Multicenter retrospective study of initial treatment outcome and feasibility of initiating dose reduction of cabozantinib in unresectable hepatocellular carcinoma.

AIM: Cabozantinib (CAB), a multiple kinase inhibitor, has been approved for use in patients with previously treated unresectable hepatocellular carcinoma (uHCC). However, real-world clinical data are lacking, particularly clinical data regarding dose modifications of CAB. We analyzed the clinical outcomes of CAB in uHCC and compared treatment outcomes between the full- and reduced-dose groups. METHODS: This multicenter, observational study included patients with uHCC who were treated with CAB from March 2021 to April 2022. Patient characteristics, efficacy, and safety were compared between the full- and reduced-dose groups. RESULTS: Twenty-six patients from eight institutes were analyzed. Cabozantinib was administered as a third-line or later treatment in 25 (96.2%) patients and postimmunotherapy in 21 (80.5%) patients. There were 15 patients in the full-dose group (60 mg CAB) and 11 in the reduced-dose group (40 or 20 mg CAB). The objective response rate (ORR) and disease control rate (DCR) were not significantly different between the two groups. The ORR was 6.7% for the full-dose group and 9.1% for the reduced-dose group, and the DCR was 53.4% and 81.8%, respectively. Progression-free survival analysis showed no significant differences between the two groups. The incidence of decreased appetite, fatigue, and diarrhea, and the rate of discontinuation and dose reduction, was significantly higher in the full-dose group. CONCLUSIONS: Our study suggests that the efficacy and safety of CAB in real-world clinical practice are comparable to those of the phase III trial (CELESTIAL), and that dose reduction of CAB may be a safer treatment option.

Sequential therapy including regorafenib for unresectable hepatocellular carcinoma: Effect of early relative changes in hepatic functional reserve after regorafenib administration on prognosis.

AIM: Regorafenib is a second-line treatment for unresectable hepatocellular carcinoma after sorafenib-refractory treatment. This study examined the effects of regorafenib administration on hepatic functional reserve and the treatment course after regorafenib discontinuation. METHODS: This retrospective, multicenter study involved 51 patients treated with regorafenib after sorafenib-refractory treatment for u-HCC at seven institutions before March 2021. RESULTS: Fourteen, 13, and 24 patients were classified based on modified albumin-bilirubin (mALBI) grade 1, 2a, and 2b, respectively. The median survival time and progression-free survival were 16.7 and 3.3 months, respectively. Only mALBI grade 2b or 3 was significantly associated with survival rate (hazard ratio, 2.13; 95% confidence interval, 1.01-4.49; p = 0.047). A comparison of median ALBI scores at the initiation of regorafenib (-2.35) with those at 4 weeks (-1.93) revealed a significant relative change (p = 0.0001). After 4 weeks, grade 1 or 2a persisted in 15 patients (Group 1); grade 1 or 2a deteriorated to 2b in 12 patients (Group 2); grade 2b or 3 before regorafenib administration was present in 22 patients (Group 3); and MST was 33.3, 12.8, and 11.3 months in the three groups, respectively (p = 0.05). Patients treated with lenvatinib (LEN) (n = 27, MST = 23.4 months) after regorafenib had a significantly longer survival time from regorafenib initiation than those not treated with LEN (n = 24, 11.8 months; p = 0.043). CONCLUSIONS: Hepatic functional reserve significantly declined after regorafenib administration. During regorafenib treatment, favorable hepatic functional reserve before administration and maintenance of favorable hepatic reserve after administration lead to prolonged prognosis.

Identification of microRNA associated with the elimination of hepatitis C virus genotype 1b by direct-acting antiviral therapies.

BACKGROUND AND AIM: Direct-acting antiviral (DAA) therapies have been proven to be highly effective for the eradication of hepatitis C virus (HCV) without resistance-associated substitutions (RASs). However, even in cases with no detected RASs, treatment sometimes fails, suggestive of the existence of some host-related factors involved in HCV eradication by DAAs. To explore such factors, we analyzed the serum microRNAs (miRNAs) of patients who received DAA treatment. METHODS: The serum miRNA expression levels of 39 patients with chronic HCV infection without any detectable RASs, who achieved sustained virological response with asunaprevir/daclatasvir or grazoprevir/elbasvir therapy, were investigated cyclopedically, using oligonucleotide microarrays. The effects of specific miRNAs on the replication of HCV were measured in the HCV genomic replicon containing Huh-7 hepatoma cells. RESULTS: Along with the disappearance of HCV, the expression quantiles of 16 miRNAs in the asunaprevir/daclatasvir group and 18 miRNAs in the grazoprevir/elbasvir group showed a tendency to increase or decrease. Among these molecules, adjustments for multiple testing yielded a significant differential expression at a false discovery rate of less than 5% for only one molecule, hsa-miR-762. Its expression quantile increased after HCV exclusion in all patients who had achieved sustained virological response. Quantitative polymerase chain reaction analysis validated a significant increase in the serum hsa-miR-762 after disappearance of HCV. On the contrary, hsa-miR-762 was decreased in the relapse and breakthrough of HCV in DAA failures. Transfection of hsa-miR-762 into cultured HCV-infected hepatocytes significantly decreased HCV-RNA replication. CONCLUSION: These data suggest that hsa-miR-762 is one of the host factors participating in HCV exclusion by DAA therapy.

A Potential Serum N-glycan Biomarker for Hepatitis C Virus-Related Early-Stage Hepatocellular Carcinoma with Liver Cirrhosis.

Detection of early-stage hepatocellular carcinoma (HCC) is beneficial for prolonging patient survival. However, the serum markers currently used show limited ability to identify early-stage HCC. In this study, we explored human serum N-glycans as sensitive markers to diagnose HCC in patients with cirrhosis. Using a simplified fluorescence-labeled N-glycan preparation method, we examined non-sialylated and sialylated N-glycan profiles from 71 healthy controls and 111 patients with hepatitis and/or liver cirrhosis (LC) with or without HCC. We found that the level of serum N-glycan A2G1(6)FB, a biantennary N-glycan containing core fucose and bisecting GlcNAc residues, was significantly higher in hepatitis C virus (HCV)-infected cirrhotic patients with HCC than in those without HCC. In addition, A2G1(6)FB was detectable in HCV-infected patients with early-stage HCC and could be a more accurate marker than alpha-fetoprotein (AFP) or protein induced by vitamin K absence or antagonists-II (PIVKA-II). Moreover, there was no apparent correlation between the levels of A2G1(6)FB and those of AFP or PIVKA-II. Thus, simultaneous use of A2G1(6)FB and traditional biomarkers could improve the accuracy of HCC diagnosis in HCV-infected patients with LC, suggesting that A2G1(6)FB may be a reliable biomarker for early-stage HCC patients.

Impact of albumin-bilirubin grade on survival in patients with hepatocellular carcinoma who received sorafenib: An analysis using time-dependent receiver operating characteristic.

BACKGROUND AND AIM: Albumin-bilirubin (ALBI) grade was developed as a new method to assess hepatic function. Sorafenib has been confirmed to be effective in improving survival in patients with advanced hepatocellular carcinoma (HCC). In this study, we investigated the impact of ALBI grade versus Child-Pugh classification on survival in HCC patients who received sorafenib. METHODS: A total of 567 patients with advanced HCC who received sorafenib were included. We analyzed survival based on Child-Pugh classification or score and ALBI grade or score. We also compared the ability of ALBI and Child-Pugh scores to predict survival using time-dependent receiver operating characteristic analysis. RESULTS: Cumulative survival rates at 90, 180, 360, and 720 days were 84.1%, 66.6%, 47.0%, and 23.3%, respectively. Median survival was 316 days (95% confidence interval, 279-377). Both Child-Pugh classification and ALBI grade were independently associated with overall survival in multivariate analyses. In addition, overall survival differed significantly between patients with ALBI grades 1 and 2 (hazard ratio, 1.44; 95% confidence interval, 1.09-1.92, P = 0.011) among patients with a Child-Pugh score of 5. Time-dependent receiver operating characteristic analysis showed that ALBI score predicted overall survival better than Child-Pugh score. CONCLUSIONS: Albumin-bilirubin grade is a better predictor of survival in patients with advanced HCC who received sorafenib therapy than Child-Pugh classification.

Hand-Foot Syndrome and Post-Progression Treatment Are the Good Predictors of Better Survival in Advanced Hepatocellular Carcinoma Treated with Sorafenib: A Multicenter Study.

OBJECTIVE: To determine the relationship between treatment outcomes and hand-foot syndrome (HFS), and the relationship between survival rate and post-progression treatment after sorafenib therapy. METHODS: The study assessed 314 patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib at 5 general hospitals in Kagawa Prefecture, Japan. RESULTS: At the start of sorafenib therapy, 23.6% of the patients had HCC of a Child-Pugh class other than A. The initial sorafenib dose was 800 mg in 9.2% of the patients and 400 mg in 64.3%. Time to progression was 129 days (95% CI: 87.3-170.7) and the median overall survival (OS) was 392 days (95% CI: 316.0-468.0). The OS of the patients with Child-Pugh class A HCC was significantly better than that of the patients with Child-Pugh class B HCC (p < 0.0001). The survival curves for Child-Pugh class A-5 points and class A-6 points were significantly different, with that for class A-5 points being better (p < 0.0001). A significant difference was observed between the patients who exhibited HFS and those who did not, with the former exhibiting a better survival rate (p < 0.001). In addition, the survival rate of the patients who received post-progression treatment after sorafenib therapy was significantly better than that of the patients who did not (p < 0.001). CONCLUSION: In sorafenib therapy, patients with HFS and those who received post-progression treatment exhibited good OS.

Hepatic Function during Repeated TACE Procedures and Prognosis after Introducing Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: Multicenter Analysis.

BACKGROUND/AIM: We evaluated the relationship of hepatic function with repeated transarterial catheter chemoembolization (TACE) and prognosis after sorafenib treatment in various patient cohorts. METHODS: Study 1 comprised of 212 Barcelona clinic liver cancer stage-B (BCLC-B) HCC patients classified as Child-Pugh A (CP-A) and who had received repeated TACE treatments (r-TACE) (naïve:recurrence = 66:146). Study 2 comprised of 435 patients with unresectable HCC classified as CP-A in who sorafenib was introduced (naïve:recurrence = 37:398; CP score 5:6 = 282:153; macro-vessel invasion [MVI]+: extrahepatic metastasis [EHM]+ both negative = 124:226:143). Changes in hepatic function along with CP and albumin-bilirubin (ALBI) score/grade during r-TACE in Study 1, and prognosis after introducing sorafenib in Study 2 were evaluated. RESULTS: Hepatic function worsened to CP-B in 9-14% with each TACE procedure, while 18-21% had a change of classification from ALBI-1 to ALBI-2. When the prognosis of patients with the best CP score of 5 was analyzed, those with ALBI-1 (n = 154) had a better outcome than those with ALBI-2 (n = 128) (MST 17.5 vs. 9.9 months; p = 0.01), while ALBI-1 (n = 43) patients also showed a better outcome than ALBI-2 (n = 34) patients with a CP score of 5 without MVI/EHM (MST: 17.5 vs. 10.0 months; p = 0.029). The Akaike's Information criterion for ALBI-grade (MST: grade 1 vs. 2 = 16.9 vs. 10.4 months; p = 0.001) was also better than that for CP (MST: score 5 vs. 6 = 14.4 vs. 10.5 months; p = 0.003) (3195.6 vs. 3197.5) in all 435 patients. CONCLUSION: The rate of patients with downgraded hepatic function during r-TACE, especially with regard to ALBI-grade, was not low. ALBI-grade was shown to be a better hepatic function assessment tool than CP in patients receiving sorafenib treatment. Strict judgment of TACE-refractory status in patients with unresectable HCC is needed to improve prognosis before downgrading the hepatic function.

Clinicopathology of recurrent hepatocellular carcinomas after radiofrequency ablation treated with salvage surgery.

AIM: Radiofrequency ablation (RFA) is an effective standard local therapy for small hepatocellular carcinoma (HCC). However, local recurrence and/or tumor seeding after RFA remain major problems. For better understanding of underlying factors, we clarified clinicopathological features of recurrent HCC treated with RFA. METHODS: This retrospective study included 21 patients who underwent surgical resection for HCC disease recurrence after RFA. Clinicopathological findings, including patterns of recurrence, immunohistochemical expression of proliferation markers (Ki-67 and p27(Kip1) ) and survival outcome were assessed. RESULTS: The median time interval after RFA until the diagnosis of intrahepatic and/or extrahepatic tumor progression was 12 months (range, 3-84). Radical surgical resection was attempted for intrahepatic local recurrence in 16 patients (18 lesions), for peritoneal dissemination in four, for lymph node metastases in three and for adrenal metastasis in two. In 14 of the 21 (67%) patients, the recurrent HCC were histologically diagnosed as of poorly differentiated type. Their average Ki-67 and p27(Kip1) labeling indices were significantly higher (P = 0.020) and lower (P < 0.001), respectively, compared with values for the 108 HCC surgically resected at the initial treatment. Portal involvement was significantly higher (P = 0.01) in recurrent tumors after RFA (72%) than in HCC surgically resected at the initial treatment (43%). The mortality rate of salvage surgery was 0%, with cumulative survival rates at 1 and 3 years of 58.9% and 35.7%, respectively. CONCLUSION: The recurrent tumors after RFA have characteristics of poor differentiation degree and abnormalities in cell-cycle regulators and are associated with aggressive vascular invasiveness.

Hand-assisted laparoscopic splenectomy for thrombocytopenia in patients with cirrhosis.

PURPOSE: Although splenectomy plays an important role in the management of patients with liver cirrhosis, the optimal technique, open surgery, total laparoscopic surgery or hand-assisted laparoscopic surgery (HALS), has not yet been defined. The present study evaluated the outcomes of HALS splenectomy for cirrhotic patients. METHODS: A total of 28 consecutive patients with cirrhosis that underwent HALS splenectomy were enrolled into this study. The preoperative laboratory and morphometric data, intraoperative variables and postoperative outcomes were reviewed from the hospital charts. RESULTS: The postoperative platelet count was remarkably elevated in all cases. A re-operation was required in 1 patient complicated with postoperative hemorrhage. Enhanced CT on POD 7 revealed a high incidence of portal or splenic vein thrombosis (PSVT; 22 patients, 78.6 %). PSVT was significantly associated with higher serum bilirubin, higher indocyanine green retention value at 15 min (ICG R-15), and larger splenic vein diameter. CONCLUSION: HALS splenectomy was a very feasible and appropriate procedure for cirrhotic patients with hypersplenism. PSVT was a frequent complication and large splenic vein diameter, high serum bilirubin, and high ICG R-15 were found to be significant risk factors for PSVT after HALS splenectomy in cirrhotic patients.

Omental flap wrapping with fixation to the cut surface of the liver for reducing delayed gastric emptying after left-sided hepatectomy.

BACKGROUND: Delayed gastric emptying (DGE) is a common complication following left-sided hepatectomy. The goal of this study was to clarify the clinical implications of an omental flap wrapping procedure that includes fixation to the cut surface of the liver to reduce the incidence of DGE after left-sided hepatectomy. METHODS: The study included 50 consecutive patients who underwent left-sided hepatectomy between January 2000 and July 2011. Clinicopathologic risk factors for DGE after left-sided hepatectomy were identified using univariate and multivariate models. The incidence of DGE, digestive symptoms, and postoperative complications were compared between two groups: 25 patients treated with the omental flap wrapping and fixation procedure and 25 patients who did not receive such a flap. RESULTS: A univariate analysis revealed that a lack of the omental flap, the lymph node clearance, and use of left hemihepatectomy were associated with postoperative DGE. The multivariate analysis indicated that the lack of the omental flap was the only independent significant factor associated with the DGE (odds ratio, 21.23; p = 0.0002). There was a significant difference in the incidence of DGE between the patients with (4 %) and without an omental flap (36 %). The incidence of gastric distension and the use of prokinetic drugs were also significantly lower in patients with an omental flap than in patients without the flap, and patients with an omental flap resumed a solid diet significantly earlier. CONCLUSIONS: This retrospective single-center study revealed that it was possible to reduce the incidence of DGE using a procedure involving omental flap wrapping with fixation to the cut surface of the liver after left-sided hepatectomy.

Omental arteriovenous fistula after splenectomy treated with transarterial embolization.

BACKGROUND: Laparoscopic splenectomy for patients with portal hypertension is associated with a high risk of bleeding. The use of vessel-sealing devices and automatic sutures is important for bleeding control. However, a rare complication of abdominal surgery is the direct communication between the arterial and portal circulation related to surgical procedures such as simultaneous ligature of an artery and adjacent vein. We describe a rare case of omental arteriovenous fistula (AVF) after laparoscopic splenectomy treated with transarterial embolization. CASE PRESENTATION: We report a case of a 46-year-old male patient with an omental AVF after a laparoscopic splenectomy 6 years ago for splenomegaly associated with alcoholic cirrhosis. Follow-up abdominal dynamic computed tomography accidentally revealed a vascular sac (25 mm in the major axis) that formed an omental AVF with anastomosis to the left colonic vein. The communication was considered to be caused by using a vessel-sealing device. No symptoms related to the AVF were observed. The AVF was embolized with microcoils using the transarterial approach. A 4-axis catheter system was used for accurate embolization due to the long and tortuous distance from the celiac artery. No recurrence or symptoms were observed after 6 months. CONCLUSIONS: Treatment of arterioportal fistula is mandatory, even in asymptomatic patients. Embolization is a less invasive alternative to surgical approaches. The 4-axis catheter system was useful for accurate embolization via a long and tortuous artery.

The Clinical Impact of Hepatic Arterial Infusion Chemotherapy New-FP for Hepatocellular Carcinoma with Preserved Liver Function.

Background: Systemic treatments are recommended for advanced hepatocellular carcinoma (HCC) in preserved liver function. However, their effects are unsatisfactory in some tumor conditions, particularly macrovascular invasion (MVI) including major portal vein tumor thrombus (PVTT). We compared the efficacy of hepatic arterial infusion chemotherapy (HAIC) regimens New-FP and sorafenib for various tumor conditions in preserved liver function. Methods: We retrospectively collected the data of 1709 patients with HCC who were treated with New-FP or sorafenib. Survival was assessed after propensity score matching. Subgroup analyses were conducted: cohort 1 (no MVI or extrahepatic spread (EHS)), cohort 2 (MVI only), cohort 3 (EHS only), cohort 4 (MVI and EHS), and cohort 5 (major PVTT). Results: The New-FP group had a longer median survival time (MST) than the sorafenib in the whole analysis (18 vs. 9 months; p < 0.0001). New-FP demonstrated a longer MST compared with sorafenib in cohort 2 and cohort 4. In cohort 5, the MST of the New-FP group was 16 months, while that of sorafenib was 6 months (p < 0.0001). For major PVTT-HCC, the response rate of New-FP was 73.0%. The MST of patients who achieved complete response with New-FP was 59 months. Conclusions: HAIC using New-FP is promising for patients with MVI- and major PVTT-HCC in preserved liver function.

Long-Term Outcomes and Evaluation of Hepatocellular Carcinoma Recurrence after Hepatitis C Virus Eradication by Direct-Acting Antiviral Treatment: All Kagawa Liver Disease Group (AKLDG) Study.

There are limited studies that have evaluated the long-term outcomes in patients with hepatocellular carcinoma (HCC) recurrence after direct-acting antiviral (DAA) treatment. In this retrospective study, we aimed to investigate the recurrence rates, recurrence factors, and prognosis of 130 patients who were treated with IFN-free DAA treatment after treatment for HCC. The median observation time was 41 ± 13.9 months after DAA treatment. The recurrence rates of HCC were 23.2%, 32.5%, 46.3%, and 59.4% at 6, 12, 24, and 36 months, respectively. A multivariate analysis showed that palliative treatment prior to DAA treatment (HR = 3.974, 95% CI 1.924-8.207, p = 0.0006) and alpha-fetoprotein at sustained virological response 12 (HR = 1.048, 95% CI 1.016-1.077, p = 0.0046) were associated with independent factors for HCC recurrence (HCC-R). The 12-, 24-, and 36-month overall survival rates were 97.6%, 94.0%, and 89.8%, respectively. The 12-, 24-, and 36-month survival rates of the non-recurrence and recurrence groups were 97.7%, 97.7%, and 94.1% and 97.6%, 92.3%, and 87.9%, respectively (p = 0.3404). The size of the main tumor lesion and the serological data were significantly improved at the time of HCC-R after DAA treatment. This study showed an improved prognosis regardless of recurrence rate, which suggests that DAA treatment in HCV patients should be considered.

Survival Benefit of Hepatic Arterial Infusion Chemotherapy over Sorafenib in the Treatment of Locally Progressed Hepatocellular Carcinoma.

BACKROUND: Not all patients with hepatocellular carcinoma (HCC) benefit from treatment with molecular targeted agents such as sorafenib. We investigated whether New-FP (fine-powder cisplatin and 5-fluorouracil), a hepatic arterial infusion chemotherapy regimen, is more favorable than sorafenib as an initial treatment for locally progressed HCC. METHODS: To avoid selection bias, we corrected the data from different facilities that did or did not perform New-FP therapy. In total, 1709 consecutive patients with HCC initially treated with New-FP or sorafenib; 1624 (New-FP, n = 644; sorafenib n = 980) were assessed. After propensity score matching (PSM), overall survival (OS) and prognostic factors were assessed (n = 344 each). Additionally, the patients were categorized into four groups: cohort-1 [(without macrovascular invasion (MVI) and extrahepatic spread (EHS)], cohort-2 (with MVI), cohort-3 (with EHS), and cohort-4 (with MVI and EHS) to clarify the efficacy of each treatment. RESULTS: New-FP prolonged OS than sorafenib after PSM (New-FP, 12 months; sorafenib, 7.9 months; p < 0.001). Sorafenib treatment, and severe MVI and EHS were poor prognostic factors. In the subgroup analyses, the OS was significantly longer the New-FP group in cohort-2. CONCLUSIONS: Local treatment using New-FP is a potentially superior initial treatment compared with sorafenib as a multidisciplinary treatment in locally progressed HCC without EHS.

A hepatic sclerosed hemangioma with drastic changes in contrast-enhanced ultrasonography.

Hepatic sclerosed hemangioma is a rare benign liver tumor that originated from hepatic cavernous hemangioma; however, the process of its formation has been unclear. We herein present the patient of a histologically proven hepatic sclerosed hemangioma that showed drastic changes in diagnostic images in a short period. A 56-year-old man was referred to our hospital for the treatment of suspicious hepatocellular carcinoma with hepatitis C, approximately 2 cm in diameter in liver segment 8. Initially, the tumor manifested as early entire enhancement with mildly delayed washout in contrast-enhanced ultrasonography; however, it manifested as continuous peripheral enhancement with the central non-enhanced area after 1 month in various diagnostic images. He completely quit drinking and smoking 1 month preoperatively. No special symptoms and signs were found to suggest tumor ischemia. Anatomical resection of segment 8 was completed. Histological examination confirmed the final diagnosis of common type hepatic sclerosed hemangioma, derived from atypically enhancing cavernous hemangioma. No signs of impaired blood flow were observed in both diagnostic images and histological examination. Sclerosing changes in hepatic cavernous hemangioma may be completed in a relatively short time with no apparent reason.

Simple scoring system for prediction of hepatocellular carcinoma occurrence after hepatitis C virus eradication by direct-acting antiviral treatment: All Kagawa Liver Disease Group Study.

Direct acting antivirals (DAA) have recently been developed to treat patients with hepatitis C virus (HCV) infection, and interferon-free DAA treatment has improved the cure rate of patients. However, the occurrence rate of hepatocellular carcinoma (HCC) following HCV eradication remains unknown. Therefore, the present study aimed to identify predictors of HCC occurrence following DAA treatment. Among 1,454 patients infected with HCV, 1,088 patients who achieved sustained virologic response and who had no history of HCC treatment were recruited between September 2014 and November 2018. The incidence of HCC in patients infected with HCV following DAA treatment, and the predictors contributing to HCC occurrence were identified using clinicopathological characteristics and blood test results. During the present study, 26 patients developed HCC. The incidence of HCC was 0.61, 1.88, 2.82 and 3.71% at 6, 12, 18 and 24 months after treatment with DAA, respectively. The results of multivariate analysis identified age [hazard ratio (HR), 1.0729; P=0.0044] and α-fetoprotein (AFP) level after DAA treatment (HR, 1.0486; P=0.0486) as independent factors that may contribute to HCC occurrence following DAA treatment. By using these two factors, a novel scoring system (0-2 points) was established to predict HCC occurrence following HCV eradication by DAA treatment. The incidence of HCC at 2 years was 0.3% in the 0 points group, 6.27% in the 1 point group and 18.37% in the 2 points group. In conclusion, AFP level after DAA treatment and age at DAA administration were identified as independent predictors of HCC occurrence in patients that were treated with DAA. The scoring system that was established in the present study is simple and easy, and using pre-treatment factors may be a convenient tool to predict the risk of HCC occurrence in HCV-free patients following DAA treatment.

Clinical characteristics of patients with hepatitis C virus-related chronic liver disease seropositive for anticentromere antibody.

The association between anticentromere antibody (ACA) and hepatitis C virus (HCV) infection remains unclear. We subjected eight patients with HCV-related chronic liver disease (CLD) seropositive for ACA to a battery of clinical and laboratory tests. The patient cohort was dominated by females, and four of the eight (50%) patients had a concomitant autoimmune disease. All of the patients had high titers of ACA (>or=1:320). The histological activity index scores in chronic hepatitis C (CH-C) patients with ACA were significantly higher than those in CH-C patients without antinuclear antibody (ANA) (12.8 +/- 1.8 vs. 8.3 +/- 4.5, P = 0.0372). The frequency of human leukocyte antigen (HLA) DR-8 in patients with HCV-related CLD seropositive for ACA was significantly higher than that in patients with CH-C seronegative for ANA (71 vs. 18%, P = 0.0108). These findings suggest that ACA is induced by chronic HCV infection in association with HLA DR-8, and that CH-C patients with ACA exhibit more severe hepatic fibrosis and inflammation than CH-C patients without ANA.

Efficacy of combined modality therapy with sorafenib following hepatic arterial injection chemotherapy and three-dimensional conformal radiotherapy for advanced hepatocellular carcinoma with major vascular invasion.

The prognosis of hepatocellular carcinoma (HCC) patients exhibiting macroscopic vascular invasion (MVI) is poor, and the most appropriate treatment approach remains unclear. The current study aimed to investigate the efficacy and safety of sorafenib treatment following chemoradiotherapy for advanced HCC exhibiting MVI. A newly reported regimen, including 5-fluorouracil and cisplatin therapy (NewFP), plus three-dimensional conformal radiotherapy (3D-CRT) for MVI was used as the initial treatment. Additionally, sorafenib, as a secondary treatment, was administered after NewFP plus 3D-CRT for MVI. The present retrospective study enrolled patients with unresectable advanced HCC that was treated with NewFP plus 3D-CRT for MVI between January 2009 and December 2017. In total, 32 HCC patients with MVI were registered. Of these 32 patients, 18 were treated with NewFP plus 3D-CRT for MVI (NewFP + 3D-CRT group) and 14 were treated with sorafenib following NewFP plus 3D-CRT for MVI (sorafenib after NewFP + 3D-CRT group). The study endpoints were overall survival, overall response rate and disease control rate. Clinical factors influencing overall survival were identified using univariate and multivariate analyses. The median survival time in the NewFP + 3D-CRT group and sorafenib following NewFP + 3D-CRT group was 6.7 and 49.2 months, respectively (P=0.0003). For patients with advanced HCC exhibiting MVI, the initial treatment with NewFP plus 3D-CRT for MVI was well tolerated. The administration of sorafenib as the secondary treatment following NewFP plus 3D-CRT for MVI was associated with a significantly higher overall response rate, disease control rate and increased overall survival as compared with the NewFP plus 3D-CRT treatment.

Outer arm fucosylation of N-glycans increases in sera of hepatocellular carcinoma patients.

Serum glycans are promising markers for early-stage cancer detection, but the research remains challenging because low concentrations of serum glycoproteins are secreted from early-stage tumors. We have established an N-glycan profiling method using liquid chromatography electrospray ionization-mass spectrometry with high sensitive derivative, trimethyl(4-aminophenyl)ammonium chloride (TMAPA). The mass sensitivity of TMAPA-labeled oligosaccharides was enhanced more than 50 times compared with 2-aminopyridine (PA) labeled oligosaccharides, and the analytical period was significantly shortened compared with traditional HPLC 2D-mapping. Using this method, we found about 28 major N-linked oligosaccharides in human sera, and we investigated their alterations in patients who developed hepatocellular carcinoma (HCC). We found that outer arm fucosylation (attached GlcNAc via an alpha 1-3/4 linkage) in highly branched oligosaccharides increased significantly in sera of HCC patients. Normalizing the level of outer arm fucosylation by taking into account platelet concentration allowed us to distinguish more clearly between HCC and LC patients.

Detection of hepatocellular carcinoma using 11C-choline PET: comparison with 18F-FDG PET.

UNLABELLED: The purpose of this study was to retrospectively investigate the feasibility of 11C-choline PET, compared with 18F-FDG PET, for the detection of hepatocellular carcinoma (HCC). METHODS: A total of 16 HCC lesions in 12 patients were examined with both 11C-choline PET and 18F-FDG PET. Tumor lesions were identified as areas of focally increased uptake, exceeding that of surrounding noncancerous liver tissue. For semiquantitative analysis, the tumor-to-liver (T/L) ratio was calculated by dividing the maximal standardized uptake value (SUV) in HCC lesions by the mean SUV in noncancerous liver tissue. RESULTS: 11C-choline PET showed a slightly higher detection rate than did 18F-FDG PET for detection of HCC (63% vs. 50%, respectively), although this difference was not statistically significant. 11C-choline PET had a better detection rate for moderately differentiated HCC lesions but not for those poorly differentiated (75% vs. 25%, respectively). In contrast, 18F-FDG PET exhibited the opposite behavior, with corresponding detection rates of 42% and 75%, respectively. The mean 11C-choline SUV and T/L ratio in moderately differentiated HCC lesions were higher than those in poorly differentiated HCC lesions. In contrast, the mean 18F-FDG SUV and T/L ratio in poorly differentiated HCC were higher than those in moderately differentiated HCC. These differences, however, were also not statistically significant. CONCLUSION: 11C-choline PET had a better detection rate for moderately differentiated HCC lesions but not for poorly differentiated HCC lesions, whereas 18F-FDG PET produced the opposite result. 11C-choline is a potential tracer to complement 18F-FDG in detection of HCC lesions.