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Cirrhosis Causes Cognitive impairment, Poor Patient Outcomes - Despite HCV, SVR in the Presence of NAFLD, Alcoholic Fatty Liver
Frailty, Psychoactive Medications, and Cognitive Dysfunction Are Associated With Poor Patient-Reported Outcomes in Cirrhosis
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Hepatology April 2019 - Elliot B. Tapper ,1 Jad Baki ,2 Neehar D. Parikh ,1 and Anna S. Lok1
From the 1 Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI; 2 University of Michigan, Ann
Arbor, MI.
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"We prospectively enrolled 300 patients with cirrhosis and portal hypertension without a history of hepatic encephalopathy (HE) and reviewed medical and pharmacy records......All patients with hepatitis C-related cirrhosis had achieved sustained virologic response (30% of this entire group; 21% had NAFL, 22% alcohol etiology. 7.3% had HCC) at time of enrollment.....Median age was 60 years, 56% were male, median years of education was 14, 70% were Child class A, and median MELD-Na score was 9. All patients had portal hypertension, including 76% with varices, 41% with a history of ascites (10% requiring paracentesis), and 37% with thrombocytopenia (PLT <80,000)......In the absence of a liver biopsy, patients had to meet at least two of the following criteria: imaging findings of cirrhosis (cirrhotic appearing liver, splenomegaly, varices, or ascites), transient elastography >13 kPa, aspartate aminotransferase/platelet ratio index >2.0, and endoscopy with presence of esophageal varices......... Ninety-one (34%) patients had impaired cognitive function......poor sleep was associated with several characteristics of this population.....Of note, 37 (12.3%) patients could not perform the ICT; 22 became frustrated and quit, 10 could not understand instructions, and 5 had adverse reactions (such as dizziness)......Cognitive function, as measured by weighted-lures, was associated with HRQOL only in patients with cured hepatitis C, no past alcohol abuse, and those not on opiates or benzodiazepines........The prevalence of cirrhosis is rising because of the increasing prevalence of nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease.......Conclusion: Disability, chair-stand performance, cognitive dysfunction, as well as psychoactive medication use are significantly associated with PROs in patients with clinically stable cirrhosis.......we show that HRQOL was associated with education, etiology of liver disease (alcohol related), severity of liver disease (Child class B, MELD-Na), use of psychoactive medications (antidepressants, opiates, benzodiazepines, and gabapentin), frailty (ADL performance, chair-stands, and falls) and cognitive function (weighted-lures)."
Discussion
The lived experience of cirrhosis can be very challenging for many patients, marked by debilitating symptoms and poor HRQOL.3 Poor PROs have been traditionally associated with cirrhosis complications such as ascites and overt HE.4-8 However, this prospective study of 300 generally clinically stable outpatients with cirrhosis, half of whom had no history of decompensation and none had a history of overt HE, highlight other, potentially modifiable targets for suboptimal PROs. Specifically, we found that markers of frailty, psychoactive medications, and cognitive function were associated with HRQOL and sleep quality.
These data come at an important time in the history of chronic liver disease. The prevalence of cirrhosis is rising because of the increasing prevalence of nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease.30, 31 At the same time, as we approach the eradication of hepatitis C, we expect to arrest the natural history of cirrhosis for many patients, extending lives substantially. Thus, more patients are living with cirrhosis and will be living longer. Awareness of, and efforts to improve, PROs are needed.
Quality of Life in Clinically Important Subgroups
In Fig. 1 and Table 3, we demonstrate model estimates in subgroups relevant to clinical practice. Only opiate use was consistently associated with poor HRQOL across subgroups. Chair-stands, a measure of frailty, was associated with HRQOL in all groups save for those with ascites or diuretic use. A history of ascites, when present, was an over-riding determinant of HRQOL. The magnitude of the association between chair-stands and HRQOL was substantially greater for patients with Child A cirrhosis (severity of liver disease was an over-riding determinant of HRQOL in those with Child B cirrhosis). Cognitive function, as measured by weighted-lures, was associated with HRQOL only in patients with cured hepatitis C, no past alcohol abuse, and those not on opiates or benzodiazepines.
Frailty and Cognitive Function
Most patients (91%) were able to carry out all their ADLs independently. Compared to men, women had significantly lower hand-grip (22.8 ± 7.3 vs. 38.5 ± 12.4 kg; P < 0.0001), but not chair-stands (10.0 ± 5.4 vs. 9.9 ± 5.5; P = 0.87). Proportion of women and men with a history of falls within the last 6 months was similar (32 [24%] vs. 33 [20%]; P = 0.33). Proportion of women and men with a history of falls within the last 6 months was similar (32 [24%] vs. 33 [20%]; P = 0.33).,,,,,,,Ninety-one (34......%) patients had impaired cognitive function based on ICT-weighted lure values. Overall cognitive performance measured as lures, targets, or weighted-lure values were not different with respect to sex, Child class, benzodiazepine or opiate use, alcohol abuse, or alcohol versus other causes of cirrhosis (Table 1). Of note, 37 (12.3%) patients could not perform the ICT; 22 became frustrated and quit, 10 could not understand instructions, and 5 had adverse reactions (such as dizziness).
Associations with Quality of Life
The median SF-8 score for HRQOL was 70 (interquartile range [IQR], 54-86), with 59 (20%) reporting scores <50. Figure 1 shows the average raw SF-8 score for the entire cohort and subgroups. In Table 2, we show that HRQOL was associated with education, etiology of liver disease (alcohol related), severity of liver disease (Child class B, MELD-Na), use of psychoactive medications (antidepressants, opiates, benzodiazepines, and gabapentin), frailty (ADL performance, chair-stands, and falls) and cognitive function (weighted-lures). When we adjusted these results for one another (with forced inclusion of age, sex, and MELD-Na), the remaining significant variables included education, chair-stands, ADL dependence, benzodiazepine use, opiate use, and weighted-lures. This final model had an R2 of 0.36, suggesting that it explained a substantial (36%) portion of the variance in quality of life in our cohort. For comparison, the respective univariable R2 associated with MELD-Na, education, chair-stands, ADL dependence, benzodiazepine use, opiate use, and weighted-lures was 0.02, 0.03, 0.15, 0.07, 0.07, 0.03, and 0.04, respectively.
Associations With Poor Sleep
Our patients reported a median PSQI score of 7 (IQR, 4-11), 187 (63%) of whom had poor sleep (PSQI >5). Although poor sleep was highly prevalent, we show that specific subgroups had greater burdens of poor sleep (Fig. 1). This included, for example, patients with Child B cirrhosis (71.4%), those with weak chair-stand performance (84.1%), and users of opiates and benzodiazepines (87.0%). We excluded benzodiazepines from regression analyses given that they are often used explicitly for poor sleep. Many factors that were strongly associated in a univariate analysis, including liver disease severity and frailty, were not significant in multivariable analysis. In Supporting Table S2, we detail the results of a multivariable logistic regression that found that only two factors were significantly associated with poor sleep: opiate use (OR, 2.85; 95%CI [1.11-7.29] and weighted-lures (1.03 [1.00-1.05]). In a sensitivity analysis excluding ICT performance, opiates (2.23 [1.04-4.78]), Child B (2.11 [1.16-3.82]), and chair-stands (per 10-stands; OR, 0.58 [0.34-0.98]) were associated with poor sleep.
Abstract
Cirrhosis is associated with disabling symptoms and diminished health-related quality of life (HRQOL). However, for patients with compensated disease, data are limited regarding associations with poor patient-reported outcomes (PROs). We prospectively enrolled 300 patients with cirrhosis and portal hypertension without a history of hepatic encephalopathy (HE) and reviewed medical and pharmacy records. We characterized determinants of PROs using the 8-item Short-Form Health Survey (SF-8) scale (0-100) and sleep quality using the Pittsburgh Sleep Quality Index (PSQI; poor sleep >5). Disability and frailty measures were assessed using activities of daily living (ADLs), falls, hand-grip, and chair-stands. Cognitive function was measured using weighted-lures from the Inhibitory Control Test (ICT). The median age of our cohort was 60 (interquartile range [IQR], 52-66) years, 56.3% were male, and 70% Child class A. All patients had portal hypertension, 76% had varices, and 41% had a history of ascites (predominantly well controlled). The median Model for End-Stage Liver Disease with Sodium (MELD-Na) score was 9 (IQR, 7-13). The overall median SF-8 was 70 (IQR, 54-86). Multivariate analysis showed that after adjusting for age, sex, education, and MELD-Na, performance on chair-stands (9.28 HRQOL points [95% confidence interval {CI}, 4.76-13.8] per 10-stands), ADL dependence (-6.06 [-10.8 to -1.36]), opiate use (-5.01 [-7.84 to -2.19]), benzodiazepine use (-3.50 [-6.58 to -0.42]), and ICT performance (-0.10 [-0.20 to 0.001] per weighted-lure) were significantly associated with HRQOL. Among patients completing the ICT, poor HRQOL (score <50) was significantly associated with chair-stands (odds ratio [OR] per 10-stands, 0.24; 95% CI [0.11-0.56]) and weighted lures (OR per weighted-lure, 1.01 [1.00-1.03]). Poor sleep quality was associated with opiate use (OR, 2.85 [1.11-7.29]) and lures (OR per-lure, 1.03 [1.00-1.05]).
Conclusion: Disability, chair-stand performance, cognitive dysfunction, as well as psychoactive medication use are significantly associated with PROs in patients with clinically stable cirrhosis.
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