Metabolic management after sustained virologic response in elderly patients with hepatitis C virus: A multicenter study.

AIMS: Hepatocellular carcinoma (HCC) develops even in patients with hepatitis C virus (HCV) eradication by direct-acting antiviral agents. Fatty liver and metabolic dysfunction are becoming major etiologies of HCC. We aimed to evaluate the impact of metabolic dysfunction-associated steatotic liver disease (MASLD), a new definition of steatotic liver disease, on the development of HCC after HCV eradication. METHODS: We enrolled 1280 elderly patients with HCV eradication and no history of HCC. We evaluated α-fetoprotein (AFP), Fibrosis-4 index and MASLD after 24 weeks of sustained virological response. Decision tree analysis was used to investigate factors associated with HCC development after HCV eradication. RESULTS: A total of 86 patients (6.7%) developed HCC during the follow-up period (35.8 ± 23.7 months). On multivariate analysis, serum AFP level (HR 1.08, CI 1.04-1.11, P = 0.0008), Fibrosis-4 index (HR 1.17, CI 1.08-1.26, P = 0.0007), and MASLD (HR 3.04, CI 1.40-6.58, P = 0.0125) at 24 weeks of sustained virological response were independent factors associated with HCC development. In decision tree analysis, the initial classifier for HCC development was AFP ≥7 ng/mL. However, in patients with AFP <7 ng/mL, MASLD, rather than Fibrosis-4 index, was the classifier for HCC development. No significant difference was observed in the cumulative incidence of HCC between patients with AFP ≥7 ng/mL and patients with AFP <7 ng/mL and MASLD. CONCLUSION: MASLD at 24 weeks of sustained virological response is a risk factor for HCC development in elderly patients with HCV eradication. Additionally, decision tree analysis revealed that MASLD was associated with HCC development, even in patients with serum AFP levels <7 ng/mL.

The impact of curative conversion therapy aimed at a cancer-free state in patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab.

BACKGROUND AND AIMS: We aimed to validate the predictive factors for tumor response and the prognostic impact of conversion therapy aimed at cancer- and drug-free states in patients with unresectable hepatocellular carcinoma (u-HCC) undergoing atezolizumab plus bevacizumab (Atez/Bev) therapy. METHODS: This retrospective study enrolled 156 patients who were Child-Pugh class A with u-HCC treated using Atez/Beva. The profile of objective response was investigated using decision-tree analysis. Progression-free, recurrence-free, and overall survival were assessed. RESULTS: The progression-free and overall survival were 6.1 and 18.0 months, respectively. Objective response and disease control rates were 32.0% and 84.0%, respectively. Decision-tree analysis revealed that neutrophil-to-lymphocyte ratio (NLR) <3, modified albumin-bilirubin grade (m-ALBI) 1 or 2a, and age < 75 were sequential splitting variables for the objective response, respectively. In the multivariate analysis, NLR <3 and m-ALBI grade 1 or 2a were identified as predictive factors for objective response. We successfully achieved eligibility for conversion therapy in 17 patients after Atez/Bev therapy significant response. Following conversion therapy, the curative therapy group, including surgical resection or radiofrequency ablation (RFA), had significantly higher recurrence-free survival than did the transcatheter arterial chemoembolization (TACE) and Atez/Bev discontinuation (surgical resection or RFA; not reached vs. TACE; 5.3 months, p = 0.008, Atez/Bev discontinuation; 3.9 months, p = 0.048, respectively) groups. CONCLUSIONS: NLR <3 and m-ALBI grade 1 or 2a were predictive factors for conversion therapy, leading to cancer- and drug-free states in patients with u-HCC undergoing Atez/Bev therapy. Moreover, surgery or RFA may be suitable for conversion therapy for cancer-free status.

A combination of hepatic encephalopathy and body mass index was associated with the point of no return for improving liver functional reserve after sofosbuvir/velpatasvir treatment in patients with hepatitis C virus-related decompensated cirrhosis.

AIMS: The real-world efficacy of sofosbuvir/velpatasvir treatment for patients with hepatitis C virus-related decompensated cirrhosis is unclear. We aimed to identify factors that improve liver functional reserve after treatment. METHODS: This was a multicenter retrospective study of 12-week sofosbuvir/velpatasvir treatment. A total of 48 patients with Child-Pugh (CP) class B or C were enrolled at 11 institutions. We evaluated changes in liver functional reserve at 24 weeks post-treatment. RESULTS: At baseline, 40 and eight patients were CP class B and C, respectively. The overall rate of sustained virologic response 12 weeks post-treatment was 95.8% (46/48). Serum albumin, alanine aminotransferase and α-fetoprotein levels, and the FIB-4 index were significantly improved post-treatment (P < 0.05). Among patients who achieved sustained virologic response 12 weeks post-treatment, those with CP class A increased from 0 to 24 patients (56%) at 24 weeks post-treatment. In multivariate analysis, body mass index (BMI) ≥25 was an independent factor that inhibited CP class improvement (P < 0.05). In decision tree analysis, after treatment, the initial divergent variable for CP class improvement was hepatic encephalopathy, followed by serum sodium level and BMI. CONCLUSION: Sofosbuvir/velpatasvir treatment improved the liver functional reserve in patients with hepatitis C virus-related decompensated cirrhosis at 24 weeks post-treatment. However, BMI ≥25 inhibited improvement in CP class. Additionally, decision tree analysis revealed that a combination of hepatic encephalopathy, serum sodium levels, and BMI were diversity profiles associated with no improvement in liver functional reserve after the treatment.

Percutaneous Radiofrequency Ablation with or without Chemolipiodolization for Hepatocellular Carcinoma: A Propensity-Score-Matched Analysis.

Chemolipiodolization (CL) is less invasive than transarterial chemoembolization (TACE) for managing hepatocellular carcinoma (HCC) because it helps avoid embolization. However, the treatment outcomes of percutaneous radiofrequency ablation (PRFA) with or without CL for HCC remain unclear. Herein, we compared the prognostic factors for overall survival (OS) following PRFA with or without CL for HCC using propensity-score-matched analysis. A total of 221 patients with HCC treated with PRFA at Saga Central Hospital between April 2004 and October 2020, with or without CL, were enrolled. No significant difference was observed in OS between PRFA with and without CL cohorts (median survival time (MST): 4.5 vs. 5.4 years; p = 0.0806). To reduce the confounding effects of 12 variables, we performed propensity-score-matched analysis to match patients treated with PRFA with or without CL. No significant difference was observed in OS between PRFA with and without CL cohorts (MST: 4.0 vs. 3.6 years; p = 0.5474). After stratification according to tumor size, no significant difference was observed in OS for patients with tumor size ≥20 mm between PRFA with and without CL cohorts (MST: 3.5 vs. 3.4 years; p = 0.8236). PRFA with CL was not a significant prognostic factor in both univariate and multivariate analyses (p = 0.5477 and 0.9600, respectively). Our findings suggest that PRFA with CL does not demonstrate more favorable prognosis than PRFA without CL for HCC, regardless of tumor size.

Hepatic Arterial Infusion Chemotherapy with Cisplatin versus Sorafenib for Intrahepatic Advanced Hepatocellular Carcinoma: A Propensity Score-Matched Analysis.

Given that the outcome of hepatic arterial infusion chemotherapy (HAIC) with cisplatin for intrahepatic advanced hepatocellular carcinoma (HCC) is unclear, we aimed to compare prognostic factors for overall survival (OS) following HAIC with cisplatin versus sorafenib for intrahepatic advanced HCC using propensity score-matched analysis. We enrolled 331 patients with intrahepatic advanced HCC who received HAIC with cisplatin (n = 88) or sorafenib (n = 243) between June 2006 and March 2020. No significant difference was observed in OS between HAIC with cisplatin and sorafenib cohorts (median survival time [MST]: 14.0 vs. 12.3 months; p = 0.0721). To reduce confounding effects, 166 patients were selected using propensity score-matched analysis (n = 83 for each treatment). HAIC with cisplatin significantly prolonged OS compared with sorafenib (MST: 15.6 vs. 11.0 months; p = 0.0157). Following stratification according to the Child-Pugh classification, for patients with class A (MST: 24.0 vs. 15.0 months; p = 0.0145), HAIC with cisplatin rather than sorafenib significantly prolonged OS. Our findings suggest that HAIC with cisplatin demonstrates longer prognostic effects than sorafenib in intrahepatic advanced HCC.

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.

Evaluation of Resistance-Associated Substitutions in NS5A Using Direct Sequence and Cycleave Method and Treatment Outcome with Daclatasvir and Asunaprevir for Chronic Hepatitis C Genotype 1.

BACKGROUND: The aim of this study was to evaluate the efficacy of daclatasvir plus asunaprevir therapy in patients infected with hepatitis C virus and determine its relevance to resistant variants. METHODS: A total of 629 consecutive patients infected with hepatitis C virus genotype 1 were assessed. Daclatasvir (60 mg/day) plus asunaprevir (200 mg/day) was given for 24 weeks. The virological responses and resistance-associated substitutions of hepatitis C virus mutants were examined by the direct sequence and cycleave methods were evaluated. RESULTS: Overall, 89.4% (555/621) of patients exhibited a sustained virological response (SVR). The SVR rates in the patients with wild type, mixed, and mutant type Y93 by direct sequencing were 92.5% (520/562), 70.3% (26/37), and 42.9% (9/21), respectively. The SVR rates in the patients with 100%, 90%, 80%-30%, and 20%-0% Y93 wild by the cycleave method were 93.4% (456/488), 88.2%(30/34), 56.0%(14/25), and 36.8%(7/19), respectively. In contrast, the SVR rates for the wild type and mixed/mutant type L31 by direct sequencing were 90.2% (534/592) and 72.4% (21/29), respectively. In the multivariate analyses, the wild type Y93, no history of simeprevir therapy, the wild type L31, and low HCV RNA level were independent factors of SVR. CONCLUSION: NS5A resistance-associated substitutions, especially Y93H, were major factors predicting the SVR. Although direct sequencing can predict the SVR rate, the cycleave method is considered to be more useful for predicting the SVR when used in combination.

Efficacy, safety, and survival factors for sorafenib treatment in Japanese patients with advanced hepatocellular carcinoma.

BACKGROUND: Sorafenib, an oral multikinase inhibitor, was approved for the treatment of advanced hepatocellular carcinoma (HCC), but has not been adequately evaluated for safety and effectiveness in Japanese patients with advanced HCC. AIMS: The purpose of this study was to prospectively assess the efficacy, safety, and risk factors for survival in patients with advanced HCC treated with sorafenib. METHODS: Between May 2009 and December 2010, 96 Japanese patients with advanced HCC (76 male, 20 female, mean age: 70.4 years) were treated with sorafenib. Eighty-eight patients had Child-Pugh class A, and 8 patients had Child-Pugh class B liver cirrhosis. Barcelona Clinic Liver Cancer stage B and C were found in 64 and 32 patients, respectively. RESULTS: Twelve patients demonstrated partial response to sorafenib therapy, 43 patients had stable disease, and 33 patients had progressive disease at the first radiologic assessment. The most frequent adverse events leading to discontinuation of sorafenib treatment were liver dysfunction (n = 8), hand-foot skin reaction (n = 7), and diarrhea (n = 4). The median survival time and time to progression were 11.6 and 3.2 months, respectively. By multivariate analysis, des-γ-carboxy prothrombin serum levels and duration of treatment were identified as independent risk factors for survival. CONCLUSIONS: This study showed that sorafenib was safe and useful in Japanese patients with advanced HCC. In addition, this study demonstrated that sorafenib should be administered as a long-term treatment for advanced HCC regardless of therapeutic effect and dosage.

Transarterial chemoembolization as salvage therapy after unsuccessful hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma.

The prognosis for advanced hepatocellular carcinoma (HCC) remains unsatisfactory. Transarterial chemoembolization (TACE) and/or hepatic arterial infusion chemotherapy (HAIC) have been reported to be useful options. However, there are few reports of salvage therapies for patients without a curative response to initial chemotherapy. The aim of this study was to elucidate the efficacy of additional TACE as salvage therapy in cases of advanced HCC which failed to respond to HAIC. Of 43 patients with advanced HCC who did not show a complete response (CR) to HAIC, 12 were treated with additional TACE as salvage therapy (Group A). The rest were enrolled as disease control subjects (Group B). Response rates and prognosis were compared. For HAIC, cisplatin (10 mg/body on days 1-5) was administered. Subsequent treatment was the infusion of 5-fluorouracil (250 mg/body on days 1-5), which was scheduled for 4 serial courses. For TACE, carboplatin (150 mg/body) or epirubicin (30 mg/body) was administered mixed with 3 ml of ethiodized oil every 4 weeks. A CR or PR, ST and PD were observed in 6, 3, and 3 patients in Group A and 13, 18 and 0 patients in Group B, respectively. The difference in response between the two groups was significant (P=0.0074). The 1-, 2- and 3-year survival rates were 83.3, 75.0 and 44.4% in Group A and 83.9, 41.5 and 11.3% in Group B, respectively. Patients in Group A had a better prognosis than did those in Group B (P=0.018). Median survival was 31.9 months (5.8-41.1) in Group A and 16.2 months (3.3-53.2) in Group B. Consequently, TACE as salvage therapy after HAIC may improve the prognosis for patients with advanced HCC.

[A case of chronic hepatitis C virus-related advanced hepatocelluar carcinoma surviving more than 8 years].

A 64-year-old man was admitted for further examinations of a liver tumor. The patient was diagnosed as chronic hepatitis C complicated with advanced hepatocelluar carcinoma (HCC) with left portal vein tumor thrombosis. As he refused surgical treatment, hepatic arterial infusion chemotherapy (HAIC) using cisplatin and 5-fluorouracil was performed initially. Administration of ursodesoxycholic acid (UDCA) was also started. Following HAIC, microwave coagulation therapy for residual tumor was added. Consequently, viable lesions of HCC disappeared completely. At present, after more than 8 years, neither signs of tumor recurrence, nor elevation of hepatic enzymes has been observed. Although the precise reason for long survival of this patient is not known, we speculate that suppression of levels of hepatic enzymes, as well as HAIC for subclinical intrahepatic metastasis, contributed to the good outcome. Therapeutic strategy for hepatic inflammation seems to be important for long-term prevention of hepatocarcinogenesis.

Clinical features of hepatitis C virus-related hepatocellular carcinoma and their association with alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II.

PURPOSE: We investigated the differences in clinical features between alpha-fetoprotein (AFP)-predominant hepatocellular carcinoma (HCC) and protein induced by vitamin K absence or antagonist-II (PIVKA-II)-predominant HCC, especially regarding host factors thought to contribute to hepatocarcinogenesis in chronic hepatitis C virus (HCV) infection. METHODS: HCV-related HCC patients (n=306) were divided into four groups according to median AFP (48.1 ng/ml) and PIVKA-II (60 mAU/ml). Host factors, tumor factors, survival, and risk factors affecting survival were compared. RESULTS: Aspartate aminotransferase (AST; IU/L), alanine aminotransferase (ALT; IU/L), and platelet count (x 10(4)/ml) were, respectively, 81, 67, and 8.2 in AFP-predominant HCC (group A; n=66) vs. 50, 42, and 11.4 in PIVKA-II-predominant HCC (group P; n=52). Tumor sizes (mm) in groups A and P were 20 and 37, respectively. Significant differences were evident. Survival was identical between the two groups. Factors affecting survival were total bilirubin, portal tumor thrombus and number of nodule in group A, and albumin and tumor distribution in group P. CONCLUSIONS: PIVKA-II-predominant HCC had a milder hepatitis and a better-preserved platelet count compared with AFP-predominant HCC. Considering the strong relation between hepatocarcinogenesis and hepatic inflammation with chronic HCV infection, these differences indicate that hepatocarcinogenic mechanisms in PIVKA-II-predominant HCC may differ from those in AFP-predominant HCC.

Partial spontaneous regression of hepatocellular carcinoma: a case with high concentrations of serum lens culinaris agglutinin-reactive alpha fetoprotein.

Spontaneous regression of hepatocellular carcinoma (HCC) is rare. There are few reports discussing spontaneous regression associated with serum lens culinaris agglutinin-reactive alpha fetoprotein (AFP-L3). We describe a case of HCC with a high level of AFP-L3, which showed a rapid increase in alpha fetoprotein (AFP) concentration after partial spontaneous regression, and which was then treated successfully. A 71-year-old woman suffering from chronic hepatitis C underwent surgical resection for HCC. Preoperative concentrations of AFP fluctuated; subsequent to a transient decrease, a rapid increase in AFP was observed. AFP-L3 concentration was extremely high. The resected tissue consisted of encapsulated moderately differentiated HCC, subcapsular coagulation necrosis, and chronic active hepatitis. The postoperative course was uneventful. At present, 24 months after diagnosis, no symptoms or signs of tumor recurrence or metastasis have been observed. Although the precise etiology of the spontaneous regression in this patient is not known, we speculate that spontaneous regression of tumor cells with high malignant potential may be related to arterial involvement and insufficient blood supply.

Interventional radiology for advanced hepatocellular carcinoma: comparison of hepatic artery infusion chemotherapy and transcatheter arterial lipiodol chemoembolization.

OBJECTIVE: The prognosis of advanced hepatocellular carcinoma remains poor. The aim of this study was to compare the efficacy of hepatic artery infusion chemotherapy and transcatheter arterial Lipiodol chemoembolization for treatment of advanced tumor. SUBJECTS AND METHODS. Thirty-seven patients with hepatocellular carcinoma and unresectable tumors were enrolled. In the hepatic artery infusion chemotherapy group (n = 16), cisplatin (10 mg/person, on days 1-5) and subsequent 5-fluorouracil (250 mg/person, on days 1-5) were administered for four serial courses. In the transcatheter arterial Lipiodol chemoembolization group (n = 21), an emulsion of Epirubicin (20-30 mg/person) and Lipiodol was administered every 3-4 weeks. RESULTS: The tumor response rates (complete response plus partial response for all cases) of the hepatic artery infusion chemotherapy and transcatheter arterial Lipiodol chemoembolization groups were 56.3% and 23.8%, respectively, showing the significantly higher rate in the former than in the latter group. The cumulative survival rates between the two groups were not significantly different; whereas in those patients whose tumors were classified as TNM stage IV or as having the maximal tumor size of greater than 5 cm, patients tended to have higher survival rates in the hepatic artery infusion chemotherapy group than in the transcatheter arterial Lipiodol chemoembolization group. Univariate analysis identified the serum aspartate aminotransferase value as solely significant. Patients' adverse reactions were successfully managed by treatment of symptoms. Adverse events, such as obstructions of the catheter or hepatic artery or infection around the catheter, rarely occurred. CONCLUSION: Hepatic artery infusion chemotherapy had a better antitumor effect than transcatheter arterial Lipiodol chemoembolization and may be a useful therapeutic option for more advanced hepatocellular carcinoma.

Clinical significance of antibody against hepatitis B virus core antigen in patients with hepatitis C virus-related hepatocellular carcinoma.

PURPOSE: We investigated the unsettled issue of whether seropositivity for antibody to hepatitis B core antigen (anti-HBc) affects characteristics of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). METHODS: Antibody status was determined by enzyme immunoassay in 243 patients with this cancer, and associations with clinicopathologic characteristics and outcome were analysed. Serum hepatitis B virus (HBV) DNA was determined by real-time polymerase chain reaction. RESULTS: Of 235 patients with unequivocal serologic status, 142 were seropositive and 93 were seronegative. Clinicopathologic characteristics and overall cumulative survival rates were comparable between the two groups. However, seropositivity tended to predict poor outcome for patients in Child class B or C (P=0.068), those in tumour-nodes-metastasis-based stage 3 or 4 (P=0.081), those with tumours exceeding 25 mm (P=0.068), and those with a past history of clinical liver disease (P=0.088). Multivariate analysis identified serum albumin, portal vein tumour thrombosis, and tumour size as independent determinants of survival. Serum HBV DNA was below 1.7 log copies/ml in all 40 patients tested. CONCLUSIONS: Overall, the clinical features of HCV-HCC were unaffected by seropositivity for anti-HBc. Seropositivity tended to worsen prognosis for subgroup with poor hepatic reserve or advanced tumours.

Diagnostic clues for recurrent hepatocellular carcinoma: comparison of tumour markers and imaging studies.

OBJECTIVE: To elucidate the usefulness of monitoring Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) and des-gamma-carboxy prothrombin detected with a revised kit (DCP-R) as clues to the diagnosis of recurrent hepatocellular carcinoma (HCC). METHODS: A total of 57 patients with HCC were enrolled in the study. They were classified into two groups: group A comprised 27 patients in whom the diagnostic clue to recurrent HCC appeared before November 1997; these patients were monitored by ultrasonography, computed tomography (CT), AFP and des-gamma-carboxy prothrombin detected with a conventional kit (DCP-C). Group B comprised 30 patients in whom the diagnostic clue to recurrent HCC was detected after November 1997; these patients were monitored by ultrasound, CT, AFP, AFP-L3 and DCP-R. RESULTS: In group A, 22 and five HCC recurrences were recognized initially by imaging studies and tumour markers, respectively. In group B, 17 and 13 HCC recurrences were recognized initially by imaging studies and tumour markers, respectively. The number of patients in whom tumour markers were the first clue to the diagnosis of recurrent HCC was significantly higher in group B than in group A. CONCLUSIONS: Periodic examination of AFP-L3 and DCP-R may be useful for the early detection of recurrent HCC.

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: analysis of 48 cases.

BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is extremely poor. The aim of this study was to elucidate the efficacy of hepatic arterial infusion chemotherapy (HAIC) for patients with advanced HCCs. METHODS: Forty-eight HCC patients with PVTT were treated by HAIC via a subcutaneously implanted injection port. Of these, 14 had PVTT in the second portal branch and 34 patients had PVTT in the first portal branch or in the main portal trunk. One course of chemotherapy consisted of daily cisplatin (7 mg/m(2) for 1 hour on Days 1-5) followed by 5-fluorouracil (170 mg/m(2) for 5 hours on Days 1-5). Patients were scheduled to receive four serial courses of HAIC. Responders were defined as having either a complete response (CR) or partial response (PR) and nonresponders were defined as exhibiting stable disease or progressive disease. The prognosis after HAIC and factors related to survival were analyzed. RESULTS: Following HAIC, 4 and 19 patients exhibited a CR and PR, respectively (response rate = 48%). The 1, 2, 3, and 5-year cumulative survival rates of 48 patients treated with HAIC were 45%, 31%, 25%, and 11%, respectively. Median survival periods for 23 responders and 25 nonresponders were 31.6 (range, 8.3-76.9) months and 5.4 (1.9-29.0) months, respectively. Therapeutic effect (P < 0.001) and hepatic reserve capacity (P = 0.021) were identified as significant prognostic factors by univariate analysis. Multivariate analysis identified only therapeutic effect as being significantly related to survival. CONCLUSIONS: HAIC using low-dose cisplatin and 5-fluorouracil may be a useful therapeutic option for patients with advanced HCC with PVTT. HCC patients with PVTT who respond to HAIC could certainly have survival benefits.

Clinical features of hepatocellular carcinoma seronegative for both HBsAg and anti-HCV antibody but positive for anti-HBc antibody in Japan.

OBJECTIVE: We determined the prevalence of patients with hepatocellular carcinoma (HCC) who were positive for only anti-hepatitis B core (anti-HBc) antibody among 284 Japanese patients and compared their clinical features to those who were hepatitis B surface antigen positive [HBsAg(+)]. METHODS: Serum HBsAg and anti-hepatitis C virus (anti-HCV) antibody were examined for all HCC patients. Testing for anti-HBc antibody was performed in the HBsAg(-)/anti-HCV(-) patients. The clinical factors and the survival rate were compared between the HBsAg(+) patients (HCC-B) and those positive for anti-HBc alone (HCC-PB). RESULTS: There were 19 (6.7%) HBsAg(+), 236 (83.1%) anti-HCV(+), seven (2.5%) HBsAg(+)/anti-HCV(+), and 22 (7.7%) HBsAg(-)/anti-HCV(-) among the 284 patients tested. Sixteen (72.7%) of the 22 HBsAg(-)/anti-HCV(-) patients were assigned to the HCC-PB group. The prevalence of positivity for anti-HBc alone among all 284 HCC patients was 5.6%. Significant differences between the HCC-PB and HCC-B groups were that age at diagnosis was higher in the HCC-PB group (72.1 yr) than in the HCC-B group (56.2 yr) (p < 0.001), the serum alpha-fetoprotein concentrations were lower in the HCC-PB group (8.2 ng/ml) than in the HCC-B group (43 ng/ml) (p = 0.0488), and a higher familial history of liver disease was observed in the HCC-B group (p = 0.0373). However, there was no significant difference in the cumulative survival rate. CONCLUSIONS: Positivity for anti-HBc alone is not rare compared to HBsAg(+), and the clinical features of positivity for anti-HBc alone are similar to those of HBsAg(+). Some differences in the clinical features between the two groups may be explained by differences in the time of first exposure to hepatitis B virus. Therefore, the natural course of acute hepatitis B may be reconsidered.