Elliot B. Tapper

Levels of Alanine Aminotransferase Confound Use of Transient Elastography to Diagnose Fibrosis in Patients With Chronic Hepatitis C Virus Infection

BACKGROUND & AIMS Hepatic elastography (HE) is a noninvasive technique that measures liver stiffness and is used to diagnose hepatic fibrosis. It can help patients who are thought to have early-stage disease avoid a staging liver biopsy, but only when confounding variables that increase liver stiffness are excluded. Chronic inflammation from hepatitis C virus (HCV) infection is not considered to be one of these variables. METHODS We identified 684 patients with HCV and METAVIR fibrosis scores of 0-2 from a prospective, multi-institutional study of liver stiffness in 2880 patients with chronic liver disease. Patients were 49.6 ± 9.0 years old, 64.3% were male, and they had an average body mass index of 26.7 ± 4.1 kg/m(2). RESULTS In a multivariate analysis, inflammation (based on histologic analysis) and level of alanine aminotransferase (ALT) were associated with liver stiffness. The chances of a patient having a level of stiffness that indicates cirrhosis increased with grade of inflammation and level of ALT. By using a conservative 14.5-kPa cutoff for the diagnosis of cirrhosis, grade 3 inflammation had an odds ratio of 9.10 (95% confidence interval, 2.49-33.4). Likewise, levels of ALT greater than 80 and 120 IU/L had odds ratios of 3.84 (95% confidence interval, 2.10-7.00) and 4.10 (95% confidence interval, 2.18-7.69), respectively. The effect of the level of ALT persisted when analysis was restricted to patients with fibrosis scores of F0 to F1. CONCLUSIONS In patients with HCV infection and early-stage fibrosis, increased levels of ALT correlate with liver stiffness among patients in the lowest strata of fibrosis (METAVIR scores 0-2). Patients without fibrosis but high levels of ALT could have liver stiffness within the range for cirrhosis. Inflammation should be considered a confounding variable in analysis of liver stiffness.

FibroScan (Vibration-Controlled Transient Elastography): Where Does It Stand in the United States Practice

With widespread screening and increasingly effective treatments for patients with viral hepatitis as well as the increasing prevalence of nonalcoholic fatty liver disease, the population presenting to the care of gastroenterologists and hepatologists is certain to increase. Assessment of advanced liver disease is traditionally invasive and expensive. Vibration-controlled transient elastography, commonly delivered by the FibroScan device, is an option recently approved by the Food and Drug Administration for the noninvasive assessment of liver disease at the point of care. Herein, we review the promise and pitfalls of vibration-controlled transient elastography with the aim of providing clinicians with a framework to interpret its results and apply this technology to the changing needs of our patients.

The risks of thromboembolism vs. recurrent gastrointestinal bleeding after interruption of systemic anticoagulation in hospitalized inpatients with gastrointestinal bleeding: a prospective study

OBJECTIVES:Anticoagulants carry a significant risk of gastrointestinal bleeding (GIB). Data regarding the safety of anticoagulation continuation/cessation after GIB are limited. We sought to determine the safety and risk of continuation of anticoagulation after GIB.METHODS:We conducted a prospective observational cohort study on consecutive patients admitted to the hospital who had GIB while on systemic anticoagulation. Patients were classified into two groups at hospital discharge after GIB: those who resumed anticoagulation and those who had anticoagulation discontinued. Patients in both groups were contacted by phone 90 days after discharge to determine the following outcomes: (i) thromboembolic events, (ii) hospital readmissions related to GIB, and (iii) mortality. Univariate and multivariate Cox proportional hazards were used to determine factors associated with thrombotic events, rebleeding, and death.RESULTS:We identified 197 patients who developed GIB while on systemic anticoagulation (n=145, 74% on warfarin). Following index GIB, anticoagulation was discontinued in 76 patients (39%) at discharge. In-hospital transfusion requirements, need for intensive care unit care, and etiology of GIB were similar between the two groups. During the follow-up period, 7 (4%) patients suffered a thrombotic event and 27 (14%) patients were readmitted for GIB. Anticoagulation continuation was independently associated on multivariate regression with a lower risk of major thrombotic episodes within 90 days (hazard ratio (HR)=0.121, 95% confidence interval (CI)=0.006–0.812, P=0.03). Patients with any malignancy at time of GIB had an increased risk of thromboembolism in follow-up (HR=6.1, 95% CI=1.18–28.3, P=0.03). Anticoagulation continuation at discharge was not significantly associated with an increased risk of recurrent GIB at 90 days (HR=2.17, 95% CI=0.861–6.67, P=0.10) or death within 90 days (HR=0.632, 95% CI=0.216–1.89, P=0.40).CONCLUSIONS:Restarting anticoagulation at discharge after GIB was associated with fewer thromboembolic events without a significantly increased risk of recurrent GIB at 90 days. The benefits of continuing anticoagulation at discharge may outweigh the risks of recurrent GIB.

Standard assessments of frailty are validated predictors of mortality in hospitalized patients with cirrhosis

The risk of morbidity and mortality for hospitalized patients with cirrhosis is high and incompletely captured by conventional indices. We sought to evaluate the predictive role of frailty in an observational cohort study of inpatients with decompensated cirrhosis between 2010 and 2013. The primary outcome was 90‐day mortality. Secondary outcomes included discharge to a rehabilitation hospital, 30‐day readmission, and length of stay. Frailty was assessed with three metrics: activities of daily living (ADL), the Braden Scale, and the Morse fall risk score. A predictive model was validated by randomly dividing the population into training and validation cohorts: 734 patients were admitted 1358 times in the study period. The overall 90‐day mortality was 18.3%. The 30‐day readmission rate was 26.6%, and the rate of discharge to a rehabilitation facility was 14.3%. Adjusting for sex, age, Model for End‐Stage Liver Disease, sodium, and Charlson index, the odds ratio for the effect of an ADL score of less than 12 of 15 on mortality is 1.83 (95% confidence interval [CI] 1.05‐3.20). A predictive model for 90‐day mortality including ADL and Braden Scale yielded C statistics of 0.83 (95% CI 0.80‐0.86) and 0.77 (95% CI 0.71‐0.83) in the derivation and validation cohorts, respectively. Discharge to a rehabilitation hospital is predicted by both the ADL (<12) and Braden Scale (<16), with respective adjusted odds ratios of 3.78 (95% CI 1.97‐7.29) and 6.23 (95% CI 2.53‐15.4). Length of stay was associated with the Braden Scale (<16) (hazard ratio = 0.63, 95% CI 0.44‐0.91). No frailty measure was associated with 30‐day readmission. Conclusions: Readily available, standardized measures of frailty predict 90‐day mortality, length of stay, and rehabilitation needs for hospitalized patients with cirrhosis. (Hepatology 2015;62:584–590

Is 3 the new 1: perspectives on virology, natural history and treatment for hepatitis C genotype 3.

Affecting 2–3% of the worlds population, hepatitis C is a common viral infection which is a significant cause of morbidity and mortality. Hepatitis C genotype 1 is the dominant viral genotype among Western patients. For the last 20 years, in the era of interferon‐based therapy, it was far more difficult to treat relative to genotypes 2 and 3. Accordingly, a significant focus of research was on new antiviral agents for the dominant genotype 1 patient. Now, as promising specific treatments are being introduced for genotype 1, the attention of clinicians and researchers has turned back to the 50–70 million patients infected with a nongenotype 1 hepatitis C. Furthermore, after recent, larger randomized trials, we have realized that genotype 2 is truly interferon sensitive while genotype 3 patients are far less successful with therapy. In this fundamentally altered landscape, genotype 3 is now potentially the most difficult to treat genotype and an area of intense research for new drug development. Herein we review the virology, natural history and the treatment of genotype 3 hepatitis C.

A Quality Improvement Initiative Reduces 30-Day Rate of Readmission for Patients With Cirrhosis.

BACKGROUND & AIMS Many hospitalized patients with cirrhosis are readmitted to the hospital within 30 days, particularly those with hepatic encephalopathy (HE). We performed a prospective study to assess the effects of a quality improvement protocol on readmission to a transplant centers liver unit within 30 days. METHODS We studied the effects of a quality improvement program in 824 unique patients with decompensated cirrhosis or receiving liver transplants (mean Model for End-Stage Liver Disease score, 17.7 ± 7.4) admitted to an inpatient hepatology unit from 2010 through 2013. The study had a year-long control period (626 admissions receiving usual care) and 2 intervention phases: a hand-held checklist phase (470 admissions) and an electronic phase that incorporated the checklist items into the electronic provider order entry system (624 admissions). The intervention phases included goal-directed lactulose therapy and rifaximin for overt HE, and prompts for antibiotic prophylaxis of spontaneous bacterial peritonitis. The primary endpoint was the difference in 30-day readmissions between the control and intervention phases. Trends in 30-day readmissions were compared with those of patients with decompensated cirrhosis admitted at another center. RESULTS During the electronic phase, study subjects had 40% lower adjusted odds of 30-day readmission than during the control period. The slope of the decline in readmissions over time was significantly greater than for patients at the other center (P < .0001). The proportion of patients with greater than grade 2 HE and 30-day readmission was 48.9% (66 of 135) in the control period versus 26.0% (27 of 104) in the electronic phase (P = .0003). Treatment of HE with rifaximin and secondary prophylaxis of spontaneous bacterial peritonitis with antibiotics (on discharge) were associated with lower adjusted odds of readmission (odds ratios, 0.39 and 0.40, respectively). The electronic phase was associated with 1.34 fewer hospital days for HE compared with the control period (P = .01). CONCLUSIONS In a prospective study, a quality improvement initiative that included electronic decision support reduced readmissions of patients with cirrhosis to the hospital within 30 days.

Refining the Ammonia Hypothesis: A Physiology-Driven Approach to the Treatment of Hepatic Encephalopathy

Hepatic encephalopathy (HE) is one of the most important complications of cirrhosis and portal hypertension. Although the etiology is incompletely understood, it has been linked to ammonia directly and indirectly. Our goal is to review for the clinician the mechanisms behind hyperammonemia and the pathogenesis of HE to explain the rationale for its therapy. We reviewed articles collected through a search of MEDLINE/PubMed, Cochrane Database of Systematic Reviews, and Google Scholar between October 1, 1948, and December 8, 2014, and by a manual search of citations within retrieved articles. Search terms included hepatic encephalopathy, ammonia hypothesis, brain and ammonia, liver failure and ammonia, acute-on-chronic liver failure and ammonia, cirrhosis and ammonia, portosytemic shunt, ammonia and lactulose, rifaximin, zinc, and nutrition. Ammonia homeostatsis is a multiorgan process involving the liver, brain, kidneys, and muscle as well as the gastrointestinal tract. Indeed, hyperammonemia may be the first clue to poor functional reserves, malnutrition, and impending multiorgan dysfunction. Furthermore, the neuropathology of ammonia is critically linked to states of systemic inflammation and endotoxemia. Given the complex interplay among ammonia, inflammation, and other factors, ammonia levels have questionable utility in the staging of HE. The use of nonabsorbable disaccharides, antibiotics, and probiotics reduces gut ammoniagenesis and, in the case of antibiotics and probiotics, systemic inflammation. Nutritional support preserves urea cycle function and prevents wasting of skeletal muscle, a significant site of ammonia metabolism. Correction of hypokalemia, hypovolemia, and acidosis further assists in the reduction of ammonia production in the kidney. Finally, early and aggressive treatment of infection, avoidance of sedatives, and modification of portosystemic shunts are also helpful in reducing the neurocognitive effects of hyperammonemia. Refining the ammonia hypothesis to account for these other factors instructs a solid foundation for the effective treatment and prevention of hepatic encephalopathy.

Paraduodenal pancreatitis: Clinical performance of MR imaging in distinguishing from carcinoma

PURPOSE To evaluate the diagnostic performance of contrast material-enhanced magnetic resonance (MR) imaging for distinguishing paraduodenal pancreatitis (PDP) from pancreatic head duct adenocarcinoma (CA) in patients with diagnoses confirmed by histopathologic analysis. MATERIALS AND METHODS This retrospective study was approved by the institutional review board and is HIPAA compliant. Between July 2007 and July 2010, 47 patients who underwent Whipple procedure and MR imaging less than 60 days before surgery were identified retrospectively. Two relatively inexperienced fellowship trainees with 9 months of body fellowship training were asked to record the presence or absence of three MR imaging features: focal thickening of the second portion of the duodenum; abnormal enhancement of the second portion of the duodenum; and cystic focus in the expected region of the accessory pancreatic duct. Strict criteria for diagnosis of PDP included presence of all three imaging features. Any case that did not fulfill the criteria was classified as CA. Sensitivity, specificity, positive predictive value, and negative predictive value for characterization of PDP was calculated for each reader with 95% confidence intervals. A κ test assessed level of agreement between readers. RESULTS Each reader correctly categorized 15 of 17 (88.2%) PDP cases when all three imaging criteria were met. Alternatively, 26 of 30 (86.7%) pancreatic duct CA were correctly categorized as inconsistent with PDP. Four patients with histopathologic diagnosis of CA were incorrectly classified as PDP by each reader. Agreement between the two readers showed substantial κ agreement for the diagnosis of PDP and differentiation from pancreatic duct CA. CONCLUSION Contrast-enhanced MR imaging may help accurately identify PDP and distinguish it from CA when strict diagnostic criteria are followed. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13112056/-/DC1.

Cost-Effective Evaluation of Nonalcoholic Fatty Liver Disease With NAFLD Fibrosis Score and Vibration Controlled Transient Elastography.

OBJECTIVES:The risk of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is traditionally assessed with a liver biopsy, which is both costly and associated with adverse events.METHODS:We sought to compare the cost-effectiveness of four different strategies to assess fibrosis risk in patients with NAFLD: vibration controlled transient elastography (VCTE), the NAFLD fibrosis score (NFS), combination testing with NFS and VCTE, and liver biopsy (usual care). We developed a probabilistic decision analytical microsimulation state-transition model wherein we simulated a cohort of 10,000 50-year-old Americans with NAFLD undergoing evaluation by a gastroenterologist. VCTE performance was obtained from a prospective cohort of 144 patients with NAFLD.RESULTS:Both the NFS alone and the NFS/VCTE strategies were cost effective at

Evaluation of proton pump inhibitor use on treatment outcomes with ledipasvir and sofosbuvir in a real‐world cohort study

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