Fucosylated Fraction of Alpha-Fetoprotein as a Predictor of Prognosis in Patients with Hepatocellular Carcinoma After Curative Treatment

Aim

The aim of this study was to evaluate the clinical usefulness of measuring the Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) for prognostic predictor in patients with hepatocellular carcinoma (HCC).

Methods

A total of 477 HCC patients who underwent percutaneous ablative therapy or hepatectomy were enrolled. Overall survival and recurrence-free survival were respectively evaluated retrospectively and prospectively. Multivariate analyses of clinical prognostic factors were performed by Cox’s stepwise proportional hazard model.

Results

AFP-L3 status was a statistically significant independent prognostic factor of long-term survival (P = 0.013) and recurrence-free survival (P = 0.006) in patients who underwent percutaneous ablative therapy. In contrast, AFP-L3 did not affect prognosis in patients who underwent hepatectomy.

Conclusions

AFP-L3 had different impacts on prognosis in patients with HCC who underwent percutaneous ablative therapy and hepatectomy. Our results suggest that AFP-L3 positivity (≥15%) might be a promising indicator for choosing therapeutic modalities in HCC patients.     

Factors predicting survival after post-transplant hepatocellular carcinoma recurrence

Background

Although factors associated with an increased risk of recurrence after liver transplantation for hepatocellular carcinoma (HCC) have been extensively studied, the history of patients with a post-transplant recurrence is poorly known.

Methods

Patients experiencing a post-transplant HCC recurrence from 1996 to 2011 in two transplant programs were included. Demographic, transplant, and post-recurrence variables were assessed.

Results

Thirty patients experienced an HCC recurrence–22 men and 8 women with a mean age of 55 ± 6 years. Sixteen (53 %) were outside the Milan criteria at the time of transplantation. Most recurrences (60 %) appeared within the first 18 months after transplantation, ranging between 1.7 and 109 months (median 14.2 months). Mean post-recurrence survival was 33 ± 31 months. On univariate analysis, total tumor volume (TTV; p = 0.047), microvascular invasion (p = 0.011), and time from transplant to recurrence (p = 0.001) predicted post-recurrence survival. On multivariate analysis, both time from transplant to recurrence (p = 0.001) and history of rejection (p = 0.043), but not the location of the recurrence or the type of recurrence treatment, predicted post-recurrence survival.

Conclusion

This study suggests that patients with early post-transplant HCC recurrence have worse outcomes. Those with a history of graft rejection have better survivals, possibly due to more active anti-cancer immunity.     

A non-smooth tumor margin in the hepatobiliary phase of gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging predicts microscopic portal vein invasion, intrahepatic metastasis, and early recurrence after hepatectomy in patients with hepatocellular carcinoma

Background

The value of the hepatobiliary phase of gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in patients with hepatocellular carcinoma (HCC) has not been evaluated in detail.

Methods

Between 2008 and 2009, 61 patients with HCC within the Milan criteria underwent Gd-EOB-DTPA-enhanced MRI and hepatectomy. The tumor margin was determined preoperatively based on hepatobiliary phase images. Microscopic portal vein invasion (MPVI), intrahepatic metastasis (IM), and recurrence of HCC within 1 year after hepatectomy were evaluated in 24 patients with non-smooth margins at the periphery of the tumor and 37 patients with smooth margins.

Results

The number of patients with MPVI and IM of HCC was significantly higher among those with non-smooth margins (42 and 38%, respectively) than among those with smooth margins (3%; p = 0.0002 and 5%; p = 0.0042, respectively). A non-smooth margin was identified as a significant predictor of MPVI (odds ratio 18.814, p = 0.024) and IM (odds ratio 6.498, p = 0.036) of HCC on multivariate analysis. Furthermore, a non-smooth margin was identified as a significant predictor of recurrence within 1 year after hepatectomy (odds ratio 4.306, p = 0.04) on multivariate analysis.

Conclusions

A non-smooth tumor margin in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI is useful to predict MPVI, IM, and early recurrence of HCC after hepatectomy.     

Hepatocellular carcinoma patients with increased oxidative stress levels are prone to recurrence after curative treatment: a prospective case series study using the d-ROM test

Purpose

Oxidative stress plays an important role in liver carcinogenesis. To determine the impact of oxidative stress on the recurrence of stage I/II hepatocellular carcinoma (HCC) after curative treatment, we conducted a prospective case series analysis.

Methods

This study included 45 consecutive patients with stage I/II HCC, who underwent curative treatment by surgical resection or radiofrequency ablation at Gifu Municipal Hospital from 2006 to 2007. In these 45 cases, recurrence-free survival was estimated using the Kaplan–Meier method. The factors contributing to HCC recurrence, including the serum levels of derivatives of reactive oxygen metabolites (d-ROM) as an index of oxidative stress, were subjected to univariate and multivariate analyses using the Cox proportional hazards model.

Results

The serum levels of d-ROM (P = 0.0231), α-fetoprotein (AFP, P = 0.0274), and fasting plasma glucose (P = 0.0400) were significantly associated with HCC recurrence in the univariate analysis. Multivariate analysis showed that the serum levels of d-ROM (hazard ratio [HR] 1.0038, 95 % confidence interval [CI] 1.0002–1.0071, P = 0.0392) and AFP (HR 1.0002, 95 % CI 1.0000–1.0003, P = 0.0316) were independent predictors of HCC recurrence. Kaplan–Meier analysis showed that recurrence-free survival was low in patients with high serum d-ROM (≥570 Carr U, P = 0.0036) and serum AFP (≥40 ng/dL, P = 0.0185) levels.

Conclusions

The serum levels of d-ROM and AFP can be used for screening patients with a high risk for HCC recurrence. Patients who show increased levels of these factors require careful surveillance.     

Laparoscopic liver resection for treating recurrent hepatocellular carcinoma

Background

It is still unknown whether laparoscopic liver resection is suitable for recurrent hepatocellular carcinoma (HCC) after previous curative hepatic resection.

Method

The perioperative outcomes of 40 patients treated with second surgery for recurrent HCC by partial hepatectomy were studied retrospectively. The second surgery was performed under laparotomy in 20 patients (laparotomy group) and under laparoscopy in 20 patients (laparoscopy group).

Results

Intraoperative blood loss (p < 0.0001) and the incidence of postoperative complications (p = 0.0004) were lower in the laparoscopy group than in the laparotomy group. The incidence rates of surgical site infection and intractable ascites were significantly higher in the laparotomy group than in the laparoscopy group (p = 0.0202, p = 0.0436, respectively). The proportion of patients classified as Clavien grade IIIa was higher in the laparotomy group than in the laparoscopy group (p = 0.0033). The duration of the postoperative hospital stay was significantly shorter in the laparoscopy group than in the laparotomy group (p < 0.0001).

Conclusions

Postoperative morbidity has been decreased by the introduction of laparoscopic liver resection in patients with recurrent HCC after curative hepatic resection. As a result, the duration of the postoperative stay is shorter.     

Hepatitis C viral load predicts tumor recurrence after curative resection of hepatocellular carcinoma regardless of the genotype of hepatitis C virus

Purpose

To clarify the prognostic impact of the hepatitis C virus (HCV) genotype after curative resection for hepatocellular carcinoma (HCC).

Methods

A total of 199 patients who underwent a curative hepatic resection for HCV-related HCC were reviewed. The clinical outcomes were compared between patients infected with HCV genotype 1b (n = 160) and those infected with other genotypes (n = 39).

Results

With a comparable median HCV viral load (6.0 vs. 5.8 log₁₀ IU/mL, p = 0.17), the 3-year recurrence-free survival (RFS) rates (25 vs. 20 %, p = 0.65) and the 5-year overall survival (OS) rates (72 vs. 65 %, p = 0.73) were similar between the two groups. A multivariate analysis confirmed that HCV viral load of +1.0 log₁₀ IU/mL [hazard ratio (HR), 1.48], major vascular invasion (HR, 3.20), recurrent tumor (HR, 1.77), and preoperative des-gamma carboxyprothrombin level >40 mAu/mL (HR, 1.64) were independent predictors of tumor recurrence, while the HCV genotype was not a significant risk factor. When the population was stratified according to the HCV viral load, a significant difference was observed in the RFS rate for both genotype 1b (p = 0.003) and the other genotypes (p = 0.037) at HCV viral load of 5.3 log₁₀ IU/mL.

Conclusions

The HCV genotype does not affect the surgical outcomes of patients with HCC. A lower HCV viral load is advantageous regardless of the HCV genotype.     

High-sensitivity Lens culinaris agglutinin-reactive alpha-fetoprotein assay predicts early detection of hepatocellular carcinoma

Background

Prognosis of patients with hepatocellular carcinoma (HCC) remains poor because HCC is frequently diagnosed late. Therefore, regular surveillance has been recommended to detect HCC at the early stage when curative treatments can be applied. HCC biomarkers, including Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), are widely used for surveillance in Japan. A newly developed immunoassay system measures AFP-L3 % with high sensitivity. This retrospective study aimed to evaluate clinical utility of high-sensitivity AFP-L3 (hs-AFP-L3) as a predictor of early stage HCC in surveillance at a single site.

Methods

Of consecutive 2830 patients in the surveillance between 2000 and 2009, 104 HCC-developed and 104 non-HCC patients were selected by eligibility criteria and propensity score matching. Samples were obtained from the HCC patients who had blood drawn annually for 3 years prior to HCC diagnosis.

Results

In the present study, hs-AFP-L3 was elevated 1 year prior to diagnosis in 34.3 % of patients. The survival rate of patients with the hs-AFP-L3 ≥ 7 % at 1 year prior to diagnosis was significantly lower than that of patients with hs-AFP-L3 < 7 %.

Conclusions

Elevation of hs-AFP-L3 was early predictive of development of HCC even at low AFP levels and in absence of ultrasound findings of suspicious HCC. The hs-AFP-L3 should be added to surveillance programs with US because elevated hs-AFP-L3 may be a trigger to perform enhanced imaging modalities for confirmation of HCC.     

Comparison of the effectiveness of infliximab and adalimumab in preventing postoperative recurrence in patients with Crohn’s disease: an open-label,pilot study

Background

Endoscopic and clinical recurrence of Crohn’s disease (CD) appears in up to 80 and 30 % of patients, respectively, 1 year after surgery. Both infliximab (IFX) and adalimumab (ADA) have been demonstrated to be effective in reducing the possibility of recurrence after surgery, but head-to-head studies have not been performed so far. The aim of this open-label prospective study was to compare endoscopic, histological and clinical recurrence after 1 year of treatment with IFX or ADA as postoperative prophylaxis in CD patients with a high risk of recurrence.

Methods

Consecutive CD patients who underwent curative ileocolonic resection were randomized to receive IFX or ADA for 1 year. Co-primary endpoints were endoscopic, histological and clinical recurrence after 12 months of therapy.

Results

Twenty consecutive CD patients (9 males and 11 females; median age 32.5 years, range 20–39 years) were enrolled after undergoing curative ileocolonic resection. Among the 10 patients treated with IFX, 2 (20 %) had endoscopic recurrence compared to 1 (10 %) in the group of 10 ADA patients (p = 1.0). Three out of 10 (30 %) IFX patients and 2 out of 10 (20 %) ADA patients had histological recurrence (p = 1.0). No significant clinical differences were found between the two groups.

Conclusions

IFX and ADA were similar in preventing histological, endoscopic and clinical recurrence after curative ileocolonic resection in high risk CD patients.     

Lipiodolized transarterial chemoembolization in hepatocellular carcinoma patients after curative resection

Purpose

To explore the effect of lipiodolized transarterial chemoembolization (lip-TACE) in hepatocellular carcinoma (HCC) patients at different risk of recurrence after curative resection.

Methods

One thousand nine hundred and twenty-four consecutive HCC patients who underwent curative resection were retrospectively analyzed. Patients who underwent resection only were classified into control group, while those received adjuvant lip-TACE were classified into intervention group. Patients were further stratified into 4 groups, that is, tumor ≤5 cm with low or high risk factors, as well as tumor >5 cm with low or high risk factors for recurrence. Tumor number and microscopic tumor thrombus were defined as risk factors for recurrence. The effect of adjuvant lip-TACE on early (<2 year) or late (≥2 year) recurrence was evaluated.

Results

There was no significant difference in recurrence curve between intervention group and control group in each stratum. Adjuvant lip-TACE showed an overall survival benefit in patients with tumor >5 cm and presenting high risk factors, mainly for those with time to recurrence (TTR) <2 years after operation. For them, the median survival was 17 months in the intervention group and 11 months in the control group (P = 0.010). For patients who were confirmed to be recurrence-free at 2 years after operation, it had the negative effect for survival (HR = 1.75, P = 0.004).

Conclusion

Adjuvant lip-TACE had no preventive effect on recurrence, but may be of benefit to detect early recurrence.     

Diffusion-weighted imaging of hepatocellular carcinoma for predicting early recurrence and survival after hepatectomy

Purpose

The effectiveness of imaging (including apparent diffusion coefficient [ADC] of diffusion-weighted magnetic resonance imaging [DWI]) and laboratory variables for predicting early tumor recurrence and overall survival after surgery in hepatocellular carcinoma (HCC) patients are analyzed.

Methods

The present study included 116 consecutive patients with HCC who underwent partial hepatectomy. Patients were classified into two groups: patients with and without early recurrence (<1 year). Preoperative imaging variables (tumor number, size, shape, capsule, ADC, and venous invasion) and laboratory variables were evaluated to predict early recurrence using univariate and multivariate analyses. Overall survival was calculated using the Kaplan–Meier method.

Results

Twenty patients (17 %) developed early recurrence after surgery. Multivariate logistic regression analysis showed that tumor ADC (p = 0.0002), aspartate aminotransferase (p = 0.0121), and serum prothrombin time activity percentage (p = 0.0082) were statistically significant for predicting early recurrence. The optimal ADC cutoff value for predicting early recurrence obtained from receiver operating characteristic analysis was ≤0.898 × 10^?3 mm²/s. In patients with ADC ≤0.898 × 10^?3 mm²/s, the 3- and 5-year survival rates (77 and 56 %, respectively) were significantly decreased compared with those in patients with ADC >0.898 × 10^?3 mm²/s (97 and 97 %, respectively; p = 0.0015).

Conclusions

Low tumor ADC value by DWI was a risk factor for early postoperative HCC recurrence and was associated with lower patient survival rates.     

Influence of serum HBV DNA load on recurrence of hepatocellular carcinoma after treatment with percutaneous radiofrequency ablation

Background

High serum load of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is a strong risk factor of hepatocellular carcinoma (HCC) development, independent of hepatitis B e antigen, serum alanine aminotransferase level, and liver cirrhosis. We evaluated whether serum HBV DNA load is associated with the risk of recurrence of HBV-related HCC treated with radiofrequency ablation (RFA).

Methods

The study population was 69 consecutive patients with HBV-related HCC treated locally completely with RFA between January 2000 and September 2007. The risk factors for HCC recurrence were analyzed based on laboratory data, including serum HBV DNA load, together with tumor size and number using univariate and multivariate proportional hazard regression analyses.

Results

HCC recurrence was observed in 42 of 69 patients during the median observation period of 1.5 years. Cumulative recurrence rates at 1, 3, and 5 years were 26.5, 57.8, and 74.3%, respectively. In univariate analysis, albumin (<3.5 g/dl), platelet count (<150 × 10³/mm³), prothrombin activity (PT) (<70%), Child-Pugh class B, serum HBV DNA load (>4.0 log10 copies/ml), and tumor number (>3) were associated with the recurrence at p ≤ 0.15. Multivariate Cox regression analysis with stepwise variable selection showed that the tumor number (risk ratio, 4.63; 95% CI, 1.50–14.25, P = 0.0076), low PT (3.39, 1.52–5.78, P = 0.0029), and high HBV DNA load (2.67, 1.16–6.14, P = 0.021) were independent risk factors for HCC recurrence.

Conclusion

Serum HBV DNA load is associated with the risk of recurrence of HBV-related HCC after RFA.     

Low CADM2 expression predicts high recurrence risk of hepatocellular carcinoma patients after hepatectomy

Purpose

To investigate the expression and clinical significance of CADM2 in hepatocellular carcinomas (HCC).

Methods

The level of expression of CADM2 mRNA was assessed in frozen tumor specimens and adjacent noncancerous tissues from 30 HCC patients by real-time PCR. The protein level was determined by immunohistochemistry on a tissue microarray containing tumor and adjacent noncancerous tissues from 234 HCC patients. Clinicopathological characteristics associated analysis was performed through SPSS18 .

Results

CADM2 was strikingly down regulated in HCC. CADM2 expression was associated with differentiation (P = 0.000), serum alpha-fetoprotein (P = 0.003), vascular invasion (P = 0.001), and hepatitis B surface antigen (HBsAg, P = 0.038). Furthermore, patients with low CADM2 expression had significantly poorer recurrence-free survival (RFS) (40.8 and 34.2 % vs. 56.3 and 50.1 % in 3- and 5-year RFS, respectively, P = 0.005). Subgroup analysis revealed that the difference in RFS between groups with low- and high-CADM2 expression still existed among patients belonging to stage 0 or A of BCLC staging system (P = 0.008), patients with tumor ≤5 cm in size (P = 0.013), and alpha-fetoprotein-negative patients (P = 0.003). Moreover, low expression was more frequently observed in the early recurrence group (within 2 years, P = 0.007). Further multivariate Cox regression analysis indicated that CADM2 expression level, tumor size, tumor number, vascular invasion, HBsAg were independent risk factors for HCC recurrence.

Conclusion

CADM2 serves as a novel predictor of RFS in HCC patients after curative resection.     

High CD44s expression is associated with the EMT expression profile and intrahepatic dissemination of hepatocellular carcinoma after local ablation therapy

Background/purpose

Local ablation therapy (LAT) is a widely used treatment for hepatocellular carcinoma (HCC) because it is less invasive than hepatic resection. The precise molecular mechanism underlying local HCC recurrence after LAT is largely unknown. The CD44 standard isoform (CD44s) is involved in epithelial–mesenchymal transition (EMT) in HCC. We investigate the significance of CD44s expression and EMT expression profile in local HCC recurrence after LAT.

Methods

We studied the expression levels of CD44s, EMT expression profile (E-cadherin^low/vimentin^high expression) and their association with clinicopathological factors in 30 HCC samples from patients with locally recurrent HCCs after LAT following hepatic resection. The alterations of CD44s expression was compared with those in initial HCCs from 150 patients without prior any anticancer treatment including LAT.

Results

A high CD44s expression was significantly associated with the EMT expression profile (P = 0.002), and it was also detected with a higher frequency in the locally recurrent HCCs after LAT compared to initial HCCs (P < 0.001). In addition, high CD44s expression was associated with the intrahepatic dissemination of HCC after LAT (P = 0.006).

Conclusions

These results suggest that high CD44s expression is associated with the aggressive recurrence pattern via EMT after LAT for HCC.     

A randomised controlled trial of meloxicam,a Cox-2 inhibitor,to prevent hepatocellular carcinoma recurrence after initial curative treatment

Background

Because the recurrence rate of hepatocellular carcinoma (HCC) is high, even after curative treatments such as hepatic resection and microwave ablation, chemopreventive agents that can effectively suppress HCC recurrence are required. Cyclooxygenase-2 (Cox-2) was recently found to be overexpressed in HCC. Therefore, Cox-2 inhibitors may offer a chemopreventive therapy for HCC. This randomised controlled trial (RCT) investigated the potential for meloxicam, a clinically used Cox-2 inhibitor, to prevent HCC recurrence after initial curative treatment.

Methods

A total of 232 consecutive patients underwent hepatic resection and/or microwave ablation as initial therapy for HCC at our institute between July 2008 and April 2011. Eight patients were excluded because of poor renal function, history of non-steroidal anti-inflammatory drug-related ulceration, or multiple cancers. The remaining 224 patients were randomised to a control group (n = 113) or a meloxicam group (n = 111). To patients in the meloxicam group, meloxicam was administered at 15 mg daily (5 mg three times a day) as long as possible. The overall survival (OS) and disease-free survival (DFS) rates were determined.

Results

The 1-, 3-, and 5-year OS rates of the meloxicam group were 95.4, 82.4, and 70.1 %, respectively. Those of the control group were 98.2, 85.1, and 71.5 %, respectively (p = 0.9549). The corresponding DFS rates of the meloxicam group were 89.2, 53.9, and 44.0 % and those of control group were 86.5, 57.0, and 43.4 %, respectively (p = 0.6722). In the OS and DFS of subsets including patients with hepatitis B or C virus infection, we could not find significant differences between the meloxicam and control groups. However, in the subgroup of analysis of patients without viral hepatitis (NBNC-HCC), significant differences were observed in the DFS between the meloxicam group (1-year DFS, 92.3 %; 3-year DFS, 75.8 %; 5-year DFS, 70.4 %) and control group (1-year DFS, 83.3 %; 3-year DFS, 48.1 %; 5-year DFS, not obtained) (p = 0.0211).

Conclusion

Administration of the Cox-2 inhibitor meloxicam may have a possibility to suppress HCC recurrence after initial curative treatments in patients with NBNC-HCC.

     

Everolimus-based immunosuppression in liver transplant recipients: a single-centre experience

Purpose

Everolimus, a mammalian target of rapamycin inhibitor, has been shown to reduce growth factor-mediated cell proliferation, but data regarding its effectiveness and impact on renal function and recurrence of hepatocellular carcinoma (HCC) in liver transplant (LT) recipients are limited.

Methods

We evaluated LT recipients with a calcineurin inhibitor (CNI)-based immunosuppression regimen in whom everolimus treatment was initiated. The changes in laboratory data, including glomerular filtration rate (GFR), compared to the baseline (i.e. the day of everolimus conversion), were assessed.

Results

Totally, 44 consecutive patients (32 men, age 55 ± 7 years) were commenced on everolimus [indications: renal dysfunction post-LT (16 patients, group 1); prevention of HCC recurrence (21 patients) or others (7 patients), group 2] at 6 months (range 1–206) post-LT. After 48 (range 12–76) months, all patients were alive without any rejection episodes. Compared to group 2 patients, group 1 patients had significantly greater improvement in renal function (DGFR: 12 ± 5 vs. ?0.4 ± 0.2 ml/min, p = 0.02). GFR at baseline (OR 0.08, p = 0.002) and the combination of everolimus + MMF (OR 0.14, p = 0.024) were the factors independently associated with improvement in renal function. Finally, HCC recurrence was observed less frequently in the everolimus group of patients (n = 21) compared to the CNI-historical control group (n = 22) with HCC before LT [0/21 (0 %) vs. 4/22 (18.5 %), log rank p = 0.055), although the two groups of recipients had similar baseline characteristics and follow-up.

Conclusions

Everolimus is effective and is associated with low rates of HCC recurrence and improvement of renal function in LT recipients.     

Assessment of hepatocellular carcinomas using conventional magnetic resonance imaging correlated with histological differentiation and a serum marker of poor prognosis

Purpose

To establish a method of assessing the malignant potential of hepatocellular carcinoma (HCC) using magnetic resonance imaging (MRI).

Methods

For 69 nodules [12 Edmondson (Ed)-I, 48 Ed-II, 9 Ed-III] in 54 HCC patients, signal intensity patterns and enhancement patterns of gadopentate dimeglumine (Gd-DTPA) dynamic studies were correlated with histological differentiation and serum lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) level, which is an indicator of poor prognosis.

Results

Hypointensity on T1-weighted imaging was seen in 17, 72, and 89% of Ed-I, Ed-II, and Ed-III HCCs, respectively (P < 0.001). Meanwhile, hyperintensity on T2-weighted imaging was seen in 42, 88, and 89% (P < 0.005). Tumor stain during the arterial phase of Gd dynamic MRI was seen in 75, 86, and 89%. Tumor stain washout during the portal phase was seen in 43% of Ed-II and 100% of Ed-III HCCs (P < 0.005). In the Ed-II and Ed-III HCCs, hypointensity on T1-weighted imaging was seen in 65% of AFP-L3-negative HCCs and 90% of AFP-L3-positive HCCs (P = 0.071). Washout of tumor stain during the portal phase was seen in 39% of AFP-L3-negative HCCs and 75% of AFP-L3-positive HCCs (P < 0.05).

Conclusions

Although hyperintensity of tumor on T2-weighted imaging and arterial hypervascularity of tumor are considered to be useful for differential diagnosis between well differentiated HCCs and moderately/poorly differentiated HCCs, hypointensity of tumor on T1-weighted imaging and tumor stain washout during the portal phase of Gd-DTPA dynamic MRI reflected poorer histological differentiation of HCCs and correlated with AFP-L3 levels.     

United States Women Receive More Curative Treatment for Hepatocellular Carcinoma Than Men

Background

Previous database studies have found gender disparities favoring men in rates of liver transplantation, which resolve in cohorts examining only patients with hepatocellular carcinoma (HCC).

Aims

Our study aims to use two large, multicenter United States (US) databases to assess for gender disparity in HCC treatment regardless of transplant listing status.

Methods

We performed a retrospective database analysis of inpatient admission data from the University Health Consortium (UHC) and the Nationwide Inpatient Sample (NIS), over a 9- and 10-year period, respectively. Adults with a primary discharge diagnosis of HCC, identified using the International Classification of Diseases 9th Edition (ICD-9) code, were included. Series of univariate and multivariate analyses were performed to examine gender disparities in metastasis, liver decompensation, treatment type, and inpatient mortality after controlling for other possible predictors.

Results

We included 26,054 discharges from the NIS database and 25,671 patients from the UHC database in the analysis. Women with HCC appear to present less often with decompensated liver disease (OR = 0.79, p < 0.001). Furthermore they are more likely to receive invasive HCC treatment, with significantly higher rates of resection across race and diagnoses (OR = 1.34 and 1.44, p < 0.001). Univariate analyses show that US women have lower unadjusted rates of transplant; however, the disparity resolves after controlling for other clinical and demographic factors.

Conclusions

US women more often receive invasive treatment for HCC (especially resection) than US men with no observed disparity in transplantation rates when adjusted for pre-treatment variables.     

Fibrosis and AST to platelet ratio index predict post-operative prognosis for solitary small hepatitis B-related hepatocellular carcinoma

Purpose

Although advanced liver fibrosis is crucial in the development of hepatocellular carcinoma (HCC) for patients with chronic hepatitis B, whether it is associated with the recurrence of HCC after resection remains obscure. This study was aimed to compare the outcomes for patients with minimal or advanced fibrosis in solitary small hepatitis B virus (HBV)-related HCC.

Methods

This study enrolled 76 patients with small (<5 cm) solitary HBV-related HCC who underwent resection. The outcomes of patients with minimal and advanced fibrosis in non-tumor areas were compared. Serum markers were tested to assess the stage of hepatic fibrosis and to predict prognosis.

Results

Fourteen patients with an Ishak fibrosis score of 0 or 1 were defined as having minimal fibrosis; the remaining 62 patients were defined as having advanced fibrosis. During a follow-up period of 77.0 ± 50.7 months, 41 patients died. The overall survival rate was significantly higher (P = 0.018) and recurrence rate was lower (P = 0.018) for patients in the minimal fibrosis group. Aspartate aminotransferase–platelet ratio index (APRI) exhibited the most reliable discriminative ability for predicting advanced fibrosis. The overall survival rate was significantly higher (P = 0.003) and recurrence rate was lower (P = 0.005) for patients with an APRI of 0.47 or less.

Conclusions

For patients with solitary small HBV-related HCC who underwent resection, minimal fibrosis is associated with a lower incidence of recurrence and with better survival. APRI could serve as a reliable marker for assessing hepatic fibrosis and predicting survival.     

Familial clustering of hepatocellular carcinoma in HBsAg-positive patients in the United States

Purpose

The impact of familial clustering of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected persons in a low HBV endemic area was investigated.

Methods

Four hundred thirteen HBsAg-positive patients, 173 with HCC and 240 without HCC, were subgrouped into those with or without a family history of HCC and analyzed for risk factors associated with HCC development. In families with HCC clustering, the ages of HCC onset in parents and siblings were compared.

Results

Forty-four of 173 (25.4 %) HCC patients, all of Asian descent, had 82 other blood relatives with HCC. Of these, 69 (84.1 %) were first-degree relatives. Compared to HCC patients without HCC family history, male HCC patients with family history developed HCC at a younger age than either their mothers or fathers with HCC (45.2 ± 10.3 years vs. 63.0 ± 6.8 years, p < 0.001 and 41.2 ± 14.8 years vs. 60.5 ± 5.5 years, p = 0.001, respectively); however, this was not observed in female HCC patients. In mothers of index HCC cases, 22/26 (84.6 %) tested were HBsAg positive and 14 (63.6 %) had HCC; in fathers, 11/21 (52.4 %) tested were HBsAg positive and 10 (90.9 %) had HCC. By multivariate analysis, independent risk factors for HCC development included family history (OR = 2.58, p = 0.05), male gender (OR = 3.23, p = 0.03), cirrhosis (OR = 2.4, p = 0.04), Child-Pugh classification (OR = 7.62, p = 0.004), AFP per log₁₀ increase (OR = 1.68, p = 0.01), precore mutation (OR = 3.77, p = 0.003), and basal core promoter mutation (OR = 8.33, p < 0.001).

Conclusions

HBsAg-positive male HCC patients presented at a younger age than their parents with HCC. In adult patients with an HCC family history, HCC surveillance should begin at the time of the initial clinic encounter.     

The influence of hepatitis?B DNA level and antiviral therapy on recurrence after initial curative treatment in patients with hepatocellular carcinoma

Background

Prediction and prevention of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) recurrence is an important clinical issue. We investigated whether HBV DNA level and antiviral therapy are associated with HCC recurrence.

Methods

This retrospective study involved 103 patients who underwent hepatic resection or radiofrequency ablation for initial HCC. Patients were divided into four groups. Thirty had high serum HBV DNA levels (>4 log₁₀ copies/mL) and had not received antiviral therapy (high virus group; HVG). Thirty-four had low HBV DNA levels (≤4 log₁₀ copies/mL) and had not received antiviral therapy (low virus group; LVG). Twenty received antiviral therapy after HCC developed (therapeutic group A, TG-A). Nineteen received antiviral therapy before HCC developed (therapeutic group B, TG-B).

Results

Cumulative HCC recurrence rates at 3 years in the HVG, LVG, TG-B, and TG-A were 71.1%, 42.2%, 42.3%, and 52.0%, respectively. Recurrence rates differed significantly between the HVG and LVG (P = 0.016) and between the HVG and TG-B (P = 0.008). Recurrence rate in the TG-A was marginally lower than in the HVG (P = 0.10). On multivariate analysis, high serum hepatitis B virus DNA levels (hazard ratio: HR 2.67; 95% CI 1.31–5.47; P = 0.007) and absence of antiviral therapy (HR 2.57; 95% CI 1.34–4.94; P = 0.005) were independent risk factors for hepatocellular carcinoma recurrence.

Conclusion

HBV DNA level and antiviral therapy are associated with HCC recurrence. For patients with high HBV DNA levels, antiviral therapy before the development of HCC is important for prevention of recurrence.