Fatty Liver (cont.)
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What are the complications of NASH?
The complications of NASH include
cirrhosis (also considered the last stage of NAFLD) and primary liver cancer
(hepatocellular carcinoma, HCC).
The risk of developing cirrhosis in a patient with NASH is still uncertain
and varies perhaps from 8% to 15%. Up to now, very few studies have followed
patients over sufficient periods of time to actually document the progression of
NASH to cirrhosis. There is indirect evidence, however, that NASH can lead to
cirrhosis For example, in some patients, at the time of an initial diagnosis of
NASH made by liver biopsy, cirrhosis is already present, along with the usual
signs of NASH.
Nonetheless, it is important to understand that in most instances when
cirrhosis develops, the fatty infiltration disappears (regresses) along with the
inflammation. Cirrhosis in NASH with loss of fat and inflammation is referred to
as burned-out cirrhosis. This situation may result from less fat coming to the
liver by way of the portal vein (the vessel that brings blood from the
intestines to the liver). In addition, a decrease in insulin secretion (with the
development of insulin dependent DM2) causes the triglyceride fats to leave the
liver.
Furthermore, more and more reports indicate that at least 50% of cases of
cryptogenic cirrhosis (cirrhosis due to unidentified causes) occur in the
setting of previous long-standing obesity and/or DM2. These observations suggest
that insulin-resistance, hence NASH, was often the basis of what was called
cryptogenic cirrhosis. In fact, the number of liver transplantations for
presumed NASH-related cirrhosis is on the rise. The high rate of recurrent NASH
developing in the new livers of patients receiving liver transplants for
cryptogenic cirrhosis further confirms the causal role of NASH. Finally, a study
from France suggests that patients with NASH have a similar risk of developing
cirrhosis as do patients with HCV. As indicated above, however, the progression
to cirrhosis in NASH is thought to be slow and the cirrhosis diagnosis is
typically made in patients in their sixties.
There are also reports of primary liver cancer (hepatocellular carcinoma,
HCC) occurring in patients with NASH-related cirrhosis. Indeed, the incidence of
HCC in NASH cirrhosis appears to be similar to that observed in HCV cirrhosis
(1-2% per year). The process that causes liver cancer to form in NASH cirrhosis
is unknown and has not yet been studied. HCC may develop as a result of liver
repair and regrowth (hepatocellular regeneration) without any factor
specifically related to NASH. Some authors, however, have suggested that insulin
resistance in this situation may promote the development of liver cancer.
Next: How are NAFLD and NASH diagnosed? »
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