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Background: Early recurrence (ER) of hepatocellular carcinoma (HCC) (within 1 year after resection) is known to be a poor prognostic factor. The aim was to identify the risk factors associated with ER after HCC resection. Methods: Data were analyzed retrospectively from patients who underwent primary resection for HCC from two hospitals. For cross‐validation, HCC resection cases were divided into the training and testing cohort. The clinicopathological factors between the ER and non‐ER groups and factors for predicting ER and prognosis after HCC resection were compared. Results: Out of 173 patients in the training dataset, 33 patients had ER and the ER group showed larger tumor size, more intrahepatic metastasis (IM), and a higher ratio of serum des‐gamma‐carboxy prothrombin (DCP) to tumor volume (TV) (DCP/TV) than the non‐ER group. Out of 203 patients in the testing dataset, 30 patients had ER and the ER group demonstrated larger tumor size, more IM, and higher serum alpha‐fetoprotein, AFP/TV, DCP/TV, AFP/tumor maximum diameter (TMD), and DCP/TMD than the non‐ER group. The patients were divided into high and low DCP/TV groups and high serum DCP/TV was associated with unfavorable overall survival in the training and testing dataset. Multivariate analysis confirmed that high serum DCP/TV and IM were independently associated with ER. Conclusion: Preoperative high serum DCP/TV may be useful for stratifying patients at risk of early HCC recurrence after curative resection. [ABSTRACT FROM AUTHOR]

Aim: In patients with liver cirrhosis, high levels of serum myostatin are associated with poor prognosis. We aimed to clarify the influence of myostatin on the prognosis of patients with non‐alcoholic fatty liver disease–hepatocellular carcinoma (NAFLD‐HCC) without cirrhosis and on the progression of liver fibrosis. Methods: Serum myostatin levels were evaluated in 234 patients who underwent primary surgical resection for single HCC. To clarify the impact of myostatin on liver fibrosis, we established human primary liver fibroblasts from resected livers, and cultured them in the presence of myostatin. Results: The median age was 67.4 years, the median L3 skeletal muscle mass index was 44.4 cm2/m2, and the median body mass index was 23.4 kg/m2. Eighty‐two (35.0%) patients had sarcopenia (L3 skeletal muscle mass index: men <42, women <38 cm2/m2). The etiologies of liver disease were hepatitis B virus (n = 61), hepatitis C virus (n = 86), and non‐B non‐C hepatitis (n = 87) including NAFLD (n = 74). High preoperative serum myostatin and vascular invasion were independent predictors of poor overall survival (OS). High serum myostatin was associated with poor OS in patients with no sarcopenia (n = 152). In patients without advanced liver fibrosis (Fibrosis stage, 0–2; n = 58), high levels of serum myostatin were also associated with poor OS, regardless of sarcopenia. Serum myostatin levels were increased with the progression of liver fibrosis. Liver fibroblasts were activated and produced collagen following stimulation with myostatin. Conclusions: In patients with NAFLD‐HCC without advanced liver fibrosis, high levels of serum myostatin were associated with poor OS. Myostatin activated primary fibroblasts and stimulated collagen production. [ABSTRACT FROM AUTHOR]

Aim: Early hepatocellular carcinoma (HCC) recurrence after curative resection is a known poor prognostic factor. We aimed to identify microRNAs associated with recurrence after curative HCC resection. Methods: To identify risk factors for early recurrence and metastasis, 694 patients who underwent primary curative HCC resection were analyzed. We evaluated microRNA expression in cancerous and non‐cancerous tissues by microarray and quantitative PCR analyses using 16 HCC samples. We defined patients who had a recurrence within 1 year of resection as the early recurrence (ER) group, patients who had a recurrence within 1–5 years as the late recurrence (LR) group, and patients who did not recur during the 5‐year observation period as the no recurrence (NR) group. We examined the relationship between microRNA expression and clinical features. Results: Multivariate analysis revealed that α‐fetoprotein >31 ng/mL, tumor size >4 cm, and intrahepatic metastasis (IM) were significant factors. Afterwards, microarray analyses revealed that microRNA (miR)‐125b‐5p and miR‐148a‐3p were significantly downregulated in recurrent cases. The ratio of miR‐125b‐5p expression in cancerous versus non‐cancerous tissue (miR‐125b ratio), but not miR‐148a‐3p, was significantly lower in the ER group. Early recurrence was associated with reduced overall survival compared with the LR and NR group. The miR‐125b ratio was significantly lower in the ER group than in the LR and NR groups. Multivariate analysis showed that a low miR‐125b ratio and IM were independently associated with ER and disease‐free survival. Conclusions: Assessing tissue miR‐125b‐5p expression and IM is useful for stratifying patients at risk of early HCC recurrence after curative resection. [ABSTRACT FROM AUTHOR]

Purposes: Lenvatinib (LEN) is a molecular-target drug, used for unresectable hepatocellular carcinoma (HCC). It is associated with adverse events (AEs), including hypertension, proteinuria, fatigue, and anorexia, which may force dose reduction or discontinuation. Ninjin'yoeito (NYT) is a Chinese–Japanese herbal compound that can effectively treat fatigue and anorexia, and which has been used for chronic liver diseases. NYT reduces AEs and improves the liver function in patients treated with sorafenib but its effect on LEN is unclear. Methods: The present study included 46 patients (male, n = 32; female, n = 14) who received LEN for HCC at our hospital. Their median age was 70 years (range 36–88 years), and their median body weight was 61.5 kg (range 38.4–97.0 kg). Patients were divided into two groups, depending on whether they received NYT medication. Their AEs and liver function were examined one month after starting LEN. Results: The NYT group suffered less fatigue (63.6% vs. 11.4%, P = 0.0014) and showed elevated aspartate aminotransferase levels (45.5% vs. 14.3%, P = 0.0433) in comparison to the non-NYT group. The non-NYT group also showed a significantly exacerbated albumin-bilirubin (ALBI) grade (P = 0.0342) and ALBI score (average change: + 0.232, P = 0.0001) at 1 month in comparison to baseline. Conclusion: NYT apparently suppressed LEN-induced fatigue and helped maintain liver function in patients with HCC. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammation has been correlated with worse survival for some cancers. We evaluated prognostic values of various inflammatory factor combinations in patients who underwent resections for hepatocellular carcinoma (HCC). Methods: We retrospectively analysed 306 consecutive patients with HCC who underwent curative liver resections. After assessing eight combinations of inflammatory markers for predictive value for recurrence, we focused on lymphocyte-to-C-reactive protein ratio (LCR) to elucidate its associations with recurrence-free survival (RFS) and overall survival (OS) in univariate and multivariate analyses (Cox proportional hazards model). We also used immunohistochemical CD34 and CD8 staining to investigate the mechanism of LCR elevation. Results: LCR showed the highest association with RFS in HCC patients among the compared indices. High preoperative LCR correlated with a high serum albumin concentration, small tumour size, early Barcelona Clinic Liver Cancer stage and low rates of microscopic vascular invasion and microscopic intrahepatic metastasis. Higher preoperative LCR was an independent predictor of longer RFS and OS in this cohort. High LCR patients had fewer vessels encapsulating tumour clusters, and higher intratumoural CD8+ T-cell counts than low LCR patients. Conclusions: Preoperative LCR is a novel and convenient prognostic marker for patients with HCC, and is associated with the tumour microenvironment immune status. [ABSTRACT FROM AUTHOR]

Although it has been recognized that those who are positive for anti-hepatitis B core antibody (anti-HBcAb) and negative for hepatitis B surface antigen (HBsAg) with normal liver function could be donors for living donor liver transplantation under appropriate prophylaxis, the negative impact of positive HBcAb on such donors themselves has not been reported. We present a case of a living donor with positive HBcAb, who donated his left lobe for his sister with unresectable giant hepatic hemangioma, and the donor himself developed a de novo hepatocellular carcinoma (HCC) 10 years after donation. He had been lost from the follow-up program since 1 year after donation. Imaging studies showed a heterogeneously enhanced mass compatible with HCC, which was 9 cm in size with portal invasion into the anterior portal vein of the remnant liver. Re-laparotomy for hepatectomy with the removal of the tumor thrombus in the anterior portal vein of the remnant liver was carried out, and he is free from recurrence 6 months after surgery on prophylactic sorafenib. At our institute, 58 (9.6%) donors among the 603 living donors were anti-HBcAb positive and anti-HBsAg negative, and we started regular HCC surveillance using sonogram every 6 months for these patients. [ABSTRACT FROM AUTHOR]