Randomized intervention and outpatient follow-up lowers 30-d readmissions for patients with hepatic encephalopathy,decompensated cirrhosis

BACKGROUND We previously reported national 30-d readmission rates of 27% in patients with decompensated cirrhosis(DC).AIM To study prospective interventions to reduce early readmissions in DC at our tertiary center.METHODS Adults with DC admitted July 2019 to December 2020 were enrolled and randomized into the intervention(INT) or standard of care(SOC) arms. Weekly phone calls for a month were completed. In the INT arm, case managers ensured outpatient follow-up, paracentesis, and medication compliance. Thirty-day readmission rates and reasons were compared.RESULTS Calculated sample size was not achieved due to coronavirus disease 2019;240 patients were randomized into INT and SOC arms. 30-d readmission rate was 33.75%, 35.83% in the INT vs 31.67% in the SOC arm(P = 0.59). The top reason for 30-d readmission was hepatic encephalopathy(HE, 32.10%). There was a lower rate of 30-d readmissions for HE in the INT(21%) vs SOC arm(45%, P = 0.03). There were fewer 30-d readmissions in patients who attended early outpatient follow-up(n = 17, 23.61% vs n = 55, 76.39%, P = 0.04).CONCLUSION Our 30-d readmission rate was higher than the national rate but reduced by interventions in patients with DC with HE and early outpatient follow-up. Development of interventions to reduce early readmission in patients with DC is needed.

Epidemiologic and socioeconomic factors impacting hepatitis B virus and related hepatocellular carcinoma

Chronic Hepatitis B is a highly prevalent disease worldwide and is estimated to cause more than 800000 annual deaths from complications such as cirrhosis and hepatocellular carcinoma(HCC).Although universal hepatitis B vaccination programs may have reduced the incidence and prevalence of chronic hepatitis B and related HCC,the disease still imposes a significant healthcare burden in many endemic regions such as Africa and the Asia-Pacific region.This is especially concerning given the global underdiagnosis of hepatitis B and the limited availability of vaccination,screening,and treatment in low-resource regions.Demographics including male gender,older age,ethnicity,and geographic location as well as low socioeconomic status are more heavily impacted by chronic hepatitis B and related HCC.Methods to mitigate this impact include increasing screening in high-risk groups according to national guidelines,increasing awareness and health literacy in vulnerable populations,and developing more robust vaccination programs in under-served regions.

Dissecting novel mechanisms of hepatitis B virus related hepatocellular carcinoma using meta-analysis of public data

BACKGROUND Hepatitis B virus(HBV) is a cause of hepatocellular carcinoma(HCC). Interestingly, this process is not necessarily mediated through cirrhosis and may in fact involve oncogenic processes. Prior studies have suggested specific oncogenic gene expression pathways were affected by viral regulatory proteins. Thus, identifying these genes and associated pathways could highlight predictive factors for HCC transformation and has implications in early diagnosis and treatment.AIM To elucidate HBV oncogenesis in HCC and identify potential therapeutic targets.METHODS We employed our Search, Tag, Analyze, Resource platform to conduct a meta-analysis of public data from National Center for Biotechnology Information’s Gene Expression Omnibus. We performed meta-analysis consisting of 155 tumor samples compared against 185 adjacent nontumor samples and analyzed results with ingenuity pathway analysis.RESULTS Our analysis revealed liver X receptors/retinoid X receptor(RXR) activation and farnesoid X receptor/RXR activation as top canonical pathways amongst others. Top upstream regulators identified included the Ras family gene rab-like protein 6(RABL6). The role of RABL6 in oncogenesis is beginning to unfold but its specific role in HBV-related HCC remains undefined. Our causal analysis suggests RABL6 mediates pathogenesis of HBV-related HCC through promotion of genes related to cell division, epigenetic regulation, and Akt signaling. We conducted survival analysis that demonstrated increased mortality with higher RABL6 expression. Additionally, homeobox A10(HOXA10) was a top upstream regulator and was strongly upregulated in our analysis. HOXA10 has recently been demonstrated to contribute to HCC pathogenesis in vitro. Our causal analysis suggests an in vivo role through downregulation of tumor suppressors and other mechanisms.CONCLUSION This meta-analysis describes possible roles of RABL6 and HOXA10 in the pathogenesis of HBV-related HCC. RABL6 and HOXA10 represent potential therapeutic targets and warrant further investigation.

Call for action:Increased healthcare utilization with growing use of percutaneous cholecystectomy tube over initial cholecystectomy in cirrhotics

Background:Acute calculous cholecystitis(ACC)is frequently seen in cirrhotics,with some being poor candidates for initial cholecystectomy.Instead,these patients may undergo percutaneous cholecystostomy tube(PCT)placement.We studied the healthcare utilization and predictors of cholecystectomy and PCT in patients with ACC.Methods:The National Database was queried to study all cirrhotics and non-cirrhotics with ACC between 2010-2014 who underwent initial PCT(with or without follow-up cholecystectomy)or cholecystectomy.Cirrhotic patients were divided into compensated and decompensated cirrhosis.Independent predictors and outcomes of initial PCT and failure to undergo subsequent cholecystectomy were studied.Results:Out of 919189 patients with ACC,13283(1.4%)had cirrhosis.Among cirrhotics,cholecystec-tomy was performed in 12790(96.3%)and PCT in the remaining 493(3.7%).PCT was more frequent in cirrhotics(3.7%)than in non-cirrhotics(1.4%).Multivariate analyses showed increased early readmis-sions[odds ratio(OR)=2.12,95%confidence interval(CI):1.43-3.13,P<0.001],length of stay(effect ratio=1.39,95%CI:1.20-1.61,P<0.001),calendar-year hospital cost(effect ratio=1.34,95%CI:1.28-1.39,P<0.001)and calendar-year mortality(hazard ratio=1.89,95%CI:1.07-3.29,P=0.030)in cir-rhotics undergoing initial PCT compared to cholecystectomy.Decompensated cirrhosis(OR=2.25,95%CI:1.67-3.03,P<0.001)had the highest odds of getting initial PCT.Cirrhosis,regardless of compensated(OR=0.56,95%CI:0.34-0.90,P=0.020)or decompensated(OR=0.28,95%CI:0.14-0.59,P<0.001),reduced the chances of getting a subsequent cholecystectomy.Conclusions:Cirrhotic patients undergo fewer cholecystectomy incurring initial PCT instead.Moreover,the rates of follow-up cholecystectomy are lower in cirrhotics.Increased healthcare utilization is seen with initial PCT amongst cirrhotic patients.This situation reflects suboptimal management of ACC in cirrhotics and a call for action.

Emerging curative-intent minimally-invasive therapies for hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the most common cause of liver malignancy and the fourth leading cause of cancer deaths universally.Cure can be achieved for early stage HCC,which is defined as 3 or fewer lesions less than or equal to 3 cm in the setting of Child-Pugh A or B and an ECOG of 0.Patients outside of these criteria who can be down-staged with loco-regional therapies to resection or liver transplantation(LT)also achieve curative outcomes.Traditionally,surgical resection,LT,and ablation are considered curative therapies for early HCC.However,results from recently conducted LEGACY study and DOSISPHERE trial demonstrate that transarterial radio-embolization has curative outcomes for early HCC,leading to its recent incorporation into the Barcelona clinic liver criteria guidelines for early HCC.This review is based on current evidence for curativeintent loco-regional therapies including radioembolization for early-stage HCC.

Application of artificial intelligence in non-alcoholic fatty liver disease and viral hepatitis

Non-alcoholic fatty liver disease(NAFLD)and chronic viral hepatitis are among the most significant causes of liver-related mortality worldwide.It is critical to develop reliable methods of predicting progression to fibrosis,cirrhosis,and decompensated liver disease.Current screening methods such as biopsy and transient elastography are limited by invasiveness and observer variation in analysis of data.Artificial intelligence(AI)provides a unique opportunity to more accurately diagnose NAFLD and viral hepatitis,and to identify patients at high risk for disease progression.We conducted a literature review of existing evidence for AI in NAFLD and viral hepatitis.Thirteen articles on AI in NAFLD and 14 on viral hepatitis were included in our analysis.We found that machine learning algorithms were comparable in accuracy to current methods for diagnosis and fibrosis prediction(MELD-Na score,liver biopsy,FIB-4 score,and biomarkers).They also reliably predicted hepatitis C treatment failure and hepatic encephalopathy,for which there are currently no established prediction tools.These studies show that AI could be a helpful adjunct to existing techniques for diagnosing,monitoring,and treating both NAFLD and viral hepatitis.