Search

Hepatitis delta virus (HDV), an RNA virus with two forms of the delta antigen (HDAg), relies on hepatitis B virus (HBV) for envelope proteins essential for hepatocyte entry. Hepatocellular carcinoma (HCC) ranks third in global cancer deaths, yet HDV's involvement remains uncertain. Among 300 HBV-associated HCC serum samples from Taiwan's National Health Research Institutes, 2.7% (8/300) tested anti-HDV positive, with 62.7% (5/8) of these also HDV RNA positive. Genotyping revealed HDV-2 in one sample, HDV-4 in two, and two samples showed mixed HDV-2/HDV-4 infection with RNA recombination. A mixed-genotype infection revealed novel mutations at the polyadenylation signal, coinciding with the ochre termination codon for the L-HDAg. To delve deeper into the possible oncogenic properties of HDV-2, the predominant genotype in Taiwan, which was previously thought to be less associated with severe disease outcomes, an HDV-2 cDNA clone was isolated from HCC for study. It demonstrated a replication level reaching up to 74% of that observed for a widely used HDV-1 strain in transfected cultured cells. Surprisingly, both forms of HDV-2 HDAg promoted cell migration and invasion, affecting the rearrangement of actin cytoskeleton and the expression of epithelial-mesenchymal transition markers. In summary, this study underscores the prevalence of HDV-2, HDV-4, and their mixed infections in HCC, highlighting the genetic diversity in HCC as well as the potential role of both forms of the HDAg in HCC oncogenesis.

The impacts of patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M-rs738409, methylenetetrahydrofolate reductase (MTHFR) Ala222Val-rs1801133, and aldehyde dehydrogenase 2 (ALDH2) Glu504Lys-rs671 on the outcomes of Taiwanese patients with steatotic liver disease (SLD) have remained elusive. An 8-year prospective cohort study of patients with (n = 546) and without (n = 580) SLD (controls) was undertaken in a Taiwanese tertiary care center. The 546 SLD patients comprised 306 (56.0%) men and 240 (44.0%) women with mean ages of 53.3 and 56.4 years, respectively. Compared with the controls, SLD patients had an increased frequency of the PNPLA3 I148M-rs738409 GG genotype (25.5 vs. 5.9%, p = 0.001). Among the SLD patients, 236 (43.1%) suffered cardiovascular events, 52 (9.5%) showed extrahepatic cancers, 13 (2.38%) experienced hepatic events, including hepatocellular carcinoma (n = 3, 0.5%) and liver cirrhosis (n = 8, 1.47%), and none died. The Fibrosis-4 (FIB-4) scores were associated with extrahepatic cancer (hazard ratio [HR] 1.325; 95% confidence interval [CI], 1.038-1.691) and cirrhosis development (HR 1.532; 95% CI, 1.055-2.224), and the PNPLA3 I148M-rs738409 G allele (β = 0.158, 95% CI, 0.054-0.325) was associated with the FIB-4 score. Stratified analyses showed that the impact of the FIB-4 score on extrahepatic cancer development was evident only in SLD patients with the PNPLA3 I148M-rs738409 GG genotype (HR 1.543; 95% CI, 1.195-1.993) and not in patients with the GC or CC genotype. Moreover, the ALDH2 Glu504Lys-rs671 G allele had a dose-dependent effect on alcoholism, and the MTHFR and ALDH2 genotypes were not significantly associated with SLD patient outcomes. In conclusion, special vigilance should be exercised for emerging extrahepatic cancer in SLD patients with the PNPLA3 I148M-rs738409 GG genotype and high FIB-4 scores., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Although targeted agents are recommended as the first-line treatments for advanced hepatocellular carcinoma (aHCC), systemic chemotherapy or hepatic arterial infusion chemotherapy (HAIC) are still being used in Asian countries. Beside economic considerations, it was found that targeted drugs could not significantly prolong overall survival in aHCC patients with distant metastasis. In addition, chemotherapy could achieve complete response in a small proportion of patients. Here, we aimed to investigate whether combination of three previously identified single nucleotide polymorphism (SNP) predictors (GALNT14-rs9679162, WWOX-rs13338697, and rs6025211) could guide our choice between systemic chemotherapy, HAIC, and targeted agents in aHCC patients. A cohort of 237 real-world aHCC patients (171 receiving systemic chemotherapy followed by various anticancer treatments including sorafenib; 66 receiving HAIC) were included for outcome analysis. By combining the three SNP markers with or without addition of two clinical criteria (tumor diameter <8 cm, neutrophils <80%), small groups of patients were found to harbor high complete response rates to systemic chemotherapy (35.3% if the 3-SNP signature alone matched; 60.0% if clinical criteria also matched). Subsequent sorafenib treatment for chemotherapy non-responders was associated with longer overall survival (P < 0.001). In HAIC-treated patients, GALNT14-rs9679162 genotype "GG" was associated with longer overall survival (P = 0.019, median survival > 10.5 months). In conclusion, pre-test for the 3-SNP signature in aHCC patients could identify potential systemic chemotherapy or HAIC responders. Chemotherapy non-responders still benefited from subsequent sorafenib treatment. Accordingly, we propose a roadmap for aHCC patients when chemotherapy or HAIC is to be used.

Liver cirrhotic patients suffer from a seemingly unpredictable risk of hepatocellular carcinoma (HCC). Here, an HCC risk score R (0 ≦ R ≦ 1) was derived from commonly tested haematological and biochemical parameters. In the score-derivation Taiwanese cohort (144 cirrhosis versus 48 HCC-remission patients), the score had an area-under-the-curve (AUC) of 0.70 (95% confidence interval [CI], 0.61-0.78, P < 0.001). When validated in a Korean cohort (78 cirrhosis versus 23 HCC-remission patients), the AUC was 0.68 (CI, 0.56-0.80, P = 0.009). In a multicentre prospective cohort (478 cirrhotic patients prospectively followed for HCC occurrence), the hazard ratio with respect to R was 2.344 (CI = 1.183-4.646, P = 0.015). The cumulative incidences of HCC at two years after patient enrolment were 9.6% and 1.7% for the high-risk (R ≧ 0.5) and low-risk (R < 0.5) groups, respectively (P < 0.001). At the end of the study, the incidences were 10.9% and 5.0%, respectively (P = 0.012). The majority of HCCs (23/26) in the high-risk group emerged within the first two years of follow-up. In conclusion, an HCC risk score was developed for cirrhotic patients that effectively predicted HCC in a prospective cohort study.

Aim: A genome-wide association study (GWAS) had identified a single nucleotide polymorphism (SNP), GALNT14-rs9679162, capable of predicting chemotherapy responses in advanced hepatocellular carcinoma (HCC). Here, we revisited the GWAS database to search for necessary SNPs that could improve our outcome prediction., Methods: A cohort of 116 HCC patients receiving split-dose chemotherapy composed of 5-fluorouracil, mitoxantrone and cisplatin was enrolled. The GALNT14-rs9679162 together with four other leading candidate SNPs (rs6025211, rs715171, LOC105369482-rs1955024 and WWOX-rs13338697) was genotyped and correlated with time-to-tumor progression (TTP) and overall survival (OS)., Results: GALNT14-rs9679162-TT genotype remained an effective predictor for favorable TTP and OS (P = 0.012 and 0.002). Additionally, it was found that WWOX-rs13338697-CT genotype was associated with unfavorable TTP (P = 0.031), independent of GALNT14-rs9679162 genotype (adjusted P = 0.045), and rs6025211-CT genotype was associated with unfavorable OS (P = 0.014), independent of GALNT14-rs9679162 genotype (adjusted P = 0.025). Combinations of these SNPs stratified patients into three groups with differential treatment outcomes. Patients with GALNT14-rs9679162-TT/WWOX-rs13338697-non-CT genotypes achieved the most favorable treatment outcomes (n = 19; median TTP, median OS and response rate were 3.9 months, 6.8 months and 4/19 [21.1%], respectively); whereas patients with GALNT14-rs9679162-non-TT/rs6025211-CT genotypes associated with the most unfavorable treatment outcomes (n = 40; median TTP, median OS and response rate were 1.9 months, 3.5 months and 1/40 [2.5%], respectively). The remaining patients constituted a third subgroup with intermediate clinical outcomes., Conclusions: Three genetic variants, GALNT14-rs9679162, WWOX-rs13338697 and rs6025211, stratified advanced HCC patients into three groups with differential treatment outcomes., (© 2017 John Wiley & Sons Australia, Ltd.)

Background: A lower neutrophil-to-lymphocyte ratio (NLR) was found to be associated with better clinical outcomes in hepatitis B-related liver cirrhosis and hepatocellular carcinoma. We aimed to identify pre-therapeutic variables capable of predicting NLR changes in patients with hepatitis B receiving peginterferon therapy., Patients and Methods: The baseline clinicopathological data were analyzed to correlate with NLR changes before and 1 year after peginterferon treatment in 71 patients with hepatitis B., Results: Univariate analysis revealed that pre-treatment NLR itself negatively predicted NLR changes following peginterferon treatment (odds ratio(OR)=0.320, p=0.013). Further analysis identified pre-treatment NLR, hemoglobin and hepatitis B surface antigen level as independent predictors for NLR changes (adjusted p=0.028, 0.005, and 0.028, respectively). A predictive score composed of these three factors had an area under the curve of 76.5% (p<0.001)., Conclusion: Pretreatment NLR, hemoglobin and hepatitis B surface antigen level in combination, effectively predicted NLR changes following peginterferon treatment., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

With the availability of potent antiviral therapies, complete suppression of hepatitis B virus (HBV) replication and total eradication of hepatitis C virus (HCV) can now be achieved. Despite these advances, hepatocellular carcinoma (HCC) still develops in a substantial proportion of cirrhotic patients, suggesting that host factors remain critical. Dysregulation of miRNAs is noted in many cancers, and circulating miRNAs can be readily assayed. In this study, we aimed to develop a circulating miRNA signature to assess the risk of HCC in cirrhotic patients. We first discovered that HBV- and HCV-related cirrhotic patients had distinguishable circulating miRNA profiles. A cohort of 330 cirrhotic patients was then compared against a cohort of 42 early HCC patients with complete remission. A score comprising 5 miRNAs and a binary etiology variable was established that was capable of differentiating between these two groups (AUC = 72.5%, P < 0.001). The 330 cirrhotic patients were further stratified into high- and low-risk groups, and all patients were longitudinally followed for 752 (11-891) days. Of them, 19 patients developed HCC. The high-risk group had significantly higher cumulative HCC incidence (P = 0.038). In summary, a circulating miRNA-based score was developed that is capable of assessing HCC risks in cirrhotic patients.

Acute hepatitis C exacerbations can occur in cancer patients carrying hepatitis C virus (HCV) when receiving systemic chemotherapy. However, clinical studies evaluating these complications remain rare due to the lack of clinically proven effective and tolerable anti-HCV treatments at late cancer stages. Furthermore, no data were available regarding hepatitis C exacerbation in advanced hepatocellular carcinoma (HCC) patients receiving chemotherapy. To address this issue, 48 patients with HCV-related advanced HCC, who underwent systemic chemotherapy using 5- fluorouracil, cisplatin, and mitoxantrone from 2008 to 2014 were analyzed. Nine patients developed acute hepatitis exacerbations defined by HCV-RNA elevation ≥10-fold and alanine transaminase (ALT) elevation ≥5-fold of the upper normal limit. Six were genotype 1b and 3 were genotype 2. Three patterns of clinical courses were observed including single episode of exacerbation (n = 5), fluctuated flares (n = 3), and delayed exacerbation (n = 1). Hepatic failure developed in five patients. Patients with acute exacerbations were less likely to have pretreatment ascites (11.1% vs. 53.8%; P = 0.028) and displayed a lower baseline ALT (44.1 ± 28.5 U/L vs. 72.6 ± 19.2 U/L; P = 0.007). Paradoxically, despite a high risk of hepatic failure, occurrence of hepatitis C exacerbation was associated with a favorable overall survival (P = 0.027; 22.8 vs. 5.4 months). In conclusion, hepatitis C exacerbation can occur in HCC patients receiving chemotherapy, leading to liver failure. However, the flare was associated with a better overall survival, possibly due to its association with a better baseline liver function. J. Med. Virol. 89:153-160, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Clinical factors associated with hepatocellular carcinoma (HCC) have been extensively studied in antiviral treatment-naive patients with chronic hepatitis B virus (HBV) infection but not in treatment-experienced patients. Owing to the wide availability of antiviral agents that effectively suppress HBV replication, we investigated HCC risk factors in treatment-experienced patients., Methods: In a cohort of 330 patients who underwent pretherapeutic liver biopsy, we analyzed the HCC incidence in relationship to clinical parameters. Ultra-deep sequencing of the viral genome was performed on 11 entecavir-treated and pegylated interferon (peginterferon)-treated patients., Results: Initial univariate/multivariate explorations indicated that cirrhosis and antiviral treatment were independently associated with HCC occurrence. The peginterferon-experienced patients had a lower HCC incidence than the nucleos(t)ide analogue-treated patients (P = .011). The peginterferon and entecavir monotherapy groups also differed in HCC incidence (P = .018). Results of analysis of baseline-matched subgroups concurred with cohort analysis (P = .009 for comparison of peginterferon-experienced vs nucleotide analogue-treated patients; P = .022 for comparison of peginterferon- vs entecavir-treated patients). Viral loads of entecavir-treated patients were constantly suppressed to levels lower than those of peginterferon-treated patients (P < .001). Oncogenic surface antigen truncation mutations were detected in entecavir-treated patients with HCC but not in peginterferon-treated patients (P = .015)., Conclusions: Treatment by peginterferon was associated with a lower HCC incidence than nucleos(t)ide-analogue treatment in chronic HBV infection., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Objective: Cisplatin is a known nephrotoxic agent requiring vigorous hydration before use. However, aggressive hydration could be life-threatening. Therefore, in cirrhotic patients with advanced hepatocellular carcinoma (HCC) under cisplatin-based chemotherapy, the risk of nephrotoxicity increased. Because previous studies showed that long-term telbivudine treatment improved renal function in chronic hepatitis B virus (HBV) infected patients, we conducted a case-control study to evaluate the clinical outcome of telbivudine preemptive therapy in HBV-related advanced HCC patients treated by combination chemotherapy comprising 5-fluorouracil, mitoxantrone and cisplatin (FMP)., Material and Methods: From June 2007 to March 2012, 60 patients with HBV-related advanced HCC, all receiving the same FMP chemotherapy protocol, were enrolled. Of them, 20 did not receive any antiviral therapy, whereas the remaining 40 patients (sex and age matched) received telbivudine preemptive therapy., Results: Progressive decrease of aminotransferase levels (p < 0.05) and progressive increase of viral clearance rates (p < 0.001) were found in telbivudine-treated group. No drug resistance developed during the course of treatment. When compared with non-antiviral-treated patients, a significantly higher post-therapeutic estimated glomerular filtration rate (eGFR) was found in the telbivudine-treated group (p < 0.001). In patients with initial eGFR >100 ml/min (n = 34), the median overall survival was significantly longer in the telbivudine-treated group (12.1 vs. 4.9 months; p = 0.042)., Conclusion: Preemptive use of telbivudine significantly prevented eGFR deterioration caused by cisplatin-based chemotherapy in HBV-related advanced HCC. In patients with initially sufficient eGFR level, telbivudine treatment was associated with a longer overall survival.

Postoperative recurrence of hepatocellular carcinoma (HCC) is presented as local recurrence (LR) or extrahepatic metastasis (EHM). Recent studies indicated that EHM requires additional cellular alterations. This study aimed to examine the clinical and molecular prognostic predictors of these two events. HCC patients (289) [training cohort (n=160) and verification cohort (n=129)] receiving surgical resection of hepatomas were included. The expression levels of six signaling molecules were quantitatively assessed for prognostic analysis. Clustering analysis revealed similar expression profiles between cancer (T) and non-cancer (N) liver tissues in the same individuals. Univariate analysis showed that phosphorylated mammalian target of rapamycin (mTOR)-T was associated with LR-free survival (P=0.002), whereas extracellular signal-related kinase (ERK2)-T (P=0.005), AKT-T (P=0.001) and glycogen synthase kinase (GSK)-T/N ratio (P=0.008) were associated with EHM-free survival. When clinical predictors were added for multivariate analysis, only prolonged prothrombin time (P=0.003) and tumor number (P=0.031) was independently associated with LR-free survival, whereas age (P=0.019), creatinine levels (P=0.001) and AKT-T (P=0.004) were associated with EHM-free survival. These factors were further examined in the verification cohort. In conclusion, postoperative LR and EHM in HCC were associated with separable sets of clinical and molecular predictors.

Comparison of microRNA (miRNA) expression profiles in the noncancerous liver tissues adjacent to hepatocelluar carcinomas (HCCs) was a strategy to identify postoperative prognostic predictors in this study. Expression profiles of 270 miRNAs were determined in the paraneoplastic liver tissues of 12 HCC patients with known postoperative prognosis. A panel of candidate miRNA predictors was identified. The prognostic predictive value of these candidate miRNAs was then verified in 216 postoperative HCC patients. Univariate analysis identified 8 and 3 miRNA predictors for recurrence-free (RFS) and overall (OS) survivals, respectively. Multivariate analysis revealed high expression levels of miR-155 (HR, 2.002 [1.324-3.027]; P = .001), miR-15a (HR, 0.478 [0.248-0.920]; P = .027), miR-432 (HR, 1.816 [1.203-2.740]; P = .015), miR-486-3p (HR, 0.543 [0.330-0.893]; P = .016), miR-15b (HR, 1.074 [1.002-1.152]; P = .043) and miR-30b (HR, 1.102 [1.025-1.185]; P = .009) were significantly associated with RFS. When clinicopathological predictors were included, multivariate analysis revealed that tumor number and miR-432, miR-486-3p, and miR-30b expression levels remained significant as independent predictors for RFS. Additionally, expression knockdown of miR-155 in J7 and Mahlavu hepatoma cells resulted in decreased cell growth and enhanced cell death in xenograft tumors, suggesting an oncogenic effect of miR-155. In conclusion, significant prognostic miRNA predictors were identified through examination of miRNA expression levels in paraneoplastic liver tissues. Functional analysis of a miRNA predictor, miR-155, suggested that the prognostic miRNA predictors identified under this strategy could serve as potential molecular targets for anticancer therapy.

Background: Development of the hepatitis B virus (HBV) rtA181T/sW172* mutant could occur during prolonged lamivudine (LAM) therapy, conferring cross resistance to adefovir. Recent studies demonstrated an increased oncogenic potential of this mutant in NIH3T3 cells. In this study, we aimed to investigate the clinical significance of this finding., Methods: Serum samples from 123 LAM-resistant chronic hepatitis B patients were submitted for virological assays. A highly sensitive amplification created restriction enzyme site (ACRES) method was devised to detect small amounts of the rtA181T mutant in the serum. Virological factors including HBV-DNA level, genotype, precore G1896A, BCP A1762T/G1764A, rtM204I/V, rtA181T and pre-S internal deletion mutations as well as clinical variables including subsequent use of rescue drugs were submitted for outcome analysis., Results: By use of the highly sensitive ACRES method, the rtA181T mutant was detectable in 10 of the 123 LAM-resistant patients. During the mean follow-up period of 26.2 ± 16.4 months (range 2 to 108 months), 3 of the 10 (30.0%) rtA181T-positive patients and 2 of the 113 (1.8%) rtA181T-negative patients developed hepatocellular carcinoma (HCC). Kaplan-Meier analysis indicated that the presence of rtA181T mutation (P < 0.001), age > 50 years (P = 0.001), and liver cirrhosis (P < 0.001) were significantly associated with subsequent occurrence of HCC. All 5 HCC patients belonged to the older age and cirrhosis groups., Conclusions: Emergence of the rtA181T/sW172* mutant in LAM-resistant patients increased the risk of HCC development in the subsequent courses of antiviral therapy.

Background: Lamivudine is widely used in patients with chronic hepatitis B virus (HBV) infection. In cirrhotic patients, long-term lamivudine therapy significantly reduced the risk of hepatocellular carcinoma (HCC). However, in a small but substantial portion of patients, HCC still developed despite lamivudine therapy. Prolonged usage of lamivudine led to mutations in the polymerase gene, where concurrent nonsense mutations in the HBV S gene occasionally occurred. The significance of such mutations in hepatocarcinogenesis remains elusive. Here, we aimed to understand the oncogenicity of HBV pre-S/S nonsense mutations identified in patients with HCC that developed after lamivudine therapy., Methods: Of 141 consecutive hepatitis B surface antigen-positive HCC patients, 8 developed HCC after receiving lamivudine therapy. The HBV pre-S/S sequences in their serum and tissue samples were analysed. A sex- and age-matched group of HCC patients who never received lamivudine therapy were included as controls. Site-directed mutagenesis experiments were performed to generate identified pre-S/S nonsense mutations in expression vectors for tumourigenicity analysis., Results: Seven of eight patients in the lamivudine-treated group harboured nonsense mutations in the S gene compared with none in the control group (P<0.001). Site-directed mutagenesis and transient transfection experiments revealed that these mutants could transactivate oncogene promoters. NIH3T3 cells stably expressing sL21*, sW156* and sW172* pre-S/S mutants had increased tumourigenicity in nude mice., Conclusions: HCCs developed in lamivudine-treated patients who frequently carried nonsense mutations in the S gene. Such pre-S/S mutants are potentially oncogenic and might counteract the effect of lamivudine in preventing hepatocarcinogenesis.

Background: Distinguishing dysplasia from hepatocellular carcinoma (HCC) by fine-needle aspiration (FNA) cytology is difficult. The aim of this study was to diagnose HCC and the distinction of liver cell dysplasia from HCC with different grades by interpreting and scoring the cyto-morphological features., Methods: Eighty-three cirrhotic patients undertook a sonography-guided FNA and subsequent needle biopsy for the tumor. HCC was confirmed in 68 cases and cirrhosis with dysplasia in 15 cases by pathology and follow-up for longer than 2 years. Eighteen cytological features were scored as degree of one, two or three according to their presence or prominence., Results: Two cases of well-differentiated HCC were diagnosed as negative for HCC initially. The sensitivity, specificity, false positive, false negative and accuracy were 97%, 100%, 0%, 3% and 97.6% for FNA cytology in the diagnosis of HCC, respectively. The score of dysplasia was 20.8 +/- 1.3 (mean +/- SD) and lower than 26.2 +/- 3.4 in Edmondson's grade I HCC (P < 0.01), 28.9 +/- 2.9 in grade II HCC (P < 0.01), and 34.9 +/- 4.3 in grade III/IV HCC (P < 0.01). The score was also significantly lower in grade II HCC than in grade III/IV HCC (P < 0.01)., Conclusions: FNA yielded a high accuracy in the distinction of dysplasia from HCC with different grades. There is a good correlation in cyto-morphological scores of liver cell dysplasia and HCC with different grades. Dysplasia displayed the lowest score and the score increased in order from dysplasia to grade III/IV HCC.

Radiofrequency (RF) ablation is considered as a relatively low-risk technique for treating liver malignancy. The pneumoperitoneum without peritoneal sign after RF ablation is previously unreported. A case is reported here of localized pneumoperitoneum unrelated to bowel injury following RF ablation for hepatocellular carcinoma.

Purpose: To compare the effectiveness of ablation techniques for hepatocellular carcinoma (HCC) with the use of four radiofrequency (RF) devices., Materials and Methods: One hundred patients with 133 HCC lesions no larger than 4 cm were treated with one of four RF devices: RF 2000 (maximum power, 100 W) and RF 3000 generators (maximum power, 200 W) with LeVeen expandable electrodes with a maximum dimension of 3.5 cm or 4 cm, internally cooled single electrode with a thermal dimension of 3 cm, and a RITA RF generator with expandable electrodes with a maximum dimension of 5 cm., Results: Numbers of RF sessions needed per HCC to achieve complete necrosis were 1.4 +/- 0.5 with the RF 2000 device and greater than 1.1 +/- 0.3 with the other three devices (P < .05). The RF 2000 device required a more interactive algorithm than the RF 3000 device. Session times per patient were 31.7 minutes +/- 13.2 in the RF 2000 group and longer than 16.6 minutes +/- 7.5 in the RF 3000 group, 28.3 minutes +/- 12 in the RITA device group, and 27.1 minutes +/- 12 with the internally cooled electrode device (P < .005 for RF 2000 vs other devices and for RF 3000 vs RITA or internally cooled electrode device). Complete necrosis and local tumor progression rates at 2 years in the RF 2000, RF 3000, RITA, and internally cooled electrode device groups were 91.1%, 97.1%, 96.7%, and 96.8% and 12%, 8%, 8.2%, and 8.3%, respectively (P = .37)., Conclusions: Ablation with the RF 3000 device required a shorter time than the other three devices and required a less interactive algorithm than the RF 2000 device. However, complete necrosis and local tumor progression rates were similar among devices.

A fragment of DNA sequence derived from a hepatotropic virus, named NV-F was isolated recently. The aim of this study was to examine whether this virus was associated with hepatocellular carcinoma (HCC). Total cellular DNA was extracted from hepatocellular carcinoma tissues. NV-F virus DNA was detected by PCR. The PCR products were subjected to sequence analysis. Of the 78 HCC samples included, 12 (15.4%) were positive for NV-F virus DNA. Sequence analysis of the 12 amplified DNA fragments revealed a point mutation in one of them. The clinicopathological parameters between patients with and without NV-F virus infection were compared. It was found that patients with NV-F virus infection were older than those without NV-F virus infection (mean ages, 61.5 versus 52.5 years; P = 0.032). Otherwise, no difference was observed between the two groups. Of the 12 HCC patients positive for NV-F virus DNA, 11 patients were co-infected by either hepatitis B or C virus. The remaining patient was a Taiwanese aboriginal inhabitant with cryptogenic cirrhosis. In conclusion, NV-F virus DNA was identified in 15.4% of HCC tissues. HCC patients with NV-F virus infection were significantly older than those without NV-F virus infection.

Objectives: To compare the effectiveness of modified automated and manual pulsed radiofrequency (RF) algorithms using internally cooled electrodes for hepatocellular carcinoma (HCC)., Methods: Seventy-seven treatment-naive cirrhotic patients with 102 HCC (< or =4 cm) underwent 109 sessions of ultrasound-guided percutaneous RF ablation using a 17-gauge, 20-cm-long, single internally cooled electrode. Patients were assigned alternatively: 40 patients to the modified automated algorithm group and 37 patients to the manual algorithm group. The mean tumor diameters were 2.34 +/- 0.9 and 2.25 +/- 0.7 cm in the automated and manual groups, respectively (p = 0.56). Primary technique effectiveness and local tumor progression were compared between the two groups., Results: More overlapping ablations (n = 112) were required in the manual than in the automated group (n = 82) to achieve similar primary technique effectiveness rates of 96.1 and 94.1%, respectively. After a mean follow-up period of 26.7 +/- 1.1 months, the local tumor progression rates at 12 and 18 months were 4 and 20% in the manual group and 12 and 24% in the modified automated group (p = 0.3). Only tumors >3 cm were independently associated with local tumor progression (odds ratio 1.25; 95% CI 1.06-2.34, p = 0.03)., Conclusions: The manual algorithm requires more overlapping ablations and treatment sessions in order to achieve similar primary technique effectiveness and local tumor progression rates compared with the modified automated algorithm., (Copyright 2007 S. Karger AG, Basel.)

Background & Aims: The aim of this study was to compare the clinical outcome of percutaneous radiofrequency (RF) ablation, conventional percutaneous ethanol injection (PEI), and higher-dose PEI in treating hepatocellular carcinoma (HCC) 4 cm or less., Methods: A total of 157 patients with 186 HCCs 4 cm or less were randomly assigned to 3 groups (52 patients in the conventional PEI group, 53 in the higher-dose PEI group, and 52 in the RF group). Clinical outcomes in terms of complete tumor necrosis, overall survival, local tumor progression, additional new tumors, and cancer-free survival were compared across 3 groups., Results: The rate of complete tumor necrosis was 88% in the conventional PEI group, 92% in the higher-dose PEI group, and 96% in the RF group. Significantly fewer sessions were required to achieve complete tumor necrosis in the RF group than in the other 2 groups (P < .01). The local tumor progression rate was lowest in the RF group (vs the conventional PEI group, P = .012; vs the higher-dose PEI group, P = .037). The overall survival rate was highest in the RF group (vs the conventional PEI group, P = .014; vs the higher-dose PEI group, P = .023). The cancer-free survival rate was highest in the RF group (vs the conventional PEI group, P = .019; vs the higher-dose PEI group, P = .024). Multivariate analysis determined that tumor size, tumor differentiation, and the method of treatment (RF vs both methods of PEI) were significant factors in relation to local tumor progression, overall survival, and cancer-free survival., Conclusions: The results show that RF ablation yielded better clinical outcomes than conventional and higher-dose PEI in treating HCC 4 cm or less.

Background: Hepatocellular carcinoma (HCC) recurrence after ablation therapy for primary tumors is common., Methods: To evaluate the effectiveness of interferon-alpha (IFN-alpha) in preventing HCC recurrence, 30 eligible patients were randomized into three groups: 11 patients treated with three mega units (MU) of IFN-alpha three times weekly for 24 months (IFN-alpha-continuous group), 9 patients treated with 3 MU of IFN-alpha daily for 10 days every month for 6 months followed by 3 MU of IFN-alpha daily for 10 days every 3 months for a further 18 months (IFN-alpha-intermittent group), and 10 patients who received no IFN-alpha therapy (control group). The three groups were comparable in terms of etiology, demographics, and laboratory data at entry and HCC characteristics., Results: After a median follow-up of 27 months (range 4-53 months), 9 patients (90%) in the control group and 9 patients (45%) in 2 treatment groups (6 patients in the IFN-alpha-continuous group and 3 patients in the IFN-alpha-intermittent group) developed an HCC recurrence (P = 0.021). Cumulative HCC recurrence rates in the IFN-alpha-intermittent, IFN-alpha-continuous, and control groups were 22.2%, 27.3%, and 40% at the end of 1 year and 33.3%, 54.6%, and 90% at the end of 4 years (P = 0.0375), respectively (control vs. IFN-alpha-intermittent group, P = 0.0123; vs. IFN-alpha-continuous group, P = 0.0822). If both IFN-alpha groups were combined, the cumulative HCC recurrence rate of the patients treated with IFN-alpha and the control group was 25% and 40% at the end of 1 year and 47% and 90% at the end of 4 years, respectively (P = 0.0135)., Conclusions: The data suggested that IFN-alpha therapy may reduce HCC recurrence after medical ablation therapy for primary tumors., (Copyright 2003 American Cancer Society.)

Objective: The purpose of this study was to compare the efficacy between standard and interactive radiofrequency ablation for treatment of hepatocellular carcinoma., Subjects and Methods: Of 97 patients with 112 nodular hepatocellular carcinomas, 59 hepatocellular carcinomas were ablated using a standard algorithm and 53 hepatocellular carcinomas, using an interactive algorithm. For the procedure using the interactive algorithm, the electrode's array was partially retracted or fully deployed depending on the change of impedance. Complete tumor necrosis was defined as the lack of enhancement on single-detector helical CT at least 4 months after the last radiofrequency ablation., Results: Complete necrosis was achieved in 101 (90%) of 112 hepatocellular carcinomas, with complete necrosis being achieved more frequently in hepatocellular carcinomas undergoing interactive ablation (96%) than standard ablation (85%) (p = 0.034). Power rolloff (a clinical end point in which power decreases as impedance increases) occurred in all of the 53 hepatocellular carcinomas that underwent interactive ablation, whereas power rolloff occurred in 48 (81%) of the 59 hepatocellular carcinomas that underwent standard ablation (p = 0.00053). Complete necrosis occurred more frequently when rolloff was achieved (96%) than without rolloff (36%) (p < 0.0001). Multivariate analysis determined that power rolloff was an independent factor in achieving complete necrosis of hepatocellular carcinomas (p < 0.0001)., Conclusion: The use of interactive radiofrequency ablation increased the frequency of power rolloff and the rate of complete necrosis in the treatment of hepatocellular carcinoma. Power rolloff was a significant determinant of whether complete necrosis was achieved in hepatocellular carcinomas treated with radiofrequency ablation.

Objective: To illustrate the cytologic changes in hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA)., Study Design: The study included 20 patients with 23 HCC who had undergone RFA under ultrasound guidance. Baseline cytomorphology of HCC was evaluated by fine needle aspiration (FNA) in all cases. Triphasic helical computed tomography (CT) and FNA cytology were done to evaluate the efficacy of the treatment within two weeks after RFA. The cytologic specimens were stained with Riu's method (Romanowsky stain)., Results: A range of cytologic findings after RFA was found, including granular and amorphous debris with artefactual aggregation, degenerated cells or necrotic material, and dyshesive, degenerated cells in a necrotic background. The cytologic patterns included necrotic cells and debris in 14 tumors and fine, granular necrosis in 9. Helical CT showed no enhancement in any of the tumors after RFA., Conclusion: The cell patterns indicated complete necrosis in HCC after RFA.