Important Unresolved Questions in the Management of Hepatic Encephalopathy: An ISHEN Consensus

Bajaj, Jasmohan S.; Lauridsen, Mette Munk; Tapper, Elliot B.; Duarte‐Rojo, Andrés; Rahimi, Robert S.; Tandon, Puneeta; Shawcross, Debbie L.; Thabut, Dominique; Dhiman, Radha K.; Romero–Gómez, Manuel; Sharma, Barjesh Chander; Montagnese, Sara

doi:10.14309/ajg.0000000000000603

Cited by 92 publications

(103 citation statements)

References 125 publications

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“…Skeletal muscle tissue plays a central role in removing ammonia from the circulation when its clearance by the liver is impaired. Thus in situations of muscle wasting, commonly precipitated by inadequate dietary intake and hyperammonemia itself in cirrhosis, the neuropsychiatric symptoms of encephalopathy are worsened[ 17 , 53 ].…”

Section: Malnutrition In Cirrhosis-etiologymentioning

confidence: 99%

“…The spectrum of neurocognitive impairment in cirrhosis ranges from minimal to overt hepatic encephalopathy, which manifest in variable degrees of impaired cognition, alertness and attentiveness[ 17 ]. This altered cognitive state, coupled with periods of increased (daytime) somnolence, limit the opportunity for cirrhotic patients with even low-grade encephalopathy to achieve an adequate dietary intake[ 54 ].…”

Section: Malnutrition In Cirrhosis-etiologymentioning

confidence: 99%

“…Malnutrition increases the incidence and severity of decompensation symptoms, contributes to compromised immune function, reduces muscle mass, decreases functional status and quality of life, delays wound healing and is associated with increased mortality[ 14 - 16 ]. Malnutrition is particularly associated with the development and severity of hepatic encephalopathy[ 17 ]. Malnourished patients also require prolonged mechanical ventilation and have longer length of stay in both the intensive care unit and hospital following liver transplant[ 18 , 19 ]; all of which translate to significantly increased healthcare costs.…”

Section: Introductionmentioning

confidence: 99%

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Malnutrition in cirrhosis: More food for thought

Chapman¹,

Sinclair²,

Gow³

et al. 2020

WJH

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Malnutrition is highly prevalent in liver cirrhosis and its presence carries important prognostic implications. The clinical conditions and pathophysiological mechanisms that cause malnutrition in cirrhosis are multiple and interrelated. Anorexia and liver decompensation symptoms lead to poor dietary intake; metabolic changes characterised by elevated energy expenditure, reduced glycogen storage, an accelerated starvation response and protein catabolism result in muscle and fat wasting; and, malabsorption renders the cirrhotic patient unable to fully absorb or utilise food that has been consumed. Malnutrition is therefore a considerable challenge to manage effectively, particularly as liver disease progresses. A high energy, high protein diet is recognised as standard of care, yet patients struggle to follow this recommendation and there is limited evidence to guide malnutrition interventions in cirrhosis and liver transplantation. In this review, we seek to detail the factors which contribute to poor nutritional status in liver disease, and highlight complexities far greater than “poor appetite” or “reduced oral intake” leading to malnutrition. We also discuss management strategies to optimise nutritional status in this patient group, which target the inter-related mechanisms unique to advanced liver disease. Finally, future research requirements are suggested, to develop effective treatments for one of the most common and debilitating complications afflicting cirrhotic patients.

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Section: Malnutrition In Cirrhosis-etiologymentioning

confidence: 99%

Section: Malnutrition In Cirrhosis-etiologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Malnutrition in cirrhosis: More food for thought

Chapman¹,

Sinclair²,

Gow³

et al. 2020

WJH

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“…There was no difference in serum ammonia levels between the intervention groups at all time points. However, while ammonia plays a central role in the pathogenesis of HE, serum ammonia concentration does not necessarily correlate with severity of HE 10‐12 …”

Section: Discussionmentioning

confidence: 99%

“…The pathophysiology of HE is complex and involves alterations in the gut‐liver axis (dysbiosis, increased intestinal permeability, bacterial translocation) and elevated serum ammonia concentrations 7‐9 . However, the correlation between serum ammonia levels does not necessarily reflect the degree of hepatic encephalopathy 10‐12 . Low serum concentrations of the BCAAs (leucine, valine and isoleucine) and elevated serum concentrations of the aromatic amino acids (AAAs, phenylalanine, tryptophan and tyrosine) are also associated with the progression of liver disease severity and development of HE 13,14 .…”

Section: Introductionmentioning

confidence: 99%

Quality of life indicators in hepatic encephalopathy following supplementation with branched chain amino acids and/or synbiotics: A post‐hoc analysis

et al. 2021

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Background and Aims Individuals with hepatic encephalopathy (HE) report impaired quality of life. We aimed to identify changes in health‐related quality of life (HRQOL) in patients with HE who were randomised to receive oral supplementation with branched chain amino acids (BCAA) and/or synbiotics. Methods Subjects with HE from a previously published study were randomised to receive placebo, BCAA, synbiotics or a combination of BCAA and synbiotics. A post‐hoc analysis of responses to the Short Form‐Liver Disease Quality of Life (SF‐LDQOL) questionnaires completed by participants at baseline, 1 month and 2 months during this study was performed. Depression, Anxiety and Stress Scales (DASS‐21) were also analysed. Results In all, 43 participants were included in the analysis. There was a self‐reported improvement in the domain of concentration and memory in the BCAA group (P = 0.003) and combined BCAA group (BCAA + BCAA/synbiotics) (P = 0.038) at 2 months compared to baseline. Further analysis comparing combined BCAA groups to non‐BCAA groups demonstrated that DASS‐Anxiety improved following intervention (P = 0.023) and was inversely correlated with DASS‐Anxiety (r = −0.579, P = 0.012). No significant changes were observed in other domains including symptoms of liver disease, effects of liver disease, health distress, sleep, loneliness, hopelessness, stigma of liver disease and sexual functioning. Conclusion Nutritional supplementation with BCAA (alone or with synbiotics) resulted in improvements in participants’ self‐reported concentration and memory but not overall HRQOL. Concentration and memory scores were found to be inversely correlated with DASS‐Anxiety scores in BCAA groups. A larger study with longer duration to investigate overall patient reported HRQOL is needed.

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Diagnosis and Management of Cirrhosis and Its Complications

Tapper

Parikh

2023

JAMA

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ImportanceCirrhosis affects approximately 2.2 million adults in the US. From 2010 to 2021, the annual age-adjusted mortality of cirrhosis increased from 14.9 per 100 000 to 21.9 per 100 000 people.ObservationsThe most common causes of cirrhosis in the US, which can overlap, include alcohol use disorder (approximately 45% of all cases of cirrhosis), nonalcoholic fatty liver disease (26%), and hepatitis C (41%). Patients with cirrhosis experience symptoms including muscle cramps (approximately 64% prevalence), pruritus (39%), poor-quality sleep (63%), and sexual dysfunction (53%). Cirrhosis can be diagnosed by liver biopsy but may also be diagnosed noninvasively. Elastography, a noninvasive assessment of liver stiffness measured in kilopascals, can typically confirm cirrhosis at levels of 15 kPa or greater. Approximately 40% of people with cirrhosis are diagnosed when they present with complications such as hepatic encephalopathy or ascites. The median survival time following onset of hepatic encephalopathy and ascites is 0.92 and 1.1 years, respectively. Among people with ascites, the annual incidence of spontaneous bacterial peritonitis is 11% and of hepatorenal syndrome is 8%; the latter is associated with a median survival of less than 2 weeks. Approximately 1% to 4% of patients with cirrhosis develop hepatocellular carcinoma each year, which is associated with a 5-year survival of approximately 20%. In a 3-year randomized clinical trial of 201 patients with portal hypertension, nonselective β-blockers (carvedilol or propranolol) reduced the risk of decompensation or death compared with placebo (16% vs 27%). Compared with sequential initiation, combination aldosterone antagonist and loop diuretics were more likely to resolve ascites (76% vs 56%) with lower rates of hyperkalemia (4% vs 18%). In meta-analyses of randomized trials, lactulose was associated with reduced mortality relative to placebo (8.5% vs 14%) in randomized trials involving 705 patients and reduced risk of recurrent overt hepatic encephalopathy (25.5% vs 46.8%) in randomized trials involving 1415 patients. In a randomized clinical trial of 300 patients, terlipressin improved the rate of reversal of hepatorenal syndrome from 39% to 18%. Trials addressing symptoms of cirrhosis have demonstrated efficacy for hydroxyzine in improving sleep dysfunction, pickle brine and taurine for reducing muscle cramps, and tadalafil for improving sexual dysfunction in men.Conclusions and RelevanceApproximately 2.2 million US adults have cirrhosis. Many symptoms, such as muscle cramps, poor-quality sleep, pruritus, and sexual dysfunction, are common and treatable. First-line therapies include carvedilol or propranolol to prevent variceal bleeding, lactulose for hepatic encephalopathy, combination aldosterone antagonists and loop diuretics for ascites, and terlipressin for hepatorenal syndrome.

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Important Unresolved Questions in the Management of Hepatic Encephalopathy: An ISHEN Consensus

Cited by 92 publications

References 125 publications

Malnutrition in cirrhosis: More food for thought

Malnutrition in cirrhosis: More food for thought

Quality of life indicators in hepatic encephalopathy following supplementation with branched chain amino acids and/or synbiotics: A post‐hoc analysis

Diagnosis and Management of Cirrhosis and Its Complications

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