Low Growth Hormone Levels Predict Poor Outcome of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure

Abstract

Background and Aims: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) remains a serious entity with high mortality. Growth hormone (GH) is related to the liver metabolism and regeneration. The present study aimed to explore the changes and prognostic efficacy of GH on the outcome of HBV-ACLF. Methods: A prospective cohort of 124 patients and a cross-sectional cohort of 142 subjects were enrolled. GH and insulin-like growth factor-1(IGF-1) were detected by ELISA. Thirty-day survival was collected and the association between GH and the 30-day mortality of HBV-ACLF was analyzed. Results: The mean age of the whole prospective cohort was 46.61 ± 12.71 years, and 19 (15.3%) patients were female. The median (IQR) of GH levels in non-survivors were 1106.55 (674.25, 1922.4) pg/ml, which were significantly lower than in survivors (p < 0.001). In the cross-sectional cohort, GH level was significantly higher in liver cirrhosis - acute decompensation (LC-AD) group than liver cirrhosis (LC) group (p < 0.001) while IGF-1 decreased significantly in LC, LC-AD, ACLF groups than health control (HC) and chronic Hepatitis B (CHB) groups (p < 0.001). The area under the receiver operating characteristic curve (AUROC) of GH for predicting 30-day mortality was 0.793. We built a new prognostic model, namely MELD-GH, which showed better predictive efficacy than Child-Pugh, MELD, CLIF-SOFA, and CLIF-C ACLF scores. Conclusions: Low GH predicted the poor outcome of HBV-ACLF patients. GH and IGF-1 levels were differently distributed among HC, CHB, LC, LC-AD, and ACLF patients. MELD-GH had better predictive accuracy when compared to Child-Pugh, MELD, CLIF-SOFA, and CLIF-C ACLF scores.

Keywords: acute-on-chronic liver failure; growth hormone; hepatitis B; mortality; prognostic model.

Figure 1

Flow chart of enrolled cohorts. ACLF-D, acute-on-chronic liver failure-death; ACLF-S, acute-on-chronic liver failure-survival; CHB, chronic Hepatitis B; HBV-ACLF, Hepatitis B related acute-on-chronic liver failure; HC, health control; LC, liver cirrhosis; LC-AD, liver cirrhosis-acute decompensation.

Figure 2

Distribution of GH in HBV-ACLF cohort. (A) GH levels were higher in survivors group than in non-survivors group. (B) Patients with 3 or more organs failure had lower GH levels than patients with 2, 1, or no organ failure. (C) Patients with MELD > 25 had lower GH levels than patients with MELD between 20 and 25. (D) patients with Grade III~IV encephalopathy had lower GH levels than no HE group. * <0.05, ** <0.01.

Figure 3

Distribution of GH in cross-sectional cohort. (A) ACLF group showed higher GH levels than HC, CHB, and LC group, but no difference from LC-AD group, and the r-value of the correlation between GH levels and severity was 0.462, p < 0.001. (B) HC group showed higher IGF-1 levels than LC, LC-AD, and ACLF group, but no difference from CHB group, and the r value of the correlation between IGF-1 levels and severity was −0.641, p < 0.001. ACLF, acute-on-chronic liver failure; CHB, chronic hepatitis B; GH, growth hormone; HC, health control; IGF-1, insulin-like growth factor-1; LC, liver cirrhosis; LC-AD, liver cirrhosis-acute decompensation. *** < 0.001.

Figure 4

Performance of GH on predicting 30-day survival of HBV-ACLF patients. (A) The AUC of GH predicting the outcome was 0.793, and low GH (<2,001 pg/ml) group (B) showed significantly worse 30-day outcome than high GH group. (C) MELD-GH score showed highest AUC than Child-Pugh, MELD, CLIF-SOFA, and CLIF-C ACLF scores. (D) The estimation of HBV-ACLF mortality based on MELD-GH score.