A risk score to predict the development of hepatic encephalopathy in a population‐based cohort of patients with cirrhosis

Tapper, Elliot B.; Parikh, Neehar D.; Sengupta, Neil; Mellinger, Jessica L.; Ratz, David; Lok, Anna S.; Su, Grace L.

doi:10.1002/hep.29628

Cited by 76 publications

(84 citation statements)

References 41 publications

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“…For instance, it may be that opioid‐induced altered mental status is being misdiagnosed as HE. However, the annual incidence of HE and other decompensation events are comparable to what has been published in the literature, providing external validity to our results . In addition, any event prompting a billing code for HE or the initiation of lactulose/rifaximin is likely to be clinically important.…”

Section: Discussionsupporting

confidence: 85%

“…In fact, one single‐centre study reported that an opioid prescription at discharge increased overall readmissions, but not hepatic encephalopathy‐related readmissions over 6 months . Furthermore, in a longitudinal cohort of United States veterans, baseline opioid use was not found to be an independent predictor of hepatic encephalopathy …”

Section: Introductionmentioning

confidence: 99%

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Opioid prescriptions are associated with hepatic encephalopathy in a national cohort of patients with compensated cirrhosis

Moon

Jiang

Rogal

et al. 2020

Aliment Pharmacol Ther

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Summary Background Opioids are often prescribed for pain in cirrhosis and may increase the risk of hepatic encephalopathy (HE). Aim To assess the association between opioids and HE in patients with well‐compensated cirrhosis. Methods We used the IQVIA PharMetrics (Durham, NC) database to identify patients aged 18‐64 years with cirrhosis. We excluded patients with any decompensation event from 1 year before cirrhosis diagnosis to 6 months after cirrhosis diagnosis. Over the 6 months after cirrhosis diagnosis, we determined the duration of continuous opioid use and classified use into short term (1‐89 days) and chronic (90‐180 days). We assessed whether patients developed HE over the subsequent year (ie 6‐18 months after cirrhosis diagnosis). We used a landmark analysis and performed multivariable Cox proportional hazards regression to assess associations between opioid use and HE, adjusting for relevant confounders. Results The cohort included 6451 patients with compensated cirrhosis, of whom 23.3% and 4.7% had short‐term and chronic opioid prescriptions respectively. Over the subsequent year, HE occurred in 6.3% patients with chronic opioid prescriptions, 5.0% with short‐term opioid prescriptions and 3.3% with no opioid prescriptions. In the multivariable model, an increased risk of HE was observed with short‐term (adjusted hazard ratio, HR 1.44, 95% CI 1.07‐1.94) and chronic opioid prescriptions (adjusted HR 1.83, 95% CI 1.07‐3.12) compared to no opioid prescriptions. Conclusion In this national cohort of privately insured patients with cirrhosis, opioid prescriptions were associated with the risk of incident HE. Opioid use should be minimised in those with cirrhosis and, when required, limited to short duration.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Opioid prescriptions are associated with hepatic encephalopathy in a national cohort of patients with compensated cirrhosis

Moon

Jiang

Rogal

et al. 2020

Aliment Pharmacol Ther

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“…For patients with nonalcoholic nonviral cirrhosis, the incidence rate of HE was lower than for other causes of cirrhosis. Data on the prediction of decompensation and HE have been drawn from younger (<60 years old) cohorts of patients with predominantly HCV or alcohol‐related cirrhosis . However, many, perhaps most, new diagnoses of cirrhosis in the United States are related to NAFLD .…”

Section: Discussionmentioning

confidence: 99%

Incidence of and Risk Factors for Hepatic Encephalopathy in a Population‐Based Cohort of Americans With Cirrhosis

et al. 2019

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Hepatic encephalopathy (HE) is a devastating complication of cirrhosis. Data are limited regarding the incidence of and risk factors for HE among contemporary patients in the context of the shifting epidemiology of cirrhosis. We examined a 20% random sample of U.S. Medicare enrollees with cirrhosis and Part D prescription coverage from 2008 to 2014. We modelled incident HE using demographic, clinical, and pharmacologic data. Risk factors for HE were evaluated, including demographics/socioeconomics, cirrhosis etiology, severity of liver disease, and pharmacotherapy, along with gastroenterology consultation, as time‐varying covariates. Among 166,192 Medicare enrollees with cirrhosis followed for 5.25 (interquartile range [IQR], 2.00‐7.00) years, the overall incidence of HE was 11.6 per 100 patient‐years. The cohort's median age was 65 years (IQR, 57‐72), 31% had alcohol‐related cirrhosis, and 49% had likely nonalcoholic fatty liver disease cirrhosis. The two strongest associations with HE were alcohol‐related cirrhosis (adjusted hazard ratio [AHR], 1.44; 95% confidence interval [CI], 1.40, 1.47, relative to nonalcoholic nonviral cirrhosis) and the presence of portal hypertension (AHR, 3.42; 95% CI, 3.34, 3.50). Adjusting for confounders, benzodiazepines (AHR, 1.24; 95% CI, 1.21, 1.27), gamma aminobutyric acid (GABA)ergics (AHR, 1.17; 95% CI, 1.14, 1.21), opioids (AHR, 1.24; 95% CI, 1.21, 1.27), and proton pump inhibitors (PPIs) (AHR, 1.41; 95% CI, 1.38, 1.45) were all associated with incident HE. Only benzodiazepines, however, were associated with the risk of hospitalization with HE (incidence‐rate ratio, 1.23; 95% CI, 1.20, 1.26). Conclusion: Novel data regarding the risk of HE for contemporary patients with cirrhosis are provided. The incidence of HE in an older population of Americans with cirrhosis is high, particularly among those with alcohol‐related cirrhosis and portal hypertension. Several medication classes, namely PPIs, opiates, GABAergics, and benzodiazepines, represent potentially modifiable risk factors for HE.

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“…One example is the model proposed by Riggio et al, who developed and validated a risk score to identify patients with cirrhosis at 1‐year risk for overt HE based on previous HE and albumin levels . Tapper et al developed a score to stratify the HE risk according to the presence of some clinical variables (laboratory tests and drugs), such as bilirubin, albumin as well as statins and non‐selective betablockers use . However, this simple risk score showed some concerns, beyond of being a retrospective study, such as the lack of some essential information (ie, previous HE episodes) or the use of inadequate statistical methods (ie, Cox regression analysis) .…”

Section: Discussionmentioning

confidence: 99%

Oral glutamine challenge is a marker of altered ammonia metabolism and predicts the risk of hepatic encephalopathy

Ampuero

Gil

Viloria

et al. 2019

Liver International

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Background The current therapies for hepatic encephalopathy (HE) are not completely effective in all patients, probably due to the physiopathological heterogeneity and the different conditions underlying the bout of HE. We hypothesized that oral glutamine challenge (OGC) is able to predict the risk of HE through the identification of various features and types of HE. Methods We included 238 cirrhotic patients (198 without and 40 with a previous HE episode) that underwent OGC, obtaining baseline and 60 minutes post‐load ammonia levels. Combined evaluation of baseline hyperammonemia (>78 mcg/dL) and impaired OGC (Δ >32 mcg/dL) defined low‐, intermediate‐ and high‐risk groups. Patients were censored at HE, liver transplantation and death or 6 years of follow‐up. Results The 28.3% (56/198) of the main cohort suffered from HE during the follow‐up. In the competing risk analysis, both intermediate‐ (subhazard ratio (sHR) 2.01 (95% CI 1.00‐4.14); P = .048) and high‐risk groups (sHR 4.67 (95% CI 2.19‐9.98); P = .0001) were associated with the first HE episode, together with age and albumin. Similar results were found for repeated HE events. The cumulative incidence for HE of the high‐risk group was two and four times greater than the intermediate‐ and low‐risk groups, respectively. The HE grade was also higher in individuals with the greatest risk (P = .035). The most common precipitant factor was diuretics in the high‐risk group, while infections and electrolyte imbalance predominated in the rest of patients. Conclusion Oral glutamine challenge identified patients at risk of HE and defined specific features of the episodes. This tool could be useful in the decision‐making process for the adequate management of HE.

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A risk score to predict the development of hepatic encephalopathy in a population‐based cohort of patients with cirrhosis

Abstract: 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).

Cited by 76 publications

References 41 publications

Opioid prescriptions are associated with hepatic encephalopathy in a national cohort of patients with compensated cirrhosis

Opioid prescriptions are associated with hepatic encephalopathy in a national cohort of patients with compensated cirrhosis

Incidence of and Risk Factors for Hepatic Encephalopathy in a Population‐Based Cohort of Americans With Cirrhosis

Oral glutamine challenge is a marker of altered ammonia metabolism and predicts the risk of hepatic encephalopathy

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