New Data May Soon Reshape Transplantation Decisions in End-Stage Liver Disease

William F. Balistreri, MD


April 12, 2016

In This Article

Editor's Note:
At The Liver Meeting®—the 66th annual meeting of the American Association for the Study of Liver Diseases—some of the significant advances in the diagnosis and management of patients with end-stage liver disease (ESLD), including innovative approaches to liver transplantation, were presented, and are highlighted herein.

Assessment and Management of ESLD

Clinicians are continually seeking improved strategies to assess and minimize the severity of liver disease, as well as to determine and optimize candidacy for liver transplantation. In view of the limitations imposed by organ donor shortage, transplant centers working in a parallel fashion are making efforts to improve recipient and donor selection and increase donor options.

Transient Elastography

Liver biopsy, the reference standard to determine the degree of fibrosis, is subject to sampling error, complications, and the requirement for sedation in children. Transient elastography measures liver stiffness and correlates with the severity of fibrosis; a cut-point of approximately 8.5 kPa is associated with a significant degree (F3-F4) of fibrosis.

To more firmly establish optimal cut-points, Lee and colleagues[1] studied patients who underwent liver stiffness measurements and had a recent liver biopsy. In a test group (n = 97), the cut-point to discriminate F3-F4 was > 8.6 kPa (sensitivity, 79%; specificity, 83%) and the cut-point for F4 was > 11.5 kPa (sensitivity, 74%; specificity, 82%). When applied to a validation group (n = 166), the cut-point of > 8.6 kPa to detect F3-F4 had a sensitivity of 67% and a specificity of 69%. The study also supported recent findings that the accuracy of transient elastography improves with fasting.

Fluid Resuscitation

The choice of fluid for use in patients with sepsis-induced hypotension generally follows the Surviving Sepsis Guidelines; however, there are no data on fluid resuscitation protocols in patients with cirrhosis.[2]

Philips and colleagues[3] investigated the comparative efficacy of human albumin (5%; 250-mL bolus over 15 minutes) compared with 0.9% normal saline (30 mL/kg over 30 minutes) in more than 300 patients with cirrhosis presenting with sepsis-induced hypotension. Resuscitation with 5% human albumin improved hemodynamics, tissue perfusion, and early survival more effectively than normal saline. Sustained reduction in heart rate also was more common in albumin recipients.

Expanding the Number of Available Organs

As the demand for liver transplantation increases, the availability of donor organs has decreased. This is in part due to the "double whammy" imposed by the current obesity epidemic. The rising prevalence of ESLD due to nonalcoholic steatohepatitis, coupled with a significant prevalence of hepatic steatosis in the general population, has created an increasing need for transplantable livers at a time when there are a diminishing number of suitable donors.

Reducing Hepatic Steatosis in Donor Candidates

The incidence of reperfusion injury is higher in steatotic transplanted livers, and if steatosis is noted in a donor liver, it may be discarded. The question remains, is there an intervention that could reduce the threat of donor steatosis?

The Optifast® (Nestlé; Vevey, Switzerland) very low-calorie meal replacement system is one intervention, and has demonstrated efficacy in reducing obesity and hepatic steatosis in candidates for bariatric surgery.

Doyle and colleagues[4] applied this strategy to reduce steatosis in potential but overweight liver donors in order to convert them to suitable donors. Among potential donors, those with a body mass index > 30 kg/m2 or evidence of significant steatosis (> 10%) on liver biopsy were offered enrollment into the trial, in which four Optifast shakes were substituted for all meals during a 6- to 8-week period. Persons who received Optifast had a reduction in median body mass index from 35 kg/m2 to 31.2 kg/m2 (range, 28-33 kg/m2). Post-Optifast biopsies showed < 10% macrovesicular steatosis (68% had no detectable steatosis).

This study demonstrates that the use of Optifast has the potential to effectively expand the volunteer donor pool in the context of the current epidemic of obesity/fatty liver and the attendant donor shortage.


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