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Progression of liver disease in NAFLD
WHO ARE THE NAFLD PATIENTS AT RISK OF DISEASE
PROGRESSION?
Chris Day
Institute of Cellular Medicine, Faculty of Medical Sciences
Newcastle University, Newcastle Upon Tyne, The United Kingdom
Email: chris.day@ncl.ac.uk
Take home messages
• The presence and severity of fibrosis on liver biopsy is currently the best indicator of long-term liver
outcome in patients with NAFLD, although non-invasive markers of fibrosis may prove to be as
good.
• Patients with mild/moderate steatosis in the absence of any inflammation can be assumed to have a
very low risk of developing fibrosis over 15-20 years. For the majority of the others fibrosis progression
will be slow progressing at around 1 stage every 6-15 years.
• 1 in 5 progressors will progress more rapidly with the presence of hypertension and possibly diabetes
at presentation, the factors most consistently associated with progression risk.
• A low platelet count and high FIB-4 score hold the most promise for risk stratification.
• Studies on the ability of genetic and other factors to predict the risk of disease progression are
awaited with interest.
Introduction
Over the last 15 years a wealth of data has emerged on the natural history of NAFLD, addressing both the
clinical course of the disease and disease progression assessed through repeat liver biopsies.This chapter
will cover both types of study, focusing particularly on factors that predict disease progression, which
may assist in patient risk stratification and management. NAFLD associated extra-hepatic morbidity
and mortality, HCC and the course of NAFLD cirrhosis will not be discussed in any detail as they are
covered elsewhere.
Long-term mortality in patients with NAFLD
Studies that have examined the overall, long-term mortality of patients with the whole spectrum of
NAFLD have observed that, within 15 years of follow-up, patients with NAFLD have a 26% risk of
dying, 34-69% higher than the general population of the same age and gender. In these studies, liver-
related mortality was the third most common cause of death after CVD and extra-hepatic malignancy,
occurring in <5% of patients [1]. Importantly, the long-term prognosis of patients with NAFLD depends
to a large extent on disease stage. Thus, there is little doubt that the vast majority of patients who
progress to end-stage liver disease and die a liver-related death present with, or progress to, advanced
fibrosis and cirrhosis. Pooled data from long-term (~10 years) follow-up studies of NAFLD patients
with advanced fibrosis and cirrhosis demonstrate a 16% mortality with 60% of the deaths liver-related
compared with only ~9% liver-related in long-term (~15 years) follow-up studies of NAFLD patients
without advanced fibrosis or cirrhosis [1]. Of note, cases of NAFLD-associated cirrhosis may be mis-
diagnosed as the steatosis has often disappeared at this stage.
Studies in patients without advanced fibrosis/cirrhosis have also revealed that those with steatosis alone
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 93
WHO ARE THE NAFLD PATIENTS AT RISK OF DISEASE
PROGRESSION?
Chris Day
Institute of Cellular Medicine, Faculty of Medical Sciences
Newcastle University, Newcastle Upon Tyne, The United Kingdom
Email: chris.day@ncl.ac.uk
Take home messages
• The presence and severity of fibrosis on liver biopsy is currently the best indicator of long-term liver
outcome in patients with NAFLD, although non-invasive markers of fibrosis may prove to be as
good.
• Patients with mild/moderate steatosis in the absence of any inflammation can be assumed to have a
very low risk of developing fibrosis over 15-20 years. For the majority of the others fibrosis progression
will be slow progressing at around 1 stage every 6-15 years.
• 1 in 5 progressors will progress more rapidly with the presence of hypertension and possibly diabetes
at presentation, the factors most consistently associated with progression risk.
• A low platelet count and high FIB-4 score hold the most promise for risk stratification.
• Studies on the ability of genetic and other factors to predict the risk of disease progression are
awaited with interest.
Introduction
Over the last 15 years a wealth of data has emerged on the natural history of NAFLD, addressing both the
clinical course of the disease and disease progression assessed through repeat liver biopsies.This chapter
will cover both types of study, focusing particularly on factors that predict disease progression, which
may assist in patient risk stratification and management. NAFLD associated extra-hepatic morbidity
and mortality, HCC and the course of NAFLD cirrhosis will not be discussed in any detail as they are
covered elsewhere.
Long-term mortality in patients with NAFLD
Studies that have examined the overall, long-term mortality of patients with the whole spectrum of
NAFLD have observed that, within 15 years of follow-up, patients with NAFLD have a 26% risk of
dying, 34-69% higher than the general population of the same age and gender. In these studies, liver-
related mortality was the third most common cause of death after CVD and extra-hepatic malignancy,
occurring in <5% of patients [1]. Importantly, the long-term prognosis of patients with NAFLD depends
to a large extent on disease stage. Thus, there is little doubt that the vast majority of patients who
progress to end-stage liver disease and die a liver-related death present with, or progress to, advanced
fibrosis and cirrhosis. Pooled data from long-term (~10 years) follow-up studies of NAFLD patients
with advanced fibrosis and cirrhosis demonstrate a 16% mortality with 60% of the deaths liver-related
compared with only ~9% liver-related in long-term (~15 years) follow-up studies of NAFLD patients
without advanced fibrosis or cirrhosis [1]. Of note, cases of NAFLD-associated cirrhosis may be mis-
diagnosed as the steatosis has often disappeared at this stage.
Studies in patients without advanced fibrosis/cirrhosis have also revealed that those with steatosis alone
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 93
