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.ME...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.展开更多
AIM: To study the prevalence, predictors and control of bleeding following N-butyl 2 cyanoacrylate (NBC) sclerotherapy of gastric varix (GV). METHODS: We analyzed case records of 1436 patients with portal hypertension...AIM: To study the prevalence, predictors and control of bleeding following N-butyl 2 cyanoacrylate (NBC) sclerotherapy of gastric varix (GV). METHODS: We analyzed case records of 1436 patients with portal hypertension, who underwent endoscopy during the past five years for variceal screening or upper gastrointestinal (GI) bleeding. Fifty patients with bleeding GV underwent sclerotherapy with a mean of 2 mL NBC for control of bleeding. Outcome parameters were primary hemostasis (bleeding control within the first 48 h), recurrent bleeding (after 48 h of esophago- gastro-duodenoscopy) and in-hospital mortality were analyzed. RESULTS: The prevalence of GV in patients with portal hypertension was 15% (220/1436) and the incidence of bleeding was 22.7% (50/220). Out of the 50 bleeding GV patients, isolated gastric varices (IGV-I) were seen in 22 (44%), gastro-oesophageal varices (GOV) on lesser curvature (GOV-Ⅰ) in 16 (32%), and GOV on greater curvature (GOV-Ⅱ) in 15 (30%). IGV-Ⅰ was seen in 44% (22/50) patients who had bleeding as compared to 23% (39/170) who did not have bleeding (P < 0.003). Primary hemostasis was achieved with NBC in all patients. Re-bleeding occurred in 7 (14%) patients after 48 h of initial sclerotherapy. Secondary hemostasis was achieved with repeat NBC sclerotherapy in 4/7 (57%). Three patients died after repeat sclerotherapy, one during transjugular intrahepatic portosystemic stem shunt (TIPSS), one during surgery and one due to uncontrolled bleeding. Treatment failure-related mortality rate was 6% (3/50). CONCLUSION: GV can be seen in 15% of patients withportal hypertension and the incidence of bleeding is 22.7%. NBC is highly effective in controlling GV bleeding. In hospital mortality of patients with bleeding GV is 6%.展开更多
Hepatorenal syndrome(HRS) plays an important role in patients with liver cirrhosis on the wait list for liver transplantation(LT). The 1 and 5-year probability of developing HRS in cirrhotic with ascites is 20% and 40...Hepatorenal syndrome(HRS) plays an important role in patients with liver cirrhosis on the wait list for liver transplantation(LT). The 1 and 5-year probability of developing HRS in cirrhotic with ascites is 20% and 40%, respectively. In this article, we reviewed current concepts in HRS pathophysiology, guidelines for HRS diagnosis, effective treatment options presently available, and controversies surrounding liver alone vs simultaneous liver kidney transplant(SLKT) in transplant candidates. Many treatment options including albumin, vasoconstrictors, renal replacement therapy, and eventual LT have remained a mainstay in the treatment of HRS. Unfortunately, even after aggressive measures such as terlipressin use, the rate of recovery is less than 50% of patients. Moreover, current SLKT guidelines include:(1) estimation of glomerular filtration rate of 30 m L/min or less for 4-8 wk;(2) proteinuria > 2 g/d; or(3) biopsy proven interstitial fibrosis or glomerulosclerosis. Even with these updated criteria there is a lack of consistency regarding longterm benefits for SLKT vs LT alone. Finally, in regards to kidney dysfunction in the post-transplant setting, an estimation of glomerular filtration rate < 60 mL /min per 1.73 m2 may be associated with an increased risk of patients having long-term end stage renal disease. HRS is common in patients with cirrhosis and those on liver transplant waitlist. Prompt identification and therapy initiation in transplant candidates with HRS may improve post-transplantation outcomes. Future studies identifying optimal vasoconstrictor regimens, alternative therapies, and factors predictive of response to therapy are needed. The appropriate use of SLKT in patients with HRS remains controversial and requires further evidence by the transplant community.展开更多
BACKGROUND:Transarterial chemoembolization(TACE) is a palliative procedure frequently used in patients with advanced hepatocellular carcinoma(HCC). We examined the national inpatient trends of TACE and related outcome...BACKGROUND:Transarterial chemoembolization(TACE) is a palliative procedure frequently used in patients with advanced hepatocellular carcinoma(HCC). We examined the national inpatient trends of TACE and related outcomes in the United States over the last decade.METHODS:We utilized the National Inpatient Sample(2002 to 2012) and performed trend analyses of TACE for HCC in all adult patients(age >18 years). Multivariate analyses for the outcomes of in-hospital "procedure-related complications"(PRCs) and "post-procedure complications"(PPCs) were performed. We also compared early(2002 to 2006) and late(2007 to 2012) eras by multivariate analyses to identify predictors of complications, healthcare resource utilization and mortality.RESULTS:Overall, 19058 patients underwent TACE for HCC where PRCs and PPCs were seen in 24.2% and 17.6% of patients, respectively. The overall trends in the use of TACE(P<0.001) and associated PRCs(P=0.006) were observed to be increasing. There was less mortality [adjusted Odds ratio(a OR):0.58; 95% CI:0.41, 0.82], reduced length of hospital stay(-1.87 days; 95% CI:-2.77,-0.97) and increased hospital charges($19232; 95% CI:11013, 27451) in the late era. Additionally, there was increased mortality(a OR:4.07; 95% CI:2.96, 5.59), PRCs(a OR:3.21; 95% CI:2.56, 4.02), and PPCs(a OR:2.70; 95% CI:2.11, 3.46) among patients with coagulopathy.CONCLUSIONS:There is an increasing trend of TACE utilization in HCC. However, the outcomes are worse in patients with coagulopathy. Although PRCs have increased, mortality has decreased in recent years. These findings should be considered during TACE evaluation in patients with HCC.展开更多
Endoscopic ultrasound guided liver biopsy(EUS-LB)has emerged as a minimally-invasive alternative to the traditional(percutaneous or transjugular)liver biopsy techniques for the diagnosis of liver parenchymal diseases....Endoscopic ultrasound guided liver biopsy(EUS-LB)has emerged as a minimally-invasive alternative to the traditional(percutaneous or transjugular)liver biopsy techniques for the diagnosis of liver parenchymal diseases.Potentially,EUS-LB combines the advantages of percutaneous and transjugular liver biopsy in addressing focused sampling in addition to measuring portal pressure.Additionally,EUS-LB facilitates access to both the lobes of the liver which is not considered with the traditional percutaneous liver biopsy.Multiple studies have compared EUS-LB with conventional liver biopsy and reported comparable diagnostic yield,increased acquisition of complete portal tracts,and longer specimen length as compared to the traditional approaches.EUS-LB is associated with lesser post-procedural pain and shorter recovery time,while providing lower risk of complications when compared to traditional liver biopsy.Innovations in needle types,needle sizes and suction techniques have aimed at further optimizing the EUS-LB technique.This review article updates current literature with focus on the variations in the technique and equipment used for EUS-LB,and compares EUS-LB with traditional methods of liver biopsy.展开更多
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 ...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.展开更多
AIM To determine the readmission rate, its reasons, predictors, and cost of 30-d readmission in patients with cirrhosis and ascites.METHODS A retrospective analysis of the nationwide readmission database(NRD) was perf...AIM To determine the readmission rate, its reasons, predictors, and cost of 30-d readmission in patients with cirrhosis and ascites.METHODS A retrospective analysis of the nationwide readmission database(NRD) was performed during the calendar year 2013. All adults cirrhotics with a diagnosis of ascites,spontaneous bacterial peritonitis, or hepatic encephalopathy were identified by ICD-9 codes. Multivariate analysis was performed to assess predictors of 30-d readmission and cost of readmission.RESULTS Of the 59597 patients included in this study, 18319(31%) were readmitted within 30 d. Majority(58%) of readmissions were for liver related reasons. Paracentesis was performed in 29832(50%) patients on index admission. Independent predictors of 30-d readmission included age < 40(OR: 1.39; CI: 1.19-1.64), age 40-64(OR: 1.19; CI: 1.09-1.30), Medicaid(OR: 1.21; CI: 1.04-1.41) and Medicare coverage(OR: 1.13; CI: 1.02-1.26), > 3 Elixhauser comorbidity(OR: 1.13; CI: 1.05-1.22), nonalcoholic cirrhosis(OR: 1.16; CI: 1.10-1.23), paracentesis on index admission(OR: 1.28; CI: 1.21-1.36) and having hepatocellular carcinoma(OR: 1.21; CI: 1.05; 1.39). Cost of index admission was similar in patients readmitted and not readmitted(P-value: 0.34); however cost of care was significantly more on 30 d readmission($30959 ± 762) as compared to index admission($12403 ± 378), P-value: < 0.001.CONCLUSION Cirrhotic patients with ascites have a 33% chance of readmission within 30-d. Younger patients, with public insurance, nonalcoholic cirrhosis and increased comorbidity who underwent paracentesis are at increased risk of readmission. Risk factors for unplanned readmission should be targeted given these patients have higher healthcare utilization.展开更多
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)placem...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.展开更多
AIM To determine the impact of transjugular intrahepatic porto-systemic shunt(TIPS) on post liver transplantation(LT) outcomes.METHODS Utilizing the United Network for Organ Sharing(UNOS) database, we compared patient...AIM To determine the impact of transjugular intrahepatic porto-systemic shunt(TIPS) on post liver transplantation(LT) outcomes.METHODS Utilizing the United Network for Organ Sharing(UNOS) database, we compared patients who underwent LT from 2002 to 2013 who had underwent TIPS to those without TIPS for the management of ascites while on the LT waitlist. The impact of TIPS on 30-d mortality, length of stay(LOS), and need for re-LT were studied. For evaluation of mean differences between baseline characteristics for patients with and without TIPS, we used unpaired t-tests for continuous measures and χ~2 tests for categorical measures. We estimated the impact of TIPS on each of the outcome measures. Multivariate analyses were conducted on the study population to explore the effect of TIPS on 30-d mortality post-LT, need for re-LT and LOS. All covariates were included in logistic regression analysis.RESULTS We included adult patients(age ≥ 18 years) who underwent LT from May 2002 to September 2013. Only those undergoing TIPS after listing and before liver transplant were included in the TIPS group. We excluded patients with variceal bleeding within two weeks of listing for LT and those listed for acute liver failure or hepatocellular carcinoma. Of 114770 LT in the UNOS database, 32783(28.5%) met inclusion criteria. Of these 1366(4.2%) had TIPS between the time of listing and LT. We found that TIPS increased the days on waitlist(408 ± 553 d) as compared to those without TIPS(183 ± 330 d), P < 0.001. Multivariate analysis showed that TIPS had no effect on 30-d post LT mortality(OR = 1.26; 95%CI: 0.91-1.76) and re-LT(OR = 0.61; 95%CI: 0.36-1.05). Pre-transplant hepatic encephalopathy added 3.46 d(95%CI: 2.37-4.55, P < 0.001), followed by 2.16 d(95%CI: 0.92-3.38, P = 0.001) by TIPS to LOS. CONCLUSION TIPS did increase time on waitlist for LT. More importantly, TIPS was not associated with 30-d mortality and re-LT, but it did lengthen hospital LOS after transplantation.展开更多
AIM To examine the effect of center size on survival differences between simultaneous liver kidney transplantation(SLKT) and liver transplantation alone(LTA) in SLKT-listed patients.METHODS The United Network of Organ...AIM To examine the effect of center size on survival differences between simultaneous liver kidney transplantation(SLKT) and liver transplantation alone(LTA) in SLKT-listed patients.METHODS The United Network of Organ Sharing database was queried for patients ≥ 18 years of age listed for SLKT between February 2002 and December 2015. Posttransplant survival was evaluated using stratified Cox regression with interaction between transplant type(LTA vs SLKT) and center volume.RESULTS During the study period, 393 of 4580 patients(9%) listed for SLKT underwent a LTA. Overall mortality was higher among LTA recipients(180/393, 46%) than SLKT recipients(1107/4187, 26%). The Cox model predicted a significant survival disadvantage for patients receiving LTA vs SLKT [hazard ratio, hazard ratio(HR) = 2.85; 95%CI: 2.21, 3.66; P < 0.001] in centers performing 30 SLKT over the study period. This disadvantage was modestly attenuated as center SLKT volume increased, with a 3% reduction(HR = 0.97; 95%CI: 0.95, 0.99; P = 0.010) for every 10 SLKs performed.CONCLUSION In conclusion, LTA is associated with increased mortality among patients listed for SLKT. This difference is modestly attenuated at more experienced centers and may explain inconsistencies between smaller-center and larger registry-wide studies comparing SLKT and LTA outcomes.展开更多
AIM:To assess the cost savings of reloading the multiband ligator in endoscopic esophageal variceal ligation (EVL) used on the same patient for subsequent sessions. METHODS:This single centre retrospective descriptive...AIM:To assess the cost savings of reloading the multiband ligator in endoscopic esophageal variceal ligation (EVL) used on the same patient for subsequent sessions. METHODS:This single centre retrospective descriptive study analysed patients undergoing variceal ligation at a tertiary care centre between 1st January, 2003 and 30th June, 2006. The multiband ligator was reloaded with six hemorrhoidal bands using hemorrhoidal ligator for the second and subsequent sessions. Analysis of cost saving was done for the number of follow-up sessions for the variceal eradication. RESULTS:A total of 261 patients underwent at least one session of endoscopic esophageal variceal ligation between January 2003 and June 2006. Out of 261, 108 patients (males 67) agreed to follow the eradication program and underwent repeated sessions. A total of 304 sessions was performed with 2.81 sessions per patient on average. Thirty-two patients could not complete the programm. In 76 patients (70%), variceal obliteration was achieved. The ratio of the costs for the session with reloaded ligator versus a session with a new ligator was 1:2.37. Among the patients who completed esophageal varices eradication, cost saving with reloaded ligator was 58%. CONCLUSION:EVL using reloaded multiband ligators for the follow-up sessions on patients undergoing variceal eradication is a cost saving procedure. Reloading the ligator thus is recommended especially for developing countries where most of the patients are not health insured.展开更多
AIM To study mortality, length of stay, and total charges in morbidly obese adults during index hospitalization for orthotopic liver transplantation.METHODS The Nationwide Inpatient Sample was queried to obtain demogr...AIM To study mortality, length of stay, and total charges in morbidly obese adults during index hospitalization for orthotopic liver transplantation.METHODS The Nationwide Inpatient Sample was queried to obtain demographics, healthcare utilization, post orthotopic liver transplantation(OLT) complications, and short term outcomes of OLT performed from 2003 to 2011(n = 46509). We divided patients into those with [body mass index(BMI) ≥ 40] and without(BMI < 40) morbid obesity. Multivariable logistic regression analysis was performedto characterize differences in in-hospital mortality, length of stay(LOS), and charges for OLT between patients with and without morbid obesity after adjusting for significant confounders. Additionally, propensity matching was performed to further validate the results.RESULTS Of the 46509 patients who underwent OLT during the study period, 818(1.8%) were morbidly obese. Morbidly obese recipients were more likely to be female(46.8% vs 33.4%, P = 0.002), Caucasian(75.2% vs 67.8%, P = 0.002), in the low national income quartile(32.3% vs 22.5%, P = 0.04), and have ≥ 3 comorbidities(modified Elixhauser index; 83.9% vs 45.0%, P < 0.001). Morbidly obese patient also had an increase in procedure related hemorrhage(P = 0.028) and respiratory complications(P = 0.043). Multivariate and propensity matched analysis showed no difference in mortality(OR: 0.70; 95%CI: 0.27-1.84, P = 0.47), LOS(β:-4.44; 95%CI:-9.93, 1.05, P = 0.11) and charges for transplantation(β: $15693; 95%CI:-51622-83008, P = 0.64) between the two groups. Morbidly obese patients were more likely to have transplants on weekdays(81.7%) as compared to those without morbid obesity(75.4%, P = 0.029).CONCLUSION Morbid obesity may not impact in-hospital mortality and health care utilization in OLT recipients. However, morbidly obese patients may be selected after careful assessment of co-morbidities.展开更多
BACKGROUND Gastrointestinal(GI)and liver diseases contribute to substantial inpatient morbidity,mortality,and healthcare resource utilization.Finding ways to reduce the economic burden of healthcare costs and the impa...BACKGROUND Gastrointestinal(GI)and liver diseases contribute to substantial inpatient morbidity,mortality,and healthcare resource utilization.Finding ways to reduce the economic burden of healthcare costs and the impact of these diseases is of crucial importance.Thirty-day readmission rates and related hospital outcomes can serve as objective measures to assess the impact of and provide further insights into the most common GI ailments.AIM To identify the thirty-day readmission rates with related predictors and outcomes of hospitalization of the most common GI and liver diseases in the United States.METHODS A cross-sectional analysis of the 2012 National Inpatient Sample was performed to identify the 13 most common GI diseases.The 2013 Nationwide Readmission Database was then queried with specific International Classification of Diseases,Ninth Revision,Clinical Modification codes.Primary outcomes were mortality(index admission,calendar-year),hospitalization costs,and thirty-day readmission and secondary outcomes were predictors of thirty-day readmission.RESULTS For the year 2013,the thirteen most common GI diseases contributed to 2.4 million index hospitalizations accounting for about$25 billion.The thirty-day readmission rates were highest for chronic liver disease(25.4%),Clostridium difficile(C.difficile)infection(23.6%),functional/motility disorders(18.5%),inflammatory bowel disease(16.3%),and GI bleeding(15.5%).The highest index and subsequent calendar-year hospitalization mortality rates were chronic liver disease(6.1%and 12.6%),C.difficile infection(2.3%and 6.1%),and GI bleeding(2.2%and 5.0%),respectively.Thirty-day readmission correlated with any subsequent admission mortality(r=0.798,P=0.001).Medicare/Medicaid insurances,≥3 Elixhauser comorbidities,and length of stay>3 d were significantly associated with thirty-day readmission for all the thirteen GI diseases.CONCLUSION Preventable and non-chronic GI disease contributed to a significant economic and health burden comparable to chronic GI conditions,providing a window of opportunity for improving healthcare delivery in reducing its burden.展开更多
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 ...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.展开更多
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 ...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.展开更多
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 fi...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.展开更多
MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like ot...MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like other tumors,seldom occurs in isolation;instead,it evolves within a microenvironment featuring oncogenic and tumor-suppressive elements.When combined with suitable delivery vehicles,miRNA technology provides the capability to directly engage with these elements,thereby hindering tumor formation and progression.Ongoing research in this domain holds the promise of enabling a more efficacious and multi-modal treatment approach for HCC in the near future.展开更多
基金GASTR29:Prospective validation of readmission risk score and interventions to prevent readmission in patients with decompensated cirrhosis(CCTS ID#:6018).
文摘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.
文摘AIM: To study the prevalence, predictors and control of bleeding following N-butyl 2 cyanoacrylate (NBC) sclerotherapy of gastric varix (GV). METHODS: We analyzed case records of 1436 patients with portal hypertension, who underwent endoscopy during the past five years for variceal screening or upper gastrointestinal (GI) bleeding. Fifty patients with bleeding GV underwent sclerotherapy with a mean of 2 mL NBC for control of bleeding. Outcome parameters were primary hemostasis (bleeding control within the first 48 h), recurrent bleeding (after 48 h of esophago- gastro-duodenoscopy) and in-hospital mortality were analyzed. RESULTS: The prevalence of GV in patients with portal hypertension was 15% (220/1436) and the incidence of bleeding was 22.7% (50/220). Out of the 50 bleeding GV patients, isolated gastric varices (IGV-I) were seen in 22 (44%), gastro-oesophageal varices (GOV) on lesser curvature (GOV-Ⅰ) in 16 (32%), and GOV on greater curvature (GOV-Ⅱ) in 15 (30%). IGV-Ⅰ was seen in 44% (22/50) patients who had bleeding as compared to 23% (39/170) who did not have bleeding (P < 0.003). Primary hemostasis was achieved with NBC in all patients. Re-bleeding occurred in 7 (14%) patients after 48 h of initial sclerotherapy. Secondary hemostasis was achieved with repeat NBC sclerotherapy in 4/7 (57%). Three patients died after repeat sclerotherapy, one during transjugular intrahepatic portosystemic stem shunt (TIPSS), one during surgery and one due to uncontrolled bleeding. Treatment failure-related mortality rate was 6% (3/50). CONCLUSION: GV can be seen in 15% of patients withportal hypertension and the incidence of bleeding is 22.7%. NBC is highly effective in controlling GV bleeding. In hospital mortality of patients with bleeding GV is 6%.
文摘Hepatorenal syndrome(HRS) plays an important role in patients with liver cirrhosis on the wait list for liver transplantation(LT). The 1 and 5-year probability of developing HRS in cirrhotic with ascites is 20% and 40%, respectively. In this article, we reviewed current concepts in HRS pathophysiology, guidelines for HRS diagnosis, effective treatment options presently available, and controversies surrounding liver alone vs simultaneous liver kidney transplant(SLKT) in transplant candidates. Many treatment options including albumin, vasoconstrictors, renal replacement therapy, and eventual LT have remained a mainstay in the treatment of HRS. Unfortunately, even after aggressive measures such as terlipressin use, the rate of recovery is less than 50% of patients. Moreover, current SLKT guidelines include:(1) estimation of glomerular filtration rate of 30 m L/min or less for 4-8 wk;(2) proteinuria > 2 g/d; or(3) biopsy proven interstitial fibrosis or glomerulosclerosis. Even with these updated criteria there is a lack of consistency regarding longterm benefits for SLKT vs LT alone. Finally, in regards to kidney dysfunction in the post-transplant setting, an estimation of glomerular filtration rate < 60 mL /min per 1.73 m2 may be associated with an increased risk of patients having long-term end stage renal disease. HRS is common in patients with cirrhosis and those on liver transplant waitlist. Prompt identification and therapy initiation in transplant candidates with HRS may improve post-transplantation outcomes. Future studies identifying optimal vasoconstrictor regimens, alternative therapies, and factors predictive of response to therapy are needed. The appropriate use of SLKT in patients with HRS remains controversial and requires further evidence by the transplant community.
文摘BACKGROUND:Transarterial chemoembolization(TACE) is a palliative procedure frequently used in patients with advanced hepatocellular carcinoma(HCC). We examined the national inpatient trends of TACE and related outcomes in the United States over the last decade.METHODS:We utilized the National Inpatient Sample(2002 to 2012) and performed trend analyses of TACE for HCC in all adult patients(age >18 years). Multivariate analyses for the outcomes of in-hospital "procedure-related complications"(PRCs) and "post-procedure complications"(PPCs) were performed. We also compared early(2002 to 2006) and late(2007 to 2012) eras by multivariate analyses to identify predictors of complications, healthcare resource utilization and mortality.RESULTS:Overall, 19058 patients underwent TACE for HCC where PRCs and PPCs were seen in 24.2% and 17.6% of patients, respectively. The overall trends in the use of TACE(P<0.001) and associated PRCs(P=0.006) were observed to be increasing. There was less mortality [adjusted Odds ratio(a OR):0.58; 95% CI:0.41, 0.82], reduced length of hospital stay(-1.87 days; 95% CI:-2.77,-0.97) and increased hospital charges($19232; 95% CI:11013, 27451) in the late era. Additionally, there was increased mortality(a OR:4.07; 95% CI:2.96, 5.59), PRCs(a OR:3.21; 95% CI:2.56, 4.02), and PPCs(a OR:2.70; 95% CI:2.11, 3.46) among patients with coagulopathy.CONCLUSIONS:There is an increasing trend of TACE utilization in HCC. However, the outcomes are worse in patients with coagulopathy. Although PRCs have increased, mortality has decreased in recent years. These findings should be considered during TACE evaluation in patients with HCC.
文摘Endoscopic ultrasound guided liver biopsy(EUS-LB)has emerged as a minimally-invasive alternative to the traditional(percutaneous or transjugular)liver biopsy techniques for the diagnosis of liver parenchymal diseases.Potentially,EUS-LB combines the advantages of percutaneous and transjugular liver biopsy in addressing focused sampling in addition to measuring portal pressure.Additionally,EUS-LB facilitates access to both the lobes of the liver which is not considered with the traditional percutaneous liver biopsy.Multiple studies have compared EUS-LB with conventional liver biopsy and reported comparable diagnostic yield,increased acquisition of complete portal tracts,and longer specimen length as compared to the traditional approaches.EUS-LB is associated with lesser post-procedural pain and shorter recovery time,while providing lower risk of complications when compared to traditional liver biopsy.Innovations in needle types,needle sizes and suction techniques have aimed at further optimizing the EUS-LB technique.This review article updates current literature with focus on the variations in the technique and equipment used for EUS-LB,and compares EUS-LB with traditional methods of liver biopsy.
文摘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.
文摘AIM To determine the readmission rate, its reasons, predictors, and cost of 30-d readmission in patients with cirrhosis and ascites.METHODS A retrospective analysis of the nationwide readmission database(NRD) was performed during the calendar year 2013. All adults cirrhotics with a diagnosis of ascites,spontaneous bacterial peritonitis, or hepatic encephalopathy were identified by ICD-9 codes. Multivariate analysis was performed to assess predictors of 30-d readmission and cost of readmission.RESULTS Of the 59597 patients included in this study, 18319(31%) were readmitted within 30 d. Majority(58%) of readmissions were for liver related reasons. Paracentesis was performed in 29832(50%) patients on index admission. Independent predictors of 30-d readmission included age < 40(OR: 1.39; CI: 1.19-1.64), age 40-64(OR: 1.19; CI: 1.09-1.30), Medicaid(OR: 1.21; CI: 1.04-1.41) and Medicare coverage(OR: 1.13; CI: 1.02-1.26), > 3 Elixhauser comorbidity(OR: 1.13; CI: 1.05-1.22), nonalcoholic cirrhosis(OR: 1.16; CI: 1.10-1.23), paracentesis on index admission(OR: 1.28; CI: 1.21-1.36) and having hepatocellular carcinoma(OR: 1.21; CI: 1.05; 1.39). Cost of index admission was similar in patients readmitted and not readmitted(P-value: 0.34); however cost of care was significantly more on 30 d readmission($30959 ± 762) as compared to index admission($12403 ± 378), P-value: < 0.001.CONCLUSION Cirrhotic patients with ascites have a 33% chance of readmission within 30-d. Younger patients, with public insurance, nonalcoholic cirrhosis and increased comorbidity who underwent paracentesis are at increased risk of readmission. Risk factors for unplanned readmission should be targeted given these patients have higher healthcare utilization.
文摘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.
文摘AIM To determine the impact of transjugular intrahepatic porto-systemic shunt(TIPS) on post liver transplantation(LT) outcomes.METHODS Utilizing the United Network for Organ Sharing(UNOS) database, we compared patients who underwent LT from 2002 to 2013 who had underwent TIPS to those without TIPS for the management of ascites while on the LT waitlist. The impact of TIPS on 30-d mortality, length of stay(LOS), and need for re-LT were studied. For evaluation of mean differences between baseline characteristics for patients with and without TIPS, we used unpaired t-tests for continuous measures and χ~2 tests for categorical measures. We estimated the impact of TIPS on each of the outcome measures. Multivariate analyses were conducted on the study population to explore the effect of TIPS on 30-d mortality post-LT, need for re-LT and LOS. All covariates were included in logistic regression analysis.RESULTS We included adult patients(age ≥ 18 years) who underwent LT from May 2002 to September 2013. Only those undergoing TIPS after listing and before liver transplant were included in the TIPS group. We excluded patients with variceal bleeding within two weeks of listing for LT and those listed for acute liver failure or hepatocellular carcinoma. Of 114770 LT in the UNOS database, 32783(28.5%) met inclusion criteria. Of these 1366(4.2%) had TIPS between the time of listing and LT. We found that TIPS increased the days on waitlist(408 ± 553 d) as compared to those without TIPS(183 ± 330 d), P < 0.001. Multivariate analysis showed that TIPS had no effect on 30-d post LT mortality(OR = 1.26; 95%CI: 0.91-1.76) and re-LT(OR = 0.61; 95%CI: 0.36-1.05). Pre-transplant hepatic encephalopathy added 3.46 d(95%CI: 2.37-4.55, P < 0.001), followed by 2.16 d(95%CI: 0.92-3.38, P = 0.001) by TIPS to LOS. CONCLUSION TIPS did increase time on waitlist for LT. More importantly, TIPS was not associated with 30-d mortality and re-LT, but it did lengthen hospital LOS after transplantation.
文摘AIM To examine the effect of center size on survival differences between simultaneous liver kidney transplantation(SLKT) and liver transplantation alone(LTA) in SLKT-listed patients.METHODS The United Network of Organ Sharing database was queried for patients ≥ 18 years of age listed for SLKT between February 2002 and December 2015. Posttransplant survival was evaluated using stratified Cox regression with interaction between transplant type(LTA vs SLKT) and center volume.RESULTS During the study period, 393 of 4580 patients(9%) listed for SLKT underwent a LTA. Overall mortality was higher among LTA recipients(180/393, 46%) than SLKT recipients(1107/4187, 26%). The Cox model predicted a significant survival disadvantage for patients receiving LTA vs SLKT [hazard ratio, hazard ratio(HR) = 2.85; 95%CI: 2.21, 3.66; P < 0.001] in centers performing 30 SLKT over the study period. This disadvantage was modestly attenuated as center SLKT volume increased, with a 3% reduction(HR = 0.97; 95%CI: 0.95, 0.99; P = 0.010) for every 10 SLKs performed.CONCLUSION In conclusion, LTA is associated with increased mortality among patients listed for SLKT. This difference is modestly attenuated at more experienced centers and may explain inconsistencies between smaller-center and larger registry-wide studies comparing SLKT and LTA outcomes.
文摘AIM:To assess the cost savings of reloading the multiband ligator in endoscopic esophageal variceal ligation (EVL) used on the same patient for subsequent sessions. METHODS:This single centre retrospective descriptive study analysed patients undergoing variceal ligation at a tertiary care centre between 1st January, 2003 and 30th June, 2006. The multiband ligator was reloaded with six hemorrhoidal bands using hemorrhoidal ligator for the second and subsequent sessions. Analysis of cost saving was done for the number of follow-up sessions for the variceal eradication. RESULTS:A total of 261 patients underwent at least one session of endoscopic esophageal variceal ligation between January 2003 and June 2006. Out of 261, 108 patients (males 67) agreed to follow the eradication program and underwent repeated sessions. A total of 304 sessions was performed with 2.81 sessions per patient on average. Thirty-two patients could not complete the programm. In 76 patients (70%), variceal obliteration was achieved. The ratio of the costs for the session with reloaded ligator versus a session with a new ligator was 1:2.37. Among the patients who completed esophageal varices eradication, cost saving with reloaded ligator was 58%. CONCLUSION:EVL using reloaded multiband ligators for the follow-up sessions on patients undergoing variceal eradication is a cost saving procedure. Reloading the ligator thus is recommended especially for developing countries where most of the patients are not health insured.
文摘AIM To study mortality, length of stay, and total charges in morbidly obese adults during index hospitalization for orthotopic liver transplantation.METHODS The Nationwide Inpatient Sample was queried to obtain demographics, healthcare utilization, post orthotopic liver transplantation(OLT) complications, and short term outcomes of OLT performed from 2003 to 2011(n = 46509). We divided patients into those with [body mass index(BMI) ≥ 40] and without(BMI < 40) morbid obesity. Multivariable logistic regression analysis was performedto characterize differences in in-hospital mortality, length of stay(LOS), and charges for OLT between patients with and without morbid obesity after adjusting for significant confounders. Additionally, propensity matching was performed to further validate the results.RESULTS Of the 46509 patients who underwent OLT during the study period, 818(1.8%) were morbidly obese. Morbidly obese recipients were more likely to be female(46.8% vs 33.4%, P = 0.002), Caucasian(75.2% vs 67.8%, P = 0.002), in the low national income quartile(32.3% vs 22.5%, P = 0.04), and have ≥ 3 comorbidities(modified Elixhauser index; 83.9% vs 45.0%, P < 0.001). Morbidly obese patient also had an increase in procedure related hemorrhage(P = 0.028) and respiratory complications(P = 0.043). Multivariate and propensity matched analysis showed no difference in mortality(OR: 0.70; 95%CI: 0.27-1.84, P = 0.47), LOS(β:-4.44; 95%CI:-9.93, 1.05, P = 0.11) and charges for transplantation(β: $15693; 95%CI:-51622-83008, P = 0.64) between the two groups. Morbidly obese patients were more likely to have transplants on weekdays(81.7%) as compared to those without morbid obesity(75.4%, P = 0.029).CONCLUSION Morbid obesity may not impact in-hospital mortality and health care utilization in OLT recipients. However, morbidly obese patients may be selected after careful assessment of co-morbidities.
文摘BACKGROUND Gastrointestinal(GI)and liver diseases contribute to substantial inpatient morbidity,mortality,and healthcare resource utilization.Finding ways to reduce the economic burden of healthcare costs and the impact of these diseases is of crucial importance.Thirty-day readmission rates and related hospital outcomes can serve as objective measures to assess the impact of and provide further insights into the most common GI ailments.AIM To identify the thirty-day readmission rates with related predictors and outcomes of hospitalization of the most common GI and liver diseases in the United States.METHODS A cross-sectional analysis of the 2012 National Inpatient Sample was performed to identify the 13 most common GI diseases.The 2013 Nationwide Readmission Database was then queried with specific International Classification of Diseases,Ninth Revision,Clinical Modification codes.Primary outcomes were mortality(index admission,calendar-year),hospitalization costs,and thirty-day readmission and secondary outcomes were predictors of thirty-day readmission.RESULTS For the year 2013,the thirteen most common GI diseases contributed to 2.4 million index hospitalizations accounting for about$25 billion.The thirty-day readmission rates were highest for chronic liver disease(25.4%),Clostridium difficile(C.difficile)infection(23.6%),functional/motility disorders(18.5%),inflammatory bowel disease(16.3%),and GI bleeding(15.5%).The highest index and subsequent calendar-year hospitalization mortality rates were chronic liver disease(6.1%and 12.6%),C.difficile infection(2.3%and 6.1%),and GI bleeding(2.2%and 5.0%),respectively.Thirty-day readmission correlated with any subsequent admission mortality(r=0.798,P=0.001).Medicare/Medicaid insurances,≥3 Elixhauser comorbidities,and length of stay>3 d were significantly associated with thirty-day readmission for all the thirteen GI diseases.CONCLUSION Preventable and non-chronic GI disease contributed to a significant economic and health burden comparable to chronic GI conditions,providing a window of opportunity for improving healthcare delivery in reducing its burden.
文摘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.
文摘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.
文摘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.
文摘MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like other tumors,seldom occurs in isolation;instead,it evolves within a microenvironment featuring oncogenic and tumor-suppressive elements.When combined with suitable delivery vehicles,miRNA technology provides the capability to directly engage with these elements,thereby hindering tumor formation and progression.Ongoing research in this domain holds the promise of enabling a more efficacious and multi-modal treatment approach for HCC in the near future.
