Pharmacotherapies for Portal Hypertension: Current Status and Expanding Indications.

Purpose: Non-selective beta blockers remain pharmacotherapy of choice for prevention of first episode of variceal bleeding (primary prevention) and for prevention of its recurrence after initial hemostasis (secondary prophylaxis). This review will update the current and emerging pharmacological therapies for portal hypertension. Recent findings: Data have emerged on carvedilol in preventing hepatic decompensation and improving patient survival among patients with clinically significant portal hypertension. Because measurement of WHVP is invasive and not feasible in routine practice, non-invasive tests with liver stiffness measurement in combination with platelet count may be accurate in identifying clinically significant portal hypertension. Summary: Carvedilol is more effective in reducing portal pressure compared to nadolol or propranolol. Its use has expanded to reduce risk of hepatic decompensation among patients with CSPH, which can be identified non-invasively using liver stiffness and platelet count. Studies are needed on non-invasive biomarkers to guide and optimize pharmacological treatment of portal hypertension.

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.

Simultaneous Management of Alcohol Use Disorder and Liver Disease: A Systematic Review and Meta-analysis.

OBJECTIVES: Management of alcohol use disorder (AUD) is rarely used in patients with liver disease. We performed a systematic review to examine the impact of AUD management among patients with liver disease. METHODS: Twenty studies fulfilling the inclusion and exclusion criteria on 38,329 patients (7072 receiving AUD intervention) with liver disease (15 with liver disease and 6 liver transplant [LT] recipients) were analyzed. One study was common to both groups. Variable follow-up period across studies was weighted for sample size and converting to person-years. Primary outcome was alcohol use, and secondary outcomes were liver decompensation and patient mortality. RESULTS: Abstinence and alcohol relapse rates/person-year with AUD intervention among liver disease patients were 0.41 (0.27-0.55) and 0.42 (0.30-0.755), similar for integrated (colocated liver and addiction clinics) versus concomitant (separate hepatology and addiction clinics) intervention. Compared with standard of care, odds for decompensation with AUD intervention (n = 1), 30-day readmission (n = 1), and patient mortality (n = 2) were lower by 44%, 59%, and 58% respectively. Similar figures were 1.24 (0.86-1.80) for abstinence and 0.52 (0.24-0.14) for relapse. Among LT recipients, odds for alcohol relapse and mortality with follow-up integrated with addiction team versus hepatology alone were 0.48 (0.25-0.72) and 0.29 (0.08-0.99), respectively. CONCLUSIONS: Follow-up of LT recipients in an integrated clinic with addiction team is associated with improved outcomes. Simultaneous management of AUD in patients with liver disease improves liver-related outcomes. Large prospective studies are needed to examine benefits of AUD intervention in patients with liver disease.

Comparison of the performance of a clinical classification tree versus clinical gestalt in predicting sepsis with extended-spectrum beta-lactamase-producing gram-negative rods.

A clinical decision tree was developed using point-of-care characteristics to identify patients with culture-proven sepsis due to extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE). We compared its performance with the clinical gestalt of emergency department (ED) clinicians and hospital-based clinicians. The developed tree outperformed ED-based clinicians but was comparable to inpatient-based clinicians.

Role of endoscopic ultrasound and cyst fluid tumor markers in diagnosis of pancreatic cystic lesions.

BACKGROUND: Pancreatic cystic lesions (PCLs) are common in clinical practice. The accurate classification and diagnosis of these lesions are crucial to avoid unnecessary treatment of benign lesions and missed opportunities for early treatment of potentially malignant lesions. AIM: To evaluate the role of cyst fluid analysis of different tumor markers such as cancer antigens [e.g., cancer antigen (CA)19-9, CA72-4], carcinoembryonic antigen (CEA), serine protease inhibitor Kazal-type 1 (SPINK1), interleukin 1 beta (IL1-ß), vascular endothelial growth factor A (VEGF-A), and prostaglandin E2 (PGE2)], amylase, and mucin stain in diagnosing pancreatic cysts and differentiating malignant from benign lesions. METHODS: This study included 76 patients diagnosed with PCLs using different imaging modalities. All patients underwent endoscopic ultrasound (EUS) and EUS-fine needle aspiration (EUS-FNA) for characterization and sampling of different PCLs. RESULTS: The mean age of studied patients was 47.4 ± 11.4 years, with a slight female predominance (59.2%). Mucin stain showed high statistical significance in predicting malignancy with a sensitivity of 87.1% and specificity of 95.56%. It also showed a positive predictive value and negative predictive value of 93.1% and 91.49%, respectively (P < 0.001). We found that positive mucin stain, cyst fluid glucose, SPINK1, amylase, and CEA levels had high statistical significance (P < 0.0001). In contrast, IL-1ß, CA 72-4, VEGF-A, VEGFR2, and PGE2 did not show any statistical significance. Univariate regression analysis for prediction of malignancy in PCLs showed a statistically significant positive correlation with mural nodules, lymph nodes, cyst diameter, mucin stain, and cyst fluid CEA. Meanwhile, logistic multivariable regression analysis proved that mural nodules, mucin stain, and SPINK1 were independent predictors of malignancy in cystic pancreatic lesions. CONCLUSION: EUS examination of cyst morphology with cytopathological analysis and cyst fluid analysis could improve the differentiation between malignant and benign pancreatic cysts. Also, CEA, glucose, and SPINK1 could be used as promising markers to predict malignant pancreatic cysts.

Impact of Fibrosis-4 Index Prior to COVID-19 on Outcomes in Patients at Risk of Non-alcoholic Fatty Liver Disease.

BACKGROUND: Severity of disease and outcomes in patient with COVID-19 has been associated with several risk factors tied to the metabolic syndrome. AIMS: We conducted a study with the objective of describing the association between the baseline Fibrosis-4 (FIB-4) index prior to SARS-CoV-2 infection and the severity of COVID-19 among patients at risk of non-alcoholic fatty liver disease (NAFLD). METHODS: This was a retrospective cohort study of patients with at least two risk factors for metabolic syndrome diagnosed with COVID-19. The main exposure of interest was FIB-4 index prior to infection, categorized into three previously validated age-specific levels. The main outcomes of interest were disease requiring hospitalization and in-hospital mortality. RESULTS: We included 373 patients [median age, 62 years; 194 male (52%); median number of metabolic syndrome risk factors, 3]. The median FIB-4 index was 1.10 (interquartile range 0.78-1.61). In models adjusting for diabetes mellitus and chronic kidney disease, patients with intermediate FIB-4 index had 67% higher odds of hospitalization compared to those in the low category {odds ratio (OR) 1.67 [(95% CI 1.06-2.64); p = 0.03]} and patients with high FIB-4 index had higher odds of mortality compared to intermediate and low category with an OR 2.22 (95% CI 1.20-4.12; p = 0.01). However, when we evaluated components of FIB-4 (age and AST/ALT ratio), we found that age alone was the best predictor of hospitalization and mortality. CONCLUSIONS: Among patients at risk of NAFLD with COVID-19 infection, elevated pre-infection FIB-4 index was associated with worsened clinical outcomes, but age was the strongest predictor.

Cap-Assisted Technique versus Conventional Methods for Esophageal Food Bolus Extraction: A Comparative Study.

BACKGROUND/AIMS: Food bolus impaction is the most common form of esophageal foreign body impaction observed in adults. Clinical guidelines recommend using the push technique or retrieval methods in such cases. The push technique can cause injuries in certain clinical situations. Notably, conventional retrieval methods are time and effort consuming. Cap-assisted endoscopic extraction of an impacted food bolus is an easy and effective technique; however, more data are needed for its validation. This study compared the capassisted extraction technique with conventional methods. METHODS: This prospective observational multicenter study compared the success and en bloc removal rates, total procedure time, and adverse events in both techniques.. RESULTS: The study included 303 patients who underwent food bolus extraction. The push technique was used in 87 patients (28.7%) and a retrieval procedure in 216 patients (71.3%). Cap-assisted extraction was performed in 106 patients and retrieval using conventional methods in 110 patients. The cap-assisted technique was associated with a higher rate of en bloc removal (80.2% vs. 15%, p<0.01), shorter procedure time (6.9±3.5 min vs. 15.7±4.1 min, p<0.001), and fewer adverse events (0/106 vs. 9/110, p<0.001). CONCLUSION: Cap-assisted extraction showed no adverse events, higher efficacy, and a shorter procedure time compared with conventional retrieval procedures.

Sofosbuvir/Ledipasvir Without Ribavirin Achieved High Sustained Virologic Response for Hepatitis C Recurrence After Liver Transplantation: Two-Center Experience.

BACKGROUND: Current recommended regimens to treat patients with hepatitis C virus (HCV) infection after liver transplantation include the use of ribavirin (RBV). Limited data are available on the efficacy of RBV-free regimens posttransplant, particularly the use of sofosbuvir (SOF)/ledipasvir (LDV) without RBV in this patient population. We aimed to assess the efficacy and safety of SOF/LDV fixed-dose combination without RBV in patients with HCV recurrence posttransplant. METHODS: This is a retrospective study of 46 patients with HCV recurrence posttransplant. SOF/LDV without RBV was used for 12 weeks in patients with early-stage fibrosis (F0-F2) or for 24 weeks in those with advanced fibrosis (F3-F4) and/or cholestatic hepatitis. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment. Secondary outcomes included relapse after treatment and adverse events. RESULTS: Forty-six patients, with a mean age of 62 ± 8 years, a median duration since time of transplant of 904 days (range, 78-3525 days), an HCV genotype 1, and a mean baseline viral load of 7.79 million IU/mL, were treated. Of these, 32 patients were treated for 12 weeks, and 14 patients were treated for 24 weeks. Twenty-five patients (54%) were treatment experienced (21 with interferon and 4 with SOF). All 46 patients (100%) achieved sustained virological response (SVR) 12. Neither virologic relapses nor serious adverse events were noted. CONCLUSIONS: The combination of SOF/LDV without RBV for 12 or 24 weeks produced 100% SVR 12 in patients with HCV recurrence after liver transplantation. The use of RBV may not be necessary to achieve SVR in this patient population.

Graft-versus-host disease after orthotopic liver transplantation: multivariate analysis of risk factors.

Graft-versus-host disease (GVHD) is a rare, fatal complication following orthotopic liver transplantation (OLT). To date, several risk factors have been proposed, but reports on these factors have been inconclusive. This is a retrospective, case-control study of prospectively collected data from 2775 OLTs performed at our institution. Eight cases of GVHD after OLT were diagnosed on the basis of the patient's clinical characteristics, and the findings were confirmed with skin and colonic biopsies. Each case was matched to three controls based on the diagnosis of liver disease, recipient's age, and blood group. Univariate and multivariate analyses were performed to identify risk factors associated with the development of GVHD after OLT. The univariate and multivariate analyses identified two main risk factors associated with development of GVHD in OLT recipients, a difference between recipient and donor age of >20 yr, and any human leukocyte antigen class I matches. Taking these two risk factors into consideration while matching prospective donors and recipients may reduce further incidence of GVHD in OLT patients. However, further studies are recommended to validate these findings.