Jessica L. Mellinger

Hepatic steatosis and cardiovascular disease outcomes: An analysis of the Framingham Heart Study

BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and is associated with development of metabolic disease including atherosclerotic cardiovascular disease (CVD). Our aim is to examine the association of hepatic steatosis with prevalent clinical and subclinical CVD outcomes in a large community-based sample, the Framingham Heart Study. METHODS Hepatic steatosis was measured in 3529 participants using multidetector computed tomography scanning. Multivariable logistic regression was used to determine whether hepatic steatosis is associated with prevalent CVD adjusted for covariates. We also tested whether associations were independent of other metabolic diseases/traits. The primary clinical outcome was composite prevalent clinical CVD defined by prior non-fatal myocardial infarction, stroke, transient ischemic attack, heart failure, or peripheral arterial disease. Subclinical cardiovascular outcomes were coronary artery calcium (CAC) and abdominal artery calcium (AAC). RESULTS 3014 participants were included (50.5% women). There was a non-significant association of hepatic steatosis with clinical CVD (OR 1.14 [p=0.07]). Hepatic steatosis was associated with both CAC and AAC (OR 1.20 [p<0.001] and OR 1.16 [p<0.001], respectively). Associations persisted for CAC even when controlling for other risk factors/metabolic diseases, but for AAC, the associations became non-significant after adjustment for visceral adipose tissue. The association between hepatic steatosis and AAC was stronger in men than in women (p sex interaction=0.022). CONCLUSION There was a significant association of hepatic steatosis with subclinical CVD outcomes independent of many metabolic diseases/traits with a trend towards association between hepatic steatosis and clinical CVD outcomes. The association with AAC was stronger in men than in women.

Multidisciplinary Management of Patients With Cirrhosis: A Need for Care Coordination

Cirrhosis is a common chronic condition with high rates of morbidity and mortality. Optimal medical management involves a multidisciplinary approach, but coordination between medical specialties needs to be improved. This clinical perspective discusses care coordination interventions that have been successful in other disease states and how they could be applied to the management of cirrhosis.

Increased Morbidity and Mortality Associated with Falls Among Patients with Cirrhosis

BACKGROUND Injuries are more morbid and complicated to manage in patients with cirrhosis. However, data are limited regarding the relative risk of injury and severity of injury from falls in patients with cirrhosis compared with those without cirrhosis. METHODS We examined the nationally representative National Emergency Department Sample, an all-payer database including all patients presenting with falls, 2009-2012. We determined the relative risks for and clinical associations with severe injuries. Outcomes included hospitalization, length of stay, costs, and in-hospital death. Outcomes were compared with those of patients with congestive heart failure. RESULTS We identified 102,977 visits involving patients with cirrhosis and 26,996,120 involving patients without cirrhosis who presented with a fall. Overall and compared with patients with congestive heart failure, the adjusted risk of severe injury was higher for patients with cirrhosis. These included intracranial hemorrhage (2.33; 95% confidence interval [CI], 2.02-2.68), skull fracture (1.75; 95% CI, 1.53-2.00), and pelvic fracture (1.71; 95% CI, 1.56-1.88). Risk was lower for less-severe injuries, such as concussion (0.95; 95% CI, 0.86-1.06) and lower-leg fracture (0.86; 95% CI, 0.80-0.91). Risk factors significantly positively associated with severe injury on multivariate analysis were hepatic encephalopathy, alcohol abuse, and infection. Cirrhosis was associated with increased risk of in-hospital death, longer length of stay, and higher costs after a fall. All outcomes were worse compared with those for patients with congestive heart failure CONCLUSION: Falls are common in patients with cirrhosis, and they are more likely to incur severe injuries, with increased hospital costs and risk of death. Poor outcomes are most associated with ascites, hepatic encephalopathy, alcohol abuse, and infection, highlighting the subgroups at highest risk and most likely to benefit from preventative interventions.

Hospital resource intensity and cirrhosis mortality in United States

AIM To determine whether hospital characteristics predict cirrhosis mortality and how much variation in mortality is attributable to hospital differences. METHODS We used data from the 2005-2011 Nationwide Inpatient Sample and the American Hospital Association Annual survey to identify hospitalizations for decompensated cirrhosis and corresponding facility characteristics. We created hospital-specific risk and reliability-adjusted odds ratios for cirrhosis mortality, and evaluated patient and facility differences based on hospital performance quintiles. We used hierarchical regression models to determine the effect of these factors on mortality. RESULTS Seventy-two thousand seven hundred and thirty-three cirrhosis admissions were evaluated in 805 hospitals. Hospital mean cirrhosis annual case volume was 90.4 (range 25-828). Overall hospital cirrhosis mortality rate was 8.00%. Hospital-adjusted odds ratios (aOR) for mortality ranged from 0.48 to 1.89. Patient characteristics varied significantly by hospital aOR for mortality. Length of stay averaged 6.0 ± 1.6 days, and varied significantly by hospital performance (P < 0.001). Facility level predictors of risk-adjusted mortality were higher Medicaid case-mix (OR = 1.00, P = 0.029) and LPN staffing (OR = 1.02, P = 0.015). Higher cirrhosis volume (OR = 0.99, P = 0.025) and liver transplant program status (OR = 0.83, P = 0.026) were significantly associated with survival. After adjusting for patient differences, era, and clustering effects, 15.3% of variation between hospitals was attributable to differences in facility characteristics. CONCLUSION Hospital characteristics account for a significant proportion of variation in cirrhosis mortality. These findings have several implications for patients, providers, and health care delivery in liver disease care and inpatient health care design.

The high burden of alcoholic cirrhosis in privately insured persons in the United States

Alcoholic cirrhosis (AC) is a major cause of liver‐related morbidity and mortality in the United States. Rising rates of alcohol use disorders in the United States will likely result in more alcoholic liver disease. Our aim was to determine the prevalence, health care use, and costs of AC among privately insured persons in the United States. We collected data from persons aged 18‐64 with AC (identified by codes from the International Classification of Diseases, Ninth and Tenth Revisions) enrolled in the Truven MarketScan Commercial Claims and Encounters database (2009‐2015). We determined yearly prevalence, weighted to the national employer‐sponsored, privately insured population. Using competing risk analysis, we estimated event rates for portal hypertensive complications and estimated the association between AC and costs as well as admissions and readmissions. In 2015, 294,215 people had cirrhosis and 105,871 (36%) had AC. Mean age at AC diagnosis was 53.5 years, and 32% were women. Over the 7 years queried, estimated national cirrhosis prevalence rose from 0.19% to 0.27% (P < 0.001) and for AC from 0.07% to 0.10% (P < 0.001). Compared to non‐AC, AC enrollees were significantly more likely to have portal hypertensive complications at diagnosis and higher yearly cirrhosis and alcohol‐related admissions (25 excess cirrhosis admissions and 6.3 excess alcohol‐related admissions per 100 enrollees) as well as all‐cause readmissions. Per‐person costs in the first year after diagnosis nearly doubled for AC versus non‐AC persons (US

Access to Subspecialty Care And Survival Among Patients With Liver Disease.

44,835 versus 23,319). Conclusion: In a nationally representative cohort of privately insured persons, AC enrollees were disproportionately sicker at presentation, were admitted and readmitted more often, and incurred nearly double the per‐person health care costs compared to those with non‐AC. (Hepatology 2018).

A Risk Score to Predict the Development of Hepatic Encephalopathy in a Population-Based Cohort of Patients with Cirrhosis

OBJECTIVES:Access to subspecialty care may be difficult for patients with liver disease, but it is unknown whether access influences outcomes among this population. Our objectives were to determine rates and predictors of access to ambulatory gastrointestinal (GI) subspecialty care for patients with liver disease and to determine whether access to subspecialty GI care is associated with better survival.METHODS:We studied 28,861 patients within the Veterans Administration VISN 11 Liver Disease cohort who had an ICD-9-CM diagnosis code for liver disease from 1 January 2000 through 30 May 2011. Access was defined as a completed outpatient clinic visit with a gastroenterologist or hepatologist at any time after diagnosis. Multivariable logistic regression was used to determine predictors of access to a GI subspecialist. Survival curves were compared between those who did and those who did not see a specialist, with propensity score adjustment to account for other covariates that may affect access.RESULTS:Overall, 10,710 patients (37%) had a completed GI visit. On multivariable regression, older patients (odds ratio (OR) 0.98, P<0.001), those with more comorbidities (OR 0.98, P=0.01), and those living farther from a tertiary-care center (OR 0.998/mi, P<0.001) were less likely to be seen in clinic. Patients who were more likely to be seen included those who had hepatitis C (OR 1.5, P<0.001) or cirrhosis (OR 3.5, P<0.001) diagnoses prior to their initial visit. Patients with an ambulatory GI visit at any time after diagnosis were less likely to die at 5 years when compared with propensity-score-matched controls (hazard ratio 0.81, P<0.001).CONCLUSIONS:Access to ambulatory GI care was associated with improved 5-year survival for patients with liver disease. Innovative care coordination techniques may prove beneficial in extending access to care to liver disease patients.

Transplantation for Alcohol-related Liver Disease: Is It Fair?

Over 40% of patients with cirrhosis will develop hepatic encephalopathy (HE). HE is associated with decreased survival, falls, motor vehicle accidents, and frequent hospitalization. Accordingly, we aimed to develop a tool to risk‐stratify patients for HE development. We studied a population‐based cohort of all patients with cirrhosis without baseline HE (n = 1,979) from the Veterans Administration from Michigan, Indiana, and Ohio (January 1, 2005‐December 31, 2010) using demographic, clinical, laboratory, and pharmacy data. The primary outcome was the development of HE. Risk scores were constructed with both baseline and longitudinal data (annually updated parameters) and validated using bootstrapping. The cohort had a mean age of 58.0 ± 8.3 years, 36% had hepatitis C, and 17% had ascites. Opiates, benzodiazepines, statins, and nonselective beta‐blockers were taken at baseline by 24%, 13%, 17%, and 12%, respectively. Overall, 863 (43.7%) developed HE within 5 years. In multivariable models, risk factors (hazard ratio, 95% confidence interval) for HE included higher bilirubin (1.07, 1.05‐1.09) and nonselective beta‐blocker use (1.34, 1.09‐1.64), while higher albumin (0.54, 0.48‐0.59) and statin use (0.80, 0.65‐0.98) were protective. Other clinical factors, including opiate and benzodiazepine use, were not predictive. The areas under the receiver operating characteristics curve for HE using the four significant variables in baseline and longitudinal models were 0.68 (0.66‐0.70) and 0.73 (0.71‐0.75), respectively. Model effects were validated and converted into a risk score. A score ≤0 in our longitudinal model assigns a 6% 1‐year probability of HE, while a score >20 assigns a 38% 1‐year risk. Conclusion: Patients with cirrhosis can be stratified by a simple risk score for HE that accounts for changing clinical data; our data also highlight a role for statins in reducing cirrhosis complications including HE. (Hepatology 2017).

Quality of care metrics in chronic hepatitis B.

Aims Alcohol-related liver disease (ALD) is the second leading cause of liver transplantation performed in the USA and Europe. We aimed to provide a narrative review of the major ethical issues governing transplantation for ALD. Methods We performed a narrative review of the ethical concepts in organ allocation for ALD, including alcoholic hepatitis. Results Ethical concerns regarding organ allocation for ALD involve issues of urgency, utility and justice. Post-transplant outcomes for ALD patients are good and ethical considerations limiting organs solely because of alcohol etiology do not bear scrutiny. Conclusion ALD will continue to be a major cause for liver failure. The main criteria for transplant in ALD should be the patients risk of return to harmful drinking, alongside standard assessments of physical and psychosocial fitness for transplant.

Alcohol Consumption in Patients with Non-alcoholic Fatty Liver Disease: Convenient vs. Inconvenient Truths

An increasing emphasis in the US health care system is being placed on improving the quality of care for patients with various common chronic diseases for which there are interventions to improve outcomes and reduce resource use. In hepatology, quality measures are best established for chronic hepatitis C virus (HCV) care such as viral load and genotype testing prior to treatment, screening for hepatocellular carcinoma (HCC) in patients with cirrhosis, and shared decision-making for treatment options. However, quality metrics for chronic hepatitis B (HBV)-related medical care are substantially lagging behind. The reasons for this may be inadequate recognition of the significant morbidity and mortality related to HBV, a lack of patient/physician advocacy, and controversy regarding meaningful quality metrics. An estimated 1.4 million to 1.8 million Americans have chronic HBV, and 15%-40% of these individuals are projected to develop complications such as cirrhosis, HCC, or liver failure during their lifetime. However, a diagnosis of chronic HBV requires a high index of suspicion based upon risk factors such as country of birth, and many providers are uncertain on how to interpret HBV serologies. Furthermore, optimal management of chronic HBV requires accurate identification of the phase of infection, reliable assessment of disease severity, and knowledge of who and when to treat. Fortunately, there are several safe and well-tolerated oral antiviral therapies that can reduce the rate of disease progression and even potentially improve survival. However, endpoints for treatment discontinuation and means to enhance hepatitis B surface antigen clearance leading to a virologic “cure” remain elusive. In this issue of HEPATOLOGY, Serper et al. analyzed the Veterans Administration (VA) claims database to determine the quality of care delivery and clinical outcomes in over 12,000 veterans with chronic HBV seen between 1999 and 2013. Although there were missing data in many of the process measures analyzed, the large size of this national data set along with the established validity of the diagnostic codes employed improve the internal validity of their findings. The authors found that >90% of veterans received appropriate initial serum alanine aminotransferase (ALT) testing but that there was low overall use of serum HBV DNA (44%) and hepatitis B e antigen (HBeAg) testing (49%) initially and during a mean follow-up of 2 years. In addition, adherence to the recommended screening for HCC was low (39%), particularly in high-risk patients without cirrhosis. Although receipt of specialty care improved the adherence rate, only one-third of patients seen by a specialist received the recommended biannual imaging. Moreover, the authors found no significant improvement in adherence to recommended care processes over the 14-year study period. The reason(s) for the low rates of adherence to HBV quality care metrics in the VA is not clear. Over the past 10 years, screening and treatment of HCV in the VA health care system have received a great deal of attention, while little, if any, focus has been directed to the diagnosis and management of chronic HBV despite the high hepatitis B surface antigen seroprevalence among Abbreviations: ALT, alanine aminotransferase; HAV, hepatitis A virus; HBeAg, hepatitis B e antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HIV, human immunodeficiency virus; VA, Veterans Administration.