, therapeutic drug monitoring seems inevitable.

S782 Increased Atherosclerotic Cardiovascular Disease and Heart Failure Risk in Inflammatory Bowel Disease Patients wWith Concomitant Non-Alcoholic Fatty Liver Disease: A Nationwide Analysis

S782 Increased Atherosclerotic Cardiovascular Disease and Heart Failure Risk in Inflammatory Bowel Disease Patients wWith Concomitant Non-Alcoholic Fatty Liver Disease: A Nationwide Analysis

Elevated liver enzymes of newly diagnosed pediatric celiac patients-a prospective-observational study.

Celiac disease clinical presentation is constantly changing. We set to determine the prevalence of elevated transaminases in newly diagnosed celiac patients and to evaluate this sub-group of patients for associated clinical and laboratory findings and assess their natural course of disease following therapeutic diet initiation. We conducted a prospective-observational study of all newly diagnosed pediatric celiac patients, between August 2016 and April 2018, in a pediatric gastroenterology clinic. Clinical data, anthropometrics, and blood test results were recorded at diagnosis and at 3, 6, and 12months, respectively, of follow-up. We compared patients with normal and elevated transaminases at diagnosis. ALT threshold was set at 24 U/l. Of 125 newly diagnosed celiac patients, 31 (24.8%) had elevated ALT at diagnosis; two (1.6%) with over 3 × ULN. Patients with elevated ALT at diagnosis were significantly younger (mean age 5.5 (SD 3.4) vs. 7.3 (SD 3.7) years, p < 0.01) and more commonly presented with diarrhea (32.3% vs. 14.9%, p = 0.03). Eighty percent of patients with elevated ALT levels normalized their ALT within 3months and all within 1year. Following gluten-free diet initiation, patients with elevated ALT had similar clinical course, growth, serology normalization rate, and laboratory results, compared to patients with normal ALT over a 1-year follow-up. A single patient was simultaneously co-diagnosed with celiac disease and autoimmune hepatitis.Conclusion: Clinically significant ALT abnormalities are rare among newly diagnosed pediatric celiac patients. Significant elevations failing to normalize on a gluten-free diet should raise concern of a concomitant primary liver disease and warrant further investigations. What is Known: • Elevated liver enzymes may be an extra-intestinal manifestation of celiac disease. • Reported prevalences of ALT elevations among children with a new diagnosis of celiac disease ranges between 5 and 40%. What is New: • ALT elevations are present in 25% of children with a new diagnosis of celiac disease. • Significant elevations (>3 × ULN) are rare (1.6%). • Elevated liver enzymes are associated with earlier age at diagnosis. • The natural history of patients with elevated liver enzymes at diagnosis is comparable to those without.

Molecular and Cellular Mediators of the Gut-Liver Axis in the Progression of Liver Diseases.

The gut-liver axis covers the bidirectional communication between the gut and the liver, and thus includes signals from liver-to-gut (e.g., bile acids, immunoglobulins) and from gut-to-liver (e.g., nutrients, microbiota-derived products, and recirculating bile acids). In a healthy individual, liver homeostasis is tightly controlled by the mostly tolerogenic liver resident macrophages, the Kupffer cells, capturing the gut-derived antigens from the blood circulation. However, disturbances of the gut-liver axis have been associated to the progression of varying chronic liver diseases, such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and primary sclerosing cholangitis. Notably, changes of the gut microbiome, or intestinal dysbiosis, combined with increased intestinal permeability, leads to the translocation of gut-derived bacteria or their metabolites into the portal vein. In the context of concomitant or subsequent liver inflammation, the liver is then infiltrated by responsive immune cells (e.g., monocytes, neutrophils, lymphoid, or dendritic cells), and microbiota-derived products may provoke or exacerbate innate immune responses, hence perpetuating liver inflammation and fibrosis, and potentiating the risks of developing cirrhosis. Similarly, food derived antigens, bile acids, danger-, and pathogen-associated molecular patterns are able to reshape the liver immune microenvironment. Immune cell intracellular signaling components, such as inflammasome activation, toll-like receptor or nucleotide-binding oligomerization domain-like receptors signaling, are potent targets of interest for the modulation of the immune response. This review describes the current understanding of the cellular landscape and molecular pathways involved in the gut-liver axis and implicated in chronic liver disease progression. We also provide an overview of innovative therapeutic approaches and current clinical trials aiming at targeting the gut-liver axis for the treatment of patients with chronic liver and/or intestinal diseases.

Outcomes After Transfemoral Transcatheter Aortic Valve Implantation With a SAPIEN 3 Valve in Patients With Cirrhosis of the Liver (a Tertiary Care Center Experience)

Little is known about the utility of transcatheter aortic valve implantation (TAVI) in patients with cirrhosis of the liver, and their outcomes have not been studied extensively in literature. We performed a retrospective analysis of patients with severe symptomatic aortic stenosis (AS) who underwent transfemoral TAVI with a SAPIEN 3 valve at our institution between April 2015 and December 2018. We identified 32 consecutive patients with evidence of cirrhosis of the liver on imaging (including ultrasound and/or computed tomography) and patients with severe symptomatic AS who underwent transfemoral TAVI with a SAPIEN 3 valve. Among 1,028 patients, 32 had cirrhosis of the liver and 996 constituted the control group without cirrhosis. Mean age in the cirrhosis group was 74.5 years compared with 81.2 years in the control group. Baseline variables were comparable between the groups. Compared with the noncirrhotic group, patients with cirrhosis had a similar 1-year mortality (12% vs 12%, p=1), a lower 30-day new pacemaker after TAVI rate (6% vs 9%, p=0.85), a higher 30-day and 1-year readmission rate for heart failure (11% vs 1% and 12% vs 5%, p=0.12, respectively), and a similar 1-year major adverse cardiac and cerebrovascular event rate (15% vs 14%, p=0.98). In conclusion, patients with severe AS with concomitant liver cirrhosis who underwent TAVI demonstrated comparable outcomes to their noncirrhotic counterparts.

Predictor value of neurohumoral disorders in patients with chronic coronary syndrome with concomitant non-alcoholic fat disease

Annotation. Today it is important to study the clinical and prognostic role of neurohumoral disorders in patients with stable forms of chronic coronary syndrome (CCS) and concomitant liver pathology. The aim of the study: to investigate the levels of markers of insulin, adipokine balance, systemic inflammation and endothelial dysfunction and their predictor value for the presence of non-alcoholic fatty liver disease (NAFLD) in patients with CCS. The prospective monocenter double open study in parallel groups involved 120 patients with CCS: stable angina pectoris II-III functional class aged 60.0 (55.0; 64.0) years, of whom 67 (55%) men and 53 (45 %) women. The control selected group included 30 healthy individuals aged 59.0 (58.0; 66.0) years, including 14 (46%) men and 16 (54%) women. Determination of the serum concentration of biomarkers (adiponectin, resistin, insulin, asymmetric dimethylarginine (ADMA), C-reactive protein) was performed using enzyme-linked immunosorbent assay. Statistical data processing was performed using the license program package “Statistica 13.0” (StatSoftInc, USA, № JPZ8041382130ARCN10-J). The hypothesis about the normality of the distribution of the studied indicators was tested using the Shapiro-Wilk test. Quantitative traits were presented as M ± m or Me (Q25; Q75), depending on the type of distribution. Significance of differences was assessed using Student's t-test (for normal distribution) or Mann-Whitney U-test for independent samples (for distribution other than normal). In order to establish the threshold values of biomarkers for predicting the presence of NAFLD ROC analysis was used. It was found that in patients with CCS with concomitant NAFLD, compared with patients with CCS without liver pathology, there is a significant (p &lt;0,05) increase in insulin levels, HOMA index, resistin, ADMA, RF-C-reactive protein and a decrease in adiponectin concentration. According to the results of ROC analysis, it was found that ADMA (Se = 80.0; Sp = 82.9; AUC = 0.91) had a high sensitivity, the optimal ratio of sensitivity and specificity for the diagnosis of NAFLD among all studied biomarkers. Other biomarkers (HOMA index, adiponectin, resistin, adiponectin/resistin ratio) also had an AUC greater than 0.8, but smaller sensitivity/specificity ratio. Thus, in patients with CCS associated with NAFLD, compared with patients without NAFLD, an imbalance of adipocytokines on the background of insulin resistance, systemic inflammation and endothelial dysfunction is observed. Asymmetric dimethylarginine has the highest sensitivity, the optimal ratio of sensitivity and specificity for the diagnosis of NAFLD in patients with coronary artery disease.

Impact of Nonalcoholic Steatohepatitis on the Outcome of Patients Undergoing Roux-en-Y Gastric Bypass Surgery: a Propensity Score\u2013Matched Analysis

PurposeIt is currently unknown whether NASH (nonalcoholic steatohepatitis), as compared to simple steatosis, is associated with impaired postoperative weight loss and metabolic outcomes after RYGB surgery. To compare the effectiveness of Roux-en-Y gastric bypass (RYGB) on patients with NASH versus those with simple nonalcoholic fatty liver (NAFL).Materials and MethodsWe retrospectively retrieved data from 515 patients undergoing RYGB surgery with concomitant liver biopsy. Clinical follow-up and metabolic assessment were performed prior to surgery and 12 months after surgery. We used multivariate analysis of variance (MANOVA) and propensity score matching and we assessed for changes in markers of hepatocellular injury and metabolic outcomes.ResultsThere were 421 patients with simple NAFL, and 94 with NASH. Baseline alanine and aspartate aminotransferases were significantly higher in patients with NASH (p < 0.01). Twelve months after the RYGB surgery, as determined by both MANOVA and propensity score matching, patients with NASH exhibited a significantly greater reduction in alanine aminotransferase (ß-coefficient − 12 iU/l [− 22 to − 1.83], 95% CI, adjusted p = 0.021) compared to their NAFL counterparts (31 matched patients in each group with no loss to follow-up at 12 months). Excess weight loss was similar in both groups (ß-coefficient 4.54% [− 3.12 to 12.21], 95% CI, adjusted p = 0.244). Change in BMI was comparable in both groups (− 14 (− 16.6 to − 12.5) versus − 14.3 (− 17.3 to − 11.9), p = 0.784).ConclusionAfter RYGB surgery, patients with NASH experience a greater reduction in markers for hepatocellular injury and similar weight loss compared to patients with simple steatosis.

Досвід застосування мінеральної води в лікуванні хворих на хронічний вірусний гепатит С із супутньою неалкогольною жировою хворобою печінки

У статті доведено доцільність внутрішнього курсового прийому мінеральної води (у подвоєному режимі дозування) у комплексному лікуванні хворих на хронічний вірусний гепатит С із супутньою неалкогольною жировою хворобою печінки з метою покращення клінічного перебігу основного та супутньо­го захворювань, відновлення функціонального стану печінки, зменшення інсулінорезистентності.

Оценка клинической эффективности заместительной терапии препаратом Декап у пациентов с сахарным диабетом типа 2 и сопутствующей неалкогольной жировой болезнью печени при дефиците витамина D

Актуальность. В последнее время дефицит витамина D считается одним из факторов развития сахарного диабета 2-го типа (СД типа 2) и неалкогольной жировой болезни печени (НАЖБП). Цель: установить эффективность препарата Декап (холекальциферол) у пациентов с его дефицитом, больных СД типа 2 с НАЖБП. Материалы и методы. Пролечены 52 пациента с НАЖБП и СД типа 2 на фоне установленного D-дефицита, которые были равномерно распределены на две группы. Больные группы сравнения (n = 26) получали исключительно традиционную антидиабетическую терапию, а больные основной группы (n = 26) дополнительно получали препарат витамина D Декап, который назначали в дозе 4000 МЕ/сут сроком на 6 месяцев. Результаты. Использование витамина D было ассоциировано со статистически значимым снижением гликемии натощак через 6 месяцев лечения на 4,2 % (p = 0,041). Уровень гликированного гемоглобина (HbA1c) в основной группе пациентов в среднем снизился на 0,38 % (р = 0,121) через 3 месяца и остался практически на том же уровне и через 6 месяцев — на 0,44 % (р = 0,088). Параллельно с улучшением параметров гликемического контроля у пациентов основной группы наблюдалась тенденция к снижению индекса HOMA-2-IR на 0,28 (–0,11; 0,86; р = 0,152) и улучшение чувствительности к инсулину на 1,39 (–10,04; 6,01; р = 0,621) по сравнению с исходным уровнем. Использование препарата витамина D (Декап) ассоциировано со снижением индексов стеатоза: FLI и TyG. Базовое значение для FLI составило 74,11 ± 18,71, для TyG — 5,21 ± 0,29, а после шестимесячного курса лечения витамином D снизилось соответственно на 4,4 % (р = 0,029) и 2,68 % (р = 0,031) по сравнению с исходными показателями. Выводы. Установлено, что использование препарата Декап у пациентов с дефицитом витамина D, больных СД типа 2 с НАЖХП, в дозе 4000 МЕ/сут на курс не менее шести месяцев приводит к улучшению параметров гликемического контроля и метаболического профиля.

Hydatid cyst of spleen: A rare presentation

: Hydatid cyst is a parasitic infestation caused by Echinococcus granulosus. The spleen being rarely involved by the parasite, commonly involved organs are liver followed by lungs. It constitutes only 4% of abdominal hydatid diseases. Its worldwide incidence is 0.5 to 4%. In this case report, we present a case of young boy with concomitant splenic and liver hydatid cysts. A 8-year-old boy, resident of Chamba district was presented with abdominal pain, fever and left upper quadrant swelling. The swelling had started enlarging over past 4 months. After necessary investigations it was diagnosed as hydatid cyst of spleen concomitant with liver and was confirmed by histopathological examination of the cyst membrane. All routine investigations other than anemia of 9.4 mg/dl and raised Ecchinococcus IGG serum levels, all other tests were within normal range. Splenic hydatid is a rare entity and among abdominal presentations of hydatid diseases its incidence is very low, being 4% only. Diagnosis can be made on CECT abdomen along with the Echinococcus IGG serum levels, cytology of aspirated cystic fluid and then can be confirmed on histopathological examination of the cyst membrane sent for the histopathological examination. This case report emphasizes the need of considering hydatid cyst as a differential with uncommon presentation of the disease even in non- endemic area, as in this case patient presented with splenomegaly and abdominal pain.

Prevalence and Impact of Fatty Liver Disease in Adult Deceased Liver Transplant Donors: Metabolic-Associated Fatty Liver Disease or Nonalcoholic Fatty Liver Disease?

Donor hepatic steatosis is associated with worse post-liver transplant (LT) outcomes, especially when >30%(1). Such donors usually have non-alcoholic fatty liver disease (NAFLD) which is defined as fatty liver (hepatic steatosis >5%) without excessive alcohol consumption (>210g/week for men, >140g/week for women) or concomitant liver disease. Recently, international consensus have proposed that the term NAFLD be replaced by metabolic-associated liver disease (MAFLD)(2). New criteria define MAFLD as fatty liver together with the presence of metabolic conditions (i.e. type 2 diabetes mellitus, elevated ethnicity-specific body mass index (BMI), or at least two of: elevated waist circumference, hypertension, dyslipidemia, prediabetes, and/or insulin resistance)(2). We know these metabolic variables such as raised BMI and diabetes mellitus in a donor also contribute to graft marginality(1, 3). We examined whether a biopsy-proven diagnosis of NAFLD or MAFLD in a liver donor impacted on outcomes.

Chronic hepatitis B infection with concomitant hepatic steatosis: Current evidence and opinion.

With the increasing incidence of obesity and metabolic syndrome worldwide, concomitant nonalcoholic fatty liver disease (NAFLD) in patients with chronic hepatitis B (CHB) has become highly prevalent. The risk of dual etiologies, outcome, and mechanism of CHB with concomitant NAFLD have not been fully characterized. In this review, we assessed the overlapping prevalence of metabolic disorders and CHB, assessed the risk of advanced fibrosis/hepatocellular carcinoma in CHB patients concomitant with NAFLD, and discussed the remaining clinical issues to be addressed in the outcome of such patients. We also explored the possible roles of hepatitis B virus in the development of steatosis and discussed difficultiesof histological evaluation. For CHB patients, it is important to address concomitant NAFLD through lifestyle management and disease screening to achieve better prognoses. The assessment of progressive changes and novel therapies for CHB patients concomitant with NAFLD deserve further research.

THE STATE OF PLATELET HEMOSTASIS IN PATIENTS WITH HYPERTENSIVE DISEASE COMBINED WITH NON-ALCOHOLIC FAT LIVER DISEASE

Relevance. Platelet activation and platelet aggregation are central processes in the pathophysiology of coronary heart disease and thrombosis. The relationship between cardiovascular morbidity and mortality varies with the presence of other concomitant cardiovascular risk factors.&#x0D; Objective. To determine the state of platelet hemostasis in patients with essential hypertension (HT), with concomitant non-alcoholic fatty liver disease (NAFLD).&#x0D; Materials and methods. 152 patients were examined: 72 men and 80 women. Three groups were identified: I - 46 patients with stage II HT without concomitant NAFLD, II - 54 patients with NAFLD without HT, group III - 52 patients with HT and concomitant NAFLD. A study of total platelet count, mean platelet volume (MPV), platelet distribution width (PDW), platelet count (PCT) and spontaneous platelet aggregation was performed.&#x0D; Results. The level of mean platelet volume (MPV) in both groups of patients with hepatic steatosis exceeded control values equally - by 6%, both in patients with NAFLD (p&lt;0.001) and in NAFLD with concomitant hypertension (p&lt;0.01). In patients of the NAFLD group and hypertension, the relative width of the platelet distribution by volume (PDW) had high values - 2% (p&lt;0.05) higher than in the control cohort, and 2.4% (p&lt;0.05) than in patients with isolated HT. An increase in the degree of spontaneous aggregation in patients of all surveyed groups compared to controls. So in patients with HT II stage. spontaneous aggregation increased 2.2 times (p&lt;0.001), while in both groups of patients with hepatic steatosis, the increase in spontaneous platelet activity was twice as high: in patients with NAFLD - 4.3 times (p&lt;0.001), in patients with HT II stage. and concomitant NAFLD - 4.1 times (p&lt;0.001).&#x0D; Conclusion. NAFLD is accompanied by an increased in MPV, the size of which correlates with their functional activity. In patients with isolated NAFLD, a statistically significant increase in spontaneous platelet aggregation is also observed, which allows considering NAFLD as one of the risk factors for thrombophilic changes in the primary hemostasis.

#50: Cytomegalovirus Retinitis Among Pediatric Hematopoietic Stem Cell and Solid Organ Transplantation Recipients: A Contemporary Review

Abstract Background Cytomegalovirus infection can cause significant morbidity and mortality after transplantation. Cytomegalovirus retinitis (CMVR) can be a major complication of tissue invasive CMV disease in transplant recipients. There are little data regarding the contemporary incidence and outcomes of CMVR among pediatric transplant recipients. Methods We performed a retrospective cohort analysis of allogeneic hematopoietic (allo-HCT) and solid organ transplant (SOT) recipients who received medical care at Nationwide Children’s Hospital (NCH) from 1/1/10–11/30/20 and had a diagnosis of CMVR to describe the incidence, timing post-transplant, ocular manifestations, management, and outcomes. Basic demographic and clinical data, pre-transplant donor/recipient CMV serostatus, and post-transplant CMV infection data were collected. Graft-specific CMV surveillance and prophylaxis strategies were performed according to NCH hospital guidelines. During the study period, quantitative plasma CMV PCR assays included copies/mL (2010–2013) and WHO international standard IU/mL (2013–2020). Results During the 10-year study period, 347 patients underwent allo-HCT (N=214) or SOT (N=133; heart N=46, liver N=36, kidney N= 52; 1 patient had concomitant kidney and liver transplantation); median age was 8.6 years [range 0.1–25.9] and 198 (56.5%) were male. In total, 98 patients had CMV DNAemia post-transplant, and CMVR was diagnosed in 3 (HCT=2, SOT=1), for an overall CMVR incidence of 0.86% among all transplant recipients and occurring in 3% of patients with CMV DNAemia. No CMVR was diagnosed in patients without CMV DNAemia. An ophthalmologic examination was performed in 58 (59%) of patients with any DNAemia compared with 67 (27%) of patients without DNAemia. CMVR was diagnosed on funduscopic examination a median of 183 days [range 34–512] post-transplant based on visual symptomatology (N=2) or by routine eye screening prompted by DNAemia (N=1). CMV DNAemia at the time of CMVR was 1,463 copies/mL, 3,000, and 14,204 IU/mL; all patients had prolonged (&amp;gt;3 months) CMV detection before CMVR. One SOT recipient had concomitant pathology confirming CMV gastrointestinal tract disease. Two of the 3 CMVR cases occurred in the setting of genotypic UL94 CMV resistance mutations (A594V, H520Q)(Figure 1). Two patients were already receiving CMV antiviral therapy (maribavir N=1; valganciclovir=1) at the time of CMVR diagnosis. After the CMVR diagnosis, all patients were prescribed systemic foscarnet. Adjunctive therapies included concurrent intravitreal antiviral therapy (ganciclovir N=1; foscarnet N=1) and adoptive immunotherapy with CMV antiviral specific T-cells (N=1, HCT). Improvement of ocular symptoms occurred in 2 patients at 15 and 20 days after starting targeted CMV antiviral therapy; one patient developed permanently impaired vision. Conclusion CMVR remains as an important complication in transplant recipients. Although CMVR incidence was low in our cohort of transplant recipients, it occurred most frequently in cases of CMV resistance, prolonged DNAemia, and led to permanent visual impairment in 1 of 3 patients. The development of resistant CMV may have a role in the occurrence, progression, and severity of CMVR. Additional pediatric-specific data are needed to better characterize CMVR and inform optimal prevention strategies.

Pituitary Iron: Effect on Pituitary Volume and Function in Transfusion Dependent Thalassemia

The association of iron toxicity with vital organ dysfunction has been extensively investigated in transfusion-dependent-thalassemia (TDT). However, pituitary iron load and its effect on function have been infrequently addressed. Growth delay, hypogonadism and infertility resulting from iron-induced pituitary toxicity are still prevalent, impacting clinical care and patients' quality of life. Early recognition and timely intervention can potentially prevent irreversible damage and restore partial function.AimsWe aimed to determine pituitary iron load and anterior pituitary volume by MRI in various age groups of TDT and examine their association with systemic and organ-specific iron measures. Additionally, we attempted to stratify the occurrence of abnormal anterior pituitary function by these MRI findings. Identifying such risk thresholds could assist in establishing timing and effectiveness of treatment intervention.MRI (1.5T) measurements of anterior pituitary iron (R2) and volume (Vol) were compared to normal controls (Noetzli 2011) with resultant Z-scores. Mean annual ferritin was calculated and cardiac and liver iron concentration (LIC) were determined by MRI-T2* and superconducting quantum interference device (SQUID) biosusceptometry, respectively. Pituitary hormones (LH and FSH) and growth hormone (Z scores for IGF-1 and IGF-BP3) were determined.ResultsFifty-three TDT patients (51% females) age 25±8 years, (range 10-45 years) were enrolled. Thirty-three (62%) had a ZR2 value >2 (mean 5.4) indicating iron accumulation above 97.5th percentile. Thirty-two patients (60%) had a Z-score for anterior-volume (ZVOL) of less than -2 (mean -2.8) indicating gland shrinkage below the 2.5th percent. In 23 patients (43%) both ZR2 and ZVOL exceeded these thresholds. ZR2 inversely correlated with ZVOL; r =-0.32, p<0.02. Pituitary iron increased with age and differed between patients <18 yr (n=14) and those 18-45 yr (n=39) with a mean ZR2 at 0.9±0.6 and 4.3±0.5, respectively (p<0.001). Anterior pituitary volume declined in older patients, lagging after the iron accumulation (Figure).LH/FSH values and ZR2 showed inverse correlation: r = -0.27 (p<0.03) and -0.3 (p< 0.006) respectively. ZVOL and LH/FSH demonstrated a positive correlation: r = 0.40, p<0.05 and 0.37, p<0.003, respectively. Z(IGF-BP3) but not Z(IGF-1) had an inverse correlation with ZR2: r = -0.5 (p<0.001).ZR2 > 4 was found to be a significant predictor for gland shrinkage; Zvol < -2 was present in 17/33 patients with a ZR2>4 compared to 3/20 with a ZR2<4 (p<0.009). Receiver operator (ROC) analysis confirmed it with an AUC of 0.68. ZR2 >4 was also predictive of presence of clinically important cardiac (T2* <20ms, AUC=0.92, p<0.001) and hepatic iron (LIC >10mg/gd.w., AUC= 0.74, p<0.005). Mean ferritin significantly correlated with ZR2 (p<0.001) but not with the gland's volume.ConclusionsAnterior pituitary iron assessed by MRI, increases with age and correlates with total body iron burden in TDT, suggesting cumulative iron toxicity. It results in a decrease in gland size and impaired gonadotropin and growth hormone secretion. Pituitary iron exceeding ZR2 >4, appears to be a significant predictor for change in gland size, that also is associated with cardiac and liver iron-overload. Pituitary MRI and the concomitant liver and cardiac iron quantification can identify patients at high-risk for further pituitary damage, suggesting that early intervention can potentially prevent additional decline in hormonal secretion. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.