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Potential predictors of fibrosis progression in patients with NAFLD
Many other factors have been associated with susceptibility to advanced NAFLD and HCC, including
genetic factors, dietary factors, caffeine and alcohol intake, gut microbiome and obstructive sleep
apnoea [10]. These associations have been made exclusively by comparing the severity of NAFLD in
patients with and without the particular factor, supported in most instances by biological plausibility
of the association derived from animal models or other mechanistic studies. None have been studied
in relation to their ability to predict the progression of NAFLD in patients with early stage disease.
Although one might predict that factors associated with advanced disease in cross-sectional studies may
well predict an adverse long-term outcome, this will almost certainly depend on the presumed duration
of the disease. For example, if a 30 year old man with recent onset obesity presents with early stage
NAFLD and has genetic and dietary factors associated with advanced disease, he is probably at higher
risk of developing advanced disease than someone without these factors. Conversely, if he presents
with mild disease 30 years later, still with the risk factors present, he is probably at an extremely low
risk of developing advanced disease as he presumably has some protective factor(s), as yet unidentified,
preventing him from developing advanced disease. Nonetheless, natural history studies including these
risk factors are awaited with interest because better ways of identifying the minority of patients at risk of
advanced disease are clearly needed.
Conclusions
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
if recent results can be confirmed. At present, 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. Just under one in five progressors will progress more rapidly, with the presence of hypertension
and possibly diabetes at presentation, the factors most consistently associated with progression risk. Of
the available laboratory tests, a low platelet count and high FIB-4 score hold the most promise for risk
stratification. Although in need of further study, a persistently low or falling platelet count, a raised/
rising FIB-4 score and new onset T2DM during follow-up may indicate the development of progressive
disease. Studies on the ability of genetic and other factors to predict the risk of disease progression are
awaited with interest given the urgent need to identify ‘rapid progressors’ for therapeutic trials and other
interventions.
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 97
Many other factors have been associated with susceptibility to advanced NAFLD and HCC, including
genetic factors, dietary factors, caffeine and alcohol intake, gut microbiome and obstructive sleep
apnoea [10]. These associations have been made exclusively by comparing the severity of NAFLD in
patients with and without the particular factor, supported in most instances by biological plausibility
of the association derived from animal models or other mechanistic studies. None have been studied
in relation to their ability to predict the progression of NAFLD in patients with early stage disease.
Although one might predict that factors associated with advanced disease in cross-sectional studies may
well predict an adverse long-term outcome, this will almost certainly depend on the presumed duration
of the disease. For example, if a 30 year old man with recent onset obesity presents with early stage
NAFLD and has genetic and dietary factors associated with advanced disease, he is probably at higher
risk of developing advanced disease than someone without these factors. Conversely, if he presents
with mild disease 30 years later, still with the risk factors present, he is probably at an extremely low
risk of developing advanced disease as he presumably has some protective factor(s), as yet unidentified,
preventing him from developing advanced disease. Nonetheless, natural history studies including these
risk factors are awaited with interest because better ways of identifying the minority of patients at risk of
advanced disease are clearly needed.
Conclusions
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
if recent results can be confirmed. At present, 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. Just under one in five progressors will progress more rapidly, with the presence of hypertension
and possibly diabetes at presentation, the factors most consistently associated with progression risk. Of
the available laboratory tests, a low platelet count and high FIB-4 score hold the most promise for risk
stratification. Although in need of further study, a persistently low or falling platelet count, a raised/
rising FIB-4 score and new onset T2DM during follow-up may indicate the development of progressive
disease. Studies on the ability of genetic and other factors to predict the risk of disease progression are
awaited with interest given the urgent need to identify ‘rapid progressors’ for therapeutic trials and other
interventions.
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 97
