Reporting the cases of alcohol-associated hepatitis using the National Inpatient Sample data

The letter is to respond to the recent publication“Trends in hospitalization for alcoholic hepatitis from 2011 to 2017:A USA nationwide study”(World J Gastroenterol 2022;28:5036-5046).We noticed a significant difference in the total numbers of reported hospitalized alcohol-associated hepatitis(AH)patients between this publication and our publication on Alcohol Clin Exp Res(2022;46:1472-1481).We believe the number of“AH-related hospitalizations”inflated by the inclusion of patients with non-AH forms of alcohol-associated liver disease.

Deep vein thrombosis and pulmonary embolism in cirrhotic patients:Systematic review

Patients with liver cirrhosis were traditionally believed to be protected against development of blood clots.Lately,studies have shown that these patients may probably be at an increased risk of venous thrombotic complications.Although the hemostatic changes in the chronic liver disease patients and the factors that may predict bleeding vs thrombotic complications remains an area of active research,it is believed that the coagulation cascade is delicately balanced in these patients because of parallel reduced hepatic synthesis of pro and anticoagulant factors.Thrombotic state in cirrhotic patients is responsible for not only portal or non-portal thrombosis[deep vein thrombosis(DVT)and pulmonary embolism(PE)];it has also been associated with progression of liver fibrosis.The use of anticoagulants in cirrhosis patients is a challenging,and often a scary situation.This review summarizes the current literature on the prevalence of venous thrombosis(DVT and PE),risk factors and safety of prophylactic and therapeutic anticoagulation in patients with chronic liver disease.

Heat shock protein 90 promotes RNA helicase DDX5 accumulation and exacerbates hepatocellular carcinoma by inhibiting autophagy

Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell growth.Heat shock protein 90(HSP90)is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival.Methods:DDX5 m RNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot,respectively.The interaction of DDX5-HSP90 was determined by molecular docking,immunoprecipitation,and laser scanning confocal microscopy.The autophagy signal was detected by Western blot.The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines.Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor.Results:HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway.The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating theβ-catenin signaling pathway.The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model.High levels of HSP90 and DDX5 protein were associated with poor prognoses.Conclusions:HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation.DDX5 and HSP90 are therefore potential therapeutic targets for HCC.

Alcoholic hepatitis: A comprehensive review of pathogenesis and treatment

Alcoholic hepatitis(AH)is an acute hepatic inflammation associated with significant morbidity and mortality.Current evidence suggests that the pathogenesis is the end result of the complex interplay between ethanol metabolism,inflammation and innate immunity.Several clinical scoring systems have been derived to predict the clinical outcomes of patients with AH;such as Child-Turcotte-Pugh score,the Maddrey discriminant function,the Lille Model,the model for end stage liver disease scores,and the Glasgow alcoholic hepatitis score.At present,Corticosteroids or pentoxifylline are the current pharmacologic treatment options;though the outcomes from the therapies are poor.Liver trans-plantation as the treatment of alcoholic hepatitis remains controversial,and in an era of organ shortage current guidelines do not recommend transplantation as the treatment option.Because of the limitations in the therapeutic options,it is no doubt that there is a critical need for the newer and more effective pharmacological agents to treat AH.

Relationship between alcohol intake and dietary pattern:Findings from NHANES Ⅲ

AIM:To examine the association between macronutrient dietary patterns and alcohol consumption using the Third National Health and Nutritional Examination Survey METHODS:A total of 9877 subjects(5144 males) constituted the study cohort.Dietary interviews were conducted with all examinees by a trained dietary interviewer in a mobile examination center(MEC).Subjects reported all foods and beverages consumed except plain drinking water for the previous 24-h time period.Physical examination and history of alcohol consumption were obtained.Pearson correlation coefficients were used to evaluate the association of the levels of alcohol consumption and the percentage of energy derived from macronutrients.Univariate and multivariate regression analyses were performed accounting for the study sampling weight to further explore the relationships between alcohol consumption and calories derived from each macronutrient.RESULTS:Subjects who drank were younger than nondrinker controls in both genders(P < 0.01).Alcohol intake was inversely associated with body mass index and body weight in women.Of all macronutrients,carbohydrate intake was the first to decrease with increasing alcohol consumption.In the multivariate analyses,the level of alcohol consumption was found to be an independent predictor associated with lower intake of other macronutrients.CONCLUSION:Our results show that there is an alteration in the daily dietary pattern with increasing alcohol consumption and that energy derived from alcoholic beverages substitutes that from other macronutrients such as carbohydrate,protein,and fat.

Corrigendum to“Long non-coding RNA in liver metabolism and disease:Current status”[Liver Res.1(2017)163e167]

The authors regret<the text“to L.Wang”should be removed from the National Natural Scientific Foundation of China(Grant No.81572443).The correct acknowledgement should read as:This work was supported by the National Institutes of Health(NIH)grants(R01DK104656,R01DK080440,R01ES025909,R21AA022482,R21AA024935,R01AA026322 to L.Wang);VA Merit Award(1I01BX002634 to L.Wang);the National Natural Scientific Foundation of China(Grant No.81572443),VA Merit Award(1I01CX000361 to S.Liangpunsakul),NIH(U01AA021840,R01DK107682,R01AA025208,R21AA024935 to S.Liangpunsakul),US DOD(W81XWH-12-1-0497 to S.Liangpunsakul).>.The authors would like to apologise for any inconvenience caused.

Clinical Predictors of Functional Cure in Children 1–6 Years-old with Chronic Hepatitis B

Background and Aims:Hepatitis B surface antigen(HBsAg)clearance is significantly more common in children with chronic hepatitis B(CHB)than in adults;however,the possible influencing factors related to HBsAg loss have yet to be found.This study aimed to explore the efficacy of long-term interferon(IFN)αtherapy in treating children with CHB and analyzed the factors influencing functional cure after treatment.Methods:A total of 236 children aged 1–6 years and diagnosed with CHB via liver biopsy were included in the study,all receiving IFNαtreatment(IFNα-2b monotherapy,IFNα-2b followed by lamivudine[LAM]or IFNα-2b combined with LAM)and followed up for 144 weeks.A comprehensive analysis was conducted on clinical data,including biochemical items,serum markers of hepatitis B virus(HBV)and immunological indexes,and logistic regression analysis was used to screen the influencing factors related to HBsAg loss.Results:The cumulative loss rates of HBsAg were 79.5%,62.1%and 42.1%at 144 weeks after the start of treatment in the 1–3 years-old group,3–5 years-old group and 5–7 years-old group,respectively(p<0.05).IFNα-2b combined with LAM treatment displayed the highest HBsAg loss rates compared with monotherapy and sequential treatment(p=0.011).Younger baseline age and lower HBsAg levels were independent factors for the prediction of HBsAg loss(p<0.05).The baseline PreS1 and hepatitis B core antibody levels in the HBsAg loss group were lower than those in the HBsAg non-loss group.In addition,the PreS1 level was positively corelated with the level of HBsAg,HBV DNA and liver inflammation.Conclusions:Long-term treatment with IFNαwas effective in achieving HBsAg loss in CHB children aged 1–6 years-old.Age less than 3 years-old and lower HBsAg levels are independent predictors of functional cure in children with CHB.

A New Prognostic Model Covering All Stages of Intrahepatic Cholangiocarcinoma

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is the second most common primary hepatic malignancy that causes a poor survival.We aimed to identify its prognostic factors and to develop a nomogram that will predict survival of ICC patients among all stages.Methods:A total of 442 patients with pathology-proven ICC registered at the Fifth Medical Center of PLA General Hospital between July 2007 and December 2019 were enrolled.Subjects were followed for survival status until June 30,2020.A prognostic model visualized as a nomogram was constructed in the training cohort using multivariate cox model,and was then validated in the validation cohort.Results:The median age was 55 years.With a median follow-up of 50.4 months,337 patients died.The median survival was 11.6 months,with 1-,3-and 5-year survival rates of 48.3%,22.7%and 16.2%,respectively.Factors associated with overall survival were multiple tumors,lymph node involvement,vascular invasion,distant metastasis,decreased albumin,elevated lactate dehydrogenase(LDH),decreased iron,elevated fi-brinogen,elevated CA125 and elevated CA19-9.A nomo-gram predicting survival of ICC patients at the time of di-agnosis achieved a Harrel’s c-statistic of 0.758,significantly higher than the 0.582 of the TNM stage alone.Predicted median survivals of those within the low,mid and high-risk subgroups were 35.6,12.1 and 6.2 months,respectively.Conclusions:A nomogram based on imaging data and serum biomarkers at diagnosis showed good ability to predict survival in patients with all stages of ICC.Further studies are needed to validate the prognostic capability of our new model.

Long non-coding RNA in liver metabolism and disease:Current status

Long non-coding RNAs(lncRNAs)are comprised of RNA transcripts exceeding 200 nucleotides in length but lacking identifiable open reading frames(with rare exceptions).Herein,we highlight emerging evidence demonstrating that lncRNAs are critical regulators of liver metabolic function and diseases.We summarize current knowledges about dysregulated lncRNAs and outline the underlying molecular mechanisms by which lncRNAs control hepatic lipid ad glucose metabolism,as well as cholestatic liver disease.Liver-specific triglyceride regulator(lncLSTR),Lnc18q22.2,steroid RNA activator(SRA),highly upregulated in liver cancer(HULC),metastasis associated in lung adenocarcinoma transcript 1(MALAT1),liver glucokinase repressor(lncLGR),maternally expressed gene 3(MEG3),and H19,lncHR1,lnc-HC,apolipoprotein A1 antisense transcript(APOA1-AS),DYNLRB2-2,and LXR-induced sequence(LeXis)are included in the discussion.

Levels of circulating follicular helper T cells,T helper 1 cells,and the prognostic significance of soluble form of CD40 ligand on survival in patients with alcoholic cirrhosis

Background:Excessive drinkers(ED)and patients with alcoholic liver disease(ALD)are several times more susceptible to bacterial and viral infections and have a decrease in antibody responses to vaccinations.Follicular helper T(TFH)cells are essential to select B cells in the germinal center and to produce antibodies.TFH cells express both a membrane-associated and a soluble form of CD40 ligand(sCD40L),in which the latter form is released to circulation upon T cell activation.The effect of alcohol on TFH cells has not been studied.Objectives:The goals of this study are to determine the levels of TFH and T helper 1(Th1)cells in ED and those with alcoholic cirrhosis(AC)when compared to healthy controls and to determine the prognostic significance of sCD40L in a cohort of patients with AC.Methods:Controls,ED,and those with AC were enrolled.Baseline demographic,laboratory tests,and peripheral blood mononuclear cells(PBMCs)were isolated and assessed via flow cytometry for TFH cells.In vitro study was performed to determine the ability of PBMCs to secrete interferon(IFN)-ɣupon stimulation.Serum sCD40L was also determined and its prognostic significance was tested in a cohort of AC patients.Results:The levels of circulating TFH(cTFH)cells were significantly lower in peripheral blood of subjects with ED and AC compared to controls(P<0.05).IFN-ɣsecretion from PBMCs upon stimulation was also lower in ED and those with cirrhosis.Serum sCD40L was significantly lower in ED and AC when compared to that in controls(P<0.0005).Its level was an independent predictor of mortality.Conclusions:Patients with AC had significantly lower level of cTFH and sCD40L.The level of sCD40L was an independent predictor of mortality in these patients.