Decrypting Cryptogenic Hepatocellular Carcinoma: Clinical Manifestations, Prognostic Factors and Long-Term Survival by Propensity Score Model

Background and Aims: The clinical aspects of cryptogenic hepatocellular carcinoma (HCC), defined as HCC in patients without hepatitis B, C or alcoholism, are not clear. We investigated its clinical presentations, long-term survival and prognostic predictors. Methods: A total of 2645 HCC patients were studied. One-to-one matched pairs between viral/alcoholic and cryptogenic HCC patients were generated by using the propensity model. The survival analysis was performed with the Kaplan-Meier method and log-rank test, and hazard ratios were calculated with Cox proportional hazards model. Results: Among 366 (14%) patients with cryptogenic HCC, 34% of patients were presented with abdominal discomfort, and 31% of patients were identified incidentally. Compared to patients with viral/alcoholic HCC, cryptogenic HCC patients were significantly older (p<0.0001), with poorer performance status (p = 0.0031) and less often underwent curative treatment (p = 0.0041). They also had larger tumor burden (p<0.0001), poorer renal function (p<0.0001), lower a-fetoprotein level (p<0.0001), and more advanced Barcelona Clinic Liver Cancer stages (p<0.0001). With propensity score model, 366 pairs of similar HCC patients were selected and similar long-term survival between the two groups of patients was found (p = 0.1038). For cryptogenic HCC patients, alpha-fetoprotein >= 49 ng/mL (hazard ratio [HR]: 1.955, p = 0.0002), Child-TurcottePugh class B/C (HR: 2.798, p, 0.0001), performance status >= 1 (HR: 2.463, p, 0.0001) and vascular invasion (HR: 1.608, p = 0.0257) were independent predictors of poor prognosis. Conclusions: Patients with cryptogenic HCC are usually diagnosed with poor general condition at late stages. However, cryptogenic HCC patients have similar prognostic predictors and long-term survival compared with viral/alcoholic HCC patients. Diagnosis at an early stage may improve their clinical outcomes.