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HCC and NASH
HCC represents 22% of the LT indications in The United States and >30% in France. Patients with
NASH-related cirrhosis are at risk of HCC. In addition, it seems that HCC can develop in NASH
even in the absence of cirrhosis. In The United States, 49% of HCC cases are due to HCV, followed by
NASH (13%), which represents a 4-fold increase between 2002 and 2012 [2].
Characteristics of patients with NASH on the waiting list
In The United States, the rate of HCC among patients on the waiting list was 21% and 24% in patients
with NASH and HCV, respectively, while it was only 7% in ALD patients. The mean MELD score at
inscription was higher in ALD patients (19.1) than in HCV patients (15.7) or in NASH patients (16).
In contrast, the mean BMI (31.6 kg/m2) and the prevalence of diabetes (46%) were higher in NASH
patients than in patients with other liver diseases.
Specific aspects of candidates for NASH-related LT
This higher rate of comorbidities in NASH patients may explain their higher rate of mortality on the
waiting list in The United States. Furthermore, the rate of perioperative complications is higher in obese
patients with wound dehiscence, ventral hernia and longer hospital stay, particularly in those with a
BMI of >40. In patients with very high BMI, particularly morbid obesity, LT might be contraindicated.
Contraindication may be solely due to BMI although the severity of associated comorbidities can also be
important. In some centres, physical exercise, and in some cases, treatment of obesity is recommended
as preparation for LT. However, surgical treatment of obesity (e.g. sleeve gastrectomy, surgical bypass)
might be difficult or impossible in patients with end-stage liver disease. Recently, temporary gastric
balloon to decrease the patient’s BMI prior to LT have been proposed.
Outcome post-LT [3]
Perioperative outcome. As previously mentioned, the rate of postoperative complications seem higher
in most series of patients with obesity due to an increase in wound healing deficiencies, respiratory
complications, and length of hospital and ICU stay after surgery. However, in patients with NASH at
three years post-LT there was no difference in survival compared with other indications.
Long-term outcome. Whatever the indications of LT, it appears that long-term complications, such
as major weight gain, obesity, diabetes and arterial hypertension are frequent, with MetS as a source of
cardiovascular complications in the long-term. The rate of de novo NAFLD and NASH was 20% and
10%, respectively, in a single centres series.
In one series the recurrence of NAFLD on the graft has been reported as >50% within the first two
years post-LT and 100% at five years. The impact of potential graft loss is still in evaluation.
Conclusion
LT for NASH is a growing indication. This trend is particularly marked in The United States and has
to be evaluated in Europe in the coming years. NASH is a growing indication in both decompensated
liver diseases and in HCC. Higher perioperative morbidity can be observed in patients with NASH,
particularly in those with severe or morbid obesity. Despite recurrence of NAFLD or NASH on the
liver graft, medium-term survival seems identical to other causes of LT. Strategies to correct MetS and
obesity before LT have to be implemented. Prevention and treatment of dysmetabolic syndrome after
LT will be essential to prevent NAFLD and NASH recurrence and to decrease cardiovascular related
complications.
References
[1] Wong RJ, Aguilar M, Cheung R, et al. Nonalcoholic steatohepatitis is the second leading etiology
of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology
2015;148:547-555.
[2] Wong RJ, Cheung R, Ahmed A. Nonalcoholic steatohepatitis is the most rapidly growing indication
for liver transplantation in patients with hepatocellular carcinoma in the U.S. Hepatology
2014;59:2188-2195.
[3] Heimbach J. Debate: A bridge too far-liver transplantation for nonalcoholic steatohepatitis will
overwhelm the organ supply. Liver Transpl 2014;20:S32-37.
108 Postgraduate Course Syllabus • Metabolic Liver Disease
HCC represents 22% of the LT indications in The United States and >30% in France. Patients with
NASH-related cirrhosis are at risk of HCC. In addition, it seems that HCC can develop in NASH
even in the absence of cirrhosis. In The United States, 49% of HCC cases are due to HCV, followed by
NASH (13%), which represents a 4-fold increase between 2002 and 2012 [2].
Characteristics of patients with NASH on the waiting list
In The United States, the rate of HCC among patients on the waiting list was 21% and 24% in patients
with NASH and HCV, respectively, while it was only 7% in ALD patients. The mean MELD score at
inscription was higher in ALD patients (19.1) than in HCV patients (15.7) or in NASH patients (16).
In contrast, the mean BMI (31.6 kg/m2) and the prevalence of diabetes (46%) were higher in NASH
patients than in patients with other liver diseases.
Specific aspects of candidates for NASH-related LT
This higher rate of comorbidities in NASH patients may explain their higher rate of mortality on the
waiting list in The United States. Furthermore, the rate of perioperative complications is higher in obese
patients with wound dehiscence, ventral hernia and longer hospital stay, particularly in those with a
BMI of >40. In patients with very high BMI, particularly morbid obesity, LT might be contraindicated.
Contraindication may be solely due to BMI although the severity of associated comorbidities can also be
important. In some centres, physical exercise, and in some cases, treatment of obesity is recommended
as preparation for LT. However, surgical treatment of obesity (e.g. sleeve gastrectomy, surgical bypass)
might be difficult or impossible in patients with end-stage liver disease. Recently, temporary gastric
balloon to decrease the patient’s BMI prior to LT have been proposed.
Outcome post-LT [3]
Perioperative outcome. As previously mentioned, the rate of postoperative complications seem higher
in most series of patients with obesity due to an increase in wound healing deficiencies, respiratory
complications, and length of hospital and ICU stay after surgery. However, in patients with NASH at
three years post-LT there was no difference in survival compared with other indications.
Long-term outcome. Whatever the indications of LT, it appears that long-term complications, such
as major weight gain, obesity, diabetes and arterial hypertension are frequent, with MetS as a source of
cardiovascular complications in the long-term. The rate of de novo NAFLD and NASH was 20% and
10%, respectively, in a single centres series.
In one series the recurrence of NAFLD on the graft has been reported as >50% within the first two
years post-LT and 100% at five years. The impact of potential graft loss is still in evaluation.
Conclusion
LT for NASH is a growing indication. This trend is particularly marked in The United States and has
to be evaluated in Europe in the coming years. NASH is a growing indication in both decompensated
liver diseases and in HCC. Higher perioperative morbidity can be observed in patients with NASH,
particularly in those with severe or morbid obesity. Despite recurrence of NAFLD or NASH on the
liver graft, medium-term survival seems identical to other causes of LT. Strategies to correct MetS and
obesity before LT have to be implemented. Prevention and treatment of dysmetabolic syndrome after
LT will be essential to prevent NAFLD and NASH recurrence and to decrease cardiovascular related
complications.
References
[1] Wong RJ, Aguilar M, Cheung R, et al. Nonalcoholic steatohepatitis is the second leading etiology
of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology
2015;148:547-555.
[2] Wong RJ, Cheung R, Ahmed A. Nonalcoholic steatohepatitis is the most rapidly growing indication
for liver transplantation in patients with hepatocellular carcinoma in the U.S. Hepatology
2014;59:2188-2195.
[3] Heimbach J. Debate: A bridge too far-liver transplantation for nonalcoholic steatohepatitis will
overwhelm the organ supply. Liver Transpl 2014;20:S32-37.
108 Postgraduate Course Syllabus • Metabolic Liver Disease
