Renal resistive index measurements by ultrasound in patients with liver cirrhosis: Magnitude and associations with renal dysfunction.

BACKGROUND: The hemodynamic alterations seen in liver cirrhosis lead to renal vasoconstriction, ultimately causing acute kidney injury (AKI). The renal resistive index (RRI) is the most common Doppler ultrasound variable for measuring intrarenal vascular resistance. AIM: To evaluate the association of the RRI with AKI in patients with liver cirrhosis and to identify risk factors for high RRI. METHODS: This was a prospective observational study, where RRI was measured using Doppler ultrasound in 200 consecutive hospitalized patients with cirrhosis. The association of RRI with AKI was studied. The receiver operating characteristic (ROC) curve analysis was utilized to determine discriminatory cut-offs of RRI for various AKI phenotypes. Multivariate analysis was conducted to determine the predictors of high RRI. RESULTS: The mean patient age was 49.08 ± 11.68 years, with the majority (79.5%) being male; the predominant etiology of cirrhosis was alcohol (39%). The mean RRI for the study cohort was 0.68 ± 0.09, showing a progressive increase with higher Child-Pugh class of cirrhosis. Overall, AKI was present in 129 (64.5%) patients. The mean RRI was significantly higher in patients with AKI compared to those without it (0.72 ± 0.06 vs 0.60 ± 0.08; P < 0.001). A total of 82 patients (41%) had hepatorenal syndrome (HRS)-AKI, 29 (22.4%) had prerenal AKI (PRA), and 18 (13.9%) had acute tubular necrosis (ATN)-AKI. The mean RRI was significantly higher in the ATN-AKI (0.80 ± 0.02) and HRS-AKI (0.73 ± 0.03) groups than in the PRA (0.63 ± 0.07) and non-AKI (0.60 ± 0.07) groups. RRI demonstrated excellent discriminatory ability in distinguishing ATN-AKI from non-ATN-AKI (area under ROC curve: 93.9%). AKI emerged as an independent predictor of high RRI (adjusted odds ratio [OR]: 11.52), and high RRI independently predicted mortality among AKI patients (adjusted OR: 3.18). CONCLUSION: In cirrhosis patients, RRI exhibited a significant association with AKI, effectively differentiated between AKI phenotypes, and predicted AKI mortality.

Novel compound heterozygous mutations in the hemojuvelin gene in a juvenile hemochromatosis patient: A case report.

BACKGROUND: Juvenile hemochromatosis (JH) is an early-onset, rare autosomal recessive disorder of iron overload observed worldwide that leads to damage in multiple organs. Pathogenic mutations in the hemojuvelin (HJV) gene are the major cause of JH. CASE SUMMARY: A 34-year-old male Chinese patient presented with liver fibrosis, diabetes, hypogonadotropic hypogonadism, hypophysis hypothyroidism, and skin hyperpigmentation. Biochemical test revealed a markedly elevated serum ferritin level of 4329 µg/L and a transferrin saturation rate of 95.4%. Targeted exome sequencing and Sanger sequencing revealed that the proband had a novel mutation c.863G>A (p.R288Q) in the HJV gene which was transmitted from his father, and two known mutations, c.18G>C (p.Q6H) and c.962_963delGCinsAA (p.C321*) in cis, which were inherited from his mother. The p.R288W mutation was previously reported to be pathogenic for hemochromatosis, which strongly supported the pathogenicity of p.R288Q reported for the first time in this case. After 72 wk of intensive phlebotomy therapy, the patient achieved a reduction in serum ferritin to 160.5 µg/L. The patient's clinical symptoms demonstrated a notable improvement. CONCLUSION: This study highlights the importance of screening for hemochromatosis in patients with diabetes and hypogonadotropic hypogonadism. It also suggests that long-term active phlebotomy could efficiently improve the prognosis in severe JH.

Acute-on-chronic liver failure; prevalence, causes, predisposing factors, and outcome.

Aim: Until now, there has been disagreement regarding the prevalence, causes, predisposing factors, and outcome of ACLF (Acute-on-chronic liver failure). As a result, we have undertaken this research study. Background: ACLF is a complex syndrome with a poor prognosis. Methods: In this cross-sectional study, we evaluated the prevalence, causes, predisposing factors, and outcomes of adult cirrhotic patients with ACLF and acute decompensation (AD). ACLF was defined based on the criteria established by APASL (Asian Pacific Association for the Study of the Liver). The severity of organ failure was assessed using both EASL-CLIF (European Association for the Study of the Liver- Chronic Liver Failure) and NACSELD (North American Consortium for the Study of End-Stage Liver Disease) scores. To investigate the impact of different independent variables on mortality, survival analysis methods were used. Results: A total of 156 patients' data were analyzed in this study. The mean age of patients with ACLF (56.62±16.19 years) was significantly lower compared to the AD group (62.30±14.28 years). Nonalcoholic steatohepatitis and infection were the most common causes and predisposing factors in both AD and ACLF groups, respectively, but the difference between the two groups was not statistically significant. The most common organ failures observed were hepatic encephalopathy and respiratory failure. The probability of death at any given time for was significantly higher in ACLF patients than in the AD group (log rank test; P<0.001). The results of Cox regression analysis revealed that low blood pressure (HR 0.97; 95% CI 0.96-0.99; P<0.001) and decreased blood pH (HR 0.53; 95% CI 0.28-0.99; P=0.04) were significant risk factors associated with increased mortality. Conclusion: ACLF patients had a lower average age and higher mortality rates compared to AD. Nonalcoholic steatohepatitis was found to be the most common underlying disease in ACLF patients, while infections were identified as the predominant predisposing factor. All cases of mortality in the ACLF group were categorized as grade 3 and 4 based on the EASL-CLIF severity score. Hemodynamic instability and metabolic acidosis emerged as the most significant risk factors associated with increased mortality.

Chinese guidelines on the management of ascites in cirrhosis : Chinese Society of Hepatology, Chinese Medical Association.

In 2023, Chinese Society of Hepatology of Chinese Medical Association convened a panel of experts to update the Chinese guidelines on the management of ascites and associated complications in cirrhosis which was launched in 2017 and renamed this guidelines as "Guidelines on the Management of Ascites in Cirrhosis." This comprehensive resource offers essential recommendations for the diagnosis and treatment of cirrhotic ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome.

Management of liver disease and portal hypertension in cystic fibrosis: a review.

INTRODUCTION: Cystic fibrosis (CF)-associated liver disease can significantly affect the quality of life and survival of people with CF. The hepatobiliary manifestations in CF are various, with focal/multilobular biliary cirrhosis more common in children and porto-sinusoidal vascular disease (PSVD) in young adults. Portal hypertensive complications, particularly bleeding from esophagogastric varices and hypersplenism are common, while liver failure is rarer and mainly linked to biliary disease. AREAS COVERED: This review explores current therapeutic options for CF-associated liver disease, presenting ongoing studies and new insights into parthenogenesis for potential future therapies. EXPERT OPINION: Monitoring for signs of portal hypertension is essential. Limited evidence supports ursodeoxycholic acid (UDCA) efficacy in halting CF liver disease progression. The effect of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on liver outcomes lacks definitive data, since patients with CF-related liver disease were excluded from trials due to potential hepatotoxicity. A proposed approach involves using UDCA and modulators in early stages, along with anti-inflammatory agents, with further therapeutic strategies awaiting randomized trials. Prevention of portal hypertensive bleeding includes endoscopic sclerotherapy or ligation of esophageal varices. Nonselective beta-blockers may also prevent bleeding and could be cautiously implemented. Other non-etiological treatments require investigation.

Differing genetic variants associated with liver fat and their contrasting relationships with cardiovascular diseases and cancer.

BACKGROUND: The underlying mechanisms for the link between steatotic liver disease and cardiovascular and cancer outcomes are poorly understood. We aimed to use MRI-derived measures of liver fat and genetics to investigate causal mechanisms that link higher liver fat to various health outcomes. METHODS: We conducted a genome-wide association study on 37,358 UK Biobank participants to identify genetic variants associated with liver fat measured from MRI scans. We used Mendelian randomization approach to investigate the causal effect of liver fat on health outcomes independent of BMI, alcohol consumption and lipids using data from published GWAS and FinnGen. RESULTS: We identified 13 genetic variants associated with liver fat that showed differing risks to health outcomes. Genetic variants associated with impaired hepatic triglyceride export showed liver fat-increasing alleles to be correlated with a reduced risk of coronary artery disease and myocardial infarction but an elevated risk of type 2 diabetes; and variants associated with enhanced de novo lipogenesis showed liver fat-increasing alleles to be linked to a higher risk of myocardial infarction and coronary artery disease. Genetically higher liver fat content increased the risk of non-alcohol liver cirrhosis, hepatocellular and Intrahepatic bile ducts and gallbladder cancers, exhibiting a dose-dependent relationship, irrespective of the mechanism. CONCLUSION: This study provides fresh insight into the heterogeneous effect of liver fat on health outcomes. It challenges the notion that liver fat per se is an independent risk factor for cardiovascular disease, underscoring the dependency of this association on the specific mechanisms that drive fat accumulation in the liver. However, excess liver fat, regardless of how achieved, appears to be causally linked to liver cirrhosis and cancers in a dose dependent manner. IMPACT AND IMPLICATION: This research advances our understanding of the heterogeneity in mechanisms influencing liver fat accumulation, providing new insights into how liver fat accumulation may impact various health outcomes. The findings challenge the notion that liver fat is an independent risk factor for cardiovascular disease and highlight the mechanistic effect of some genetic variants on fat accumulation and the development of cardiovascular diseases. This study is of particular importance for healthcare professionals including physicians and researchers as well as patients as it allows for more targeted and personalised treatment by understanding the relationship between liver fat and various health outcomes. The findings emphasise the need for a personalised management approach and a reshaping of risk assessment criteria. It also provides room for prioritising a clinical intervention aimed at reducing liver fat content (likely by intentional weight loss, however, achieved) that could help protect against liver related fibrosis and cancer.

Complete Match of Streptococcus salivarius from Oral Saliva and Stool in a Patient with Hepatic Encephalopathy.

We herein report a 67-year-old Japanese woman with liver cirrhosis caused by primary biliary cholangitis. The patient was admitted to the hospital with loss of consciousness. Hepatic encephalopathy (HE) was diagnosed after diagnostic imaging and symptom assessments. Molecular biology tests were performed on oral saliva and stool samples. The test results indicated sequence similarity between urease-positive S. salivarius in both oral saliva and stool, as revealed by the signals in the overlapping peaks. This bacterium can potentially increase ammonia production in the gut, leading to HE in patients with liver cirrhosis.

Prevalence and Precipitants of Hepatic Encephalopathy in Hospitalized Children With Chronic Liver Disease.

Objective: Hepatic encephalopathy (HE) is a marker of poor prognosis in adults with chronic liver disease (CLD). We prospectively studied the prevalence and precipitants of HE in children with CLD as there is a paucity of literature on the same. Methods: Children (1-18 years) admitted with CLD were examined daily for the presence and grading of HE (West Haven/Whittington grading). Precipitants were classified as infection, dyselectrolytemia, gastrointestinal bleeding, constipation and dehydration. Changes in grades of HE and outcome were noted. Results: One hundred and sixty children (age 120 [84-168] months) were enrolled. HE was present in 50 (31.2%) patients with a total of 61 episodes. Maximum grade of HE was grade I (n = 16), II (n = 23), III (n = 11) and IV (n = 11). Forty-two cases had single and 8 had recurrent (2-5) episodes. Median duration of HE episodes was 96 (72-192) hours. Precipitants were identified in 55/61 (90.2%) episodes with infection (45/61, 73.7%) and dyselectrolytemia (33/61, 54%) being the most common. Lower albumin and sodium, higher INR and presence of infection were significantly associated with presence of HE. Overall, HE resolved in 33 (54%) episodes, while it progressed and persisted in 28 (45.9%) episodes. Patients with HE had a poorer outcome (25/50 vs 13/110; P < 0.01) with both higher in-hospital (11/50 vs 9/110; P = 0.02) and 1-month post discharge (14/39 vs 4/101; P < 0.01) mortality than those without HE. Conclusion: One-third of admitted CLD children have HE, with identifiable precipitants in 90% of cases. Children with HE have poorer liver functions, higher rate of infections and worse outcome than those without HE.

Impact of coagulopathy assessment with thromboelastography and thromboelastometry on transfusion requirements in critically ill cirrhosis with nonvariceal bleeding: A prospective observational study.

Background: Viscoelastic tests are now routinely used for coagulopathy correction in patients with cirrhosis. Thromboelastography (TEG®) and rotational thromboelastometry (RoTEM®) are the most widely studied tests in this population. However, they have not been compared with each other in critically ill patients with liver disease presenting with nonvariceal bleed. Hence, we aimed to compare these tests for coagulopathy correction in patients with liver disease presenting with nonvariceal bleeding. Methods: Sixty adult patients with liver cirrhosis presented to the liver intensive care unit, presenting with a nonvariceal upper gastrointestinal (GI) bleed (diagnosed by doing upper GI endoscopy which revealed bleeding from a nonvariceal source) oral or nasal bleed were enrolled. The patients were allocated to the TEG® group (Group T) or RoTEM® group (Group R) depending on the immediate availability of the viscoelastic test. Coagulopathy correction was done in each group as per established protocols and the results were compared. Results: There was a significant difference in the fresh frozen plasma (FFP) transfusion between the groups. The TEG® group received more FFP when compared to the RoTEM® group (P = 0.001). Conclusion: RoTEM®-based coagulopathy correction leads to lesser use of blood products with similar control of bleeding when compared to TEG, in critically ill patients with cirrhosis.

Quantitative PCR-based high-sensitivity detection of HBV-DNA levels reflects liver function deterioration in patients with hepatitis B virus-related cirrhosis.

OBJECTIVES: To investigate the clinical implication of quantitative polymerase chain reaction (PCR)-based high-sensitivity detection of hepatitis B virus (HBV)-DNA levels in patients with HBV-related liver cirrhosis (LC). METHODS: From January 2020 to December 2022, 100 fasting serum samples were collected and retrospectively analyzed from patients with treated HBV-related LC attending the Suzhou Hospital of Integrated Traditional Chinese and Western Medicine and Suzhou Guangci Cancer Hospital. Patients were divided into a negative group (HBV-DNA < 20 IU/mL) and a positive group (HBV-DNA ≥ 20 IU/mL) according to their high-sensitivity HBV-DNA test results. The clinical characteristics and serological indicators of the two groups were compared, mainly including gender, age, liver function [total protein (TP), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL)], lipids [total cholesterol (TC) and triglycerides (TG)], platelets (PLT), five serum liver fibrosis markers [cholyglycine (CG), hyaluronic acid (HA), laminin (LN), precollagen type III (PCIII), and type IV collagen (IV-C)], serum gastrointestinal tumor markers [α-fetoprotein (AFP) and carcinoembryonic antigen (CEA)], and hepatitis B surface antigen (HBsAg). The differences between the two groups in terms of liver function Child-Pugh grades and the incidence of hepatocellular carcinoma (HCC) were also compared. RESULTS: There were 39 patients in the positive group, including 29 males and 10 females, and 61 patients in the negative group, including 38 males and 23 females, with no statistically significant differences in gender and age distribution between the two groups (P > 0.05). The levels of serological indicators (TP, ALB, AST, GGT, ALP, TBIL, DBIL, IBIL, TC, TG, PLT, CG, HA, LN, PCIII, IV-C, AFP, CEA, and HBsAg) in both groups showed no significant differences (P > 0.05), but the ALT level in the positive group was higher than that in the negative group (P < 0.0001). The positive group had worse Child-Pugh grades and higher HCC incidence compared to the negative group (P < 0.0001, P = 0.028). CONCLUSIONS: Patients with HBV-related LC and HBV-DNA ≥ 20 IU/mL have higher serum ALT levels, worse liver function Child-Pugh grades, and higher HCC incidence than those with HBV-DNA < 20 IU/mL. High-sensitivity HBV-DNA quantification can reflect the deterioration of liver function in patients with HBV-related LC to some extent.

Quantitative assessment of self-management in patients with non-alcoholic fatty liver disease: An unmet clinical need.

In this editorial we comment on the article titled "Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease" by Zeng et al published in a recent issue of the World Journal of Gastroenterology. Non-alcoholic fatty liver disease (NAFLD) represents one of the current challenges in hepatology and public health, due to its continuous growing prevalence and the rising incidence of NAFLD-related fibrosis, non-alcoholic steatohepatitis and cirrhosis. The only effective therapeutic strategy for this disease is represented by encouraging patients to improve their lifestyle through the modification of dietary intake and increased physical exercise, but the effective application of such modifications is often limited by various factors such as lack of information, psychological barriers or poor social support. While poor adherence to a healthy lifestyle can be decisive in determining the clinical outcome, in daily practice there is a lack of quantitative instruments aimed at identifying patients with the lowest adherence to lifestyle changes and higher risk of disease progression in the course of follow-up. In this article, Zeng et al propose a quantitative scale to assess the grade of adherence of patients with NAFLD to healthy lifestyle intervention, called the Exercise and Diet Adherence Scale (EDAS). This scale, consisting of 33 items divided into 6 dimensions which relates to six subjective aspects in the self-management of NAFLD, has shown a good correlation with the identification of the sub-cohort of patients with the highest reduction in caloric intake, increase in physical exercise, probability of a reduction in liver stiffness measurement and alanine aminotransferase levels. The correlation among clinical outcomes and specific dimensions of this scale also highlights the pivotal role of a good and confidential doctor-patient relationship and of an effective communication. There is an urgent need for practical and effective instruments to assess the grade of self-management of NAFLD patients, together with the development of multidisciplinary teams with the aim of applying structured behavioral interventions.

Comparison Between Creatinine-Modified Pugh Score and Child-Pugh Score for Prognostication in Decompensated Cirrhosis.

Introduction, aim, and objective: Despite recent evidence suggesting the blood creatinine level is a significant predictor of survival in liver cirrhosis patients, the conventional Child-Pugh (CP) score has held a longstanding position as a valuable prognostic indicator in cirrhotic individuals. This study aimed to compare the predictive capabilities of the modified CP score and the traditional CP score in decompensated cirrhosis patients to evaluate their prognostic power. The objective of this study was to assess the prognostic value of the modified and traditional CP scores in individuals with decompensated cirrhosis by assessing their predictive accuracy. METHODS: A total of 100 patients diagnosed with decompensated cirrhosis participated in this prospective study. Each patient's Child-Pugh score and class were determined using admission data, with scores ranging from 5 to 15. Serum creatinine was incorporated as the sixth variable to compute the modified CP score, which ranges from 5 to 19. RESULTS: The percentages of individuals aged 16-30, 31-40, 41-50, 51-60, and above 60 years were as follows: 16.0%, 29.0%, 26.0%, and 11.0%, respectively. The patients had a mean age of 44.71 years and a standard deviation of 13.40 years. Out of the 100 patients studied, 26% were female and 74% were male. Fifty-two percent of patients had mild hepatic encephalopathy, while 24% had moderate encephalopathy and 24% had severe encephalopathy. In cases of moderate and severe hepatic encephalopathy, the creatinine-modified Pugh score showed a considerably large area under the curve (AUC=0.852) on the receiver operating characteristics (ROC) curve. CONCLUSION:  When blood creatinine is taken into account, it can enhance the Child-Pugh classification's prognostic usefulness. This is especially true for patients with moderate to severe hepatic encephalopathy, where serum creatinine is a key factor in accurately predicting both survival and complications associated with cirrhosis.

Hydrogen Sulfide Promotes Platelet Autophagy via PDGFR-α/PI3K/Akt Signaling in Cirrhotic Thrombocytopenia.

Background and Aims: The role of platelet autophagy in cirrhotic thrombocytopenia (CTP) remains unclear. This study aimed to investigate the impact of platelet autophagy in CTP and elucidate the regulatory mechanism of hydrogen sulfide (H2S) on platelet autophagy. Methods: Platelets from 56 cirrhotic patients and 56 healthy individuals were isolated for in vitro analyses. Autophagy markers (ATG7, BECN1, LC3, and SQSTM1) were quantified using enzyme-linked immunosorbent assay, while autophagosomes were visualized through electron microscopy. Western blotting was used to assess the autophagy-related proteins and the PDGFR/PI3K/Akt/mTOR pathway following treatment with NaHS (an H2S donor), hydroxocobalamin (an H2S scavenger), or AG 1295 (a selective PDGFR-α inhibitor). A carbon tetrachloride-induced cirrhotic BALB/c mouse model was established. Cirrhotic mice with thrombocytopenia were randomly treated with normal saline, NaHS, or hydroxocobalamin for 15 days. Changes in platelet count and aggregation rate were observed every three days. Results: Cirrhotic patients with thrombocytopenia exhibited significantly decreased platelet autophagy markers and endogenous H2S levels, alongside increased platelet aggregation, compared to healthy controls. In vitro, NaHS treatment of platelets from severe CTP patients elevated LC3-II levels, reduced SQSTM1 levels, and decreased platelet aggregation in a dose-dependent manner. H2S treatment inhibited PDGFR, PI3K, Akt, and mTOR phosphorylation. In vivo, NaHS significantly increased LC3-II and decreased SQSTM1 expressions in platelets of cirrhotic mice, reducing platelet aggregation without affecting the platelet count. Conclusions: Diminished platelet autophagy potentially contributes to thrombocytopenia in cirrhotic patients. H2S modulates platelet autophagy and functions possibly via the PDGFR-α/PI3K/Akt/mTOR signaling pathway.

Real-world Effectiveness and Tolerability of Interferon-free Direct-acting Antiviral for 15,849 Patients with Chronic Hepatitis C: A Multinational Cohort Study.

Background and Aims: As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6. Methods: We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021. Results: The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12. Conclusions: In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (>91%).

Association of Omega-3 Polyunsaturated Fatty Acids with Sarcopenia in Liver Cirrhosis Patients with Hepatocellular Carcinoma.

Background and Aims: Sarcopenia is associated with the prognosis of patients with liver cirrhosis and hepatocellular carcinoma (HCC). Given their diverse physiological activities, we hypothesized that plasma fatty acids might influence the progression of sarcopenia. This study aimed to clarify the association between fatty acids and sarcopenia in cirrhotic patients with HCC. Methods: In this single-center retrospective study, we registered 516 cases and analyzed 414 cases of liver cirrhosis and HCC. The skeletal muscle mass index was measured using a transverse computed tomography scan image at the third lumbar vertebra. The cutoff value for sarcopenia followed the criteria set by the Japan Society of Hepatology. Fatty acid concentrations were measured by gas chromatography. Results: Fatty acid levels, particularly omega-3 (n-3) polyunsaturated fatty acid (PUFA), were lower in patients with poor liver function (Child-Pugh grade B/C) and were negatively correlated with the albumin-bilirubin score (p<0.0001). The prognosis of HCC patients with low PUFA levels was significantly worse. Among the different fatty acid fractions, only n-3 PUFAs significantly correlated with skeletal muscle mass index (p=0.0026). In the multivariate analysis, the n-3 PUFA level was an independent variable associated with sarcopenia (p=0.0006). Conclusions: A low level of n-3 PUFAs was associated with sarcopenia in patients with liver cirrhosis and HCC.

Association of Baseline Hepatitis B Virus DNA and On-Treatment Risk of Cirrhosis and Hepatocellular Carcinoma.

Background: Recent studies suggest an inverse relationship between baseline levels of hepatitis B virus (HBV) DNA and on-treatment risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). However, data are limited to Asian cohorts, and it is unclear if similar associations hold true for non-Asians with CHB. We aimed to evaluate association of baseline HBV DNA with long-term risks of cirrhosis and HCC among a predominantly non-Asian cohort of CHB patients in the USA. Methods: Using longitudinal data from the national Veterans Affairs database, we evaluated the risk of cirrhosis or HCC among adults with non-cirrhotic CHB who are on continuous antiviral therapy, stratified by moderate levels of baseline HBV DNA (4.00 - 6.99 log10 IU/mL) vs. high levels of baseline HBV DNA (7.00 log10 IU/mL or higher). Propensity score weighting was applied, and competing risks cumulative incidence functions and Cox proportional hazards models were utilized. Results: Among 1,129 non-cirrhotic CHB patients (41% non-Hispanic White, 36% African American, mean age 57.0 years, 62.2% hepatitis B e antigen (HBeAg) positive), 585 had moderate levels of baseline HBV DNA and 544 had high HBV DNA. After propensity score weighting, no significant difference in risk of cirrhosis was observed between moderate vs. high baseline HBV DNA (4.55 vs. 5.22 per 100 person-years, hazard ratio (HR): 0.87, 95% confidence interval (CI): 0.69 - 1.09, P = 0.22), but risk of HCC was significantly higher in patients with moderate vs. high baseline HBV DNA (0.84 vs. 0.69 per 100 person-years, HR: 1.33, 95% CI: 1.09 - 1.62, P < 0.01). Conclusions: Among a national cohort of predominantly non-Asian US veterans with non-cirrhotic CHB on antiviral therapy, moderate levels of baseline HBV DNA was associated with higher risk of HCC than high HBV DNA.

Predictors of Non-Variceal Hemorrhage in a National Cohort of Patients With Chronic Liver Disease.

Background: Non-variceal hemorrhage in patients with chronic liver disease (CLD) increases morbidity, mortality, and healthcare costs. There are limited data on risk factors for non-variceal hemorrhage in the CLD population. The aim of this study was to assess the predictive value of various clinical and laboratory parameters for non-variceal hemorrhage in CLD patients. Methods: We conducted a retrospective cohort study of US veterans diagnosed with CLD between 2002 and 2018 within the Veterans Health Administration database. We derived candidate variables from existing risk prediction models for hemorrhage, risk calculators for severity of liver disease, Charlson index of prognostic comorbidities, and prior literature. We used a competing risk analysis to study the relationship between putative risk factors and incidence of non-variceal hemorrhage in patients with CLD. Results: Of 15,183 CLD patients with no history of cancer or anticoagulation use, 674 experienced non-variceal hemorrhage within 1 year of CLD diagnosis. In multivariable analysis, 11 of the 26 candidate variables independently predicted non-variceal hemorrhage: race, international normalized ratio (INR) > 1.5, bilirubin ≥ 2 mg/dL, albumin ≤ 3.5 g/dL, anemia, alcohol abuse, antiplatelet therapy, chronic kidney disease, dementia, proton pump inhibitor prescription, and recent infection. Conclusions: In this study of almost 15,000 veterans, risk factors for non-variceal bleeding within the first year after diagnosis of CLD included non-Caucasian race, laboratory parameters indicating severe liver disease and recent infection in addition to the risk factors for bleeding observed in a general non-CLD population.

Single-cell sequencing and multiple machine learning algorithms to identify key T-cell differentiation gene for progression of NAFLD cirrhosis to hepatocellular carcinoma.

Introduction: Hepatocellular carcinoma (HCC), which is closely associated with chronicinflammation, is the most common liver cancer and primarily involves dysregulated immune responses in the precancerous microenvironment. Currently, most studies have been limited to HCC incidence. However, the immunopathogenic mechanisms underlying precancerous lesions remain unknown. Methods: We obtained single-cell sequencing data (GSE136103) from two nonalcoholic fatty liver disease (NAFLD) cirrhosis samples and five healthy samples. Using pseudo-time analysis, we systematically identified five different T-cell differentiation states. Ten machine-learning algorithms were used in 81 combinations to integrate the frameworks and establish the best T-cell differentiation-related prognostic signature in a multi-cohort bulk transcriptome analysis. Results: LDHA was considered a core gene, and the results were validated using multiple external datasets. In addition, we validated LDHA expression using immunohistochemistry and flow cytometry. Conclusion: LDHA is a crucial marker gene in T cells for the progression of NAFLD cirrhosis to HCC.

Novel Use of AXIOS Stent for Concurrent Management of Achalasia and Esophageal Varices in a Cirrhotic Patient.

AXIOS stents create an anastomotic connection between 2 lumens, facilitating bypass of blockages and strictures as well as drainage of large fluid collections. Historically, AXIOS stents have primarily been used for draining pancreatic fluid collections, with no documented cases of their use within the esophagus until now. In this article, we present a case of a 65-year-old man with cirrhosis admitted for dysphagia. On evaluation, he was diagnosed with type 1 achalasia and concurrent esophageal varices. A novel approach was used, utilizing an AXIOS stent, to provide both symptomatic relief and targeted treatment for his varices.

Comparison of Clinical Manifestations and Related Factors of Hepatocellular Carcinoma with Chronic Hepatitis B.

Background: The aim of this study was to describe the demographic and clinical characteristics of hepatitis B virus (HBV) associated hepatocellular carcinoma (HCC), analyse the risk factors associated with HBV-associated HCC, and to provide some references to the diagnosis and treatment of HCC. Methods: This study retrospectively enrolled 730 patients, including 390 patients with chronic hepatitis B (CHB) as controls, and 340 patients with CHB complicated with HCC as patients. Relevant information and medical records of these participants were collected, including age, sex, cigarette smoking, alcoholism, diabetes mellitus (DM), hypertension, coronary heart disease (CHD), cirrhosis, occupation, ascites, HBV-DNA load, the qualitative analysis of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb serological markers, and levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), gamma-glutamyltransferase (GGT), TNM stage, tumor size and tumor number. The T test, Chi-square test, non-parametric rank-sum test, logistic regression analyses were used to explore the influencing factors and their degree of association with HCC in patients with HBV. Results: The proportion of smoking, alcoholism, married status, DM, hypertension, and the rate of HBV-DNA with a viral load of ≥500 copies/mL were significantly higher in the HCC group than in the controls (all p<0.05). Cirrhosis was more common among patients with CHB+HCC than in controls (p=0.013). The proportion of patients with HBsAg, HBeAb, and HBcAb positive was greater in CHB+HCC group than that in CHB group. Logistic regression analysis indicated that age ≥60 years (OR: 1.835, 95% CI: 1.020-3.302, p=0.043), HBeAb positive (OR: 9.105, 95% CI: 4.796-17.288, p<0.001), antiviral treatment with entecavir (OR: 2.209, 95% CI: 1.106-4.409, p=0.025), and GGT (OR: 1.004, 95% CI: 1.001-1.007, p=0.002) were risk factors for HCC in patients with CHB. Conclusion: Advanced age, HBeAb positive, antiviral treatment with entecavir, and GGT were independent risk factors for HCC in HBV patients.