Updates and advancements in the management of hepatocellular carcinoma patients after hepatectomy.

Introduction: The 5-year recurrence rate of hepatocellular carcinoma (HCC) after hepatic resection or local ablation is up to 70%. Adjuvant therapies to prevent HCC recurrence have been reported but are not currently recommended by EASL or AASLD guidelines. This review examined evidence from randomized controlled trials, meta-analyses and systematic reviews on the safety and efficacy of adjuvant therapies and chemotherapies in HCC patients after resection or local ablation.Areas covered: PubMed was searched through 15 June 2019. Available evidence was assessed based on the GRADE system.Expert commentary: Transarterial chemoembolization is the best adjuvant therapy for HCC patients at high risk of recurrence, antiviral therapy with nucleoside analogs is effective for preventing recurrence of HBV-related HCC, and interferon-α is effective for preventing recurrence of HCV-related HCC. Further studies are needed to clarify the efficacy of adjuvant immune checkpoint inhibitors. Adjuvant sorafenib appears to offer negligible clinical benefit and high risk of adverse effects.

High expression of AKR1B10 predicts low risk of early tumor recurrence in patients with hepatitis B virus-related hepatocellular carcinoma.

To clarify the relationship between aldo-keto reductase family 1 member B10 (AKR1B10) expression and early hepatocellular carcinoma (HCC) recurrence, this study detected AKR1B10 expression in tumor and adjacent non-tumor tissues from 110 patients with hepatitis B virus (HBV)-related HCC underwent liver resection and analyzed its correlations with clinicopathological characteristics and prognosis of these patients. Detected by quantitative reverse transcription polymerase chain reaction, AKR1B10 mRNA expression showed significantly higher in HCC tissues than in adjacent non-tumor tissues, with a low level in normal liver tissues. Similar results was confirmed at the protein level using immunohistochemistry and Western blotting. High AKR1B10 expression was negatively correlated with serum alpha-fetoprotein level and positively correlated with HBV-DNA level. Patients with high AKR1B10 expression had significantly higher disease-free survival than those with low expression within 2 years after liver resection. Multivariate analysis also confirmed high AKR1B10 expression to be a predictor of low risk of early HCC recurrence. In addition, high AKR1B10 expression was found to be a favorable factor of overall survival. These results suggest that AKR1B10 is involved in HBV-related hepatocarcinogenesis, but its high expression could predict low risk of early tumor recurrence in patients with HBV-related HCC after liver resection.

Effects of antiviral therapy on post-hepatectomy HBV reactivation and liver function in HBV DNA-negative patients with HBV-related hepatocellular carcinoma.

The ability of antiviral therapy to reduce risk of post-hepatectomy hepatitis B virus (HBV) reactivation in patients negative for viral DNA is unclear. This prospective study involved 174 consecutive patients with hepatitis B virus related hepatocellular carcinoma who were negative for hepatitis B virus DNA in serum and who underwent hepatic resection. Hepatitis B virus reactivation occurred in 30 patients in the non-antiviral group (27.8%) but in only 2 patients in the antiviral group (3.0%, P < 0.001). Based on multivariate analysis, risk of hepatitis B virus reactivation was associated with minor hepatectomy and absence of antiviral therapy. Liver function indicators at one week after resection did not differ significantly between the two groups, or between patients who experienced hepatitis B virus reactivation or not. Nevertheless, alanine aminotransferase and albumin at 1 month after resection were significantly higher in the antiviral group than in the non-antiviral group, and they were significantly higher in patients who did not experience hepatitis B virus reactivation than in those who did. Therefore, patients with hepatitis B virus related hepatocellular carcinoma face substantial risk of hepatitis B virus reactivation after hepatectomy, even if they are negative for viral DNA at baseline. Antiviral therapy can reduce the risk of reactivation, helping improve liver function after surgery.

Preoperative Ratio of Neutrophils to Lymphocytes Predicts Postresection Survival in Selected Patients With Early or Intermediate Stage Hepatocellular Carcinoma.

This study aims to clarify the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) for patients with hepatocellular carcinoma (HCC) after potentially curative hepatic resection (HR). The prognostic value of the NLR for HCC patients has not been definitely reviewed by large studies, especially for those with different Barcelona Clinic Liver Cancer (BCLC) stages.A consecutive sample of 963 HCC patients who underwent potentially curative HR was classified as having low or high NLR using a cut-off value of 2.81. Overall survival (OS) and tumor recurrence were compared for patients with low or high NLR across the total population, as well as in subgroups of patients in BCLC stages 0/A, B, or C. Clinicopathological parameters, including NLR, were evaluated to identify risk factors of OS and tumor recurrence after potentially curative hepatic resection. Multivariate analyses were performed using the Cox proportional hazards model or subdistribution hazard regression model.Multivariate analyses showed that NLR (>2.81), tumor number (>3), incomplete capsule, serum albumin (≤35 g/L), alanine transaminase activity (>40 U/L), and macrovascular invasion were risk factors for low OS, whereas NLR (>2.81), tumor size (>5 cm), alpha fetal protein concentration (>400 ng/L), and macrovascular invasion were risk factors for low tumor recurrence. NLR > 2.81 was significantly associated with poor OS and tumor recurrence in the total patient population (both P < 0.001), as well as in the subgroups of patients in BCLC stages 0/A or B (all P < 0.05). Moreover, those with high NLR were associated with low OS (P = 0.027), and also with slightly higher tumor recurrence than those with low NLR for the subgroups in BCLC stage B (P = 0.058). Neither association, however, was observed among patients with BCLC stage C disease.NLR may be an independent predictor of low OS and tumor recurrence after potentially curative HR in HCC patients in BCLC stages 0/A or B.

Combination of 5-fluorouracil and 2-morphilino-8-phenyl-4H-chromen-4-one may inhibit liver cancer stem cell activity.

This work aims to evaluate the impact of 2-morpholino-8-phenyl-4H-chromen-4-one (LY294002) combined 5-fluorouracil (5-FU) for the activity of CD90+ liver cancer cells derived from the human liver cancer cell line MHCC97H. MHCC97H sphere-forming cells (MSFCs) were amplified in serum-free medium and CD90+ cells were isolated from bulk MSFCs using flow cytometry. The phenotype of these CD90+ cells which show liver cancer stem cells (LCSCs) behavior was validated in vitro and in a xenograft model in nude mice. MSFCs, CD90+ liver cancer cells (CD90+ LCCs), and parental MHCC97H cells were treated with no drug, LY294002 alone, 5-FU alone, or both drugs together and then compared in terms of stem cell-related gene expression, proliferation, and invasion. Stem cell phenotype increased with increasing proportion of CD90+ cells, in ascending order: parental MHCC97H cells, MSFCs, and CD90+ liver cancer cells. LY294002 reduced the expression of CD90, Nanog, SALL4, and SHP2 in a concentration-dependent manner in CD90+ LCCs and MSFCs, but not in parental cells. LY294002 blocked AKT phosphorylation via the PI3K/AKT signaling pathway and inhibited CD90+ LCCs proliferation and tumorigenicity in vitro and in vivo. CD90+ liver cancer cells can express liver cancer stem cell phenotype. LY294002 inhibits the proliferation and invasion of MHCC97H-derived CD90+ LCCs and sensitized CD90+ LCCs-derived tumors to 5-FU in the current study which may provide insight into the association between the LY294002 combined 5-FU and liver cancer stem cell (LCSCs).

Historical Comparison of Overall Survival after Hepatic Resection for Patients With Large and/or Multinodular Hepatocellular Carcinoma.

The present study compared the efficacy of hepatic resection (HR) in patients with large hepatocellular carcinoma (HCC) and those with multinodular tumor and examined how that efficacy has changed over time in a large medical center.The intermediate stage of HCC comprises a highly heterogeneous patient population. Moreover, official guidelines have different views on the suitability of HR to treat such patients.A consecutive sample of 927 patients with preserved liver function and large and/or multinodular HCC who were treated by initial HR were divided into 3 groups: those with a single tumor ≥5 cm in diameter (n = 588), 2 to 3 tumors with a maximum diameter >3 cm (n  = 225), or >3 tumors of any diameter (n = 114). Hospital mortality and overall survival (OS) in each group were compared for the years 2000 to 2007 and 2008 to 2013.Patients with >3 tumors showed the highest incidence of hospital mortality of all groups (P < 0.05). Kaplan-Meier survival analysis showed that OS varied across the 3 groups as follows: single tumor > 2 to 3 tumors > 3+ tumors (all P < 0.05). OS at 5 years ranged from 24% to 41% in all 3 groups for the period 2000 to 2007, and from 35% to 46% for the period 2008 to 2013. OS was significantly higher during the more recent 6-year period in the entire patient population, those with single tumor, and those with 3+ tumors (all P < 0.05). However, in patients with 2 to 3 tumors, OS was only slightly higher during the more recent 6-year period (P = 0.084).Prognosis can vary substantially for these 3 types of HCC. Patients with >3 tumors show the highest hospital mortality and lowest OS after HR. OS has been improving for all 3 types of HCC at our medical center as a consequence of improvements in surgical technique and perioperative management.

Hepatic resection is safe and effective for patients with hepatocellular carcinoma and portal hypertension.

BACKGROUND & AIMS: Official guidelines do not recommend hepatic resection (HR) for patients with hepatocellular carcinoma (HCC) and portal hypertension (PHT). This study aims to investigate the safety and efficacy of HR for patients with HCC and PHT. METHODS: Mortality and survival after HR were analyzed retrospectively in a consecutive sample of 1738 HCC patients with PHT (n = 386) or without it (n = 1352). To assess the robustness of findings, we repeated the analysis using propensity score-matched analysis. We also comprehensively searched the PubMed database for studies evaluating the efficacy and safety of HR for patients with HCC and PHT. RESULTS: The 90-day mortality rate was 6.7% among those with PHT and 2.1% among those without it (P<.001). Patients without PHT had a survival benefit over those with PHT at 1, 3, and 5 years (96% vs 90%, 75% vs 67%, 54% vs 45%, respectively; P = .001). In contrast, PHT was not associated with worse short- or long-term survival when only propensity score-matched pairs of patients and those with early-stage HCC or those who underwent minor hepatectomy were included in the analysis (all P>.05). Moreover, the recurrence rates were similar between the two groups. Consistent with our findings, all 9 studies identified in our literature search reported HR to be safe and effective for patients with HCC and PHT. CONCLUSIONS: HR is safe and effective in HCC patients with PHT and preserved liver function. This is especially true for patients who have early-stage HCC or who undergo minor hepatectomy.