Outcomes of liver transplantation for non-alcoholic steatohepatitis: A European Liver Transplant Registry study

Abstract

Background & aims: Little is known about outcomes of liver transplantation for patients with non-alcoholic steatohepatitis (NASH). We aimed to determine the frequency and outcomes of liver transplantation for patients with NASH in Europe and identify prognostic factors.

Methods: We analysed data from patients transplanted for end-stage liver disease between January 2002 and December 2016 using the European Liver Transplant Registry database. We compared data between patients with NASH versus other aetiologies. The principle endpoints were patient and overall allograft survival.

Results: Among 68,950 adults undergoing first liver transplantation, 4.0% were transplanted for NASH - an increase from 1.2% in 2002 to 8.4% in 2016. A greater proportion of patients transplanted for NASH (39.1%) had hepatocellular carcinoma (HCC) than non-NASH patients (28.9%, p <0.001). NASH was not significantly associated with survival of patients (hazard ratio [HR] 1.02, p = 0.713) or grafts (HR 0.99; p = 0.815) after accounting for available recipient and donor variables. Infection (24.0%) and cardio/cerebrovascular complications (5.3%) were the commonest causes of death in patients with NASH without HCC. Increasing recipient age (61-65 years: HR 2.07, p <0.001; >65: HR 1.72, p = 0.017), elevated model for end-stage liver disease score (>23: HR 1.48, p = 0.048) and low (<18.5 kg/m²: HR 4.29, p = 0.048) or high (>40 kg/m²: HR 1.96, p = 0.012) recipient body mass index independently predicted death in patients transplanted for NASH without HCC. Data must be interpreted in the context of absent recognised confounders, such as pre-morbid metabolic risk factors.

Conclusions: The number and proportion of liver transplants performed for NASH in Europe has increased from 2002 through 2016. HCC was more common in patients transplanted with NASH. Survival of patients and grafts in patients with NASH is comparable to that of other disease indications.

Lay summary: The prevalence of non-alcoholic fatty liver disease has increased dramatically in parallel with the worldwide increase in obesity and diabetes. Its progressive form, non-alcoholic steatohepatitis, is a growing indication for liver transplantation in Europe, with good overall outcomes reported. However, careful risk factor assessment is required to maintain favourable post-transplant outcomes in patients with non-alcoholic steatohepatitis.

Keywords: Aetiology; ELTR database; Long-term follow-up; NAFLD; NASH; Prognosis.

Graphical abstract

Fig. 1

Flow chart of case selection from the ELTR database. AiLD, autoimmune liver disease; ALD, alcohol-related liver disease; CC, cryptogenic cirrhosis; CLD, chronic liver disease; ELTR, European Liver Transplant Registry; HBV, hepatitis B virus infection; HCC, hepatocellular carcinoma; HCV, hepatitis C virus infection; NASH, non-alcoholic steatohepatitis.

Fig. 2

Trends of annual primary liver transplants performed for different indications in the ELTR region. AiLD, autoimmune liver disease; ALD, alcohol-related liver disease; CC, cryptogenic cirrhosis; ELTR, European Liver Transplant Registry; HBV, hepatitis B virus infection; HCV, hepatitis C virus infection; NASH, non-alcoholic steatohepatitis. (This figure appears in colour on the web.)

Fig. 3

Survival analysis for patients undergoing primary liver transplantation for different indications. Kaplan-Meier curves of patient survival for cases without (A), and with (B) HCC (log-rank: p <0.001 for both). AiLD, autoimmune liver disease; ALD, alcohol-related liver disease; CC, cryptogenic cirrhosis; ELTR, European Liver Transplant Registry; HBV, hepatitis B virus infection; HCV, hepatitis C virus infection; LT, liver transplant; NASH, non-alcoholic steatohepatitis. (This figure appears in colour on the web.)

Fig. 4

Survival analysis for patients with and without HCC undergoing primary LT for NASH and non-NASH indications. Kaplan-Meier analysis demonstrated no significant survival differences between patients transplanted for NASH and non-NASH indications amongst those without HCC (log-rank: p = 0.081) or with HCC (log-rank: p = 0.155). There is a significant difference between patients transplanted with and without HCC overall (log-rank: p <0.001). HCC, hepatocellular carcinoma; LT, liver transplant; NASH, non-alcoholic steatohepatitis. (This figure appears in colour on the web.)

Fig. 5

Overall allograft survival analysis for patients undergoing primary liver transplantation for different indications. Kaplan-Meier curves of overall allograft survival for cases without (A), and with HCC (B) (log-rank: p <0.001 for both). AiLD, autoimmune liver disease; ALD, alcohol-related liver disease; CC, cryptogenic cirrhosis; HBV, hepatitis B virus infection; HCV, hepatitis C virus infection; LT, liver transplant; NASH, non-alcoholic steatohepatitis. (This figure appears in colour on the web.)