Waitlist and posttransplant outcomes of pregnancy-related acute liver failure in the United States.

Data on the liver transplant (LT) outcomes of women with acute liver failure (ALF) due to liver diseases unique to pregnancy (P-ALF) are limited. Using United Network of Organ Sharing (UNOS) data (1987-2021), we analyzed waitlist and post-LT outcomes of ALF in women of childbearing age comparing P-ALF versus ALF due to liver diseases not unique to pregnancy. Baseline characteristics were compared between groups at the time of listing for LT. Of 3542 females aged 16-43 years and listed for LT for ALF, 84 (2%) listed for P-ALF were less likely to be Black (11 vs. 21%, p =0.033), have lower international normalized ratio (2.74 vs. 4.53 p <0.002), but more likely to have respiratory failure (56% vs. 41%, p <0.005), be on pressors (58% vs. 43%, p <0.005), and require dialysis (23% vs. 10%, p <0.001). The cumulative 90-day waitlist mortality (WLM) was lower in P-ALF vs. ALF due to liver diseases not unique to pregnancy (7.4 vs. 16.6%, p <0.001). Posttransplant survival rates at 5 years were similar (82% vs. 79%, p =0.89). In a Fine and Gray regression model controlled for listing year and Model for End-Stage Liver Disease score, 90-day WLM was lower in P-ALF with a sub-HR of 0.42 (95% CI: 0.19-0.94, p =0.035). Of 84 women with P-ALF and listed for LT, 45 listed for hemolysis-elevated liver enzymes-low platelets (HELLP) versus 39 for acute fatty liver of pregnancy had higher 90-day WLM (19.3% vs. 5.7% p <0.005). The 90-day WLM was about 10-fold higher in HELLP versus acute fatty liver of pregnancy with a sub-HR of 9.97 (95% CI: 1.64-60.55, p =0.013). In this UNOS database analysis of ALF among women of childbearing age, the waitlist outcome is better in women with P-ALF compared to women with ALF due to liver diseases not unique to pregnancy. Among women with P-ALF, the 90-day WLM is worse for HELLP versus acute fatty liver of pregnancy. Further studies are needed to improve the management of HELLP and prevent the development of ALF in this subgroup population.

Dilation balloon-occlusion technique for EUS-guided gastrojejunostomy.

Video 1Dilation balloon-occlusion technique for EUS-guided gastrojejunostomy.

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.

Outcomes of Nonvariceal Upper Gastrointestinal Bleeding in Patients With Cirrhosis: A National Analysis.

GOALS: We sought to evaluate hospital outcomes of cirrhosis patients with nonvariceal upper gastrointestinal bleeding (NVUGIB). BACKGROUND: NVUGIB is common in patients with cirrhosis. However, national outcome studies of these patients are lacking. STUDY: We utilized the 2014 Nationwide Readmission Database to evaluate NVUGIB in patients with cirrhosis, further stratified as no cirrhosis (NC), compensated cirrhosis (CC), or decompensated cirrhosis (DC). Validated International Classification of Diseases, Ninth Revision, Clinical Modification codes captured diagnoses and interventions. Outcomes included 30-day readmission rates, index admission mortality rates, health care utilization, and predictors of readmission and mortality using multivariable regression analysis. RESULTS: Overall, 13,701 patients with cirrhosis were admitted with NVUGIB. The 30-day readmission rate was 20.8%. Patients with CC were more likely to undergo an esophagogastroduodenoscopy (EGD) within 1 calendar day of admission (74.1%) than patients with DC (67.9%) or NC (69.4%). Patients with DC had longer hospitalizations (4.1 d) and higher costs of care ($11,834). The index admission mortality rate was higher in patients with DC (6.2%) than in patients with CC (1.7%, P <0.001) or NC (1.4%, P <0.001). Predictors of 30-day readmission included performing an EGD >1 calendar day from admission (OR: 1.21; 95% CI, 1.00 to 1.46) and DC (OR: 1.78; 95% CI, 1.54 to 2.06). DC was a predictor of index admission mortality (OR: 3.68; 95% CI, 2.67 to 5.05). CONCLUSIONS: NVUGIB among patients with DC is associated with higher readmission rates, mortality rates, and health care utilization compared with patients with CC and NC. Early EGD is a modifiable variable associated with reduced readmission rates. Early identification of high-risk patients and adherence to guidelines may improve clinical outcomes.

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 non-tumor 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.

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.

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 curative-intent loco-regional therapies including radioembolization for early-stage HCC.

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 919 189 patients with ACC, 13 283 (1.4%) had cirrhosis. Among cirrhotics, cholecystectomy was performed in 12 790 (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 readmissions [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 cirrhotics 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.

Apprising the choice of bariatric surgery in patients with compensated cirrhosis with morbid obesity: results of a national analysis.

Bariatric surgery (BS) was proved safe in carefully selected patients with compensated cirrhosis (CC). However, limited data exist on differential impact of bariatric surgery type on clinical outcomes and health care utilization. This retrospective study utilizes the 2010-2014 Nationwide Readmissions Database. We included obese adults with CC who underwent the two most commonly used BS, Roux-en-Y (RYGB) and laparoscopic sleeve gastrectomy (LSG). Those with decompensation within 6 months of BS were excluded. Rates of hepatic decompensation (new-onset ascites, variceal bleed, encephalopathy, spontaneous bacterial peritonitis, and/or hepatorenal syndrome), surgical complications, health care utilization, and mortality were compared between RYGB and LSG. Multivariable analysis was performed to fit various models. A total of 3032 patients with CC underwent BS, including 1864 (61.5%) RYGB and 1168 (38.5%) LSG. The majority (56%) of BS were performed at large, metropolitan teaching hospitals. There were no significant differences in various decompensations and surgical complications comparing RYGB to LSG. Healthcare utilization including index length of stay (RYGB: 3.4 days vs LSG: 3.0 days), 30-day readmission rate (RYGB: 9.5% vs LSG: 3.7%), and cost of admission (RYGB: $14,006 vs LSG: $12,523) were higher in RYGB (p values < 0.001). Index admission and calendar year mortality could not be analyzed due to the few number of events. Two types of bariatric surgeries in obese patients with compensated cirrhosis have similar rates of decompensated cirrhosis events and surgical complications. However, RYGB procedure incurred increased healthcare utilization. Therefore, LSG may be the preferred BS for patients with CC. Prospective, randomized studies comparing the types of BS are needed to confirm our observations.

Trends and Health Care Outcomes Among Living Liver Donors: Are We Ready to Expand the Donor Pool With Living Liver Donations?

We studied the trends and various outcomes, including the readmission rates, health care utilization, and complications among living liver donors (LLDs) in the United States. We queried the National Database for data from 2010 to 2017 for all LLDs. The primary outcomes were 30-day and 90-day readmission rates. The secondary outcomes included health care use (length of stay [LOS], cost of care), index admission, and calendar-year mortality. Logistic regression models were fit for various outcomes. A total of 1316 LLDs underwent hepatectomy during the study period. The median donor age was 35.0 years (interquartile range, 27.4-43.6), and donors were predominantly women (54.2%). The trend of LLD surgeries remained stable at large medical centers (85.3%). The 30-day and 90-day readmission rates were low at 5% and 5.9%, respectively. Older age (50 years and older; 8%; confidence interval [CI], 0.6%-15.9%; P = 0.03) and hepatectomy at small to medium-sized hospitals were associated with increased index LOS (13.4%; 95% CI, 3.1%-24.7%; P = 0.01). Moreover, older age of donor (-11.3%; 95% CI, -20.3% to -1.4%; P = 0.03), Elixhauser score ≥3 (17%; 95% CI, 1.2%-35.3%; P = 0.03), and Medicaid insurance (24.5%; 95% CI, 1.2%-53.1%; P = 0.04) were also associated with increased cost. The overall rate of any complications during index admission was 42.8%. Male sex (odds ratio [OR], 1.63; 95% CI, 1.19-2.23) was an independent predictor of post-LLD complications. There was no index admission or calendar-year mortality reported during the study period. This is the largest national report of LLDs to date, showing that the trend of LLD surgeries is stable in the United States. With established safety, fewer complications, and less health care utilization, LLDs can be a potential source of continuation of liver transplantation in the context of changing liver allocation policies in the United States.

Bariatric Surgery in Patients with Cirrhosis: Careful Patient and Surgery-Type Selection Is Key to Improving Outcomes.

PURPOSE: Previous reports suggest an increased mortality in cirrhotic patients undergoing bariatric surgery (BS). With advancements in management of BS, we aim to study the trends, outcomes, and their predictors in patients with cirrhosis undergoing BS. MATERIALS AND METHODS: A retrospective study was performed using the National Database from 2008 to 2013. Outcomes of BS in patients with cirrhosis were studied. In-hospital mortality, length of stay, and cost of care were compared between patients with no cirrhosis (NC), compensated cirrhosis (CC), and decompensated cirrhosis (DC). Multivariable logistic regression analysis was performed to study the predictors of mortality. RESULTS: Of the 558,017 admissions of patients who underwent BS during the study period, 3086 (0.55%) had CC and 103 (0.02%) had DC. An upward trend of vertical sleeve gastrectomy (VSG) utilization was seen during the study period. On multivariate analysis, mortality in CC was comparable with those in NC (aOR 1.88; CI 0.65-5.46); however, it was higher in DC (aOR 83.8; CI 19.3-363.8). Other predictors of mortality were older age (aOR 1.06; CI 1.04-1.08), male (aOR 2.59; CI 1.76-3.81), Medicare insurance (aOR 1.93; CI 1.24-3.01), lower income (aORs 0.44 to 0.55 for 2nd to 4th income quartile vs. 1st quartile), > 3 Elixhauser Comorbidity Index (aOR 5.30; CI 3.45-8.15), undergoing Roux-en-Y gastric bypass as opposed to VSG (aOR 3.90; CI 1.79-8.48), and centers performing < 50 BS per year (aOR 5.25; CI 3.38-8.15). Length of stay and hospital cost were also significantly higher in patients with cirrhosis as compared with those with NC. CONCLUSION: Patients with compensated cirrhosis can be considered for bariatric surgery. However, careful selection of patients, procedure type, and volume of surgical center is integral in improving outcomes and healthcare utilization in patients with cirrhosis undergoing BS.

Antiviral therapy for recurrent hepatitis C reduces recurrence of hepatocellular carcinoma following liver transplantation.

Recurrence of hepatocellular carcinoma (HCC) is one of the major concerns following liver transplantation (LT). With the potential antitumor properties of interferon (IFN), their role in prevention of HCC recurrence is to be defined. We retrospectively reviewed 46 patients who underwent LT for hepatitis C virus (HCV)-related HCC between January 2004 and December 2008. Twenty-four (52.2%) patients with biopsy-proven HCV recurrence received antiviral therapy (IFN group); their outcomes were compared with 22 patients (control group). There was no significant difference for tumor size, number, and type of neo-adjuvant therapy between the two groups. The 1- and 3-year overall patient survival (100% vs. 90.9% and 87.3% vs. 71.8%; P = 0.150) and tumor-free survival (100% vs. 72.7% and 83.1% vs. 67.5%; P = 0.214) between IFN and control group were comparable. HCC recurrence was the most common cause of death (n = 6 of 12, 50%), all in the control group. During follow-up, seven (15.2%) patients developed HCC recurrence: one (4.1%) in the IFN group and six (27.3%) in the control group (P < 0.05). In conclusions, HCC recurrence rate and related deaths were significantly lower in patients that received post-transplant antiviral therapy for recurrent HCV.

Chronic HBV with pregnancy: reactivation flare causing fulminant hepatic failure.

Chronic HBV infection is a dynamic state of interaction between HBV, hepatocytes, and the immune system of the host. A series of reactivation flares and remissions may occur due to multiple causes. Among them, spontaneous reactivation and immunosuppressive drugs including steroids or cancer chemotherapy are well known. This is due to immune-mediated destruction of HBV-expressing cells following withdrawal of immunosuppressive effect. Few cases have been reported in females during postpartum period. We report a case of fulminant hepatic failure during pregnancy in a previously unrecognized hepatitis B positive female requiring emergent liver transplantation.

Associations among behavior-related susceptibility factors in porphyria cutanea tarda.

BACKGROUND & AIMS: Porphyria cutanea tarda (PCT) is the most common of the human porphyrias and results from an acquired deficiency of hepatic uroporphyrinogen decarboxylase (UROD). Some susceptibility factors have been identified; we examined associations among multiple factors in a large cohort of patients. METHODS: Multiple known or suspected susceptibility factors and demographic and clinical features of 143 patients (mean age 52 years, 66% male, 88% Caucasian) with documented PCT (mean onset at 41 +/- 8.8 years) were tabulated; associations were examined by contingency tables, classification and regression tree (CART) analysis, and logistic regression. RESULTS: The most common susceptibility factors for PCT were ethanol use (87%), smoking (81%), chronic hepatitis C virus (HCV) infection (69%), and HFE mutations (53%; 6% C282Y/C282Y and 8% C282Y/H63D). Of those who underwent hepatic biopsy or ultrasound, 56% had evidence of hepatic steatosis. Of those with PCT, 66% of females took estrogen, 8% were diabetic, 13% had human immunodeficiency virus (HIV) infection, and 17% had inherited uroporphyrinogen decarboxylase (UROD) deficiency (determined by low erythrocyte UROD activity). Three or more susceptibility factors were identified in 70% of patients. HCV infection in patients with PCT was significantly associated with other behavior-related factors such as ethanol use (odds ratio [OR], 6.3) and smoking (OR, 11.9). CONCLUSIONS: Susceptibility factors for PCT were similar to previous studies; most patients had 3 or more susceptibility factors. Associations between PCT and HCV, ethanol or smoking could be accounted for by a history of multiple substance abuse; other factors are distributed more randomly among patients.

Are 10 wet swallows an appropriate sample of esophageal motility? Yes and no.

BACKGROUND: Traditionally 10 wet swallows are used to assess esophageal motility. Given this relative small number of swallows concerns have been raised whether the abnormal findings based on 10 wet swallows would persist with another set of 10 wet swallows. PURPOSE: To evaluate whether 10 wet swallows during esophageal manometry is an adequate sampling of esophageal motility. METHODS: Over a 4-month-period 100 consecutive patients (excluding patients with achalasia) were given 20 liquid (5 ml each) swallows. The standard manometry technique in our laboratory was performed using 10 wet swallows with pressure transducers placed 4 cm and 9 cm above the lower esophageal sphincter (LES). The diagnosis was based on the initial 10 swallows. The additional 10 swallows were blinded and separately analyzed, then compared with the initial swallows for each patient. RESULTS: Of the 100 studies (64 women; mean age 51; range 21-85), 91 had a consistent diagnosis for both pairs of 10 swallows. The number of abnormal swallows (ineffective or simultaneous) differed between the 2 sets of 10 swallows in 9 patients, but, when the first 10 were analyzed vs. all 20 swallows only 2 patients had discordant diagnoses. There was an excellent agreement between the 1st and 2nd set of 10 swallows (kappa = 0.846) and between the first 10 and all 20 swallows (kappa = 0.965). CONCLUSIONS: Ten wet swallows are sufficient for making a manometric diagnosis, because additional swallows are likely to change the diagnosis in only 2% of patients.

Schatzki's ring: a benign cause of dysphagia in adults.

The lower esophageal mucosal ring, or Schatzki's ring, was first described by Templeton. Anatomically, it represents the lower end of the esophagus. Patients classically present with intermittent dysphagia to solids. Diagnosis is made by endoscopy or a barium esophagram. Gastroesophageal reflux disease has been suggested as an etiology. It can usually be treated by passing a large dilator. Further controlled studies are needed to study its cause.