Nsult group had a higher 90-day mortality[19]. In addition, infection, typically a non-hepatic insult, is known to be an independent prognostic factor[20, 21].PLOS ONE | DOI:10.1371/journal.pone.0146745 January 20,14 /Acute-on-Chronic Liver FailureTherefore, considering the large proportion and high mortality rate, non-hepatic insults should be considered as important precipitating events in ACLF. The two ACLF definitions define underlying CLD differently. This difference might be due to differences in underlying CLDs and acute insults. More patients had viral infections as underlying CLD and viral superinfections or reactivation of HBV as acute insults in the East than the West[6, 17]. Cirrhosis is not necessary for the development of liver failure by reactivation of HBV or acute viral superinfection. Even ICG-001MedChemExpress ICG-001 without cirrhosis, acute viral superinfections in patients with CLD presented with a more severe course and higher mortality than those without CLD[22, 23]. In this study, non-cirrhotic CLD patients with ACLF according to the AARC definition showed a higher 90-day mortality, although not statistically significant (Fig 6). In addition, the short-term mortality rates (28-day and 90-day) did not differ between two groups, regardless of the presence of ACLF. This suggests that the presence of cirrhosis per se is not associated with increased mortality in ACLF patients. Although this study included small number of non-cirrhotic patients (118 patients), jir.2012.0140 because of the high 90-day mortality of the noncirrhotic ACLF patients, it would be better to consider non-cirrhotic CLD as an underlying CLD of ACLF. The interesting finding is that the etiologies of ACLF was changed. In the 2000’s, the main cause of underlying disease in ACLF was alcohol use in Europe[24], whereas in the Asia-Pacific region, it was hepatitis B virus[25, 26]. However, according to recent studies of Asia-Pacific region, alcohol use was the most common etiology of underlying CLD[17, 27]. Similarly, our multicenter study in Korea wcs.1183 also found that the main cause of underlying liver disease in CLD with acute deterioration was alcohol use. These results may have come from the introduction of universal HBV vaccination program as well as the widespread application of oral antiviral therapy for HBV infection in Korea[28]. Another difference in underlying CLD between the two definitions is whether patients with previous decompensation are included or not. Patients with previous decompensation with jaundice, HE, and ascites are excluded in the AARC definition[5]. On the JNJ-26481585 web contrary, the CANONIC study included these patients, if it was a new AD episode[6]. In this study, there was no difference between patients with and without previous AD according to the CLIF-C definition(P = 0.128). However, patients who had AD within 1 year showed a significantly lower survival rate than those with AD more than 1 year prior and those without previous AD. Therefore, considering the high mortality rate, it would be better to include the patients who developed AD within 1 year in the definition of ACLF. Interestingly, these results contradict the result of the CANONIC study, which reported that the patients without previous AD had higher mortality rate than those without previous AD owing to a lack of tolerance[6]. High mortality of patients with previous AD in this study could be explained by reduced hepatic functional reserve. Patients with previous AD, especially within 1 year, are likely to have redu.Nsult group had a higher 90-day mortality[19]. In addition, infection, typically a non-hepatic insult, is known to be an independent prognostic factor[20, 21].PLOS ONE | DOI:10.1371/journal.pone.0146745 January 20,14 /Acute-on-Chronic Liver FailureTherefore, considering the large proportion and high mortality rate, non-hepatic insults should be considered as important precipitating events in ACLF. The two ACLF definitions define underlying CLD differently. This difference might be due to differences in underlying CLDs and acute insults. More patients had viral infections as underlying CLD and viral superinfections or reactivation of HBV as acute insults in the East than the West[6, 17]. Cirrhosis is not necessary for the development of liver failure by reactivation of HBV or acute viral superinfection. Even without cirrhosis, acute viral superinfections in patients with CLD presented with a more severe course and higher mortality than those without CLD[22, 23]. In this study, non-cirrhotic CLD patients with ACLF according to the AARC definition showed a higher 90-day mortality, although not statistically significant (Fig 6). In addition, the short-term mortality rates (28-day and 90-day) did not differ between two groups, regardless of the presence of ACLF. This suggests that the presence of cirrhosis per se is not associated with increased mortality in ACLF patients. Although this study included small number of non-cirrhotic patients (118 patients), jir.2012.0140 because of the high 90-day mortality of the noncirrhotic ACLF patients, it would be better to consider non-cirrhotic CLD as an underlying CLD of ACLF. The interesting finding is that the etiologies of ACLF was changed. In the 2000’s, the main cause of underlying disease in ACLF was alcohol use in Europe[24], whereas in the Asia-Pacific region, it was hepatitis B virus[25, 26]. However, according to recent studies of Asia-Pacific region, alcohol use was the most common etiology of underlying CLD[17, 27]. Similarly, our multicenter study in Korea wcs.1183 also found that the main cause of underlying liver disease in CLD with acute deterioration was alcohol use. These results may have come from the introduction of universal HBV vaccination program as well as the widespread application of oral antiviral therapy for HBV infection in Korea[28]. Another difference in underlying CLD between the two definitions is whether patients with previous decompensation are included or not. Patients with previous decompensation with jaundice, HE, and ascites are excluded in the AARC definition[5]. On the contrary, the CANONIC study included these patients, if it was a new AD episode[6]. In this study, there was no difference between patients with and without previous AD according to the CLIF-C definition(P = 0.128). However, patients who had AD within 1 year showed a significantly lower survival rate than those with AD more than 1 year prior and those without previous AD. Therefore, considering the high mortality rate, it would be better to include the patients who developed AD within 1 year in the definition of ACLF. Interestingly, these results contradict the result of the CANONIC study, which reported that the patients without previous AD had higher mortality rate than those without previous AD owing to a lack of tolerance[6]. High mortality of patients with previous AD in this study could be explained by reduced hepatic functional reserve. Patients with previous AD, especially within 1 year, are likely to have redu.
