Advice for Combating Frailty's Fatal Impact in Liver Disease

Rowen K. Zetterman, MD


January 22, 2018

Role of Sarcopenia

Frailty in patients with cirrhosis appears to be in part a consequence of sarcopenia.[16] In those with cirrhosis, sarcopenia is associated with decreased survival, increased risk for complications (eg, infection), and a poorer outcome after surgical intervention or transplantation.[16,17,18] Factors associated with greater sarcopenia and cirrhosis include older patient age, the severity of associated liver disease, other chronic comorbidities, and the duration of end-stage liver disease.

Caloric intake is frequently reduced in patients with advanced liver disease, as is total protein intake.[17] Patients with ascites may have reduced oral intake owing to compression of their stomach by intra-abdominal fluid while at the same time having increased energy expenditure. Such complications as sepsis, bacterial endocarditis, encephalopathy, and associated hepatocellular carcinoma may result in increased metabolic demand or reduced protein-calorie intake.[16] However, the mechanism of sarcopenia does not appear to be simply related to protein malnutrition. Other factors, including decreased testosterone and growth hormone levels, muscle breakdown as a caloric source, endotoxemia, and hyperammonemia, may play a role.

The presence of sarcopenia in patients with end-stage liver disease is often established by using ultrasound, CT, or MRI to measure muscle mass along the lumbar spine at L3 and L4, or by assessment of extremity muscle (eg, the leg).[19] In a study of thigh muscle thickness by ultrasound, similar rates of sarcopenia were noted compared with measurements using lumbar spine imaging.[19]

The Perils of the Liver Transplantation Waiting List

Frailty increases the risk for mortality for the patient with cirrhosis on the waiting list for liver transplantation.[20] Patients with documented frailty have a twofold increase in wait-list mortality and a greater likelihood of being delisted for transplantation compared with patients who are not frail. The effect of frailty as a predictor of mortality increases as frailty worsens while patients remain on the waiting list. This effect of frailty as a risk for wait-list mortality or delisting is independent of liver disease severity.[21] Frailty also increases the likelihood of hospitalization while awaiting transplantation.[22]

Frailty reduces ADL, such as personal care, bathing, and transferring between chair and bed.[23] The assessment of ADL in frail patients can be used to identify those with greater wait-list mortality.[7] Similarly, preoperative assessment using the Braden scale, a measure of pressure ulcer risk in hospitalized patients, can also predict the length of hospitalization and occurrence of mortality after liver transplantation.[24]


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