Differential Survival Impact of Diabetes Mellitus on Hepatocellular Carcinoma: Role of Staging Determinants

[[abstract]]Background: Diabetes mellitus (DM) is common in patients with hepatocellular carcinoma (HCC) and may impact survival. Very few studies focused on the influence of DM in different clinical scenarios. We evaluated the prognostic impact of DM on HCC patients stratified by liver dysfunction, Milan criteria, and performance status defined in the Barcelona Clínic Liver Cancer staging parameters. Methods: A prospective dataset of 3573 HCC patients between 2002 and 2016 was retrospectively analyzed. The multivariate Cox proportional hazards model was used to identify independent prognostic predictors. The Kaplan-Meier method with a log-rank test was applied to compare the survival distributions between different patient groups. Results: Among all, DM was not an independent prognostic predictor in the Cox multivariate analysis (p = 0.1044). In the subgroup analysis, DM was not a significant prognostic predictor in Child-Turcotte-Pugh class A or class B/C patients. However, DM was associated with a decreased survival in patients within the Milan criteria (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.155-1.601, p = 0.0002) and in those with the performance status 0 (HR 1.213, 95% CI 1.055-1.394, p = 0.0067) in the multivariate Cox analysis, but not in those beyond the Milan criteria and poor performance status. Conclusions: DM is highly prevalent in HCC patients and has a distinct survival impact. DM is an independent survival predictor among patients within the Milan criteria and good performance status. These high-risk patients should be closely monitored, and aggressive anticancer treatment should be considered

Definitions for the original and modified CTP classifications.

<p>Modified CTP class 0: Fulfill all criteria of albumin ≧4.0 g/dL, bilirubin ≦0.8 mg/dL, prothromin time prolongation <0 seconds, no ascites and no encephalopathy.</p><p>Modified CTP class A: total scores of 5–6 and not fulfilling criteria for class 0; class B: total scores of 7–9; class C: total scores of 10–15.</p><p><b>Abbreviations</b>: CTP, Child-Turcotte-Pugh.</p

The proposed criteria for original and modified models of the CLIP and TIS staging systems.

<p><b>Abbreviations</b>: CTP, Child-Turcotte-Pugh; CLIP, Cancer of the Liver Italian Program; TIS, Taipei Integrated Scoring.</p

Comparison of the prognostic ability among 4 BCLC-, 4 CLIP- and 4 TIS-based staging systems.

<p><b>Abbreviations</b>: BCLC, Barcelona Clinic Liver Cancer; CLIP, Cancer of the Liver Italian Program; TIS, Taipei Integrated Scoring.</p

Definitions for the original and modified CTP classifications.

<p>Modified CTP class 0: Fulfill all criteria of albumin ≧4.0 g/dL, bilirubin ≦0.8 mg/dL, prothromin time prolongation <0 seconds, no ascites and no encephalopathy.</p><p>Modified CTP class A: total scores of 5–6 and not fulfilling criteria for class 0; class B: total scores of 7–9; class C: total scores of 10–15.</p><p><b>Abbreviations</b>: CTP, Child-Turcotte-Pugh.</p

Univariate and multivariate Cox regression survival analysis in HCC patients.

<p><b>Abbreviations</b>: HCC, hepatocellular carcinoma; HR, hazard ratio; CI, confidence interval; HBsAg, hepatitis B surface antigen; AFP, α-fetoprotein; TTV, total tumor volume; ECOG, Eastern Cooperative Oncology Group; CTP, Child-Turcotte-Pugh.</p

The distribution of HCC patients after modification of the CTP classifications.

<p><b>Abbreviations</b>: CTP, Child-Turcotte-Pugh; HCC, hepatocellular carcinoma; No., number.</p

Baseline demographics of all HCC patients and HCC patients with modified CTP class 0, A, B and C.

<p><b>Abbreviations</b>: HCC, hepatocellular carcinoma; CTP, Child-Turcotte-Pugh; SD, standard deviation; HBV, hepatitis B virus; HCV, hepatitis C virus; BUN, blood urea nitrogen; INR, international normalized ratio; PT, prothrombin time; ALT, alanine aminotransferase; AFP, α-fetoprotein; IQR, interquartile range; MELD, model for end-stage liver disease; No., number; TTV, total tumor volume; TACE, transcatheter arterial chemoembolization; BCLC, Barcelona Clinic Liver Cancer; CLIP, Cancer of the Liver Italian Program; TIS, Taipei Integrated Scoring.</p