[Show abstract][Hide abstract] ABSTRACT: A subset of patients with non-variceal gastrointestinal bleeding fail, or are unsuitable candidates for, endoscopic, radiologic, and surgical interventions. Endoscopic ultrasound (EUS)-guided intervention might be effective in these patients. We performed EUS-guided hemostatic interventions for 17 patients with non-variceal gastrointestinal bleeding from June 2003 through May 2014 who failed, or were unsuitable candidates for, additional therapies. Indications for treatment included gastrointestinal stromal tumors, colorectal vascular malformations, duodenal masses or polyps, Dieulafoy lesions, duodenal ulcers, rectally invasive prostate cancer, pancreatic pseudoaneurysms, ulcerated esophageal cancer, and ulceration following Roux-en-Y gastric bypass. Following the procedure, 88% of patients have had no further bleeding related to the treated lesion, over a median follow-up period of 12 months. EUS-guided hemostatic therapy is therefore feasible and useful for select patients with clinically severe, refractory, or recurrent non-variceal gastrointestinal bleeding.
Clinical Gastroenterology and Hepatology. 09/2014;
[Show abstract][Hide abstract] ABSTRACT: Bacterial infections, particularly repeated infections, are significant causes of morbidity and mortality among patients with cirrhosis. We investigated and characterized risk factors for repeat infections in these patients.
Clinical Gastroenterology and Hepatology. 08/2014;
[Show abstract][Hide abstract] ABSTRACT: Chronic passive hepatic congestion (congestive hepatopathy) leads to hepatic fibrosis; however the mechanisms involved in this process are not well understood. We developed a murine experimental model of congestive hepatopathy through partial ligation of the inferior vena cava (pIVCL). C57BL/6 and transgenic mice overexpressing tissue factor pathway inhibitor (SM22α -TFPI) were subjected to pIVCL or SHAM. Liver and blood samples were collected and analyzed in immunohistochemical, morphometric, real-time polymerase chain reaction and western blot assays. Hepatic fibrosis and portal pressure were significantly increased after pIVCL concurrent with hepatic stellate cell (HSC) activation. Liver stiffness, as assessed by magnetic resonance elastography, correlated with portal pressure and preceded fibrosis in our model. Hepatic sinusoidal thrombosis as evidenced by fibrin deposition was demonstrated both in mice after pIVCL as well as in humans with congestive hepatopathy. Warfarin treatment and TFPI overexpression both had a protective effect on fibrosis development and HSC activation after pIVCL. In vitro studies show that congestion stimulates HSC fibronectin (FN) fibril assembly through direct effects of thrombi as well as by virtue of mechanical strain. Pretreatment with either Mab13 or Cytochalasin-D, to inhibit β-integrin or actin polymerization, respectively, significantly reduced fibrin and stretch induced FN fibril assembly. Conclusion: Chronic hepatic congestion leads to sinusoidal thrombosis and strain, which in turn promote hepatic fibrosis. These studies mechanistically link congestive hepatopathy to hepatic fibrosis. (Hepatology 2014;)
[Show abstract][Hide abstract] ABSTRACT: Primary prevention of variceal bleeding is an important and long-debated topic in the management of patients with cirrhosis and esophageal varices. Prophylaxis is recommended for high-risk patients with small esophageal varices (advanced liver disease and/or presence of red wale marks) and those with medium/large varices. Nonselective β-blockers and endoscopic band ligation have been shown to be equally effective in primary prevention of variceal bleeding and are the only currently recommended therapies. Controversy still exists, however, regarding which one of these strategies is preferred. This article reviews the established recommendations and recent advances in the prevention of first esophageal variceal bleeding.
[Show abstract][Hide abstract] ABSTRACT: Background
Data on bacterial infections in hospitalised patients in the US with cirrhosis are derived largely from single centre data. Countrywide data in this population are lacking.AimTo assess prevalence of infections among hospitalised patients in the US and examine their impact on in-hospital mortality and health care resources utilisation.Methods
Nationwide Inpatient Sample (1998–2007) was queried for hospitalisations with cirrhosis and examined for infections including spontaneous bacterial peritonitis (SBP), urinary tract infection (UTI), skin and soft tissue infections, pneumonia and Clostridium difficile infections (CDI). In-hospital mortality, length of stay (LOS) and total charges were analysed.ResultsOf 742 391 admissions with cirrhosis, 168 654 (23%) had discharge diagnosis of any infection. Between 1998 and 2007, there was a trend towards increasing prevalence of infections (21–25%). Higher rates of infection were associated with ascites (22–25%) and renal insufficiency (RI) (38–43%). Infection with RI increased from 13% in 1998 to 27% in 2007. UTI was the most common infection (9–12%) followed by subcutaneous tissue infections (5–6%) and SBP (2–3%, around 12% in patients with ascites). Infection rate was similar among teaching and nonteaching hospitals with CDI and SBP being more common in teaching hospitals. In-hospital mortality was about 5%, over fivefold higher in infected cirrhotics, and associated with higher LOS and charges. Sepsis (38–42%), pneumonia (23–30%), SBP (16–23%) and CDI (11–16%) contributed most to in-hospital mortality.Conclusions
The prevalence of infections among hospitalised patients with cirrhosis in the US is increasing and is associated with in-hospital mortality, renal insufficiency and costs.
[Show abstract][Hide abstract] ABSTRACT: Analysis of the National Health and Nutrition Evaluation Survey (NHANES) 1988-1994 dataset found a relatively high seroprevalence (21%) of hepatitis E virus (HEV) infection in the US general population. Using data obtained within the NHANES 2009-2010 survey where a high performance assay for HEV was utilized, we have estimated the weighted sero-prevalence of HEV infection among US individuals 6 years and older. We also evaluated factors associated with HEV sero-positivity. A total of 8,814 individuals were included in the analysis. The median age of study participants was 37 years (IQR 17-58 years), with 51.2% being female. The weighted national seroprevalence of HEV was 6% (95% CI 5.1%-6.9%). About 0.5% of those with HEV had evidence of recent exposure (IgM positive). In the univariate analyses, factors associated with HEV seropositivity were increasing age (P-trend <0.001), birth outside of the US, Hispanic race, and “meat” consumption (>10times/month). No significant association was observed with low socio-economic status, water source or level of education. In the multivariate analysis, only older age remained predictive of HEV seropositivity. Conclusions: The weighted national seroprevalence of HEV in the US is much less than previously reported. Using data obtained with a high performance assay, the sero-prevalence of HEV was estimated at 6.0% in the US. Based on these results, the sero-prevalence of HEV is only one-third as high as previously reported. (Hepatology 2014)
[Show abstract][Hide abstract] ABSTRACT: Though hepatic involvement is common in patients with hereditary haemorrhagic telangiectasia (HHT), symptomatic liver disease is rare but potentially fatal without liver transplantation. Factors associated with clinically significant liver disease in patients with HHT are unknown.
In this prospective cohort study, we included consecutive patients from 2001 to 2011 with definite HHT, who underwent systematic protocol screening including contrast-enhanced hepatic CT and/or abdominal ultrasound. Using a multivariable logistic regression model, we developed a simple clinical scoring index to identify the presence of symptomatic liver disease (cardiac failure, portal hypertension, or biliary disease) or 'at-risk' liver disease (hepatic bruit, abnormal liver biochemistry, or elevated cardiac index).
Of 316 patients with definite HHT, 171 patients (54.1%; age 53.4±15.2 y, 101 females) had hepatic involvement on imaging. Twenty-nine patients had symptomatic liver disease (22 patients with high-output heart failure); 45 patients were 'at-risk' for liver disease. Using multivariable logistic regression analysis, we derived a score using age, gender, hemoglobin and alkaline phosphatase at presentation which could accurately distinguish patients with clinically significant liver involvement from patients with no or incidental liver lesions (c-statistic=0.80). A score <3 indicated low risk (<5%) and score >6 indicated high risk (>80%) of harboring clinically significant liver disease in HHT.
A simple scoring system can distinguish patients at low, moderate, and high risk of harboring clinically significant liver disease. With validation, this score may be used to identify patients for individualized screening and enrollment in clinical trials.
Journal of Hepatology 03/2014; · 9.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Infections worsen survival in cirrhosis; however, simple predictors of survival in infection-related acute-on-chronic liver failure (I-ACLF) derived from multi-center studies are required in order to improve prognostication and resource allocation. Methods: Using the NACSELD database, data from 18 centers were collected for survival analysis of prospectively enrolled cirrhotic patients hospitalized with an infection. We defined organ failures as (i) shock, (ii) grade III/IV hepatic encephalopathy(HE), (iii) need for dialysis (iv) mechanical ventilation. Determinants of survival with these organ failures were analyzed. Results: 507 patients were included (55 yrs, 52% HCV, 15.8% nosocomial infection, 96% Child score≥7) and 30-day evaluations were available in 453 patients. Urinary tract infection (UTI) (28.5%), and spontaneous bacterial peritonitis (SBP) (22.5%) were most prevalent. During hospitalization, 55.7% developed HE, 17.6% shock, 15.1% required renal replacement, and 15.8% needed ventilation; 23% died within 30-days and 21.6% developed second infections. Admitted patients developed none (38.4%), one (37.3%), two (10.4%), three (10%) or four (4%) organ failures. 30-day survival worsened with higher number of extra-hepatic organ failures, none (92%), one (72.6%), two (51.3%), three (36%) and all four (23%). I-ACLF was defined as ≥2 organ failures given the significant change in survival probability associated at this cutoff. Baseline independent predictors for development of ACLF were nosocomial infections, MELD score, low mean arterial pressure (MAP), and non-SBP infections. Independent predictors of poor 30-day survival were I-ACLF, second infections, and admission values of high MELD, low MAP, high white blood count and low albumin. In conclusion, using multi-center study data in hospitalized decompensated infected cirrhotic patients, I-ACLF defined by the presence of two or more organ failures using simple definitions is predictive of poor survival. (Hepatology 2014;).
[Show abstract][Hide abstract] ABSTRACT: Hepatic encephalopathy (HE) develops in up to 50% of patients with cirrhosis and is a feature of decompensated cirrhosis. With the goal of reviewing the evidence for treatment and prevention of overt hepatic encephalopathy, pubmed was searched using search terms hepatic encephalopathy AND treatment, limited to human studies from January 1, 2003, through December 1, 2013, and supplemented by key references. The inpatient incidence of HE is approximately 23,000 annually, and management of these patients is common for internists and subspecialists. Treatment of the hospitalized patient with HE has changed in recent years. Treatment entails 2 phases: induction and maintenance of remission. Most cases of significant HE are precipitated by infection, gastrointestinal bleeding, medications, or other culprits. All patients should be evaluated for secondary triggers of HE, and treatment should be initiated with a nonabsorbable disaccharide (ie, lactulose) in most patients. Rifaximin (off label) can be added in patients not responding to lactulose. Neomycin is a less preferred alternative to rifaximin owing to its adverse effect profile. Other therapies, including zinc, l-ornithine-l-aspartate, and branched-chain amino acids, can be considered for patients not responding to disaccharides and nonabsorbable antibiotics. Large portosystemic shunts may be embolized in patients with medically refractory recurrent or severe HE with otherwise well-compensated cirrhosis. Molecular Adsorbent Recirculating System is now available for patients with severe HE who do not respond to medical therapy. It is critically important that patients hospitalized with significant HE continue maintenance therapy at the time of dismissal to prevent further episodes. Patients with a first-time episode of HE can be administered lactulose, and careful instructions should be provided to patients and caregivers about dose titration to achieve 3 bowel movements daily. Patients with recurrent HE episodes despite lactulose use benefit from the addition of rifaximin, which decreases the frequency of recurrent HE episodes and related hospitalizations. Last, patients and their families should be counseled about the risk of motor vehicle accidents, which require mandatory reporting to the Department of Motor Vehicles in some states.
Mayo Clinic Proceedings 01/2014; · 5.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Non-invasive predictors identifying subjects with compensated liver disease at highest risk for transitioning to a decompensated state are lacking. We hypothesized that liver shear stiffness as measured by magnetic resonance elastography is an important non-invasive predictor of hepatic decompensation.
Among patients with advanced fibrosis undergoing magnetic resonance elastography (2007-11), a baseline cohort and follow up cohort (compensated liver disease) were established. Cause specific cox proportional hazards analysis adjusting for competing risks was utilized to determine the association between elevated liver shear stiffness and development of decompensation (hepatic encephalopathy, ascites, variceal bleeding).
In the baseline cohort (n=430), subjects with decompensated liver disease had a significantly higher mean liver shear stiffness (6.8 kPa, IQR 4.9-8.5) as compared to subjects with compensated liver disease (5.2 kPa, IQR 4.1-6.8). After adjustment for Model for End Stage Liver Disease score, hepatitis C, age, gender, albumin, and platelet count, the mean liver shear stiffness (OR=1.13, 95%CI 1.03-1.27) was an independently associated with decompensated cirrhosis at baseline. Over a median follow up of 27 months (n=167), 7.2% of subjects with compensated disease experienced hepatic decompensation. In the follow up cohort, the hazard of hepatic decompensation was 1.42 (95% CI 1.16 -1.75) per unit increase in liver shear stiffness over time. The hazard of hepatic decompensation was 4.96 (95% CI 1.4-17.0, p=0.019) for a subject with compensated disease and meanLSS value ⩾ 5.8 kPa as compared to an individual with compensated disease and lower mean LSS values.
Baseline liver shear stiffness assessed by magnetic resonance elastography is independently associated with decompensated liver disease.
Journal of Hepatology 12/2013; · 9.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Participants at a consensus conference proposed that cirrhosis-associated acute kidney injury (AKI) be defined based on an increase serum level of creatinine by >50% from the stable baseline value in <6 months or by ≥0.3 mg/dL in <48 hrs. We performed a prospective study to evaluate the ability of these criteria to predict mortality within 30 days of hospitalization among patients with cirrhosis and infection.
We followed 337 patients with cirrhosis who were admitted to the hospital with an infection or developed one during hospitalization (56% men; 56±10 y old; model for end-stage liver disease [MELD] score, 20±8) at 12 centers in North America. We compared data on 30-day mortality, length-of-stay in the hospital, and organ failure between patients with and without AKI.
Of the patients, 166 (49%) developed AKI during hospitalization, based on the consensus criteria. Patients who developed AKI were admitted with higher Child-Pugh scores than those who did not develop AKI (11.0±2.1 vs 9.6±2.1; P<.0001), as well as higher MELD scores (23±8 vs17±7; P<.0001) and lower mean arterial pressure (81±16 mm Hg vs 85±15 mm Hg; P<.01). Higher percentages of patients with AKI died within 30 days of hospitalization (34% vs 7%), were transferred to the intensive care unit (46% vs 20%), required ventilation (27% vs 6%), or went into shock (31% vs 8%); patients with AKI also had longer stays in the hospital (17.8±19.8 days vs 13.3±31.8 days) (all P<.001). Of AKI episodes, 56% were transient, 28% persistent, and 16% resulted in dialysis. Mortality was higher among those without renal recovery (80%), compared to partial (40%) or complete recovery (15%), or those who did not develop AKI (7%; P<.0001).
Among patients with cirrhosis, 30-day mortality is 10-fold higher among those with irreversible AKI than those without AKI. The consensus definition of AKI accurately predicts 30-day mortality, length of hospital stay, and organ failure.
[Show abstract][Hide abstract] ABSTRACT: & Aims: Liver stiffness measurements (LSMs), made by elastography, could independently predict outcomes of patients with chronic liver diseases (CLD). However, there is much variation in reporting and consistency of findings. We performed a systematic review and meta-analysis to evaluate the association between LSM and outcomes of patients with CLD.
We performed a systematic review of the literature, through February 2013, for studies that followed patients with CLD prospectively for at least 6 months and reported the association between baseline LSM and development of decompensated cirrhosis or hepatocellular carcinoma (HCC), as well as mortality. Summary adjusted relative risk (RR) estimates per unit of LSM and 95% confidence intervals (CI) were estimated using the random effects model.
Our final analysis included 17 studies, reporting on 7058 patients with CLD. Baseline LSMs were significantly associated with risk of hepatic decompensation (6 studies; RR, 1.07; 95% CI, 1.03-1.11), HCC (9 studies; RR, 1.11; 95% CI, 1.05-1.18), death (5 studies; RR, 1.22; 95% CI, 1.05-1.43) or a composite of these outcomes (7 studies; RR, 1.32; 95% CI, 1.16-1.51). We observed considerable heterogeneity among studies-primarily in the magnitude of effect, rather than the direction of effect. This heterogeneity could not be a result of the meta-regression analysis based on study location, etiology and stage of CLD, technique of LSM, or whether studies adjusted for covariates and method of imputing relationship.
Based on meta-analysis of cohort studies, degree of liver stiffness is associated with risk of decompensated cirrhosis, HCC, and death in patients with CLD. LSMs might therefore be used in risk stratification.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 08/2013; · 5.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Alcoholic hepatitis is a distinct clinical syndrome amongst people with chronic and active alcohol abuse with a potential for 30-40% mortality at one month amongst those with severe disease. Corticosteroids or pentoxifylline are the current pharmacological treatment options but provide only about 50% survival benefit. These agents are recommended for patients with modified discriminant function (mDF) of ≥32 or model for end-stage disease (MELD) score of ≥18. The Lille score is used to determine response to steroids. Currently, a minimum of 6 months abstinence from alcohol use is required for patients to receive a liver transplant, a requirement that cannot be met by patients with severe alcoholic hepatitis non-responsive to steroids (Lille score ≥0.45). Data are emerging on the benefit of liver transplantation in select patients with first episode of severe alcoholic hepatitis. This review also focuses on recent treatment trials in alcoholic hepatitis including liver transplantation and its associated controversies, as well as possible future targets and pharmacological treatment options for patients with alcoholic hepatitis that are being pursued through upcoming consortium studies.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 06/2013; · 5.64 Impact Factor