Liver Resection For Hepatitis Research Articles

Synergistic impact of resection margin and microscopic vascular invasion for patients with HBV-related intrahepatic cholangiocarcinoma

ABSTRACT Objectives The resection margin (RM) status and microscopic vascular invasion (MVI) are known prognostic factors for intrahepatic cholangiocarcinoma (ICC). An enhanced understanding of their impact on long-term prognosis is required to improve oncological outcomes. Methods A total of 711 consecutive patients who underwent curative liver resection for hepatitis B virus–related ICC were retrospectively analyzed. The different impact of the RM status (narrow, <1 cm, or wide, ≥1 cm) and MVI (positive, +, or negative, -) on overall survival (OS) and recurrence-free survival (RFS) were analyzed. Results The 1-, 3-, and 5-year OS rates were 67.6%, 42.5%, and 33.2% in wide RM & MVI (-), 58.0%, 36.1%, and 26.5% in narrow RM & MVI (-), 51.0%, 27.0%, and 24.3% in wide RM & MVI (+), and 39.0%, 20.4% and 14.3% in narrow RM & MVI (+) (p < 0.001). Multivariate analysis showed that RM & MVI were independent risk factors for the OS and RFS. Conclusion Combined analysis of RM and MVI can better stratify the risks of postoperative death and recurrence in patients with HBV-related ICC, which may help subsequent adjuvant therapy and closer follow-up.

Risk Factors, Patterns and Long-Term Prognosis of Early and Late Recurrence in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma

Background: Survival after liver resection of hepatocellular carcinoma (HCC) remains poor due to a high incidence of recurrence. We sought to investigate risk factors, patterns, and long-term prognosis among patients with early and late recurrence after liver resection for hepatitis B virus (HBV)-associated HCC.

Early and Late Recurrence of Hepatitis B Virus-Associated Hepatocellular Carcinoma.

Survival after liver resection of hepatocellular carcinoma (HCC) remains poor because of a high incidence of recurrence. We sought to investigate risk factors, patterns, and long-term prognosis among patients with early and late recurrence after liver resection for hepatitis B virus (HBV)-associated HCC. Data of consecutive patients undergoing curative resection for HBV-associated HCC were analyzed. According to the time to recurrence after surgery, recurrence was divided into early (≤2 years) and late recurrence (>2 years). Characteristics, patterns of initial recurrence, and postrecurrence survival (PRS) were compared between patients with early and late recurrence. Risk factors of early and late recurrence and predictors of PRS were identified by univariable and multivariable Cox regression analyses. Among 894 patients, 322 (36.0%) and 282 (31.5%) developed early and late recurrence, respectively. On multivariable analyses, preoperative HBV-DNA >104 copies/mL was associated with both early and late recurrence, whereas postoperative no/irregular antiviral therapy was associated with late recurrence. Compared with patients with late recurrence, patients with early recurrence had a lower proportion of intrahepatic-only recurrence (72.0% vs. 91.1%, p < .001), as well as a lower chance of receiving potentially curative treatments for recurrence (33.9% vs. 50.7%, p < .001) and a worse median PRS (19.1 vs. 37.5 months, p < .001). Multivariable analysis demonstrated that early recurrence was independently associated with worse PRS (hazard ratio, 1.361; 95% confidence interval, 1.094-1.692; p = .006). Although risk factors associated with early recurrence and late recurrence were different, a high preoperative HBV-DNA load was an independent hepatitis-related risk for both early and late recurrence. Early recurrence was associated with worse postrecurrence survival among patients with recurrence. Liver resection is the main curative treatment for hepatocellular carcinoma (HCC), but postoperative survival remains poor because of high recurrence rates. This study investigated the risk factors and patterns of early and late recurrence and found that a high preoperative hepatitis B virus (HBV) DNA load was an independent hepatitis-related risk factor for both. Early recurrence was also independently associated with worse postrecurrence survival. These data may provide insights into different biological origin and behavior of early versus late recurrence after resection for HBV-associated HCC, which could be helpful to make individualized treatment decision for recurrent HCC, as well as strategies for surveillance recurrence after resection.

Prior hepatitis B virus infection as a co-factor of chronic hepatitis C patient survival after resection of hepatocellular carcinoma

BackgroundPrior hepatitis B virus infection (PBI) may increase the risk of developing hepatocellular carcinoma (HCC), but the impact of PBI on clinical outcomes following treatment for HCC remains unknown. The aim of this study was to clarify whether PBI affects clinical outcomes after liver resection for hepatitis C virus (HCV)-related HCC by retrospective cohort study.MethodsPBI patients were defined as those negative for hepatitis B surface antigen and positive for anti-hepatitis B core antibody. Surgical outcomes of HCV-related HCC patients with PBI were compared to those without PBI. Survival of patients with non-B non-C HCC with and without PBI were also compared.ResultsIn the HCV group, the median overall survival of 165 patients with PBI was 4.7 years (95% confidence interval [CI], 3.9–5.9), and was significantly shorter compared with 263 patients without PBI (6.6 years [5.3–9.8]; p = 0.015). Conversely, there was no significant difference in recurrence-free survival between the two groups (1.8 years [95% CI, 1.4–2.0] vs 2.0 years [1.7–2.3]; p = 0.205). On Cox proportional hazards regression model, independent factors for overall survival were PBI (hazard ratio 1.38 [95% CI, 1.02–1.87]; p = 0.033), multiple tumors (p = 0.007), tumor size (p = 0.002), and liver cirrhosis (p < 0.001). On the other hand, in the non-B non-C HCC group, both the median overall survival (6.5 years [95% CI, 4.8–7.1]) and recurrence-free survival (2.4 years, [95% CI, 1.5–3.3]) in 104 patients with PBI were not significantly different from those (7.5 years [5.5 − NA; p = 0.932]; and 2.2 years [1.7–2.7; p = 0.983]) in 213 patients without PBI.ConclusionsPBI and HCV in conjunction with each other affect the survival of patients that have undergone resection for HCC.

Myeloid-derived suppressor cells in the patients with liver resection for hepatitis B virus-related hepatocellular carcinoma

Liver resection remains the popular treatment for hepatocellular carcinoma (HCC). The aim of this study was to explore the alteration of immune cells in HCC patients with liver resections. Nineteen patients were included and their peripheral blood samples were taken before and after liver resections for immune-cell analysis. The clinical characteristics showed that the median diameter of the resected tumors was 7.5 cm with a range from 1.4 to 16.5 cm. The analysis of immune cells showed that the percentage of CD4+ T-cells were not altered by liver resection, but the percentage of CD8+ T-cell was decreased from 31.7 ± 12.4% to 20.2 ± 10.4% at one week after liver resection (p = 0.006). For immunosuppressor cells, regulatory T-cells were not altered, but myeloid-derived suppressor cells (MDSC) were decreased from 7.75 ± 8.16% to 1.51 ± 1.32% at one month after liver resection (p = 0.022) in 10 of 19 patients with high frequency of MDSC. Furthermore, it was also found that MDSC population was linearly correlated to tumor volume. In conclusion, CD8+ T-cells and MDSC were altered by liver resection. The percentage of CD8+ T-cells was decreased by surgery, but the accumulation of MDSC was abrogated.

Nomogram for Preoperative Estimation of Microvascular Invasion Risk in Hepatitis B Virus-Related Hepatocellular Carcinoma Within the Milan Criteria.

The presence of microvascular invasion (MVI) decreases surgical outcomes of hepatocellular carcinoma (HCC). An accurate preoperative prediction of MVI can help surgeons to better choose surgical procedures, but accuracy is still difficult to achieve. To develop a nomogram to predict MVI presence before liver resection for hepatitis B virus (HBV)-related HCC within the Milan criteria (solitary nodule ≤5 cm; ≤3 nodules, none >3 cm; and no macrovascular invasion). Data on 1004 consecutive patients who underwent liver resection for HBV-related HCC within the Milan criteria at the Eastern Hepatobiliary Surgery Hospital between April 6, 2004, and February 22, 2011, were prospectively collected. Of these, patients who underwent surgery in an earlier period formed the training cohort (n = 707) for nomogram development, and those who underwent surgery thereafter formed the validation cohort (n = 297) to confirm the model's performance. Data analysis was conducted from August 1 to November 11, 2014. Liver resection for HCC. Overall survival and time to recurrence after liver resection were measured. Multivariate logistic regression was used to identify the independent risk factors associated with MVI that then were incorporated into the nomogram. Histopathologically identified MVI was found in 211 of 707 patients (29.8%) and 89 of 297 patients (30.0%) in the training and validation cohorts, respectively. In the training cohort, the 5-year recurrence and overall survival rates were 78.5% and 46.9%, respectively, in patients with MVI and 58.4%, and 70.9%, respectively, in patients without MVI (both P < .001). The preoperative factors associated with MVI were large tumor diameter, multiple nodules, incomplete capsule, α-fetoprotein level greater than 20 ng/mL, platelet count less than 100 × 103/µL, hepatitis B virus DNA load greater than 104 IU/mL, and a typical dynamic pattern of tumors on contrast-enhanced magnetic resonance imaging. Incorporating these 7 factors, the nomogram achieved good concordance indexes of 0.81 (95% CI, 0.78-0.85) and 0.80 (95% CI, 0.75-0.86) in predicting MVI in the training and validation cohorts, respectively, and had well-fitted calibration curves. The positive and negative predictive values (95% CIs) of the nomogram were calculated, resulting in positive predictive values of 57.2% (52.0%-64.9%) and 57.9% (49.2%-68.5%) and negative predictive values of 87.2% (83.2%-89.4%) and 83.2% (76.0%-87.7%) for the training and validation cohorts, respectively. Patients who had a nomogram score of less than 200 or 200 or greater were considered to have low or high risks of MVI presence, respectively. The nomogram achieved an optimal preoperative prediction of MVI in HBV-related HCC within the Milan criteria. Using the model, the risk for an individual patient to harbor MVI can be determined, which can lead to a rational therapeutic choice.

Erratum to: Effects of antiviral therapy on long‐term outcome after liver resection for hepatitis B virus‐related hepatocellular carcinoma

Erratum to: Effects of antiviral therapy on long‐term outcome after liver resection for hepatitis B virus‐related hepatocellular carcinoma

Effects of antiviral therapy on long‐term outcome after liver resection for hepatitis B virus‐related hepatocellular carcinoma

We investigated the effects of nucleos(t)ide analogues (NAs) on long-term outcome in patients following curative treatment for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study involved 70 of the 76 patients who had undergone liver resection for HBV-related HCC in our department; 6 patients were excluded due to non-curative resection or advanced cancer. The 70 patients were divided into three groups, as follows: 13 patients with high serum concentration of HBV DNA (≥4log(10)copies/mL) and no antiviral therapy (high viral group); 46 patients who received antiviral therapy during the serial follow up (antiviral therapy group) because of high viral concentration (≥4log(10)copies/mL); and 11 patients with low serum concentration of HBV DNA (<4log(10)copies/mL) and no antiviral therapy (low viral group). Tumor-free survival rate was significantly higher in the low viral group than in the high viral group (P=0.0058). Multivariate analysis revealed that a high serum concentration of HBV DNA (≥4log(10)copies/mL) (risk ratio 6.717, 95% confidence interval 1.435-31.434, P=0.0156) was an independent risk factor for a short tumor-free survival time. Tumor-free survival rate was significantly higher in the antiviral therapy group than in the high viral group (P=0.0478). Multivariate analysis revealed that presence of multiple tumors (risk ratio 2.857, 95% confidence interval 1.403-5.816, P=0.0038) was an independent risk factor for a short tumor-free survival time. The cumulative survival rate was significantly higher in the antiviral therapy group than in the high viral group (P=0.0025). Multivariate analysis revealed that not undergoing antiviral therapy (risk ratio 0.121, 95% confidence interval 0.024-0.608, P=0.0104) was an independent risk factor for a short survival time. A high serum concentration of HBV DNA (≥4log(10)copies/mL) was a strong risk factor for HCC recurrence after resection of HBV-related HCC. Antiviral therapy with NAs improved the long-term outcome after resection of HBV-related HCC in patients with high serum concentrations of HBV DNA.

Reactivation of viral replication after liver resection in patients infected with hepatitis B virus.

To investigate the mechanisms and risk factors underlying postoperative reactivation of hepatitis after liver resection for hepatitis B virus-related hepatocellular carcinoma. Although risk factors for acute hepatic failure after liver resection have been reported in patients with chronic liver disease, the issue of reactivation of hepatitis B virus replication after liver resection is unresolved. Fifty-five patients with hepatocellular carcinoma and hepatitis B surface antigen underwent liver resection. In 25 of these 55 patients, serum levels of hepatitis B virus DNA and the type of hepatitis B virus were determined before and after surgery. Postoperative hepatitis occurred in 13 of the 55 patients (24%). Reactivation of viral replication occurred after liver resection in 7 of the 25 patients tested, and alanine aminotransferase activity increased in 6 of these 7 patients. High preoperative alanine aminotransferase activity, high levels of hepatitis B virus DNA, presence of wild-type DNA, and detection of hepatitis B core antigen in hepatocytes, all features of the immune clearance phase in the natural course of hepatitis B virus infection with no surgery, were more likely to be found in patients with reactivation than in patients without reactivation. During the immune clearance phase of hepatitis B virus infection, especially the period of acute exacerbation, changes in serum hepatitis B virus DNA level should be monitored for early warnings of reactivation of viral replication, likely to cause severe postoperative hepatitis and acute hepatic failure.