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driven manner for over 10 years [5]. In this study, the control population was an age, gender and race-
matched population of subjects with cirrhosis due to HCV who were seen concurrently. All subjects
provided informed consent to participate in a study to examine the natural history of their disease.
Cirrhosis was defined by liver histology in all cases. Cirrhosis was attributed to underlying NASH by
(1) histologic features of steatohepatitis; (2) an absence of clinically significant alcohol consumption (40
gm/week assessed clinically) and (3) negative tests for alternate causes of cirrhosis. In the presence of
cirrhosis, steatosis with varying combinations of cytologic ballooning, MDBs and inflammation were
used as histologic evidence of concurrent NASH. With progression towards cirrhosis, central to central
and central to portal bridges develop, distorting the hepatic lobular architecture. Zone III, pericellular
fibrosis is therefore difficult to define in subjects with cirrhosis and was not considered an independent
criterion for NASH and cirrhosis. A nurse and a physician independently interviewed the patient and
labelled the condition to be ‘non-alcoholic’ if the weekly alcohol consumption was <40 gm/week. These
strict criteria were chosen based on the available literature when the study was initiated and to exclude
the confounding effects of moderate alcohol consumption.
Mortality. Subjects with compensated cirrhosis have an approximately 3.5-4% risk of mortality
annually. This is related to increased risk of cardiovascular events, clinical decompensation with sepsis
and multi-organ failure and HCC [5]. This risk is slightly but statistically significantly lower than that
seen in those with compensated cirrhosis due to HCV infection. These data have been corroborated
in another independent cohort [6]. Subjects with NASH related cirrhosis have a significantly higher
rate of cardiovascular mortality compared to HCV related cirrhosis. Once cirrhosis progressed from
a compensated to a decompensated stage, i.e. CPT stage B or C, the mortality was similar to that in
the literature for other causes of decompensated cirrhosis such as HCV. BMI and CPT score were
independent predictors of mortality. When MELD was included in the model, BMI was no longer
significant. This was driven mainly by creatinine as virtually all subjects with a creatinine >2 mg/dl died
without a liver transplant. A creatinine of 1.65 was the best single predictive laboratory parameter of
mortality (Fig. 1) [5].
Figure 1. Creatinine as a predictor of mortality in NASH-related cirrhosis.
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 103
matched population of subjects with cirrhosis due to HCV who were seen concurrently. All subjects
provided informed consent to participate in a study to examine the natural history of their disease.
Cirrhosis was defined by liver histology in all cases. Cirrhosis was attributed to underlying NASH by
(1) histologic features of steatohepatitis; (2) an absence of clinically significant alcohol consumption (40
gm/week assessed clinically) and (3) negative tests for alternate causes of cirrhosis. In the presence of
cirrhosis, steatosis with varying combinations of cytologic ballooning, MDBs and inflammation were
used as histologic evidence of concurrent NASH. With progression towards cirrhosis, central to central
and central to portal bridges develop, distorting the hepatic lobular architecture. Zone III, pericellular
fibrosis is therefore difficult to define in subjects with cirrhosis and was not considered an independent
criterion for NASH and cirrhosis. A nurse and a physician independently interviewed the patient and
labelled the condition to be ‘non-alcoholic’ if the weekly alcohol consumption was <40 gm/week. These
strict criteria were chosen based on the available literature when the study was initiated and to exclude
the confounding effects of moderate alcohol consumption.
Mortality. Subjects with compensated cirrhosis have an approximately 3.5-4% risk of mortality
annually. This is related to increased risk of cardiovascular events, clinical decompensation with sepsis
and multi-organ failure and HCC [5]. This risk is slightly but statistically significantly lower than that
seen in those with compensated cirrhosis due to HCV infection. These data have been corroborated
in another independent cohort [6]. Subjects with NASH related cirrhosis have a significantly higher
rate of cardiovascular mortality compared to HCV related cirrhosis. Once cirrhosis progressed from
a compensated to a decompensated stage, i.e. CPT stage B or C, the mortality was similar to that in
the literature for other causes of decompensated cirrhosis such as HCV. BMI and CPT score were
independent predictors of mortality. When MELD was included in the model, BMI was no longer
significant. This was driven mainly by creatinine as virtually all subjects with a creatinine >2 mg/dl died
without a liver transplant. A creatinine of 1.65 was the best single predictive laboratory parameter of
mortality (Fig. 1) [5].
Figure 1. Creatinine as a predictor of mortality in NASH-related cirrhosis.
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 103
