Nomogram Analysis for HBV Related Acute-on-chronic Liver Failure

Establishment and Validation of Prognostic Nomograms for HBV-related Acute-on-Chronic Liver Failure in South of China

Acute-on-chronic liver failure (ACLF) is an acute deterioration of chronic liver diseases, which progresses rapidly, with a mortality rate of more than 50%.MELD score is used to evaluate the patients' condition. However, MELD score only concerned about the variables of total bilirubin, international normalize ratio (INR) and creatinine which is not enough to access ACLF patients' condition accurately.

Scholars of US and China suggested to divided ACLF patients into 3 subgroups base on the different "chronic liver disease" . Type A ACLF patients have chronic liver disease without cirrhosis. Type B ACLF patients with compensated cirrhosis, while type C ACLF patients with decompensated cirrhosis. Currently, no studies have assessed the prognosis of different types of ACLF patients, especially for HBV-related ACLF patients.

Investigators conducted a retrospective study which enrolls HBV-related ACLF patients between January 2010 and March 2018 in the Third Affiliated Hospital of Sun Yat-sen University. Clinical data, survival time and information regarding liver transplantation after enrolment were collected. A nomogram was formulated based on the results of multivariable Cox regression analysis. The performance of the nomogram was evaluated by the concordance index (C-index) and assessed by comparing nomogram-predicted vs observed Kaplan-Meier estimates of survival probability, and bootstraps with 1000 resamples were applied to these activities. Comparisons between the nomogram, MELD Score，MELD-Na Score and CTP Score in the entire population were performed and were tested by the C-index. A larger C-index indicated more accurate prognostic stratification.

Acute-on-chronic liver failure (ACLF) is an acute deterioration of chronic liver diseases, which progresses rapidly, with a mortality rate of more than 50%. Liver transplantation is the only therapy that has been proven beneficial, but the number of liver donor is limited. MELD score is used to evaluate the patients' condition before transplantation to decide who is in greatest need. However, MELD score only concerned about the variables of total bilirubin, international normalize ratio (INR) and creatinine. Other important valuables such as age, hepatic encephalopathy, and indexes of infection (e.g. white blood cell counts) were excluded. Many studies showed that application of MELD score only is not enough to access the liver failure patients' condition accurately.

Both APASL and Chinese Society of Infectious Disease considered the "chronic liver disease" included chronic liver disease with/without cirrhosis. Scholars of US and China suggested to divided ACLF patients into 3 subgroups base on the different "chronic liver disease" . Type A ACLF patients have chronic liver disease without cirrhosis. Type B ACLF patients with compensated cirrhosis, while type C ACLF patients with decompensated cirrhosis. Currently, no studies have assessed the prognosis of different types of ACLF patients, especially for HBV-related ACLF patients.

Investigators conducted a retrospective study which enrolls HBV-related ACLF patients between January 2010 and March 2018 in the Third Affiliated Hospital of Sun Yat-sen University. Clinical data of demographic data, admission causes, cirrhosis complications, and precipitating events associated with acute decompensation or severe liver injury, laboratory measurements (e.g., serum albumin, sodium, alanine aminotransferase, aspartate aminotransferase, total bilirubin, INR and creatinine levels), mean arterial pressure, HBV infection biomarkers, HBV-DNA levels, antiviral treatment for HBV (nucleoside analogues, including lamivudine, adefovir, entecavir, telbivudine and tenofovir, within 6 months prior to and during hospitalisation), and prognosis would be collected. Survival time and information regarding liver transplantation after enrolment were also collected. A nomogram was formulated based on the results of multivariable Cox regression analysis. The performance of the nomogram was evaluated by the concordance index (C-index) and assessed by comparing nomogram-predicted vs observed Kaplan-Meier estimates of survival probability, and bootstraps with 1000 resamples were applied to these activities. Comparisons between the nomogram, MELD Score, MELD-Na Score and CTP Score in the entire population were performed and were tested by the C-index. A larger C-index indicated more accurate prognostic stratification.

Inclusion Criteria:

• Age ≥ 18 years; Serum total bilirubin ≥ 10 mg/dl; International normalized ratio≥1.5 or prothrombin activity <40%; Complicated within 4 weeks by ascites and/or encephalopathy; Positive serum hepatitis B surface antigen for more than 6 months.

Exclusion Criteria:

• Drug induce liver diseases; Autoimmune liver diseases; Alcohol or drug abusers (average alcohol consumption >40g/d for men, >20g/d for women); Liver diseases caused by metabolic factors; Superinfection with hepatitis A, C, D, E viruses; Infected by HIV virus; Pregnancy or lactation; Liver failure caused by recurrence of hepatitis b after transplantation.