Chronic Liver Condition Research Articles

Update on the STING Signaling Pathway in Developing Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition with limited treatment options. Inflammation caused by metabolic disturbances plays a significant role in NAFLD development. Stimulator of interferon gene (STING), a critical regulator of innate immunity, induces the production of interferons and other pro-inflammatory factors by recognizing cytoplasmic DNA to defend against pathogen infection. The STING-mediated signaling pathway appears to play a vital role in hepatic inflammation, metabolic disorders, and even carcinogenesis. Promisingly, pharmacological interventions targeting STING have shown improvements in the pathological state of NAFLD. Macrophages, dendritic cells, natural killer cells, and T cell pathways regulated by STING present potential novel druggable targets for NAFLD treatment. Further research and development in this area may offer new therapeutic options for managing NAFLD effectively.

Cross-talk between gut microbiota and liver steatosis: Complications and therapeutic target.

Liver steatosis is the most widespread chronic liver condition. Its global incidence is rising swiftly and is currently estimated to be 24%. Liver steatosis is strongly related with numerous metabolic syndrome characteristics, like obesity, insulin resistance, hyperlipidemia, and hypertension. The gastrointestinal tract contains about 100 trillion commensal organisms and more than 7,000 distinct bacterial strains. Fat deposition in the liver without secondary causes is known as liver steatosis. Dysregulation of the gut flora is one of the factors connected to the onset of fatty liver disease. Dietary choices may alter constitution of the microbiome and cause gut microbiome dysbiosis, particularly due to the intake of food high in fructose sugars, animal products, and saturated fats. Various gut bacteria cause nutrient metabolism in multiple ways, setting off different inflammatory cascades that encourage liver disease and pathways that help fat build up in the liver. Due to their relatively stable nature, genetic factors may not be responsible for the constant increase in liver steatosis incidence. Genetic factors set the stage for liver steatosis pathogenesis. This review will offer an overview of our present knowledge of the roles played by gut microbiota in regulating the development of liver steatosis, potential side effects, and potential treatment targets.

Familial coaggregation of MASLD with hepatocellular carcinoma and adverse liver outcomes: Nationwide multigenerational cohort study

Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD) is the fastest growing cause of hepatocellular carcinoma (HCC) worldwide. However, whether family members of individuals with MASLD also share an increased risk of developing HCC is unknown. This nationwide multigenerational cohort study involved family members of all Swedish adults diagnosed with biopsy-proven MASLD (1969-2017), and matched general population comparators. Using the Swedish Multi-generation Register, we identified 38,018 first-degree relatives (FDRs: parents, siblings, offspring) and 9,381 spouses of patients with MASLD, as well as 197,303 comparator FDRs and 47,572 comparator spouses. We used Cox proportional hazards models to calculate adjusted hazard ratios (aHRs) for HCC, major adverse liver outcomes (cirrhosis, decompensated liver disease or liver transplantation), liver-related mortality, extrahepatic cancer, and non-liver-related mortality. Over a median of 17.6 years, the rate of the primary outcome HCC was higher in MASLD FDRs vs. comparator FDRs (13 vs. 8/100,000 person-years [PY]; aHR 1.80, 95% CI 1.36-2.37). The HCC risk was further increased in FDRs of individuals with liver fibrosis/cirrhosis (aHR 2.14, 95% CI 1.07-4.27; PHeterogeneity= 0.03). MASLD FDRs also had higher rates of major adverse liver outcomes (73 vs. 51/100,000 PY; aHR 1.52, 95% CI 1.36-1.69) and liver-related mortality (20 vs. 11/100,000 PY; aHR 2.14, 95% CI 1.67-2.74). MASLD FDRs with any concomitant chronic liver condition experienced accelerated progression of liver disease (aHR 1.47, 95% CI 1.29-1.67). MASLD spouses were at higher risks of major adverse liver outcomes (86 vs. 74/100,000 PY; aHR 1.23, 95% CI 1.01-1.51) and liver-related mortality (25 vs. 19/100,000 PY; aHR 1.93, 95% CI 1.15-3.23), but not of HCC (aHR 1.43, 95% CI 0.87-2.35). There is distinct familial clustering of adverse liver-related outcomes in families of individuals with biopsy-proven MASLD, with higher relative risks of HCC, progressive liver disease, and liver-related mortality, but absolute risks are low. Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly termed NAFLD) clusters in families with high genetic susceptibility and shared environmental risk factors, but the risks of developing hepatocellular carcinoma and other major liver-related outcomes in family members of individuals with MASLD are largely unknown. This large nationwide multigenerational cohort study involving family members (first-degree relatives and spouses) of individuals with biopsy-proven MASLD and of matched general population comparators found slightly increased risks of hepatocellular carcinoma in first-degree relatives, and of developing cirrhosis and liver-related mortality in all family members of individuals with biopsy-proven MASLD. The findings of this study provide large-scale evidence to inform clinical practice guidelines for recommendations on the early identification of individuals at higher risk of liver-related morbidity and mortality.

FIB 4 Score (Liver Fibrosis) and Attending Level of Vitamin D in Chronic Hepatitis C Patients

Millions of people around the world are affected by chronic hepatitis C (HCV), which is a global health issue. It is a major contributor to chronic liver conditions such as cirrhosis, hepatocellular carcinoma, and liver fibrosis. For optimal therapy and intervention, prompt identification of liver fibrosis is essential. The rate of hepatic fibrosis progression in HCV-infected patients varies substantially. Objective: To evaluate the vitamin D level and liver fibrosis degree by non-invasive Fib 4 score among chronic hepatitis patients. Methods: This Cross-sectional study was conducted at a tertiary care hospital in Karachi, Pakistan, from August 2020 to September 2022. 65 participants were recruited through a non-probability sampling technique. Results: Study findings show that 21.9% of the patients have low risk for advanced fibrosis, whereas 9.2% have an Intermediate risk for advanced fibrosis, and 69.2% have a high risk for advanced fibrosis. Moreover, findings also revealed that among 65 patients, 66.2% have a deficient amount of Vitamin D, whereas 16.9% have an insufficient amount of Vitamin D level and 16.9% have a sufficient amount of vitamin D. Furthermore, the findings also showed significant association based on p-value (0.001) between Age and Fib4 score of the participant. Conclusions: In conclusion, the study revealed that a significant proportion of chronic hepatitis C patients were at high risk for advanced fibrosis, while vitamin D deficiency/ insufficiency were prevalent among the majority of the patients.

Ultrasonic elastographic and morphological features of fatty hepatosis

BACKGROUND: Non-alcoholic fatty liver disease is a common chronic liver condition characterized by pathological accumulation of fatty droplets, which is not associated with alcohol consumption. The main reason in the development of complications and adverse outcomes of the disease is fibrotic changes in the liver, leading to cirrhosis.
 AIM: To determ the informative value of two-dimensional shear wave elastography in hepatosis by a comparative analysis of morphological and ultrasound elastometric findings.
 METHODS: The study included 40 patients aged 3560 years. The control group consisted of 25 healthy people with a body mass index of 2426. Among 40 patients, F1, F2 and F3 stages were detected in 15 (37.5%), 20 (50%), and 5 (12.5%) cases, respectively. The diagnosis was based on clinical, laboratory, and ultrasound examinations conducted with a Mindray Consona N9 device using a convex transducer at 2.03.5 MHz. In the absence of contraindications, all patients underwent puncture biopsy under ultrasound navigation in compliance with aseptic and antiseptic requirements.
 RESULTS: At the first (F1) stage of hepatic fibrosis (n=15), the elastometry index averaged 5.4 (4.86.2) kPa, and the shear wave velocity was 1.10.2 m/s. Histomorphological examination in this group revealed mild fatty liver dystrophy, with liver tissue having varying degrees of dystrophic changes. In the second (F2) stage of fibrosis (n=20), the mean elastometry values were 6.9 (6.37.9) kPa, while the shear wave velocity increased to 1.50.2 m/s. In patients of this group, histological examination showed that moderate to large fatty dystrophy developed in hepatocytes. In the F3 stage (n=5), the elastometry index averaged 8.3 (8.113.5) kPa, and the shear wave velocity reached 1.70.2 m/s. In this case, hepatocytes with fatty dystrophy in the focus surrounded by a cluster of lipophages were determined. Coincidence of fibrosis stage determined by elastometry data with morphological examination of liver biopsy specimen was observed in 36 (90%) patients with fatty hepatosis.
 CONCLUSIONS: Comparison of the results of two-dimensional shear wave elastography and morphological changes of liver parenchyma in hepatosis showed high (90%) correlation with the data of the above examinations. If puncture biopsy is contraindicated, shear wave elastography may serve as a valuable diagnostic method to clarify the stage of fibrosis in hepatosis.

Outcomes of Portal Vein Thrombosis in Smokers With and Without Cirrhosis and Predictors of Mortality: A Nationwide Assessment.

Portal vein thrombosis (PVT) is a rare condition that can lead to numerous complications, like variceal bleeding, hepatic encephalopathy, and chronic liver disease. PVT has various etiologies, including liver disease, infections, and hyper-coagulable disorders. Cirrhosis, a chronic progressive liver condition characterized by liver fibrosis, is one of the risk factors for the development of PVT. Secondly, smoking also increases the risk of PVT. The aim of this study is to identify outcomes in patients with PVT who smoked with and without cirrhosis. This study was performed using the National Inpatient Sample (NIS) database for the years 2016, 2017, and 2018. The study identified 33,314 patients diagnosed with PVT who smoked, of which 14,991 had cirrhosis, and 18,323 did not have cirrhosis. Patients with PVT and cirrhosis had significantly higher in-hospital mortality, upper gastrointestinal bleeds, acute kidney injury, and peritonitis compared to patients without cirrhosis. The results of the study show that patients with PVT and cirrhosis who smoke have a higher risk of unfavorable outcomes.

Effects of Monacolin K in Nondiabetic Patients with NAFLD: A Pilot Study.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver condition with significant risk of progression to steatohepatitis and cirrhosis. Therapeutic strategies in NAFLD include lifestyle changes mainly related to dietary interventions and use of drugs or nutritional components that could improve plasma lipid profiles and insulin sensitivity and decrease the local inflammatory response. In this study, we tested the effects of monacolin K, an inhibitor of HMCoA reductase. In a prospective, uncontrolled, open study, we treated 24 patients with NAFLD and mild hypercholesterolemia with 10 mg/day of monacolin K. At baseline and after 26 weeks, we measured in plasma liver tests, lipids, malondialdehyde, and oxidized glutathione, and assessed biochemical steatosis scores, liver elastography, and body composition with bioimpedance analysis. Monacolin K significantly reduced plasma alanine aminotransferase, cholesterol, triglycerides and the homeostatic model assessment (HOMA) index that indicated improved insulin sensitivity. No significant changes were found in body fat mass and visceral fat, nor in liver elastography, while the fatty liver index (FLI) was significantly decreased. Plasma levels of both malondialdehyde and oxidized glutathione were markedly reduced by monacolin K treatment, suggesting a reduction in oxidative stress and lipid peroxidation. In summary, this pilot study suggests possible benefits of monacolin K use in NAFLD patients that could be linked to a reduction in oxidative stress. This hypothesis should be further investigated in future studies.

Ferroptosis in hepatocellular carcinoma: from bench to bedside.

The most widespread type of liver cancer, HCC, is associated with disabled cellular death pathways. Despite therapeutic advancements, resistance to current systemic treatments (including sorafenib) compromises the prognosis of patients with HCC, driving the search for agents that might target novel cell death pathways. Ferroptosis, a form of iron-mediated nonapoptotic cell death, has gained considerable attention as a potential target for cancer therapy, especially in HCC. The role of ferroptosis in HCC is complex and diverse. On one hand, ferroptosis can contribute to the progression of HCC through its involvement in both acute and chronic liver conditions. In contrast, having ferroptosis affect HCC cells might be desirable. This review examines the role of ferroptosis in HCC from cellular, animal, and human perspectives while examining its mechanisms, regulation, biomarkers, and clinical implications.

Liver Fat Quantification: When do We Need It?

In recent years the most rapidly emerging disease in general hepatology is the Metabolic dysfunction-Associated Fatty Liver Disease (MAFLD) [1] [2]. This a new definition, which was suggested to replace and extend what was previously known as Non Alcoholic Fatty Liver Disease (NAFLD) and Non Alcoholic Steatohepatitis (NASH) [1]. The new proposal of MAFLD was set forward because the criterion for diagnosing NAFLD/NASH requires absence of any other chronic liver condition (e. g. viral hepatitis, immune-related cholestatic liver disease, etc) and absence of any over threshold intake of alcohol [1] . The terms NAFLD/NASH are correct to establish a diagnosis of liver disease purely caused by metabolic dysfunction, useful to better understand the natural history of the disease, especially in a scientific setting, but does not reflect the real-life situation, where many patients may actually suffer from metabolic liver disease on top of other liver conditions and the two conditions may or may not both contribute to the progression and complications of the liver disease with different and not well definable relevance [3]. For instance, the persistence of minimally elevated liver enzymes in slightly overweight patients after cure of HCV or after full dosage of ursodesoxycholic acid in Primary Biliary Cholangitis or Primary Sclerosing Cholangitis or after drastic reduction or the suspension of alcohol intake often raise the question whether an underlying MAFLD is present. This adds obviously to the question of whether some elevation of liver enzymes in the absence of any known etiological factor may be due to NAFLD when ultrasonography does not detect an obvious bright liver. In all these and in other situations the precise assessment of liver fat content may be crucial, when this is not obvious on conventional ultrasonography.

Understanding the Potential Role of Nanotechnology in Liver Fibrosis: A Paradigm in Therapeutics.

The liver is a vital organ that plays a crucial role in the physiological operation of the human body. The liver controls the body's detoxification processes as well as the storage and breakdown of red blood cells, plasma protein and hormone production, and red blood cell destruction; therefore, it is vulnerable to their harmful effects, making it more prone to illness. The most frequent complications of chronic liver conditions include cirrhosis, fatty liver, liver fibrosis, hepatitis, and illnesses brought on by alcohol and drugs. Hepatic fibrosis involves the activation of hepatic stellate cells to cause persistent liver damage through the accumulation of cytosolic matrix proteins. The purpose of this review is to educate a concise discussion of the epidemiology of chronic liver disease, the pathogenesis and pathophysiology of liver fibrosis, the symptoms of liver fibrosis progression and regression, the clinical evaluation of liver fibrosis and the research into nanotechnology-based synthetic and herbal treatments for the liver fibrosis is summarized in this article. The herbal remedies summarized in this review article include epigallocathechin-3-gallate, silymarin, oxymatrine, curcumin, tetrandrine, glycyrrhetinic acid, salvianolic acid, plumbagin, Scutellaria baicalnsis Georgi, astragalosides, hawthorn extract, and andrographolides.

Apigenin role against thioacetamide-triggered liver fibrosis: Deciphering the PPARγ/TGF-β1/NF-κB and the HIF/FAK/AKT pathways

Introduction: Liver tissue malfunction is a severe worldwide health concern that arises from various chronic liver conditions. The goal of this investigation was to look into the anti-fibrotic effect of apigenin (APG), an antioxidant found in various plants, versus thioacetamide (TAA)-triggered hepatic scarring in rats and the potential mechanisms behind it. Methods: TAA was administered thrice weekly (100 mg/kg, i.p.) for two weeks to produce hepatic scarring. APG was administered after TAA for 14 days (5 or 10 mg/kg, orally). Thereafter, hepatic liver enzymes, inflammatory markers, fibrotic indicators, and histopathological changes were evaluated. Results: TAA increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), reduced albumin and total protein, elevated hepatic level of lipid peroxidation, focal adhesion kinase (FAK), hypoxia-inducible factor-1α (HIF-1α), and inflammatory cytokines, decreased interleukin-10 (IL-10), reduced hepatic expression of peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor-erythroid factor 2-related factor 2 (Nrf2), and elevated serine-threonine protein kinase (AKT) expression. Furthermore, TAA increased hepatic contents of collagen I, connective tissue growth factor (CTGF), hydroxyproline, and alpha-smooth muscle actin. On the other hand, APG evaded these changes and mitigated the harmful effects of TAA in a dose-dependent way. Histopathological and immunohistochemical observations reinforced these biochemical outcomes. Conclusion: APG can potentially alleviate liver fibrosis mediated via FAK and HIF1 inhibiting signaling pathways.

Sex differences in cardiovascular and all-cause mortality in nonalcoholic fatty liver disease in the US population

Background and aimsNonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver condition. In the United States (US), the prevalence of NAFLD in men is higher than that in women. This study aimed to evaluate sex differences in long-term all-cause and cardiovascular (CV) outcomes in patients with NAFLD. Methods and resultsWe collected data from participants aged ≥18 years from the National Health and Nutrition Examination Surveys, 2000–2014, which included seven continuous 2-year surveys. A US Fatty Liver Index score of ≥30 was used to define NAFLD. We used a weighted Cox proportional hazards model to compare sex differences in overall and CV mortality. The all-cause and CV mortality rates were obtained from the National Center for Health Statistics. From the selected 2627 participants with NAFLD, 65.4% were males. Men had a significantly higher all-cause mortality than women (12.4% vs. 7.7%; p = 0.005), and the risk of CV death was higher in women with NAFLD aged ≤60 years (adjusted hazard ratio 0.214, 95% confidence interval 0.053–0.869, p = 0.031). Men with a body mass index >30 kg/m2 and diabetes showed a higher risk of all-cause mortality. Sex differences in CV events were not apparent in the patients aged >60 years. ConclusionMale sex was associated with all-cause mortality in all the age groups. However, CV death is influenced by age, with a higher risk in young and middle-aged women and no apparent difference in older patients.

Differences in hospitalizations associated with severe COVID-19 disease among foreign- and Swedish-born.

Differences in pre-existing health conditions are hypothesized to explain immigrants' excess COVID-19 mortality compared to natives. In this study, we evaluate whether immigrants residing in Sweden before the outbreak were more likely to be hospitalized for conditions associated with severe COVID-19 disease. A cohort study using population-register data was conducted with follow-up between 1 January 1997 and 31 December 2017. Poisson regression was fitted to estimate incidence rate ratio (RR) and 95% confident intervals (95% CI) for 10 causes of hospitalization. Compared to Swedish-born individuals, most immigrant groups showed a decreased risk of hospitalization for respiratory chronic conditions, CVD, cancer, chronic liver conditions and neurological problems. All immigrant groups had increased risk of hospitalization for tuberculosis [RR between 88.49 (95% CI 77.21; 101.40) for the Horn of Africa and 1.69 (95% CI 1.11; 2.58) for North America], HIV [RR between 33.23 (95% CI 25.17; 43.88) for the rest of Africa and 1.31 (95% CI 0.93; 1.83) for the Middle East] and, with a few exceptions, also for chronic kidney conditions, diabetes and thalassemia. Foreign-born individuals-including origins with excess COVID-19 mortality in Sweden-did not show increased risk of hospitalizations for most causes associated with severe COVID-19 disease. However, all groups showed increased risks of hospitalization for tuberculosis and HIV and, with exceptions, for chronic kidney conditions, diabetes and thalassemia. Although studies should determine whether these health conditions explain the observed excess COVID-19 mortality, our study alerts to an increased risk of hospitalization that can be avoidable via treatment or preventive measures.

Peonidin-3-O-Glucoside from Purple Corncob Ameliorates Nonalcoholic Fatty Liver Disease by Regulating Mitochondrial and Lysosome Functions to Reduce Oxidative Stress and Inflammation.

A frequent chronic liver condition across the world is nonalcoholic fatty liver disease (NAFLD). Oxidative stress caused by lipid accumulation is generally considered to be the main cause of NAFLD. Anthocyanins can effectively inhibit the production of reactive oxygen species and improve oxidative stress. In this work, six major anthocyanins were separated from purple corncob by semi-preparative liquid chromatography. The effects of the 6 kinds of anthocyanins against NAFLD were investigated using a free fatty acid (FFA)-induced cell model. The results showed that peonidin 3-O-glucoside (P3G) can significantly reduce lipid accumulation in the NAFLD cell model. The treatment with P3G also inhibited oxidative stress via inhibiting the excessive production of reactive oxygen species and superoxide anion, increasing glutathione levels, and enhancing the activities of SOD, GPX, and CAT. Further studies unveiled that treatment with P3G not only alleviated inflammation but also improved the depletion of mitochondrial content and damage of the mitochondrial electron transfer chain developed concomitantly in the cell model. P3G upregulated transcription factor EB (TFEB)-mediated lysosomal function and activated the peroxisome proliferator-activated receptor alpha (PPARα)-mediated peroxisomal lipid oxidation by interacting with PPARα possibly. Overall, this study added to our understanding of the protective effects of purple corn anthocyanins against NAFLD and offered suggestions for developing functional foods containing these anthocyanins.

Non-alcoholic Fatty Liver Disease with Type 2 DM in Rural and Urban Areas in Bangladesh

Introduction: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver condition that affects up to one-third of adults in developed nations. NAFLD refers to a group of non-alcoholic diseases that are histologically and clinically distinct. Fatty liver (NAFL, steatosis hepatitis) and steatohepatitis can lead to cirrhosis and rare cases of hepatocellular carcinoma.
 Materials and Methods: This was a cross-sectional descriptive study conducted in the medicine department, Rajshahi medical college, Rajshahi, among ninety-one T2DM patients. The study population included outdoor patients as well as hospitalized consecutive 91 patients (50 Urban and 41 Rural) in the medicine department with type 2 DM diagnosed according to the American Diabetes Association (ADA) 2011 criteria. NAFLD was detected and graded using abdominal ultrasonography and blood pressure, BMI, waist circumference, HbA1c, lipid profile, and liver function tests. All data were analyzed by SPSS 16, and p-value <0.05 was assumed as statistically significant in this study.
 Results: A total of 91 patients were enrolled during the study. NAFLD prevalence was higher in urban patients (54.54%) than in rural patients (45.45%). Males were affected more than female patients in both groups. Patients in the urban population had higher weight, waist circumference, hip circumference, and BMI and were diagnosed with NAFLD at a younger age than those in the rural group. Metabolic syndrome was shown to be prevalent in both groups.
 Conclusion: The prevalence of NAFLD was shown to be greater in the urban population compared to the rural population, with male patients being more impacted than female patients. Although the risk factors for NAFLD were similar in both the study groups, better anthropometric parameters (lower weight), waist circumference, hip circumference, and BMI had a role in reduced prevalence of NAFLD in rural as compared to urban population patients.
 TAJ 2022; 35: No-2: 151-158

A Case Report on Septic Arthritis caused by Burkholderia pseudomallei

Melioidosis is an emerging infection in India caused by the environmental saprophyte Burkholderia pseudomallei. It is a gram negative, oxidase-positive bacillus that is intrinsically resistant to gentamycin, penicillin, and colistin. Risk factors for this infection include diabetes mellitus, heavy alcohol use, malignancy, chronic lung infection, liver, and kidney conditions. B. pseudomallei can lead to variable clinical manifestations, ranging from mild localised abscesses to invasive infections. However, a proper identification system for early detection and speciation is not universally available in all laboratories, and it can be easily misidentified as Pseudomonas species due to its unfamiliarity. Consequently, there may be a delay in diagnosis and failure to initiate appropriate and effective treatment, which can worsen the outcome. In this report, the author presents a case of septic arthritis in a 44-year-old diabetic male with clinical symptoms of melioidosis and involvement of multiple organs.

Correlation of ultrasound attenuation imaging versus MRI proton density fat fraction in non-alcoholic fatty liver

Background: Attenuation Imaging (ATI) is a novel method for assessment of hepatic steatosis, based on ultrasound attenuation by calculating attenuation coefficient which increases in the fatty liver condition. The previous published data comparing ATI and Magnetic Resonance Proton Density Fat Fraction (MR-PDFF) has moderate to high correlation coefficient (r=0.66-0.81). However, fatty liver is commonly associated with obesity which may be an influencing factor of the ATI measurement. Objective: The purpose of this study was to evaluate diagnostic accuracy of ATI in non-alcoholic fatty liver disease (NAFLD) compared to MRI-PDFF Materials and Methods: The 62 non-alcoholic fatty liver disease (NAFLD) patients with available ATI, MRI-PDFF, and MRE examination, excluding cirrhosis, history of significant alcohol drinking, and chronic liver condition were retrospectively evaluated. Results: The correlation coefficient (r) of ATI vs MRI-PDFF were in good correlation (r = 0.63-0.69, p<0.001). The inter-observer reliability of two observers was 100% with the Cohen kappa coefficient of 1.00 (p < 0.001).Area under the receiver operating characteristics of ATI for diagnosis of steatosis grade > 0 was 0.96 and for diagnosis of steatosis grade > 1 was 0.83. Conclusions: ATI is a novel ultrasound method to quantify the degree of fat deposition with a good correlation to MRI-PDFF with high interobserver’ reliability. Obesity commonly associated with fatty liver may be an interfering factor of ATI measurement.

Association of Liver Fibrosis with Cognitive Test Performance and Brain Volume Changes in the UK Biobank Study

AbstractBackgroundLiver fibrosis is a chronic liver condition that, though frequently subclinical, has widespread systemic effects. We hypothesized that liver fibrosis is associated with worse cognitive performance and corresponding brain imaging changes.MethodWe examined the association of liver fibrosis with cognition and brain volumes among adults in the UK Biobank study, which prospectively enrolled approximately 500,000 people starting in 2007 and subsequently collected cognitive test and brain MRI data for some participants. We included participants with available liver fibrosis, cognitive test, and brain imaging data. Liver fibrosis was defined at baseline using validated cutoffs of the Fibrosis‐4 (FIB‐4) liver fibrosis score. The primary cognitive test outcome was the Digit Symbol Substitution Test (DSST), a multidomain test. Secondary cognitive test outcomes were executive function tests (Trails A, Trails B, Reaction Time) and memory tests (Numeric Memory, Pairs Matching). The primary imaging outcome was white matter hyperintensity volume; secondary outcomes were hippocampal volume and total brain volume. We used multiple linear regression models to evaluate the association of liver fibrosis with cognitive test performance and brain volumes while adjusting for potential confounders.ResultsAmong 105,313 participants with cognitive test data, the mean age was 56.1 years and 56% were women. Standard liver chemistries were largely in the normal range. However, 2.0% (95% CI, 1.9‐2.1%) had liver fibrosis based on FIB‐4 scores. Cognitive tests were completed a median of 5.8 years after baseline liver fibrosis assessment. After adjusting for demographics, socioeconomics, education, body mass index, metabolic syndrome, hypertension, diabetes, dyslipidemia, and tobacco and alcohol use, liver fibrosis was associated with worse performance on the DSST (β = ‐0.40; 95% CI, ‐0.60, ‐0.20; P<0.001) (Figure). Liver fibrosis was associated with worse executive function but not memory test performance (Table). We included 34,730 participants with brain MRI, obtained a median of 9.3 years after baseline. In adjusted models, liver fibrosis was associated with lower hippocampal volume (β = ‐58.8; 95% CI, ‐94.7, ‐22.9; P = 0.001) and higher white matter hyperintensity volumes (β = 1142.8; 95% CI, 311.6, 1973.9; P = 0.007) (Table, Figure).ConclusionLiver fibrosis is associated with worse cognitive performance, perhaps explained by hippocampal volume loss and white matter hyperintensity burden.

Profile of Liver Cirrhosis Patients at Imelda Pekerja Indonesia General Hospital (RSU IPI) Period January 2020 – December 2021

Liver cirrhosis is the result or complication of a chronic liver condition where the liver parenchyma is damaged so that its function decreases. This study aims to study the profile of patients with liver cirrhosis at the Imelda Pekerja Indonesia General Hospital in Medan for the period January 2020 - December 2021. This study is a descriptive observational study. A total of 40 samples of medical records of patients with a diagnosis of liver cirrhosis at the Imelda Pekerja Indonesia General Hospital in (IPI) Medan were included in this study. Univariate analysis in the form of frequency distribution data tabulation was used to present the data. The results showed that most patients with liver cirrhosis were male (72.5%), aged 56-65 years (32.5%), and the main complaint was nausea and vomiting (47.5%). The most physical examination results were ascites (52.5%), abnormal lab results were increased SGPT (75%), SGOT (80%), total bilirubin (85%), prothrombin time (75%) and decreased albumin (85%) and Hb (55%), most of the patients were in the category of Child-Pugh Score B (37.5%) and C (37.5%), and the most complication was hepatorenal syndrome (55%). In conclusion, the profiles of patients with liver cirrhosis are mostly male, aged 56-65 years, with the most complaints of nausea and vomiting and the most physical examination findings of ascites. There was an increase in SGPT, SGOT, total bilirubin, and prothrombin time, as well as a decrease in albumin and Hb.

S3260 A Case of Smoldering Multiple Myeloma in a Patient With Gaucher’s Disease Diagnosed on Liver Biopsy

Introduction: We describe a rare case of Gaucher Disease (GD) diagnosed on liver biopsy in a patient with thrombocytopenia and hepatic steatosis with subsequent findings of smoldering multiple myeloma (SMM). Case Description/Methods: 59-year-old male with history of chronic thrombocytopenia presented to the clinic for mild elevation in liver enzymes. At the time of evaluation, patient was asymptomatic and denied any history or risk factors for liver disease. Labs were notable for ALT 53, AST 43, Total bilirubin 0.5, alkaline phosphatase 111, INR 1, platelet 73, and ferritin 1157. Serology for hemochromatosis, autoimmune hepatitis, and viral hepatitis were negative. A CT scan of abdomen revealed hepatic steatosis and splenomegaly. Transient elastography was consistent with stage F3-F4 fibrosis. Subsequent liver biopsy showed features of steatohepatitis and sinusoidal cells with pale-gray striated cytoplasm characteristic of Gaucher’s cells. No evidence of iron overload and cirrhosis on trichome stain. The degree of thrombocytopenia and splenomegaly were out of proportion to the liver disease, prompting further hematological evaluation. Serum protein electrophoresis showed 1300 mg/dL IgA kappa monoclonal protein spike. Bone marrow biopsy revealed hypercellular marrow (50%), Gaucher cells, and plasma cell neoplasm ( >20%) consistent with Type I GD with smoldering multiple myeloma given absence of end organ damage. He was treated conservatively with close monitoring for disease progression. (Figure) Discussion: GD is a rare autosomal recessive disorder characterized by deficiency of the lysosomal enzyme glucocerebrosidase that leads to accumulation of glycophospholipids in the cells of the reticuloendothelial system. It is a multisystem progressive disorder with involvement of bone marrow, liver and spleen. Type 1 GD is the most common non-neuropathic variant in adults with prevalence of 1:1000. Predominant clinical features include thrombocytopenia, hepatosplenomegaly with variable patterns of liver involvement ranging from sub-clinical to decompensated cirrhosis. GD is often associated with laboratory abnormalities including hyperferritinemia or hypergammaglobulinemia that may lead to misdiagnosis with other chronic liver conditions. Additionally, there is an increased risk of multiple myeloma and other gammopathies in type 1 GD. Lack of awareness of early clinical course and its associated conditions can lead to delay in diagnosis and treatment.Figure 1.: (A) There is mild pericellular fibrosis, but no periportal or bridging fibrosis. Mild steatosis supportive of a component of NASH accompany the Gaucher's cells is seen (Trichrome, 100X). (B) Sinusoidal cells are enlarged and show pale-gray striated cytoplasm representing Gaucher's cells whereas the hepatocytes are ballooned. Inflammatory infiltrates are absent(hematoxylin and eosin, 200X). (C) The Gaucher's cell are positive for the histiocytic marker CD68 (Immunohistochemistry, 200X).