Clinical outcomes of transarterial chemoembolization in Child-Turcotte Pugh class A patients with a single small (≤3 cm) hepatocellular carcinoma.

BACKGROUND AND AIM: Transarterial chemoembolization (TACE) is one of the standard modalities used to treat unresectable hepatocellular carcinoma (HCC), but the effectiveness of TACE for treating patients with a solitary small (≤3 cm) HCC and well-preserved liver function has not been definitively established. This study aimed to determine the therapeutic impact of TACE in patients with these characteristics. METHODS: This multicenter (four university hospitals) retrospective cohort study analyzed the medical records of 250 patients with a solitary small (≤3 cm) HCC and Child-Turcotte-Pugh (CTP) class A liver function diagnosed over 10 years. Posttreatment outcomes, including overall survival (OS), recurrence-free survival (RFS), and adverse events, were assessed following TACE therapy. RESULTS: One hundred and thirty-eight of the 250 patients (55.2%) treated with TACE achieved complete remission (CR). Overall median OS was 77.7 months, and median OS was significantly longer in the CR group than in the non-CR group (89.1 vs. 58.8 months, P = 0.001). Median RFS was 19.1 months in the CR group. Subgroup analysis identified hypertension, an elevated serum albumin level, and achieving CR as significant positive predictors of OS, whereas diabetes, hepatitis c virus infection, and tumor size (>2 cm) were poor prognostic factors of OS. CONCLUSIONS: The study demonstrates the effectiveness of TACE as a viable alternative for treating solitary small (≤3 cm) HCC in CTP class A patients.

Risk factors associated with late hepatocellular carcinoma detection in patients undergoing regular surveillance.

Hepatocellular carcinoma (HCC) has a very poor prognosis with a 5-year survival rate of < 20%; hence, early diagnosis is crucial. Despite regular checkups for high-risk groups of HCC, there are a few cases in which it is discovered as a late-stage HCC. Therefore, this study aimed to investigate the characteristics of patients with delayed HCC detection during regular surveillance. Between January 2010 and December 2020, we analyzed patients with newly diagnosed HCCs who underwent HCC surveillance by ultrasound or computed tomography scan at least twice and were followed up for more than 1 year for hepatitis B, hepatitis C, and chronic liver disease. The mean age of 223 HCC patients was 70 years, of which 152 were male, accounting for 68.1%. Among them, 196 patients (87%) were diagnosed with Barcelona clinic liver cancer stage 0 or A, while 27 (13%) were diagnosed with Barcelona clinic liver cancer stages B and C. When classified according to the TNM criteria, 154 patients (69%) were in stage I, and 69 (31%) were in stage II or higher. Multivariate analysis was performed to identify the risk factors for patients diagnosed with late-stage HCC. The Child-Turcotte-Pugh (CTP) score was identified as a highly significant factor (P = .002, HR 1.547, 95% CI 1.177-2.032), whereas the presence of cirrhosis, body mass index, and sex had no significant effect. We found that in patients with chronic liver disease who were screened regularly, those with higher CTP scores were more likely to be diagnosed with HCC in the late-stages. Therefore, although the presence of cirrhosis is also important for HCC surveillance, careful attention is needed in patients with high CTP scores.

Recurrence of hepatocellular carcinoma in noncirrhotic patients with nonalcoholic fatty liver disease versus hepatitis B infection.

BACKGROUND AND AIMS: This study aimed to compare the long-term cumulative recurrence rates of hepatocellular carcinoma (HCC) and prognosis after curative resection for HCC in noncirrhotic patients with nonalcoholic fatty liver disease (NAFLD) versus hepatitis B virus (HBV) infection. METHODS: We retrospectively analyzed the data of 791 patients without recurrence within 1 year after curative resection for HCC from January 2005 to December 2015. Of these, 63 and 728 were NAFLD and HBV patients without cirrhosis, respectively. RESULTS: Recurrence of HCC was observed in 6 (9.5%) and 210 (28.8%) patients in the NAFLD and HBV groups, respectively, during median follow-ups of 69.9 and 85.2 months. Cumulative recurrence rates in the NAFLD group at 2, 4, 6, 8 and 10 years (3.6, 9.4, 12.4, 12.4 and 12.4%, respectively) were significantly lower than in the HBV group (1.7, 16.9, 27.2, 37.1 and 44.4%, respectively) ( P = 0.008). Cumulative overall survival (OS) rates in the NAFLD group at 2, 4, 6, 8 and 10 years (98.2, 96.0, 84.0, 84.0 and 84.0 %, respectively) were significantly lower than in the HBV group (99.3, 98.4, 97.3, 95.7 and 93.6%, respectively) ( P = 0.003). HBV infection, with or without fatty liver compared to NAFLD, were significant predictors for the recurrence of HCC ( P < 0.05 for all) and OS ( P < 0.05 for all), respectively. CONCLUSIONS: Noncirrhotic NAFLD patients showed lower recurrence rates of HCC but poorer survival outcomes than noncirrhotic HBV patients with or without fatty liver. The recurrence risk of HCC remains even in noncirrhotic NAFLD patients.

Noninvasive imaging biomarkers for liver fibrosis in nonalcoholic fatty liver disease: current and future.

Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent worldwide and becoming a major cause of liver disease-related morbidity and mortality. The presence of liver fibrosis in patients with NAFLD is closely related to prognosis, including the development of hepatocellular carcinoma and other complications of cirrhosis. Therefore, assessment of the presence of significant or advanced liver fibrosis is crucial. Although liver biopsy has been considered the "gold standard" method for evaluating the degree of liver fibrosis, it is not suitable for extensive use in all patients with NAFLD owing to its invasiveness and high cost. Therefore, noninvasive biochemical and imaging biomarkers have been developed to overcome the limitations of liver biopsy. Imaging biomarkers for the stratification of liver fibrosis have been evaluated in patients with NAFLD using different imaging techniques, such as transient elastography, shear wave elastography, and magnetic resonance elastography. Furthermore, artificial intelligence and deep learning methods are increasingly being applied to improve the diagnostic accuracy of imaging techniques and overcome the pitfalls of existing imaging biomarkers. In this review, we describe the usefulness and future prospects of noninvasive imaging biomarkers that have been studied and used to evaluate the degree of liver fibrosis in patients with NAFLD.

Association between small dense LDL levels and hepatic fibrosis in patients with nonalcoholic fatty liver disease.

While patients with nonalcoholic fatty liver disease (NAFLD) continue to increase worldwide, few hematological biomarkers are helpful. This study examined the potential of small dense low density lipoprotein (sdLDL) as a noninvasive biomarker for NAFLD and investigated the relevance of liver fibrosis. One hundred seventy two patients were enrolled: 121 NAFLD patients and 51 healthy controls. The lipoprotein profiles of NAFLD patients and controls were analyzed, and transient elastography (Fibroscan®) was performed to evaluate the degree of NAFLD. The liver biopsy results in some NAFLD patients were also analyzed. Age-gender matching was performed among the 172 patients, and a comparison with 46 NAFLD patients with the control group confirmed that the sdLDL (P < .001) is significantly higher in the NAFLD group. A liver fibrosis test performed on 121 NAFLD patients confirmed a positive correlation between the degree of hepatic fibrosis and the sdLDL/LDL ratio (R = 0.215, P = .017). The area under the curve of the sdLDL for the diagnosis of NAFLD was 0.734 (95% CI, 0.631-0.838), and the area under the curve of the sdLDL/LDL ratio was 0.730 (95% CI, 0.621-0.829). The sdLDL and NAFLD activity scores of the 11 NAFLD patients who underwent liver biopsy showed a positive correlation, but it was not statistically significant. The sdLDL was higher in NAFLD patients than in controls and showed a tendency to increase gradually with increasing degree of hepatic steatosis and fibrosis. In particular, the sdLDL/LDL ratio showed a significant correlation with the degree of hepatic fibrosis, and the sdLDL measurement could be useful in NAFLD patients.

Surgery versus radiofrequency ablation in patients with Child- Pugh class-A/single small (≤3 cm) hepatocellular carcinoma.

BACKGROUND/AIMS: We compared the post-treatment overall survival (OS) and recurrence-free survival (RFS) between patients with Child-Turcotte-Pugh (CTP) class-A and single small (≤3 cm) hepatocellular carcinoma (HCC) treated by surgical resection (SR) and radiofrequency ablation (RFA). METHODS: We retrospectively analyzed 391 HCC patients with CTP class-A who underwent SR (n=232) or RFA (n=159) as first-line therapy for single small (≤3 cm) HCC. Survival was compared according to the tumor size (≤2 cm/2-3 cm) and the presence of cirrhosis. Inverse probability of treatment weighting (IPW) method was used to estimate the average causal effect of treatment. RESULTS: The median follow-up period was 64.8 months (interquartile range, 0.1-162.6). After IPW, the estimated OS was similar in the SR and RFA groups (P=0.215), and even in patients with HCC of ≤2 cm (P=0.816) and without cirrhosis (P=0.195). The estimated RFS was better in the SR group than in the RFA groups (P=0.005), also in patients without cirrhosis (P<0.001), but not in those with HCC of ≤2 cm (P=0.234). The weighted Cox proportional hazards model with IPW provided adjusted hazard ratios (95% confidence interval) for OS, and the RFS after RFA versus SR were 0.698 (0.396-1.232) (P=0.215) and 1.698 (1.777-2.448) (P=0.005), respectively. CONCLUSION: SR was similar for OS compared to RFA, but was better for RFS in patients with CTP class-A and single small (≤3 cm) HCC. The RFS was determined by the presence or absence of cirrhosis. Hence, SR rather than RFA should be considered in patients without cirrhosis to prolong the RFS, although there is no OS difference.

The best predictive model for hepatocellular carcinoma in patients with chronic hepatitis B infection.

Chronic hepatitis B (CHB) seriously threatens human health. About 820,000 deaths annually are due to related complications such as hepatitis B and hepatocellular carcinoma (HCC). Recently, the use of oral antiviral agents has significantly improved the prognosis of patients with CHB infection and reduced the risk of HCC. However, hepatitis B virus still remains a major factor in the development of HCC, raising many concerns. Therefore, numerous studies have been conducted to assess the risk of HCC in patients with CHB infection and many models have been proposed to predict the risk of developing HCC. However, as each study has different models for predicting HCC development that can be applied depending on the use of antiviral agents or the type of antiviral agents, it is necessary to properly understand characteristics of each model when using it for the evaluation of HCC in patients with CHB infection. In addition, because different variables such as host factor, viral activity, and cirrhosis are used to evaluate the risk of HCC development, it is necessary to assess the risk by carefully verifying which variables are used. Recently, studies have also evaluated the risk of HCC using risk prediction models through transient elastography and artificial intelligence (AI) system. These HCC risk predication models are also noteworthy. In this review, we aimed to compare HCC risk prediction models in patients with CHB infection reported to date to confirm variables used and specificity between each model to determine an appropriate HCC risk prediction method.

Association between HBs Ag quantification and the risk of hepatocellular carcinoma in patients treated with tenofovir disoproxil fumarate or entecavir.

ABSTRACT: This study evaluated the clinical implications of hepatitis B surface antigen quantification (qHBs Ag) in chronic hepatitis B (CHB) patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) and identified the association between qHBs Ag and the risk of hepatocellular carcinoma (HCC) in these patients.Between January 2007 and December 2018, the qHBs Ag and clinical data of 183 CHB patients who initially received ETV (n = 45, 24.6%) or TDF (n = 138, 75.4%) were analyzed.The mean follow-up period of the 183 CHB patients was 45.3 months, of which 59 (32.2%) patients showed a reduction in qHBs Ag by >50% after 1 year of antiviral treatment (ETV or TDF). The HCC development (P = .179) or qHBs Ag reduction (P = .524) were similar in the ETV and TDF groups. Patients with a ≥50% decrease in qHBs Ag had a significantly lower incidence of HCC or decompensated cirrhosis complications (P = .005). Multivariate analysis showed that a >50% reduction of qHBs Ag (hazard ratio 0.085, P = .018) and the presence of cirrhosis (hazard ratio 3.32, P = .016) were independent factors predicting the development of HCC.Patients whose qHBs Ag value decreased >50% at 1 year after antiviral treatment for CHB showed a significant decrease in HCC or decompensated cirrhosis events. A reduction in qHBs Ag could be used as a predictive factor of HCC development or critical complications in CHB patients treated with TDF or ETV.

Resection or ablation versus transarterial therapy for Child-Pugh A patients with a single small hepatocellular carcinoma.

ABSTRACT: Data from a direct comparison of the long-term survival outcomes of surgical resection (SR) or radiofrequency ablation (RFA) versus transarterial therapy in Child-Turcotte-Pugh (CTP)-class A patients with a single small T1/T2 stage hepatocellular carcinoma (HCC) (≤3 cm) are still lacking. This study retrospectively compared the therapeutic outcomes of these treatment types for CTP-A patients with a single small HCC.Using a nationwide Korean registry, we identified 2314 CTP-A patients with SR (n = 722), RFA (n = 731), or transarterial therapy (n = 861) for a single (≤3 cm) T1/T2 stage HCC from 2008 to 2014. The posttreatment overall survival (OS) of transarterial therapy with either SR or RFA were compared using the Inverse Probability of treatment Weighting (IPW). The median follow-up period was 50 months (range 1-107 months).After IPW, the cumulative OS rates after SR or RFA were significantly higher than those after transarterial therapy in all subjects (all P values < .05). The OS rates after SR or RFA were better than those after transarterial therapy in patients with the hepatitis B or C virus (all P values < .05), and in patients aged <65 years (all P values < .05). The cumulative OSs between RFA and transarterial therapy were statistically comparable in patients with a 2 to 3 cm HCC and aged ≥65 years, respectively. For all subjects, the weighted Cox proportional hazards model using IPW provided the adjusted hazard ratios (95% confidence interval) for the OS after SR versus transarterial therapy and after RFA versus transarterial therapy of 0.42 (0.30-0.60) (P < .001) and 0.78 (0.61-0.99) (P = .044), respectively.In CTP-A patients with a single (≤3 cm) T1/T2 HCC, SR or RFA provides a better OS than transarterial therapy, regardless of the HCC etiology (hepatitis B virus or hepatitis C virus), especially in patients with HCC of <2 cm and aged <65 years.

Association between telomere length and hepatic fibrosis in non-alcoholic fatty liver disease.

Telomere length has been linked to the prevalence and progression of metabolic disease. However, clinical implications of telomere length in biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients remain unclear. Therefore, this study aimed to investigate the association of telomere length with the histological severity of NAFLD. The cross-sectional data derived from the prospectively enrolled Boramae NAFLD registry (n = 91) were analyzed. The liver tissues and clinical information were obtained from both NAFLD patients and non-NAFLD subjects. Binary logistic regression was performed to identify the independent association between telomere length and the histological severity of NAFLD. A total of 83 subjects with or without biopsy-proven NAFLD were included for analysis: non-NAFLD in 23 (27.7%), non-alcoholic fatty liver in 15 (18.1%), and non-alcoholic steatohepatitis (NASH) in 45 (54.2%). Telomere length measured from liver tissues showed a strong negative correlation (p < 0.001) with age, regardless of NAFLD status. Therefore, telomere length was corrected for age. Age-adjusted telomere length than decreased gradually with an increasing severity of fibrosis in patients with NAFLD (p < 0.028). In multivariate analysis, age-adjusted telomere length (odds ratio [OR] 0.59; 95% CI 0.37-0.92; p = 0.019) and high-density lipoprotein cholesterol (OR 0.94; 95% CI 0.80-0.99; p = 0.039) were independently associated with significant fibrosis. The age-adjusted telomere length tends to decrease along with the fibrosis stage of NAFLD. In particular, among the histological components of NAFLD, fibrosis severity seems to be related to telomere length in the liver.

Addition of liver stiffness enhances the predictive accuracy of the PAGE-B model for hepatitis B-related hepatocellular carcinoma.

BACKGROUND: The modified PAGE-B (mPAGE-B) and PAGE-B models reliably predict the risk of developing chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC). AIM(S): To investigate whether the addition of liver stiffness (LS) value, assessed using transient elastography, enhanced the predictive accuracies of these models METHODS: Patients with CHB who started anti-viral therapy (AVT) between 2007 and 2017 were enrolled. The training (Yonsei University Hospital) and validation (seven Korean referral institutes) cohorts contained 1211 and 973 patients, respectively. RESULTS: Based on multivariate analysis, older age (hazard ratio [HR] = 1.051, 95% confidence interval [CI] = 1.031-1.071), male sex (HR = 2.265, 95% CI = 1.463-3.506), lower platelet count (HR = 0.993, 95% CI = 0.989-0.997) and greater LS values (HR = 1.015, 95% CI = 1.002-1.028) were independently associated with an increased risk of HCC development (all P < 0.05). Thus, we developed a modified PAGELS -B model (maximum score 34) that included age, male sex, platelet count and LS value. The integrated area under the curve of the modified PAGELS model was greater than those of the PAGE-B and mPAGE-B models (0.760 vs 0.714 and 0.716, respectively) in the derivation dataset. The cumulative HCC incidence was significantly higher in the high-risk (modified PAGE-BLS score ≥ 24) group than in the intermediate-risk (modified PAGELS -B score 12-24) or low-risk (modified PAGELS -B score < 12) group (all P < 0.001). Similar results were observed in the validation cohort. CONCLUSIONS: The predictive accuracies of the PAGE-B and mPAGE-B models were validated in Korean patients with CHB receiving AVT. However, the modified PAGELS -B model featuring the addition of LS value showed higher predictability than the PAGE-B and mPAGE-B models.

Dynamics of liver stiffness-based risk prediction model during antiviral therapy in patients with chronic hepatitis B.

OBJECTIVE: The liver stiffness-based risk prediction models predict hepatocellular carcinoma (HCC) development. We investigated the influence of antiviral therapy (AVT) on liver stiffness-based risk prediction model in patients with chronic hepatitis B (CHB). METHODS: Patients with CHB who initiated AVT were retrospectively recruited from 13 referral Korean institutes. The modified risk estimation for hepatocellular carcinoma in chronic hepatitis B (mREACH-B) model was selected for the analysis. RESULTS: Between 2007 and 2015, 1034 patients with CHB were recruited. The mean age of the study population (639 men and 395 women) was 46.8 years. During AVT, the mREACH-B score significantly decreased from the baseline to 3 years of AVT (mean 9.21 → 7.46, P < 0.05) and was maintained until 5 years of AVT (mean 7.23, P > 0.05). The proportion of high-risk patients (mREACH-B score ≥11) was significantly reduced from the baseline to 2 years of AVT (36.4% → 16.4%, P < 0.001) and was maintained until 5 years of AVT (12.2%, P > 0.05). The mREACH-B scores at baseline and 1 year of AVT independently predicted HCC development (hazard ratio = 1.209-1.224) (all P < 0.05). The cumulative incidence rate of HCC was significantly different at 5 years of AVT among risk groups (high vs. high-intermediate vs. low-intermediate vs. low) from baseline (4.5% vs. 3.2% vs. 1.5% vs. 0.8%) and 1 year (11.8% vs. 4.6% vs. 1.8% vs. 0.6%) (all P < 0.05, log-rank tests). CONCLUSIONS: The mREACH-B score was dynamically changed during AVT. Thus, repeated assessment of the mREACH-B score is required to predict the changing risk of HCC development in patients with CHB undergoing AVT.

Incidence and Clinical Features of Hepatitis C Virus-associated Hepatocellular Carcinoma Patients without Liver Cirrhosis in Hepatitis B Virus-endemic Area.

Background/objective: Hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) is rarely observed in patients without liver cirrhosis (LC). We evaluated the incidence and clinical feature of HCV-associated HCC patients with or without LC. Methods: The medical records of 1,516 patients diagnosed as having primary HCC at our hospital between January 2005 and December 2017 were retrospectively reviewed. Of these, 154 (10.2%) HCV-associated HCC patients were analyzed. LC was diagnosed histologically or clinically. Results: Seventeen (11.0%) of the 154 patients had non-cirrhotic HCC, and all were of Child-Turcotte-Pugh (CTP) class A, Among the 17 patients, 88.2% were male, all had nodular type HCC, and only 2 (11.8%) were under HCC surveillance. Median overall survival (OS) of HCV-associated HCC patients with and without LC was 15 months and 37 months, respectively. Cumulative OS rates were not different between non-cirrhotic patients and cirrhotic patients with CTP class A (P=0.229). Cumulative OS rates were significantly higher in non-cirrhotic patients than in cirrhotic patients of CTP class B (P<0.001) or C (P<0.001). Multivariate analyses showed serum AST (hazard ratio [HR] 1.01, P=0.003) and AFP levels (HR 1.01, P=0.016), antiviral therapy (HR 0.25, P=0.022), and LC of CTP class B (HR, 5.24, P=0.006) or C (HR 21.79, P<0.001) were significantly associated with prognosis in HCV-associated HCC patients. Conclusions: HCC in a non-cirrhotic liver was found in 11% of HCV-associated HCC patients. OSs of HCV-associated HCC patients were better in those of CTP A, regardless of LC than in those with LC of CTP class B or C.

Acute-on-chronic liver failure as a major predictive factor for mortality in patients with variceal bleeding.

BACKGROUND/AIMS: This study examined the risk factors associated with mortality in cirrhotic patients hospitalized with variceal bleeding, and evaluated the effects of acute-on-chronic liver failure (ACLF) on the prognosis of these patients. METHODS: This study was retrospectively conducted on patients registered in the Korean acute-on-chronic liver failure study cohort, and on 474 consecutive cirrhotic patients hospitalized with variceal bleeding from January 2013 to December 2013 at 21 university hospitals. ACLF was defined as described by the European Association for the Study of Liver-Chronic Liver Failure Consortium. RESULTS: Among a total of 474 patients, 61 patients were diagnosed with ACLF. The cumulative overall survival (OS) rate was lower in the patients with ACLF than in those without (P<0.001), and patients with higher ACLF grades had a lower OS rate (P<0.001). The chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score was identified as a significant prognostic factor in patients hospitalized with variceal bleeding (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.30-1.50; P<0.001), even in ACLF patients with variceal bleeding (HR, 1.32; 95% CI, 1.19-1.46, P<0.001). Concerning the prediction of the mortality risk at 28- and 90-day using CLIF-SOFA scores, c-statistics were 0.895 (95% CI, 0.829-0.962) and 0.897 (95% CI, 0.842-0.951), respectively, and the optimal cut-off values were 6.5 and 6.5, respectively. CONCLUSION: In cirrhotic patients hospitalized with variceal bleeding, the prognosis was poor when accompanied by ACLF, especially depending upon CLIF-SOFA score. CLIF-SOFA model well predicted the 28-day or 90-day mortality for cirrhotic patients who experienced variceal bleeding.

Correlation between the small dense LDL level and nonalcoholic fatty liver disease: Possibility of a new biomarker.

Small dense low-density lipoprotein (sdLDL) is a distinct low-density lipoprotein (LDL) cholesterol subclass that has been reported to be associated with metabolic disease. On the other hand, the relationship between the sdLDL level and the nonalcoholic fatty liver disease (NAFLD) severity is unclear. In this study, the sdLDL level was measured in patients with NAFLD to assess its potential as a biomarker for evaluating NAFLD. One hundred and twenty-six patients diagnosed with NAFLD at a single referral hospital from January 2018 to August 2019 were enrolled. The lipoprotein profile was analyzed from a blood test of NAFLD patients, and transient elastography (TE, Fibroscan) was performed to evaluate the degree of NAFLD. Among the 126 patients, 83 patients that could confirm the lipoprotein profile and TE results were finally enrolled in the study. The controlled attenuation parameter (CAP) value obtained from TE did not show any correlation with the total cholesterol, LDL. But, the sdLDL level showed a significant positive correlation with the CAP value (r = 0.237, P = .031), and the sdLDL/LDL ratio also showed a significant positive correlation with the CAP value (r = 0.235, P = .032). The liver stiffness (LS) measured by TE and the sdLDL level were positively correlated in patients with NAFLD (rho = 0.217, P = .049). The sdLDL/LDL ratio also showed a significant positive correlation with the LS value (rho = 0.228, P = .038). In addition, the fatty liver index also showed a significant positive correlation with the sdLDL/LDL ratio (r = 0.448, P = .000). In this study, the sdLDL level measured by a blood test of NAFLD patients showed a positive correlation with the CAP value and LS, which indicate the degree of hepatic steatosis and fibrosis. These results suggest the possibility of the sdLDL level as a new biomarker of NAFLD, but further studies will be needed to support these results.

Survival Outcomes According to Body Mass Index in Hepatocellular Carcinoma Patient: Analysis of Nationwide Cancer Registry Database.

BACKGROUND AND AIMS: Body mass index (BMI) is known to be closely related to the prognosis and mortality of various diseases. The aim of our study was to evaluate differences in post-treatment overall survival (OS) according to BMI with hepatocellular carcinoma (HCC) and to understand the meaning of BMI. Among the records of 10,578 HCC patients registered at the Korean Central Cancer Registry from 2008 through 2014, we selected Barcelona Clinic Liver Cancer (BCLC) 0, A, and B staged HCC patients (n = 4,926). HCC patients showed a good prognosis in the order of overweight, normal weight, obesity, and underweight. However, comparing normal-weight (BMI 18.5-24.9 kg/m2) to overweight (BMI 25-29.9 kg/m2) after propensity score matching (PSM), there was no significant difference in OS (p = 0.153). Overweight males had a better prognosis than normal-weight males (p = 0.014), but, normal-weight females had a better prognosis than overweight. To determine the gender-specific OS differences, we examined the differences according to the HCC treatment type. In males, overweight patients had better OS after transarterial chemoembolization (TACE) (p = 0.039) than normal-weight, but not after surgical resection (p = 0.618) nor radiofrequency ablation (p = 0.553). However, in females, all of those HCC treatments resulted in significantly better OS in normal-weight patients than overweight. In patients with HCC of BCLC stages 0-B, unlike females, overweight males had a better prognosis than normal-weight, especially among TACE-treated patients. Our results carefully suggest that the meaning of normal BMI in patients with HCC may have gender difference.

Predictive score for hepatocellular carcinoma after hepatitis B e antigen loss in patients treated with entecavir or tenofovir.

The risk of developing hepatocellular carcinoma (HCC) after hepatitis B e antigen seroclearance (ESC) remains unclear. We established and validated a new risk prediction model for HCC development after ESC in patients with chronic hepatitis B (CHB) receiving antiviral therapy (AVT). Between 2006 and 2016, 769 patients (training cohort) and 1,061 patients (validation cohort) with CHB who experienced ESC during AVT using entecavir (ETV) or tenofovir disoproxil fumarate (TDF) were recruited. In the multivariate analysis, male sex (hazard ratio [HR] = 2.092; 95% confidence interval [CI] = 1.152-3.800), cirrhosis (HR = 5.141; 95% CI = 2.367-11.167) and fibrosis-4 index (FIB-4) of >3.25 (HR = 2.070; 95% CI = 1.184-3.620) were the independent risk factors for HCC development (all P < .05). Accordingly, a novel HCC-ESCAVT model was developed (1x[sex: male = 1, female = 0] + 3x(cirrhosis = 1, noncirrhosis = 0) + 1x(FIB-4: >3.25 = 1, ≤3.25 = 0). The cumulative risk for HCC development was significantly different among the risk groups based on the HCC-ESCAVT category (0-1, 2-4 and 5 for the low-, intermediate- and high-risk groups, respectively) (overall P < .001, log-rank test). The area under the receiver operating characteristic curve (AUC) for predicting HCC development 3, 5 and 10 years after ESC was 0.791, 0.771 and 0.790, respectively (all P < .05). The predictive value of the HCC-ESCAVT model was similar in the validation cohort (AUC = 0.802, 0.774 and 0.776 at 3, 5 and 10 years, respectively; all P < .05). Hence, we have developed and validated a new HCC-ESCAVT model for HCC development, which includes male sex, cirrhosis and FIB-4 of >3.25 as constituent variables.

Extremely low risk of hepatocellular carcinoma development in patients with chronic hepatitis B in immune-tolerant phase.

BACKGROUND: Anti-viral therapy is not indicated for patients with chronic hepatitis B (CHB) in the immune-tolerant phase. AIMS: To investigate the cumulative incidence of phase change and hepatocellular carcinoma (HCC) and independent predictors for phase change in patients with CHB in immune-tolerant phase. METHODS: In total, 946 patients in immune-tolerant phase, defined as hepatitis B e antigen positivity, HBV-DNA >20 000 IU/mL and alanine aminotransferase (ALT) ≤40 IU/L, between 1989 and 2017 were enrolled from eight institutes. RESULTS: The mean age of study population (429 men and 517 women) was 36.7 years. The mean ALT and HBV-DNA levels were 24.6 IU/L and 8.50 log10 IU/mL, respectively. Of the study population, 476 (50.3%) patients remained in immune-tolerant phase throughout the study period (median: 63.6 months). The cumulative incidence rates of phase change and HCC at 10 years were 70.7% and 1.7%, respectively. Multivariate analyses revealed that HBV-DNA level >107  IU/mL was associated independently with a reduced risk of phase change (hazard ratio [HR] = 0.734, P = 0.008), whereas a high ALT level, above the cut-off recommended in the Korean Association for the Study of the Liver guidelines (34 IU/L for men and 30 IU/L for women), was associated independently with a greater risk of phase change (HR = 1.885, P < 0.001). CONCLUSIONS: The criterion of HBV-DNA level > 107  IU/mL may be useful to define immune-tolerant phase. In addition, an extremely low risk of HCC development was observed in patients with CHB in immune-tolerant phase.