Etiology Of Liver Disease Research Articles

Aspartate aminotransferase-to-platelet ratio index can predict the outcome in patients with stable decompensated cirrhosis.

Platelet (PLT)-based biomarkers have been studied for the evaluation of liver fibrosis and cirrhosis. There are no data regarding their prognostic significance in decompensated cirrhosis. We studied 525 stable decompensated patients from the 2 Greek transplant centers. We measured PLT values, mean PLT volume (MPV), red cell distribution width, γ-globulins, and calculated PLT-based scores: aspartate aminotransferase-to-PLT ratio index (APRI), γ-globulin-to-PLT model, and γ-glutamyl transpeptidase-to-PLT ratio (GPR). We followed our cohort for 12 (range: 1-84) months. Baseline mean model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores were 15±6 and 8±2, respectively. On univariate analysis, MPV/PLT (hazard ratio [HR] 3.75, 95% confidence interval [CI] 1-14.5; P=0.05), APRI (HR 1.03, 95%CI 1.006-1.06; P=0.016), GPR (HR 1.096, 95%CI 1.016-1.182; P=0.017) were significantly associated with our patients' outcome (survival vs. death or liver transplantation). In a multivariate model without MELD and CTP scores, APRI was the only significant factor associated with the outcome (HR 1.054, 95%CI 1.009-1.101; P=0.018). APRI had good discriminative ability for the outcome (area under the curve 0.723 vs. 0.675 and 0.656 for MELD and CTP scores, respectively). The optimal cutoff point was 1.3 (sensitivity 71%, specificity 65%). There were 200 patients (38%) with APRI scores <1.3 who had better survival than patients with APRI >1.3 (log rank 22.4, P<0.001). This study found a prognostic role for APRI in stable decompensated cirrhosis, regardless of the underlying etiology of chronic liver disease. This suggests new perspectives for PLT-based noninvasive scores to discriminate patients' outcomes.

Non-alcoholic fatty liver disease and sleep quality: a single center cross-sectional survey study

Sleep-wake disorders are probably a part of Nonalcoholic Fatty Liver Disease (NAFLD) etiology. This study aimed to evaluate the relationship between NAFLD and the Pittsburgh Sleep Quality Index (PSQI) components. Sleep quality was assessed by the PSQI, which comprised seven components. Participants diagnosed with hepatic steatosis using ultrasonographic imaging and healthy volunteers were given the questionnaire. The percentage of subjects with poor sleep quality was noticeably higher in the NAFLD patients than in the non-NAFLD control group (OR: 4.58, 95% CI: 2.67-7.85) (p&lt;0.001). Compared to the control group, the NAFLD group reported shorter sleep duration (p=0.044), a longer sleep onset delay (p&lt;0.001), worse subjective sleep quality (p&lt;0.001), a higher percentage of subjects with sleep disturbances (p&lt;0.001), a higher percentage of subjects using hypnotic drugs (p=0.009), and a higher percentage of subjects with daytime dysfunction (p&lt;0.001). When the subjects were split into two groups based on gender, global PSQI sleep quality and subjective sleep quality were significantly worse in both genders with NAFLD than in the non-NAFLD group (p&lt;0.001). The sleep onset delay of the NAFLD group was substantially longer in males (p=0.002) and females (p&lt;0.001) compared to controls. Sleep disturbances were significantly higher in both sexes with NAFLD compared to controls (p&lt;0.001). The rate of those with daytime dysfunction in the NAFLD group was considerably higher in both genders compared to the non-NAFLD group (p=0.001). Only among the male patients in the NAFLD group the prevalence of hypnotic drug use was substantially greater (p=0.033) than in the non-NAFLD group. Poor sleep was associated with NAFLD in both genders.

Efficacy of a two-dose hepatitis B vaccination with a novel immunostimulatory sequence adjuvant (Heplisav-B) on patients with chronic liver disease: a retrospective study.

Patients with chronic liver disease (CLD) are more likely to have severe morbidity and mortality due to superimposed acute or chronic hepatitis B virus (HBV) infection and should receive routine vaccination against the virus. Heplisav-B is a two-dose, inactivated, yeast-derived vaccine that uses a novel immunostimulatory adjuvant. Our primary objective was to determine the efficacy of hepatitis B vaccination with Heplisav-B in patients with CLD. This retrospective cohort analysis included patients ≥18 years old with CLD who received Heplisav-B from January 2018 to January 2021. All patients had anti-HBs <10 IU/L prior to vaccination and received two doses of Heplisav-B. Post-vaccination anti-HBs of ≥10 IU/L was considered successful vaccination. Basic demographic information, laboratory markers, and medical history were collected from the electronic health record. A total of 120 patients were included in analysis. The average age of patients was 59 years, 37% were female, and the most common etiology of liver disease was nonalcoholic fatty liver disease. Median days from 2nd vaccination to post-vaccination HBsAb levels was 121 days. 81/120 (67.5%) of patients had evidence of active immunity after receipt of Heplisav-B. On multivariable analysis, age >50 was associated with reduced odds of successful vaccination (OR =0.19, 95% CI: 0.03-0.76). In patients with CLD, Heplisav-B's overall efficacy (67.5%) is greater than reports of Engerix-B (33-45%), and thus is an effective hepatitis B vaccine in this patient population, particularly in cirrhotic patients. Further studies regarding this vaccine are needed in patients with CLD and after liver transplantation.

An Unusual Manifestation of Elevated Liver Enzymes and Architecture

Question: A 68-year-old woman with a past medical history of cerebral vascular accident and chronic kidney disease underwent an outpatient anorectal examination under anesthesia for evaluation of a 6-month history of rectal bleeding and constipation. She was found to have a rectal mass involving the posterior vaginal wall. Biopsy specimens from the rectal and vaginal lesions showed invasive squamous cell carcinoma (SCC) with venous invasion (Figures A and B). The carcinoma was p16+ representing a high-risk human papilloma virus–induced SCC (Figure C). Computed tomography of the chest, abdomen, and pelvis showed the vaginal mass and a nodular liver suggestive of cirrhosis. With regard to the patient’s risk factors for liver disease, the patient had remote social alcohol consumption in her 20s without a history of intravenous drug use, family history of liver disease, autoimmune diseases, or hepatitis. In preparation for palliative chemotherapy, blood work was obtained, which was pertinent for white blood cell count of 8.8 103/μL, hemoglobin of 12.7 g/dL, platelets 257 103/μL, aspartate aminotransferase 127 U/L, alanine aminotransferase 65 U/L, alkaline phosphatase 1133 U/L, bilirubin 4.8 mg/dL, prothrombin time of 15.3 seconds, and international normalized ratio of 1.2. Serologic work-up was unremarkable for viral, autoimmune, or metabolic etiologies of liver disease, so magnetic resonance cholangiopancreatography was obtained (Figure D). Subsequently, the patient underwent transjugular hepatic hemodynamic pressure measurements with results as follows: right atrial pressure = 7 mm Hg, free hepatic vein pressure = 15 mm Hg, wedged hepatic vein pressure = 27 mm Hg, and corrected sinusoidal pressure = 12 mm Hg, followed by nontargeted liver biopsy (Figure E).

Myosteatosis Is Not Associated with Complications or Survival in HCC Patients Undergoing Trans Arterial Embolization.

Alterations in nutritional status, in particular sarcopenia, have been extensively associated with a poor prognosis in cirrhotic patients regardless of the etiology of liver disease. Less is known about the predictive value of myosteatosis, defined as pathological fat infiltration into the skeletal muscle. We retrospectively analyzed a cohort of 151 cirrhotic patients with unresectable hepatocellular carcinoma (HCC) who underwent their first trans-arterial embolization (TAE) between 1 March 2011 and 1 July 2019 at our Institution. Clinical and biochemical data were collected. Sarcopenia was assessed using the L3-SMI method while myosteatosis with a dedicated segmentation suite (3D Slicer), using a single slice at an axial plane located at L3 and calculating the IMAC (Intramuscular Adipose Tissue Content Index). The sex-specific cut-off values for defining myosteatosis were IMAC > −0.44 in males and >−0.31 in females. In our cohort, 115 (76%) patients were included in the myosteatosis group; 128 (85%) patients had a coexistent diagnosis of sarcopenia. Patients with myosteatosis were significantly older and showed higher BMI than patients without myosteatosis. In addition, male gender and alcoholic- or metabolic-related cirrhosis were most represented in the myosteatosis group. Myosteatosis was not associated with a different HCC burden, length of hospitalization, complication rate, and readmission in the first 30 days after discharge. Overall survival was not influenced by the presence of myosteatosis.

Longitudinal multi-omics analyses of the gut-liver axis reveals metabolic dysregulation in hepatitis C infection and cirrhosis.

The gut and liver are connected via the portal vein, and this relationship, which includes the gut microbiome, is described as the gut-liver axis. Hepatitis C virus (HCV) can infect the liver and cause fibrosis with chronic infection. HCV has been associated with an altered gut microbiome; however, how these changes impact metabolism across the gut-liver axis and how this varies with disease severity and time is unclear. Here we used multi-omics analysis of portal and peripheral blood, faeces and liver tissue to characterize the gut-liver axis of patients with HCV across a fibrosis severity gradient before (n = 29) and 6 months after (n = 23) sustained virologic response, that is, no detection of the virus. Fatty acids were the major metabolites perturbed across the liver, portal vein and gut microbiome in HCV, especially in patients with cirrhosis. Decreased fatty acid degradation by hepatic peroxisomes and mitochondria was coupled with increased free fatty acid (FFA) influx to the liver via the portal vein. Metatranscriptomics indicated that Anaerostipes hadrus-mediated fatty acid synthesis influences portal FFAs. Both microbial fatty acid synthesis and portal FFAs were associated with enhanced hepatic fibrosis. Bacteroides vulgatus-mediated intestinal glycan breakdown was linked to portal glycan products, which in turn correlated with enhanced portal inflammation in HCV. Paired comparison of patient samples at both timepoints showed that hepatic metabolism, especially in peroxisomes, is persistently dysregulated in cirrhosis independently of the virus. Sustained virologic response was associated with a potential beneficial role for Methanobrevibacter smithii, which correlated with liver disease severity markers. These results develop our understanding of the gut-liver axis in HCV and non-HCV liver disease aetiologies and provide a foundation for future therapies.

Poor Outcomes of Patients With NAFLD and Moderate Renal Dysfunction or Short-Term Dialysis Receiving a Liver Transplant Alone.

The outcomes of patients with moderate renal impairment and the impact of liver disease etiology on renal function recovery after liver transplant alone (LTA) are largely unknown. We explored whether NAFLD patients with pre-LTA moderate renal dysfunction (GFR 25-45ml/min/1.73m2) may be more susceptible to develop post-LTA severe renal dysfunction (GFR<15ml/min/1.73m2) than ALD patients, as well as other overall outcomes. Using the UNOS/OPTN database, we selected patients undergoing liver transplant for NAFLD or ALD (2006-2016), 15,103 of whom received LTA. NAFLD patients with moderate renal dysfunction were more likely to develop subsequent GFR<15ml/min/1.73m2 than ALD patients (11.1% vs. 7.38%, p < 0.001). Patients on short-term dialysis pre-LTA (≤12weeks) were more likely to develop severe renal dysfunction (31.7% vs. 18.1%), especially in NAFLD patients, and were more likely to receive a further kidney transplant (15.3% vs. 3.7%) and had lower survival (48.6% vs. 50.4%) after LTA (p < 0.001 for all). NAFLD was an independent risk factor for post-LTA severe renal dysfunction (HR = 1.2, p = 0.02). NAFLD patients with moderate renal dysfunction and those receiving short-term dialysis prior to LTA are at a higher risk of developing subsequent severe renal dysfunction. Underlying etiology of liver disease may play a role in predicting development and progression of renal failure in patients receiving LTA.

Incident portal vein thrombosis in liver transplant recipients in New Zealand: Predictors of risk and validation of portal vein thrombosis risk index calculator.

The risk of spontaneous portal vein thrombosis (PVT) is increased in patients on the waiting list for liver transplantation and increases perioperative risks. A predictive PVT risk-index (PVT-RI) calculator has been proposed to determine the risk of incident PVT. We performed a retrospective analysis on adult liver transplant recipients at the NZ Liver Transplant Unit between January 1998 and February 2020. Variables reviewed included age at listing and transplantation, wait time from listing to transplant, indication for listing, gender, ethnicity, etiology of liver disease, listing MELD score, hepatocellular carcinoma (HCC), moderate-to-severe ascites, hepatic encephalopathy (>grade 2), transjugular intrahepatic portosystemic shunt (TIPSS), spontaneous bacterial peritonitis (SBP), and diabetes. Incident PVT was determined by imaging of patients while on the waiting list and assessment at transplantation. A total of 553 out of 706 patients met the inclusion criteria. Of those 553, 18 (3.3%) patients had incident PVT. The PVT-RI calculator was not validated in our cohort with only one of those 18 (6%) patients having a score of >4.6 (high risk cut-off score). Longer waiting time for transplant and listing for liver failure rather than HCC were independent predictors of the risk of incident PVT. There was no statistically significant difference in the incidence of PVT in viral vs. non-viral and cholestatic vs. non-cholestatic etiology of chronic liver disease. Patients with longer waiting times on the transplant waiting list should be monitored regularly for PVT.

Liver Transplantation from a Human Leukocyte Antigen-Matched Sibling Donor: Effectiveness of Direct-Acting Antiviral Therapy against Hepatitis C Virus Infection

Through living-donor liver transplantation (LDLT) from a human leukocyte antigen (HLA)-matched sibling donor, it may be possible to stop the use of immunosuppressants. It is possible that acute antibody-mediated rejection and chronic active antibody-mediated rejection through the positivity of donor-specific anti-HLA antibodies and/or T cell-mediated rejection may affect the prognosis of liver transplantation. The etiologies of liver diseases of the recipient may also affect the post-transplantation course. Herein, we report on the successful re-treatment with direct-acting antiviral (DAA) therapy against hepatitis C virus (HCV) infection in a patient who underwent a LDLT from HLA-matched sibling donor. After liver transplantation for HCV-related liver diseases, it is easy for HCV to re-infect the graft liver under a lack of immunosuppressants. DAA therapy against HCV re-infection immediately after transplantation should be commenced, and it is important to eradicate HCV for better prognosis of the recipients in LDLT for HCV-related liver diseases.

Serum determination of MMP-2 and MMP-9 in chronic liver disease according to alcohol consumption, non-alcoholic fatty liver disease and hepatitis C

This study aimed to evaluate serum concentration of MMP-2 and -9 in different etiologies of liver disease also according to fibrosis stages. Cross-sectional multicentric study, including subjects with no alcoholic fatty liver disease (NAFLD), chronic Hepatitis C (CHC), alcohol cirrhosis (CiOH) and alcoholism (OH), groups with alcohol drinking habits were classified according to OMS criteria, with clinical and biochemical evidence of alcoholic liver disease (ALD). Transitional elastography (Fibroscan) was performed in NAFLD and CHC, considering mild fibrosis (FL: F0, F1, F2) and severe fibrosis (FA: F3, F4). As controls, subjects without alcohol consumption (CT) were recruited. Multiplex®-MERCK© was used for MMP-2 and -9 quantification. Statistical analysis was performed by Mann Whitney-U test, p<0.05, with SPSS V.22. The groups included were: 27 NAFLD (mild fibrosis: F0, F1, F2), 36 NAFLD (severe fibrosis: F3, F4), 48 CHC (mild fibrosis: F0, F1, F2), 54 CHC (severe fibrosis: F3, F4), 45 (CiOH), 99 (OH), and 138 CT. Both gelatinases, MMP-2 y MMP-9, were found elevated in CHC (mild and severe fibrosis) vs. CT; and decreased in OH, CiOH, HGNA (mild and severe fibrosis) vs. CT, plus there are significant differences between all etiologies, p<0.001. In patients with CHC, MMP-2 y -9 serum concentration increases, particularly in severe fibrosis stages, although it has no effect on ECM (extracellular matrix) degradation, as they are inactive. Nevertheless, there is a significant decrease in these gelatinases in ALD and NAFLD. MMP-2 y MMP-9 module depends on the etiological agent involved, which can be useful for the differential diagnosis of liver diseases. This work was partially financed by CONACyT SALUD-2016-272579 (GRG) and PAPIIT- UNAM TA200515 (GRG). The authors declare no potential conflicts of interest.

Pathophysiological changes of the liver-muscle axis in end-stage liver disease: what is the right target?

Liver diseases and in particular end stage liver diseases are frequently complicated by muscle modifications that are linked to worse clinical outcome. In addition, recent studies have demonstrated the negative impact of these muscle changes on liver function leading to the hypothesis of a bidirectional relationship referred in the literature as "muscle-liver axis". In a context of evolution towards a more holistic and less organocentric vision of medicine, studying frailty, myosteatosis and sarcopenia and their underlying pathophysiological mechanisms has led to many publications in the last five years. These studies are describing several pathophysiological mechanisms, highlighting the extremely complex character of this relationship. This review aims to summarize these mechanisms as well as potential therapeutic targets, independently of liver disease etiology.

Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm.

Fatty liver disease is an emerging contributor to disease burden worldwide. The past decades of work established the heterogeneous nature of non-alcoholic fatty liver disease (NAFLD) etiology and systemic contributions to the pathogenesis of the disease. This called for the proposal of a redefinition in 2020 to that of metabolic dysfunction-associated fatty liver disease (MAFLD) to better reflect the current understanding of the disease. To date, several clinical cohort studies comparing NAFLD and MAFLD hint at the relevancy of the new nomenclature in enriching for patients with more severe hepatic injury and extrahepatic comorbidities. However, the underlying systemic pathogenesis is still not fully understood. Preclinical animal models have been imperative in elucidating key biological mechanisms in various contexts, including intrahepatic disease progression, interorgan crosstalk and systemic dysregulation. Furthermore, they are integral in developing novel therapeutics against MAFLD. However, substantial contextual variabilities exist across different models due to the lack of standardization in several aspects. As such, it is crucial to understand the strengths and weaknesses of existing models to better align them to the human condition. In this review, we consolidate the implications arising from the change in nomenclature and summarize MAFLD pathogenesis. Subsequently, we provide an updated evaluation of existing MAFLD preclinical models in alignment with the new definitions and perspectives to improve their translational relevance.

Healthcare Costs for Medicare Patients With Hepatocellular Carcinoma in the United States

Hepatocellular carcinoma (HCC) has an increasing mortality in the United States and is a leading cause of morbidity and mortality in patients with cirrhosis. We aimed to estimate the financial burden related to HCC in a large nationally representative United States cohort. We used the Surveillance, Epidemiology, and End Results program (SEER)-Medicare database to identify 4525 adult patients who were diagnosed with HCC between 2011 and 2015. We generated a 1:1 propensity score-matched cohort of patients with cirrhosis but no HCC as a comparator group to define incremental HCC-specific costs beyond costs related to underlying cirrhosis. Our main outcomes were patient liabilities and Medicare payments in the first year after HCC diagnosis. Compared with patients with cirrhosis, those with HCC had higher incremental patient liabilities (median+$7166; interquartile range, $2401-$16,099) and Medicare payments (+$50,110; interquartile range, $142,42-$136,239; P < .001 for both) in the first year after diagnosis. Patients with HCC had significantly higher inpatient, outpatient, and physician service costs compared with the matched cohort with cirrhosis (P < .001 for all). Patients with early-stage HCC had lower incremental patient liabilities (median, $4195 vs $8238; P < .001) and Medicare payments (median, $28,207 vs $59,509; P < .001) than those with larger tumor burden. In multivariable median regression analysis, incremental patient liabilities and Medicare payments were significantly associated with the National Cancer Institute comorbidity index, nonalcoholic fatty liver disease etiology, presence of ascites, and presence of hepatic encephalopathy. Patients with HCC suffer from cancer-related financial burden, highlighting a need for policy interventions and financial support systems.

Indian patients with human immunodeficiency virus infection have high prevalence but mild severity of non-alcoholic fatty liver disease

Background and aimsAntiretroviral therapy (ART) has substantially decreased AIDS-related mortality. Non-AIDS related diseases like chronic liver disease are becoming more frequent in people living with HIV-AIDS (PLHA). Non-alcoholic fatty live disease (NAFLD) is a common etiology of liver disease in the general population. Our aim was to analyse the prevalence and risk factors of NAFLD in Indian PLHA. MethodsOne hundred consecutive adults (age:36.89 ± 10.4 years, males:65%) with HIV infection were prospectively enrolled. Patients with significant alcohol intake, Hepatitis B or Cco-infection, other liver disease, malignancy or HIV stage IV were excluded. Hepatic steatosis was assessed using hepatobiliary ultrasoundand controlled attenuation parameter (CAP). Fibrosis was assessed non-invasively using FIB-4, NAFLD fibrosis score (NFS) and liver stiffness measurement (LSM). Metabolic and HIV-related risk factors were compared between PLHA with and without NAFLD. ResultsPrevalence of NAFLD using CAP was 60%. Among patients with NAFLD, 27 (45%) were lean. Majority had mild-moderate steatosis. Advanced fibrosis was present in 1 (1.67%) and 4 (6.67%) patients using NFS and LSM and none using FIB-4. PLHA with NAFLD were more likely to be overweight or obese (OR = 4.21,p = 0.002) with a higher proportion of abdominal obesity (OR:25.26,p = 0.001). Other metabolic comorbidities, duration of HIV infection, duration and type of ART, CD4-count or HIV-stagewere not significantly different among PLHA with or without NAFLD. ConclusionPrevalence of NAFLD among Indian PLHA is high although most have mild disease. Almost half of these patients are lean. HIV-related factors do not impact the risk of NAFLD.

Neutrophil extracellular traps and complications of liver transplantation.

Many end-stage liver disease etiologies are attributed to robust inflammatory cell recruitment. Neutrophils play an important role in inflammatory infiltration and neutrophil phagocytosis, oxidative burst, and degranulation. It has also been suggested that neutrophils may release neutrophil extracellular traps (NETs) to kill pathogens. It has been proven that neutrophil infiltration within the liver contributes to an inflammatory microenvironment and immune cell activation. Growing evidence implies that NETs are involved in the progression of numerous complications of liver transplantation, including ischemia-reperfusion injury, acute rejection, thrombosis, and hepatocellular carcinoma recurrence. NETs are discussed in this comprehensive review, focusing on their effects on liver transplantation complications. Furthermore, we discuss NETs as potential targets for liver transplantation therapy.

Ultrasound-Based Diagnostic Methods: Possible Use in Fatty Liver Disease Area.

Liver steatosis is a chronic liver disease that is becoming one of the most important global health problems, due to its direct connection with metabolic syndrome, its significant impact on patients' socioeconomic status and frailty, and the occurrence of advanced chronic liver disease. In recent years, there has been rapid technological progress in the ultrasound-based diagnostics field that can help us to quantitatively assess liver steatosis, including continuous attenuation parameters in A and B ultrasound modes, backscatter coefficients (e.g., speed of sound) and ultrasound envelope statistic parametric imaging. The methods used in this field are widely available, have favorable time and financial profiles, and are well accepted by patients. Less is known about their reliability in defining the presence and degree of liver steatosis. Numerous study reports have shown the methods' favorable negative and positive predictive values in comparison with reference investigations (liver biopsy and MRI). Important research has also evaluated the role of these methods in diagnosing and monitoring non-alcoholic fatty liver disease (NAFLD). Since NAFLD is becoming the dominant global cause of liver cirrhosis, and due to the close but complex interplay of liver steatosis with the coexistence of liver fibrosis, knowledge regarding NAFLD's influence on the progression of liver fibrosis is of crucial importance. Study findings, therefore, indicate the possibility of using these same diagnostic methods to evaluate the impact of NAFLD on the patient's liver fibrosis progression risk, metabolic risk factors, cardiovascular complications, and the occurrence of hepatocellular carcinoma. The mentioned areas are particularly important in light of the fact that most of the known chronic liver disease etiologies are increasingly intertwined with the simultaneous presence of NAFLD.

Liver abnormalities in celiac disease and response to gluten free diet: A systematic review and meta-analysis.

Liver involvement in celiac disease (CeD) is known but its various etiologies and the effect of gluten free diet (GFD) on it is understudied. We searched PubMed, Medline and Embase databases from date of inception to March 7, 2022, to look for studies reporting on CeD and liver abnormalities. Pooled proportion of CeD patients with deranged transaminases, etiologies of various other liver diseases with CeD and the response to GFD were estimated. Subgroup analyses based on the age group, geographic distribution and duration of GFD were also carried out. Total 42 studies (8976 patients) reported hyper-transaminasemia in patients with celiac disease. The pooled proportion of patients with elevated transaminases was 21.42% (95% CI: 17.02-26.59, I2 =94%) overall, with similar prevalence among adults (21.20%) and children (21.51%). The commonest etiology was celiac hepatitis at 49.23% (95% CI: 30.09-68.59, I2 =87%). Compliance with GFD was noted in 90.27%. The proportion of CeD patients with liver abnormalities who showed response to GFD was 86.39% (95% CI: 80.04-90.95, I2 =74%) overall. Liver involvement was noted in 21.42% of CeD patients. Celiac hepatitis was reported in nearly half of them. Good compliance and response were noted with GFD.

Identification of polyunsaturated fatty acids related key modules and genes in metabolic dysfunction-associated fatty liver disease using WGCNA analysis.

Polyunsaturated fatty acids (PUFAs) play important roles in the aetiology and pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD). However, the underlying molecular mechanisms are not understood. We analysed a public GEO dataset, GSE89632, to identify differentially expressed genes (DEGs) in MAFLD. Weighted gene coexpression network analysis (WGCNA) was used to reveal the core gene regulation network and to explore the PUFA-related hub genes in MAFLD. We experimentally verified these genes by quantitative reverse transcription PCR in high-fat diet (HFD)-fed mice. A total of 286 common DEGs (89 upregulated; 197 downregulated), mostly related to inflammatory and immune responses, were identified. Six modules were constructed using WGCNA, and 2 modules showed significant correlations with PUFAs. After combining these 2 modules with DEGs, the top 10 hub genes were identified. We further established a MAFLD mouse model with liver steatosis, as proved by HE and Oil Red O staining. Of the hub genes, ADAM metallopeptidase with thrombospondin type 1 motif 1 (adamts1) (p = 0.005) and transforming growth factor β3 (tgfβ3) (p < 0.001) showed significantly lower mRNA expression in MAFLD in vivo. adamts1 and tgfβ3 bridged PUFAs and MAFLD, which might be potential causative genes and therapeutic targets of MAFLD.

Biological Mechanisms and Related Natural Inhibitors of CD36 in Nonalcoholic Fatty Liver.

Non-alcoholic fatty liver disease (NAFLD), a spectrum of liver disorders from non-alcoholic fatty liver (NAFL) to the more severe non-alcoholic steatohepatitis (NASH), is the leading etiology of chronic liver disease and its global prevalence is increasing. Hepatic steatosis, a condition marked by an abnormal buildup of triglycerides in the liver, is the precursor to NAFLD. Differentiated cluster 36 (CD36), a scavenger receptor class B protein, is a membrane receptor that recognizes multiple lipid and non-lipid ligands. It is generally agreed that CD36 contributes significantly to hepatic steatosis by taking part in fatty acid uptake as well as triglyceride storage and secretion. While there has not been any conclusive research on how CD36 inhibitors prevent NAFLD from progressing and no clinically approved CD36 inhibitors are currently available for use in NAFLD, CD36 remains a target worthy of further investigation in NAFLD. In recent years, the potential role of natural products acting through CD36 in treating non-alcoholic fatty liver disease has attracted much attention. This paper offers an overview of the pathogenesis of CD36 in NAFLD and summarizes some of the natural compounds or extracts that are currently being investigated for modulating NAFLD via CD36 or the CD36 pathway, providing an alternative approach to the development of CD36-related drugs in NAFLD.

RF06 | PSAT153 Osteoporosis Screening of Liver Transplant Patients in a Tertiary Urban Medical Center

Abstract Background Liver transplantation is an established treatment for patients with end-stage liver disease. In 2021 more than 8,400 liver transplants were performed in the United States. Although successful transplantation can reverse many complications of end organ failure, disturbance of bone and mineral metabolism may persist, which can contribute substantially to morbidity and mortality. It is important to assess whether liver transplant patients are getting bone density screening and treatment. Objective Our goal is to assess current practice in bone density screening in patients who have undergone liver transplant at our medical center, to identify if these patients are being screened for metabolic bone disease before and after transplant, and to improve management of such patients by initiating a provider work flow that is based on available data and evidence. Study Design: The first phase was a survey of the liver transplant team to assess the current protocol for screening. The second phase involved retrospective chart review of patients at our institution who had a liver transplant between October 2008 and April 2021. The findings will be used to create an institutional protocol for osteoporosis screening and management. Results Survey results: 62.5% of liver transplant providers knew that guidelines or a protocol are being used to screen liver transplant recipients for osteoporosis. 75% said that dual-energy x-ray absorptiometry (DXA) scans are always obtained before liver transplantation, while 25% said they are sometimes obtained. There were mixed results regarding monitoring post transplant. All respondents agreed that creating a protocol for osteoporosis screening would improve outcomes of bone health in transplant patients. Chart review results: We reviewed 243 liver transplant recipients between October 2008 and April 2021. After excluding duplicate transplants and those less than 18 years old, 234 patients were included in analysis. 59% of patients were men with a median age of 63.5. The most common etiologies of pre-transplant liver disease were Hepatocellular Carcinoma (29%), Hepatitis C (17%), alcoholic cirrhosis (16%) and NASH (5%). 72% of transplant patients had a DXA before transplant and 28% did not. Of those with a pre-transplant DXA, 28% had normal bone density, 50% had osteopenia, and 20% had osteoporosis. The remainder did not have data available. Among those with a diagnosis of osteoporosis pre-transplant, 41% received treatment while 56% did not receive any bone-specific therapy. Discussion The majority of providers in our liver transplant team are aware of the need for bone health screening and treatment in liver transplant candidates. Most patients received a DXA prior to transplant however less than half of the patients with osteoporosis were started on treatment. Our study shows the need for developing an institutional work flow to optimize bone health in patients undergoing liver transplant. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:06 p.m. - 1:11 p.m.