Achieving Complete Remission of Hepatocellular Carcinoma: A Significant Predictor for Recurrence-Free Survival after Liver Transplantation

BACKGROUND: Liver transplantation (LT) is a curative treatment for hepatocellular carcinoma (HCC) and the underlying primary liver disease; however, tumor recurrence is still a major issue. Therefore, the aim of this study was to assess predictors and risk factors for HCC recurrence after LT in patients within and outside the Milan criteria with a special focus on the impact of different bridging strategies. METHODS: All patients who underwent LT for HCC between 07/2002 and 09/2016 at the University Hospital of Muenster were consecutively included in this retrospective study. Database research was performed and a multivariable regression analysis was conducted to explore potential risk factors for HCC recurrence. RESULTS: A total of 82 patients were eligible for the statistical analysis. Independent of bridging strategy, achieving complete remission (CR) was significantly associated with a lower risk for tumor recurrence (p = 0.029; OR = 0.426, 95% CI 0.198-0.918). A maximal diameter of lesion < 3 cm was also associated with lower recurrence rates (p = 0.040; OR = 0.140, 95% CI 0.022-0.914). Vascular invasion proved to be an independent risk factor for HCC recurrence (p = 0.004; OR = 11.357, 95% CI 2.142-60.199). CONCLUSION: Achieving CR prior to LT results in a significant risk reduction of HCC recurrence after LT independent of the treatment modalities applied

Circulating microRNA-200 Family as Diagnostic Marker in Hepatocellular Carcinoma.

In this clinical study, we aimed to evaluate the role of circulating microRNA-200 family as a non-invasive tool to identify patients with cirrhosis-associated hepatocellular carcinoma (HCC).Prognosis of HCC remains poor with increasing incidence worldwide, mainly related to liver cirrhosis. So far, no reliable molecular targets exist for early detection of HCC at surgically manageable stages. Recently, we identified members of the microRNA-200 family as potential diagnostic markers of cirrhosis-associated HCC in patient tissue samples. Their value as circulating biomarkers for HCC remained undefined.Blood samples and clinicopathological data of consecutive patients with liver diseases were collected prospectively. Expression of the microRNA-200 family was investigated by qRT-PCR in blood serum samples of 22 HCC patients with and without cirrhosis. Serum samples of patients with non-cancerous chronic liver cirrhosis (n = 22) and of healthy volunteers (n = 15) served as controls.MicroRNA-141 and microRNA-200a were significantly downregulated in blood serum of patients with HCC compared to liver cirrhosis (p<0.007) and healthy controls (p<0.002). MicroRNA-141 and microRNA-200a could well discriminate patients with cirrhosis-associated HCC from healthy volunteers with area under the receiver-operating characteristic curve (AUC) values of 0.85 and 0.82, respectively. Additionally, both microRNAs could differentiate between HCC and non-cancerous liver cirrhosis with a fair accuracy.Circulating microRNA-200 family members are significantly deregulated in patients with HCC and liver cirrhosis. Further studies are necessary to confirm the diagnostic value of the microRNA-200 family as accurate serum marker for cirrhosis-associated HCC

Factorial analysis by anti-image-matrix (A) and Varimax-matrix rotation (B).

<p>Sufficient suitability of microRNA expression and etiological parameters with coefficients >0.5 (^a suitability criteria). Rotated matrix of components shows a high factorial load by combining microRNA expression and HCC. Factor annotations of initial variables are in bold.</p

Diagnostic performance of microRNA-141 and microRNA-200a.

<p>Receiver operating characteristic (ROC) curve of microRNA-141 (A) and microRNA-200a (B) in three groups (Healthy <i>vs</i>. HCC; Healthy <i>vs</i>. Cirrhosis; HCC <i>vs</i>. Cirrhosis). Area under the curve (AUC) values are presented by the estimate with 95% confidence interval.</p

The ΔCt expression level of the five circulating microRNA-200 family members.

<p>ΔCt levels are inversely proportional to the amount of target microRNA in the sample. Asterisks indicate to a significant difference of <i>p</i>< 0.05, respectively.</p