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Several prediction scores for the early detection of hepatocellular carcinoma (HCC) are available. We validated the predictive accuracy of age, albumin, sex, liver cirrhosis (AASL), RESCUE-B, PAGE-B and modified PAGE-B (mPAGE-B) scores in chronic hepatitis B (CHB) patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF). Between 2007 and 2014, 3171 patients were recruited (1645, ETV; 1517, TDF). The predictive accuracy of each prediction score was assessed. The mean age of the study population (1977 men; 1194 women) was 48.8 years. Liver cirrhosis was present in 1040 (32.8%) patients. During follow-up (median, 58.2 months), 280 (8.8%) patients developed HCC; these patients were significantly older; more likely to be male; had significantly higher proportions of liver cirrhosis, hypertension and diabetes; and had significantly higher values for the four risk scores than those who did not develop HCC (all P < .05). Older age (hazard ratio [HR] = 1.048), male sex (HR = 2.142), liver cirrhosis (HR = 3.144) and prolonged prothrombin time (HR = 2.589) were independently associated with an increased risk of HCC (all P < .05), whereas a higher platelet count (HR = 0.996) was independently associated with a decreased risk of HCC (P < .05). The predictive accuracy of AASL score was the highest for 3- and 5-year HCC predictions (areas under the curve [AUCs] = 0.818 and 0.816, respectively), followed by RESCUE-B, PAGE-B and mPAGE-B scores (AUC = 0.780-0.815 and 0.769-0.814, respectively). In conclusion, four HCC prediction scores were assessed in Korean CHB patients treated with ETV or TDF. The AASL score showed the highest predictive accuracy., (© 2020 John Wiley & Sons Ltd.)

Background & Aims: Researchers previously developed a scoring system to determine the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection, based on the presence of cirrhosis, patient age, male sex, and diabetes (called the CAMD scoring system). We validated the CAMD scoring system and compared its performance with that of other risk assessment models in an independent cohort., Methods: We followed up 3277 patients with chronic HBV infection (mean age, 48.7 y; 62.6% male; 32.4% with cirrhosis) who were treated with entecavir (n = 1725) or tenofovir (n = 1552) as the first-line antiviral agent in 4 academic teaching hospitals in the Republic of Korea. The primary outcome was development of HCC. We evaluated the ability of the CAMD, PAGE-B, and mPAGE-B scoring systems to identify patients who would develop HCC using integrated area under the curve (iAUC) analysis., Results: Over a median follow-up period of 58.2 months, 8.9% of the patients developed HCC. Patients who developed HCC were older, more likely to be male, and had higher proportions of cirrhosis and diabetes than patients who did not develop HCC (all P < .05). CAMD scores identified patients who developed HCC with an iAUC of 0.790, mPAGE-B scores with an iAUC of 0.769, and PAGE-B scores with an iAUC of 0.760. The 5-year cumulative risks of HCC were 1.3% in patients with low CAMD scores (<8), 8.0% in patients with intermediate CAMD scores (8-13), and 24.3% in patients with high CAMD scores (>13) (P < .001 for comparison of low- vs intermediate-score groups and between intermediate- vs high-score groups). The predicted and observed probabilities of HCC had excellent agreement., Conclusions: We validated the CAMD scoring system in determining the risk of HCC in patients with chronic HBV treatment receiving entecavir or tenofovir treatment. Validation was performed in a cohort of patients in the Republic of Korea, where most patients have genotype C2 HBV infection., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background/aims: Nonalcoholic fatty liver disease (NAFLD) is becoming a worldwide epidemic, and is frequently found in patients with chronic hepatitis B (CHB). We investigated the impact of histologically proven hepatic steatosis on the risk for hepatocellular carcinoma (HCC) in CHB patients without excessive alcohol intake., Methods: Consecutive CHB patients who underwent liver biopsy from January 2007 to December 2015 were included. The association between hepatic steatosis (≥ 5%) and subsequent HCC risk was analyzed. Inverse probability weighting (IPW) using the propensity score was applied to adjust for differences in patient characteristics, including metabolic factors., Results: Fatty liver was histologically proven in 70 patients (21.8%) among a total of 321 patients. During the median (interquartile range) follow-up of 5.3 (2.9-8.3) years, 17 of 321 patients (5.3%) developed HCC: 8 of 70 patients (11.4%) with fatty liver and 9 of 251 patients (3.6%) without fatty liver. The five-year cumulative incidences of HCC among patients without and with fatty liver were 1.9% and 8.2%, respectively (P=0.004). Coexisting fatty liver was associated with a higher risk for HCC (adjusted hazards ratio [HR], 3.005; 95% confidence interval [CI], 1.122-8.051; P=0.03). After balancing with IPW, HCC incidences were not significantly different between the groups (P=0.19), and the association between fatty liver and HCC was not significant (adjusted HR, 1.709; 95% CI, 0.404-7.228; P=0.47)., Conclusion: Superimposed NAFLD was associated with a higher HCC risk in CHB patients. However, the association between steatosis per se and HCC risk was not evident after adjustment for metabolic factors.

Purpose: The purpose of this study was to demonstrate the prognostic significance of changes in body composition in patients with newly diagnosed hepatocellular carcinoma (HCC)., Materials and Methods: Patients (n=178) newly diagnosed with HCC participated in the study between 2007 and 2012. Areas of skeletal muscle and abdominal fat were directly measured using a three-dimensional workstation. Cox proportional-hazards modes were used to estimate the effect of baseline variables on overall survival. The inverse probability of treatmentweighting (IPTW) method was used to minimize confounding bias., Results: Cutoff values for sarcopenia, obtained from receiver-operating characteristic curves, were defined as skeletal muscle index at the third lumbar vertebra of ≤ 45.8 cm/m2 for males and ≤ 43.0 cm/m2 for females. Sarcopenia patients were older, more likely to be female, and had lower body mass index. Univariable analysis showed that the presence of sarcopenia and visceral to subcutaneous fat area ratio (VSR) were significantly associatedwith prognosis. The multivariable analyses revealed that VSR was predictive of overall survival. However, in the multivariable Cox model adjusted by IPTW, sarcopenia, not VSR, were associated with overall survival., Conclusion: The presence of sarcopenia at HCC diagnosis is independently associated with survival.

Background: A proportion of chronic hepatitis B (CHB) patients are diagnosed with advanced hepatocellular carcinoma (HCC) despite regular surveillance., Aims: To determine predictors for HCC detection failure in CHB patients who underwent regular surveillance., Methods: CHB patients with well-preserved liver function, who underwent ultrasonography and alpha-foetoprotein (AFP) analysis every 6 months, were enrolled. Cox regression analysis was used to identify predictors for detection failure, defined as HCC initially diagnosed at Barcelona Clinic Liver Cancer (BCLC) stage B or C., Results: Of the 4590 CHB patients (mean age, 52.1 years; men, 61.6%), 169 patients were diagnosed with HCC (3.68%) and 35 (20.7%) HCC patients were initially diagnosed with HCC BCLC stage B or C. The cumulative incidence of HCC detection failure was 0.2% at year 1 and 1.3% at year 5. Multivariate analyses indicated that cirrhosis (hazard ratio [HR], 3.078; 95% CI, 1.389-6.821; P = 0.006), AFP levels ≥9 ng/mL (HR, 5.235; 95% CI, 2.307-11.957; P = 0.010), and diabetes mellitus (HR, 3.336; 95% CI, 1.341-8.296; P = 0.010) were independent predictors of HCC detection failure. Another model that incorporated liver stiffness (LS) values identified LS values ≥11.7 kPa (HR, 11.045; 95% CI, 2.066-59.037; P = 0.005) and AFP levels ≥9 ng/mL (HR, 4.802; 95% CI, 1.613-14.297; P = 0.005) as predictors of detection failure., Conclusions: In CHB patients undergoing regular surveillance with ultrasonography and alpha-foetoprotein (AFP) analysis every 6 months, the HCC detection failure rate was not high (0.8% per person; 0.1% per test). However, careful attention should be paid in patients with advanced liver fibrosis (clinical cirrhosis or LS value >11.7 kPa), high AFP levels, or diabetes mellitus, who are prone to surveillance failure., (© 2018 John Wiley & Sons Ltd.)

Background & Aims: A new hepatocellular carcinoma risk prediction model, PAGE-B, which includes age, gender and platelet count as constituent variables, has recently been proposed in Caucasian chronic hepatitis B patients. We validated PAGE-B model and compared its accuracy with that of conventional risk prediction models in Asian chronic hepatitis B patients., Methods: Chronic hepatitis B patients treated with entecavir or tenofovir were consecutively recruited. The performance of PAGE-B and three conventional risk prediction models (CU-HCC, GAG-HCC and REACH-B) were analysed., Results: A total of 1092 chronic hepatitis B patients (668 men, 61.2%) were selected between August 2006 and January 2015. The mean age was 48 years. During the follow-up period (median, 43.6 months), 36 (3.3%) patients developed hepatocellular carcinoma. Older age (hazard ratio [HR]=1.077), male gender (HR=3.676) and lower platelet count (HR=0.984) were independent predictors of hepatocellular carcinoma development. The PAGE-B showed similar area under receiver operating characteristic curves (AUROCs) to GAG-HCC and CU-HCC at 3 years (0.777 vs 0.793 and 0.743, respectively; all P>.05) and 5 years (0.799 vs 0.803 and 0.744, respectively; all P>.05), whereas the AUROCs of PAGE-B were significantly higher than those of the REACH-B (0.602 at 3 years and 0.572 at 5 years, P<.05)., Conclusions: Our study demonstrated that PAGE-B is applicable to Asian chronic hepatitis B patients receiving ETV or TDF therapy. The PAGE-B showed similar predictive performance to GAG-HCC and CU-HCC., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Single-nucleotide polymorphisms (SNPs) in microRNA machinery genes might affect microRNA processing and subsequently impact tumorigenesis. The aim of this study was to investigate the associations between SNPs in microRNA machinery genes and hepatocellular carcinoma (HCC) in a Korean population. Genotyping of six SNPs in microRNA machinery genes was performed using blood samples from 147 patients with HCC and 209 healthy control subjects. None of the six SNPs in microRNA machinery genes were significantly associated with HCC development. However, among the models for six polymorphic loci-DICER (rs3742330 and rs13078), DROSHA (rs10719 and rs6877842), RAN (rs14035) and XPO5 (rs11077)-one allele combination (A-A-T-C-C-C) showed synergistic effects in terms of an increased risk of HCC development (odds ratio = 8.881, 95% confidence interval [CI] = 1.889-41.750; P = 0.002). Multivariate Cox proportional hazard regression analysis showed a significant survival benefit for the DICER rs3742330 GG compared with the AA type (hazard ratio [HR], 0.314; 95% CI, 0.135-0.730; P = 0.007) and for the RAN rs14035 CT compared with the CC genotype (HR, 0.587; 95% CI, 0.349-0.987; P = 0.044). Although we found no direct association between DICER (rs3742330 and rs13078), DROSHA (rs10719 and rs6877842), RAN (rs14035) or XPO5 (rs11077) polymorphisms and HCC risk, we demonstrated that DICER (rs3742330) and RAN (rs14035) were associated with the survival of HCC patients. Future studies with larger samples are needed to determine associations of SNPs in microRNA machinery genes with HCC risk and prognosis., Competing Interests: The authors have declared that no competing interests exist.

Radiation dermatitis can develop after fluoroscopy-guided interventional procedures. Cases of fluoroscopy-induced radiation dermatitis have been reported since 1996, mostly documented in the fields of radiology, cardiology and dermatology. Since diagnosis and treatment of fluoroscopy-induced radiation dermatitis can be difficult, high grade of suspicion is required. The extent of this reaction is determined by radiation dose, duration of exposure, type of procedure, and host factors and can be aggravated by concomitant use of photosensitizers. Follow-up is important after long and complicated procedures and efforts to minimize radiation exposure time will be necessary to prevent radiation dermatitis. Herein, we report a case of a 58-year-old man with hepatocellular carcinoma presenting with subacute radiation dermatitis after prolonged fluoroscopic exposure during transarterial chemoembolization and chemoport insertion. Physicians should be aware that fluoroscopy is a potential cause of radiation dermatitis.

Aim: To investigate associations between the tumor necrosis factor alpha (TNF-α) -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A polymorphisms and HCC in Korea., Methods: Hepatocellular carcinoma (HCC) cases were diagnosed at CHA Bundang Medical Center from June 1996 to August 2008. The association between TNF-α polymorphisms and HCC was analyzed in 157 HCC patients and 201 controls using a polymerase chain reaction-restriction fragment length polymorphism assay. We investigated five TNF-α polymorphisms, which are TNF-α -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A. The TNF-α genotype frequencies, genotype combinations and haplotypes were analyzed to disclose the association with HCC., Results: None of the TNF-α polymorphisms was significantly associated with HCC. However, nine genotype combinations had associations with increased likelihood of HCC. Among them, TNF-α -1031/-857/-238 TT/CC/GA (AOR = 18.849, 95%CI: 2.203-161.246, P = 0.007), TNF-α -1031/-308/-238 TT/GG/GA (AOR = 26.956, 95%CI: 3.071-236.584, P = 0.003), and TNF-α -1031/-238 TT/GA (AOR = 21.576, 95%CI: 2.581-180.394, P = 0.005) showed marked association with HCC. There were five haplotypes of TNF-α polymorphisms which were significantly associated with HCC. They are TNF-α -1031/-863/-857/-308/-238 T-C-C-G-A (OR = 25.824, 95%CI: 1.491-447.223, P = 0.0005), TNF-α -1031/-857/-308/-238 T-C-G-A (OR = 12.059, 95%CI: 2.747-52.950, P < 0.0001), TNF-α -1031/-857/-238 T-C-A (OR = 10.696, 95%CI: 2.428-47.110, P = 0.0001), TNF-α -1031/-308/-238 T-G-A (OR = 7.556, 95%CI: 2.173-26.280, P = 0.0002) and TNF-α -1031/-238 T-A (OR = 10.865, 95%CI: 2.473-47.740, P = 0.0001). Moreover, HCC Okuda stage III cases with the TNF-α -1031 CC genotype had better survival than those with the TT genotype (AOR = 5.795, 95%CI: 1.145-29.323)., Conclusion: Although no single TNF-α polymorphism is associated with HCC in this study, some TNF-α genotype combinations and haplotypes are associated with HCC. In addition, HCC Okuda stage III cases with the TNF-α -1031 TT genotype may have a better prognosis than those with the CC genotype.

Background: Numerous studies have focused on the association between miR-34 family members, which are direct p53 targets, and carcinogenesis of many cancers, including hepatocellular carcinoma (HCC). This study aimed to assess whether polymorphisms in the single-nucleotide polymorphism miR-34b/c T>C (rs4938723) and TP53 Arg72Pro (rs1042522) increase the risk of HCC and influence outcome in patients with HCC., Patients and Methods: We enrolled 157 HCC patients and 201 cancer-free control subjects from the Korean population. MicroRNA polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method., Results: We found that the miR-34b/c TC+CC frequency was significantly higher in HCC patients than in controls (adjusted odds ratio [AOR]: 1.580; 95% confidence interval [CI]: 1.029-2.426). The miR-34b/c CC-TP53 Arg/Arg combination significantly increased the risk of HCC (AOR: 13.644; 95% CI: 1.451-128.301). The SNPs miR-34b/c T>C and TP53 Arg72Pro(G>C) had no influence on survival of HCC patients., Conclusions: Our findings suggest that loss of the T allele in miR-34b/c T>C, and the miR-34b/c CC-TP53 Arg/Arg combination increases the risk of HCC in the Korean population., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Recent studies have suggested that common genetic polymorphisms alter the processing of microRNA (miRNA) and may be associated with the development and progression of cancer., Patients and Methods: The association of miRNA polymorphisms with HCC survival was analyzed in 159 HCC patients and 201 controls by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method., Results: The risk of HCC was significantly lower for the miR-499A>G, AG+GG in HCC patients (AOR=0.603, 95% CI=0.370-0.984) and hepatitis B virus (HBV)-related HCC patients (AOR=0.561, 95% CI 0.331-0.950). In addition, the risk of HCC was significantly lower for the miR-149C>T, CT and CT+CC in HCC patients (CT; AOR=0.542, 95% CI=0.332-0.886, CT+CC; AOR=0.536, 95% CI=0.335-0.858) and HBV-related HCC patients (CT: AOR=0.510, 95% CI 0.305-0.854, CT+CC: AOR=0.496, 95% CI 0.302-0.813). The miR-149C>T polymorphism was also associated with survival rate of HCC patients in OKUDA II stage., Conclusions: miR-149C>T and miR-499A>G were associated with HBV-related HCC. Further studies on larger populations will need to be conducted to confirm these results., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Among 92 surgically resected human hepatocellular carcinomas (HCCs) < or = 3 cm in diameter, 23 tumors (25%) grossly showed a nodule-in-nodule appearance indicating stepwise progression of HCC. The central nodules showed destructive growth of HCC, which was less differentiated than the surrounding area histologically, while the surrounding area showed growth of very-well-differentiated HCC with no, or only minimal, destruction of the underlying liver structures. Previously, we proposed the term "early HCC" for HCCs without definite destructive growth, and the nodule-in-nodule lesions described here are considered to be in the transitional stage from early HCC to advanced HCC, and are therefore named early advanced HCC (eAd HCC). DNA cytophotometry was performed in 12 cases of eAd HCC, in which the early HCC component, advanced HCC component and non-tumorous liver tissue showing chronic hepatitis or cirrhosis were analyzed separately. The early HCC component showed a diploid pattern in eight of the 12 cases. The advanced HCC component showed an aneuploid peak in seven cases, and in three of these the peak was detected only in the advanced HCC component and not in the early HCC component. The mean nuclear DNA content was significantly increased from non-tumorous liver to the early HCC component and from the early HCC component to the advanced HCC component. Polyploid cells containing more than 4.8C DNA were exceptional in non-tumorous liver, but were detectable in the early HCC component and increased in number in the advanced HCC component. These findings suggest that DNA instability may have an important role to play in the subclonal progression of human HCC.