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.

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.

Aromatase Inhibitors and Newly Developed Nonalcoholic Fatty Liver Disease in Postmenopausal Patients with Early Breast Cancer: A Propensity Score-Matched Cohort Study.

BACKGROUND: Unlike tamoxifen, the relationship between aromatase inhibitor use in postmenopausal patients with breast cancer and nonalcoholic fatty liver disease (NAFLD) has not been delineated. MATERIALS AND METHODS: A retrospective analysis of 253 patients with early breast cancer without baseline NAFLD and treated with nonsteroidal aromatase inhibitors was performed. Among them, 220 patients were matched for sex, age, and menstruation status with healthy patients, and the prevalence of NAFLD was compared. NAFLD was determined by hepatic steatosis index in the absence of other known liver diseases. The presence of significant liver fibrosis in patients with NAFLD was determined noninvasively by AST-platelet ratio index, FIB-4 score, and NAFLD fibrosis score (NFS). RESULTS: Postmenopausal patients with breast cancer undergoing treatment with aromatase inhibitors had higher prevalence of NAFLD independent of body mass index (BMI) and underlying diabetes mellitus (DM). Although the aromatase inhibitor group showed higher fibrotic burden by NFS, independent of BMI and DM, the proportion of advanced fibrosis did not show statistically significant differences between AI-treated patients and the healthy patients. Those with abnormal baseline fasting glucose levels are suggested to have increased risk of NAFLD development after aromatase inhibitor treatment. In addition, patients with NAFLD developed after aromatase inhibitor use had significantly lower disease-free survival than those without NAFLD, although there was no significant difference in overall survival. CONCLUSION: Results of this study suggest that inhibition of estrogen synthesis in postmenopausal women undergoing treatment with aromatase inhibitors could increase the risk of NAFLD, which might have some influence on the prognosis of patients with breast cancer. IMPLICATIONS FOR PRACTICE: Unlike tamoxifen, the role of aromatase inhibitor treatment use in postmenopausal patients with breast cancer in development of fatty liver is not well known. In this propensity-matched cohort study, postmenopausal patients with breast cancer treated with aromatase inhibitors had increased risk of nonalcoholic fatty liver disease compared with healthy women after menopause, independent of obesity and diabetes mellitus. The results show possible adverse influence of the newly developed fatty liver on breast cancer disease-free survival and suggest a necessity for further validation. Fatty liver may need to be considered as an adverse event for aromatase inhibitor treatment.

Antiviral Therapy in Patients With Chronic Hepatitis C-related Hepatocellular Carcinoma Responding to Palliative Treatment.

BACKGROUND/AIM: Advances in hepatitis C virus (HCV) treatment offer high sustained virologic response rates with minimal side-effects. However, benefits of eradicating HCV in hepatocellular carcinoma (HCC) patients whose life expectancies are hard to be determined after palliative therapy still needs to be assessed. This study sought to evaluate prognostic factors for survival in HCV-related HCC patients that responded to the palliative HCC treatment to speculate whether treating HCV would be beneficial in these patients. MATERIALS AND METHODS: In this retrospective cohort study, the medical records of 97 patients that showed complete or partial response to the initial HCC treatment were included. RESULTS: Receiving HCV treatment [hazard ratio (HR), 0.244; 95% confidence interval (CI), 0.075-0.788; P=0.018] increased the survival, whereas partial response to the initial HCC treatment (HR, 1.795; 95% CI, 1.071-3.008; P=0.026) and increased Child-Turcotte-Pugh score (HR, 2.017; 95% CI, 1.196-3.403; P=0.009) reduced the survival. From 97 patients, 16 patients were eventually treated for HCV. The mean time from the last HCC therapy to HCV treatment was 16.9±13.9 months. The median time of follow-up after HCV treatment was 10.0 months (range, 3 to 47 mo). Among the HCV-treated patients 3 patients had HCC recurred. The time to progression in HCV-treated patients were significantly longer than those untreated for HCV (P=0.032). CONCLUSIONS: Although treating HCV in HCC patient that undergo noncurative HCC treatment is still debatable, this study results carefully suggest that HCV-related HCC patients that responded to the initial HCC palliative treatment might benefit from HCV treatment.

Remaining hepatocellular carcinoma risk in chronic hepatitis B patients receiving entecavir/tenofovir in South Korea.

AIM: We aimed to identify the incidence rate of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with entecavir or tenofovir in South Korea, and to identify predictors of HCC development in these patients. METHODS: Between January 2007 and December 2015, 582 CHB patients initially received entecavir (n = 406, 69.8%) or tenofovir (n = 176, 30.2%) for CHB. RESULTS: During a median follow-up of 57.1 months, HCC developed in 38 (6.5%) of the 582 patients, regardless of antiviral agent type. Entecavir- and tenofovir-treated patients had similar HCC development rates (P = 0.471). For the 582 patients, 2-, 4-, and 6-year cumulative HCC development rates were 2.6%, 4.4%, and 8.3%, respectively, and the 2-, 4-, and 6-year cumulative HCC development rates of patients with liver cirrhosis were significantly greater than those of patients without liver cirrhosis (6.2%, 9.8%, and 18.4% vs. 0.3%, 1.1%, and 2.2%, respectively; P < 0.001). Older (≥60 years) patients, regardless of the presence of cirrhosis, and cirrhotic patients aged ≥40 years showed significantly higher risk of HCC development compared to others (both P < 0.05). Multivariate analysis showed that an older age (≥50 years; hazard ratio [HR] 5.02, P = 0.009), and the presence of cirrhosis (HR 4.95, P = 0.002) independently predicted HCC development. CONCLUSIONS: The 6-year cumulative HCC development rate was 6.5% in CHB patients treated with entecavir or tenofovir. Age ≥50 years and liver cirrhosis were found to predict HCC development in these patients.

Real-life prevalence of resistance-associated variants against non-structural protein 5A inhibitors and efficiency of Daclatasvir + Asunaprevir therapy in Korean patients with genotype 1b hepatitis C.

BACKGROUND: Direct-acting antivirals (DAAs) for chronic hepatitis C (CHC) treatment are tolerable and highly effective in a shorter period of time than before. However, resistance-associated variants (RAVs) can affect the efficacy of DAAs. The aim of this study was to investigate the real-life prevalence of RAVs against non-structural protein 5A (NS5A) inhibitors in Korean patients with genotype 1b chronic hepatitis C. METHODS: All consecutive patients with CHC genotype 1b who underwent a RAV test at a single referral hospital were enrolled. RESULTS: A total of 142 patients (male 53, female 89) were tested for RAVs. The average age of the patients was 58 years. Liver cirrhosis was found in 34.5% (49/142) of patients, and 19.0% (29/142) of patients had previously undergone interferon-based treatment. Twenty-nine patients (20.4%) had RAVs (Y93 or L31). Y93H, L31, or Y93H with L31 were detected in 22 (15.5%), 8 (5.6%), and 1 (0.7%) patients, respectively. The presence of RAV was not affected by previous interferon-based treatment or by the existence of liver cirrhosis. Among 113 patients without baseline NS5A RAVs, 72 patients started daclatasvir (DCV) + asunaprevir (ASV) treatment and 95% (68/72) patients achieved virologic response at week 4. Virologic response at end of treatment and sustained virologic response at 12 weeks after treatment were achieved by 94% (68/72) and 94% (68/72), respectively. CONCLUSIONS: In Korean patients with genotype 1b CHC, 20.4% (29 of 142) of patients showed RAVs against NS5A inhibitors. Patient without RAVs who received treatment with DCV + ASV showed high virologic response rates in Korea.

Dexras1 mediates glucocorticoid-associated adipogenesis and diet-induced obesity.

Adipogenesis, the conversion of precursor cells into adipocytes, is associated with obesity and is mediated by glucocorticoids acting via hitherto poorly characterized mechanisms. Dexras1 is a small G protein of the Ras family discovered on the basis of its marked induction by the synthetic glucocorticoid dexamethasone. We show that Dexras1 mediates adipogenesis and diet-induced obesity. Adipogenic differentiation of 3T3-L1 cells is abolished with Dexras1 depletion, whereas overexpression of Dexras1 elicits adipogenesis. Adipogenesis is markedly reduced in mouse embryonic fibroblasts from Dexras1-deleted mice, whereas adiposity and diet-induced weight gain are diminished in the mutant mice.

Monoacylglycerol O-acyltransferase 1 is regulated by peroxisome proliferator-activated receptor γ in human hepatocytes and increases lipid accumulation.

Monoacylglycerol O-acyltransferase (MGAT) is an enzyme that is involved in triglyceride synthesis by catalyzing the formation of diacylglycerol from monoacylglycerol and fatty acyl CoAs. Recently, we reported that MGAT1 has a critical role in hepatic TG accumulation and that its suppression ameliorates hepatic steatosis in a mouse model. However, the function of MGAT enzymes in hepatic lipid accumulation has not been investigated in humans. Unlike in rodents, MGAT3 as well as MGAT1 and MGAT2 are present in humans. In this study, we evaluated the differences between MGAT subtypes and their association with peroxisome proliferator-activated receptor γ (PPARγ), a regulator of mouse MGAT1 expression. In human primary hepatocytes, basal expression of MGAT1 was lower than that of MGAT2 or MGAT3, but was strongly induced by PPARγ overexpression. A luciferase assay as well as an electromobility shift assay revealed that human MGAT1 promoter activity is driven by PPARγ by direct binding to at least two regions of the promoter in 293T and HepG2 cells. Moreover, siRNA-mediated suppression of MGAT1 expression significantly attenuated lipid accumulation by PPARγ overexpression in HepG2 cells, as evidenced by oil-red-O staining. These results suggest that human MGAT1 has an important role in fatty liver formation as a target gene of PPARγ, and blocking MGAT1 activity could be an efficient therapeutic way to reduce nonalcoholic fatty liver diseases in humans.

Nuclear receptor PPARγ-regulated monoacylglycerol O-acyltransferase 1 (MGAT1) expression is responsible for the lipid accumulation in diet-induced hepatic steatosis.

Recently, hepatic peroxisome proliferator-activated receptor (PPAR)γ has been implicated in hepatic lipid accumulation. We found that the C3H mouse strain does not express PPARγ in the liver and, when subject to a high-fat diet, is resistant to hepatic steatosis, compared with C57BL/6 (B6) mice. Adenoviral PPARγ2 injection into B6 and C3H mice caused hepatic steatosis, and microarray analysis demonstrated that hepatic PPARγ2 expression is associated with genes involved in fatty acid transport and the triglyceride synthesis pathway. In particular, hepatic PPARγ2 expression significantly increased the expression of monoacylglycerol O-acyltransferase 1 (MGAT1). Promoter analysis by luciferase assay and electrophoretic mobility shift assay as well as chromatin immunoprecipitation assay revealed that PPARγ2 directly regulates the MGAT1 promoter activity. The MGAT1 overexpression in cultured hepatocytes enhanced triglyceride synthesis without an increase of PPARγ expression. Importantly, knockdown of MGAT1 in the liver significantly reduced hepatic steatosis in 12-wk-old high-fat-fed mice as well as ob/ob mice, accompanied by weight loss and improved glucose tolerance. These results suggest that the MGAT1 pathway induced by hepatic PPARγ is critically important in the development of hepatic steatosis during diet-induced obesity.

Non-invasive prediction of post-sustained virological response HCC in HCV: A systematic review and meta-analysis.

Background: Despite advances in antiviral therapy for hepatitis C virus (HCV) infection, hepatocellular carcinoma (HCC) still develops even after sustained viral response (SVR) in patients with advanced liver fibrosis or cirrhosis. This meta-analysis investigated the predictive performance of transient elastography (TE) and fibrosis 4-index (FIB-4) for the development of HCC after SVR. Methods: We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library for studies examining the predictive performance of these tests in adult patients with HCV. Two authors independently screened the studies' methodological quality and extracted data. Pooled estimates of sensitivity, specificity, and area under the curve (AUC) were calculated for HCC development using random-effects bivariate logit normal and linear-mixed effect models. Results: We included 27 studies (169,911 patients). Meta-analysis of HCC after SVR was possible in nine TE and 15 FIB-4 studies. Regarding the prediction of HCC development after SVR, the pooled AUCs of pre-treatment TE >9.2-13 kPa and FIB-4 >3.25 were 0.79 and 0.73, respectively. TE >8.4-11 kPa and FIB-4 >3.25 measured after SVR, maintained good predictive performance, albeit slightly reduced (pooled AUCs: 0.77 and 0.70, respectively). The identified optimal cut-off value for HCC development after SVR was 12.6 kPa for pre-treatment TE. That of TE measured after the SVR was 11.2 kPa. Conclusion: TE and FIB-4 showed acceptable predictive performance for HCC development in patients with HCV who achieved SVR, underscoring their utility in clinical practice for guiding surveillance strategies. Future studies are needed to validate these findings prospectively and validate their clinical impact.

Optimal cut-offs of transient elastography and magnetic resonance elastography in diagnosing advanced liver fibrosis in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background/aims: Opinions differ regarding transient elastography and magnetic resonance elastography (TE/MRE) cut-offs for diagnosing advanced fibrosis (AF) in patients with non-alcoholic fatty liver disease (NAFLD). We investigated the diagnostic performance and optimal cut-off values of TE and MRE for diagnosing AF. Methods: Literature databases, including Medline, EMBASE, Cochrane Library, and KoreaMed, were used to identify relevant studies published up to June 13, 2023. We selected studies evaluating TE and MRE regarding the degree of liver fibrosis using liver biopsy as the reference. The sensitivity, specificity, and area under receiver operating characteristics curves (AUCs) of the pooled data for TE and MRE for each fibrosis stage and optimal cut-offs for AF were investigated. Results: A total of 19,199 patients from 63 studies using TE showed diagnostic AUC of 0.83(95% confidence interval: 0.80-0.86), 0.83(0.80-0.86), 0.87(0.84-0.90), and 0.94(0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. Similarly, 1,484 patients from 14 studies using MRE showed diagnostic AUC of 0.89(0.86-0.92), 0.92(0.89-0.94), 0.89(0.86-0.92), and 0.94(0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages respectively. The diagnostic AUC for AF using TE was highest at 0.90 with a cut-off of 7.1-7.9 kPa, and that of MRE was highest at 0.94 with a cut-off of 3.62-3.8 kPa. Conclusions: TE(7.1-7.9 kPa) and MRE(3.62-3.8 kPa) with the suggested cut-offs showed favorable accuracy for diagnosing AF in patients with NAFLD. This result will serve as a basis for clinical guidelines for non-invasive tests and differential diagnosis of AF.

Assessment of the postoperative prognosis in patients with hepatocellular carcinoma using transient elastography: A systemic review and meta-analysis.

Background and Aims: This meta-analysis examined whether preoperative vibration-controlled transient elastography (VCTE) can predict postoperative complications and recurrence in patients undergoing hepatic resection for hepatocellular carcinoma (HCC). Methods: A systematic literature search was conducted using Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases. Out of 431 individual studies, thirteen published between 2008 and 2022 were included. Five studies focused on HCC recurrence, while eight examined postoperative complications. Results: The meta-analysis of five studies on HCC recurrence showed that the high-risk group with a high VCTE score had a significantly increased recurrence rate after hepatic resection (hazard ratio [HR], 2.14). The cutoff value of VCTE in the high-risk group of HCC recurrence was 7.4-13.4kPa, the sensitivity was 0.60 (95% CI 0.47-0.72), and the specificity was 0.60 (95% CI 0.46-0.72). The area under the receiver operating characteristic curve (AUC) of the liver stiffness measured by VCTE to predict the HCC recurrence was 0.63 (95% CI 0.59-0.67). The meta-analysis on the postoperative complications revealed a significantly increased risk of postoperative complications in the high-risk group (12-25.6kPa) with a high VCTE value (risk ratio [RR], 8.32). The AUC of the liver stiffness measured by VCTE to predict the postoperative complications was 0.87(95% CI 0.84-0.90), the sensitivity was 0.76 (95% CI 0.55-0.89) and the specificity was 0.85 (95% CI 0.73-0.92). Conclusions: This meta-analysis suggests that preoperative VCTE in patients undergoing hepatic resection for HCC is useful in identifying individuals at a high risk of postoperative complications and HCC recurrence.

Diagnostic Accuracy of Transient Elastography for Staging Liver Fibrosis in Autoimmune Liver Diseases: A Systematic Review and Meta-Analysis.

Background/Aims: The assessment of liver fibrosis is crucial for managing autoimmune liver diseases such as primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). However, data on the efficacy of noninvasive tests (NITs) for these diseases are limited. This meta-analysis evaluated the diagnostic accuracy of vibration-controlled transient elastography (VCTE) for staging fibrosis in patients with autoimmune liver disease. Methods: Searches were conducted in PubMed, Embase, CINAHL, Web of Science, and Cochrane Library databases to assess the diagnostic accuracy of VCTE against histology as the reference standard in adult patients with autoimmune liver disease. The summary area under the curve (sAUC) and diagnostic odds ratio were calculated for significant fibrosis (SF), advanced fibrosis (AF), and cirrhosis, defined as METAVIR stages F≥2, F≥3, and F=4, respectively, according to liver biopsy. Results: Fourteen articles were included, comprising 559 PBC patients from six studies, 388 AIH patients from five studies, and 151 PSC patients from three studies. VCTE demonstrated good performance for fibrosis staging in PBC, AIH, and PSC. In PBC, sAUCs of VCTE were 0.87 (95% confidence interval, 0.80-0.94), 0.89 (0.85-0.94), and 0.99 (0.96-1.00) for staging SF, AF, and cirrhosis, respectively. In AIH, the sAUCs were 0.88 (0.84-0.92), 0.88 (0.83-0.93), and 0.92 (0.88-0.96), respectively, while in PSC, they were 0.88 (0.82-0.95), 0.95 (0.90-1.00), and 0.92 (0.84-0.99), respectively. The cutoff values for AF were 7.5-17.9 kPa in PBC, 8.18-12.1 kPa in AIH, and 9.6 kPa in PSC. Conclusions: VCTE shows high diagnostic accuracy for staging liver fibrosis in patients with autoimmune liver diseases such as PBC, AIH, and PSC. This non-invasive and reliable method serves as a valuable tool for the evaluation and monitoring of fibrosis in these lifelong diseases.

Risk Assessment of Hepatitis B virus-related Hepatocellular Carcinoma Development Using Transient Elastography: Systematic Review and Meta-analysis.

Background and Aims: Liver stiffness measurement (LSM) using transient elastography (TE) can assess fibrotic burden in chronic liver diseases. The systematic review and meta-analysis was conducted to determine whether LSM using TE can predict the risk of development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. Methods: A systematic literature search of the Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases (from January 2010 to June 2023) was conducted. Of the 1,345 individual studies identified, 10 studies that used TE were finally registered. Hazard ratios (HRs) and the 95% confidence interval (CIs) were considered summary estimates of treatment effect sizes of ≥ 11 kilopascal (kPa) standard for HCC development. Meta-analysis was performed using the restricted Maximum Likelihood random effects model. Results: Among the ten studies, data for risk ratios for HCC development could be obtained from nine studies. When analyzed for the nine studies, the HR for HCC development was high at 3.33 (95% CI, 2.45-4.54) in CHB patients with a baseline LSM of ≥ 11 kPa compared to patients who did not. In ten studies included, LSM of ≥ 11 kPa showed the sensitivity and specificity for predicting HCC development were 61% (95% CI, 50-71%) and 78% (95% CI, 66-86%), respectively, and the diagnostic accuracy was 0.74 (95% CI, 0.70-0.77). Conclusions: The risk of HCC development was elevated in CHB patients with TE-determined LSM of ≥11 kPa. This finding suggests that TE-determined LSM values may aid the risk prediction of HCC development in CHB patients.

Transient elastography for significant fibrosis in treatment-naïve CHB patients: A systematic review and meta-analysis.

Background and Aims: Accurate diagnosis of significant liver fibrosis in patients with chronic hepatitis B (CHB) is crucial when determining whether to initiate antiviral treatment (AVT). We conduct a meta-analysis to assess the diagnostic performance of transient elastography (TE) for significant liver fibrosis in AVT-naïve CHB patients with serum alanine transaminase (ALT) levels within 5-fold the upper limit of normal (ULN). Methods: The Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases were searched to identify studies that compared the performance of TE and liver biopsy (reference standard) when diagnosing significant liver fibrosis (≥ F2) in AVT-naïve CHB patients with ALT within 5-fold the ULN. A hierarchical summary receiver operating characteristic curve (HSROC) and bivariate model were performed to evaluate the diagnostic performance of TE in the meta-analysis. Results: Eight studies (2,003 patients) were included. The summary sensitivity and specificity for diagnosis of significant liver fibrosis were 0.78 [95% confidence interval (CI), 0.66-0.86] and 0.72 (95% CI, 0.60-0.82), respectively. The HSROC for the diagnosis of significant liver fibrosis was 0.81 (95% CI, 0.72-0.86). The optimal cut-off value of TE for diagnosis of significant liver fibrosis was 7.7 kPa with a sensitivity of 0.64 (95% CI, 0.50-0.76) and specificity of 0.83 (95% CI, 0.72-0.90). Conclusions: Our study demonstrated that TE has an acceptable diagnostic performance for significant liver fibrosis in AVT-naïve CHB patients with ALT within 5-fold the ULN.

Diagnostic accuracy of the Fibrosis-4 index for advanced liver fibrosis in metabolic dysfunction-associated steatotic liver disease with type 2 diabetes: A systematic review and meta-analysis.

Background/Aims: The Fibrosis-4 index (FIB-4) is a non-invasive test widely used to rule out advanced liver fibrosis (AF) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, its diagnostic accuracy in MASLD patients with type 2 diabetes mellitus (T2DM) are controversial due to the high prevalence of AF in this population. Methods: Research focusing on the diagnostic accuracy of FIB-4 for liver fibrosis as validated by liver histology in MASLD patients with T2DM was included, and 12 studies (n=5,624) were finally included in the meta-analysis. Sensitivity, specificity, hierarchical summary receiver operating characteristic (HSROC), positive predictive values (PPVs), and negative predictive values (NPVs) at low cutoffs (1.3-1.67) and high cutoffs (2.67-3.25) for ruling in and out AF, were calculated. Results: At low cutoffs, the meta-analysis revealed a sensitivity of 0.74, specificity of 0.62, and HSROC of 0.75. At high cutoffs, the analysis showed a sensitivity of 0.33, specificity of 0.92, and HSROC of 0.85, suggesting FIB-4 as useful for identifying or excluding AF. In subgroup analyses, high mean age and F3 prevalence were associated with lower sensitivity. The calculated NPV and PPV were 0.82 and 0.49 at low cutoffs, whereas the NPV was 0.28 and the PPV was 0.70 at high cutoffs. There were insufficient estimated NPVs <0.90 at a hypothesized prevalence of AF >30% at an FIB-4 cutoff range of 1.3-1.67. Conclusions: Collectively, FIB-4 has moderate diagnostic accuracy for identifying or excluding AF in MASLD patients with T2DM, but more evidence must be accumulated due to the limited number of currently reported studies and their heterogeneity.

Prevalence of clinically significant liver fibrosis in the general population: A systematic review and meta-analysis.

Background/Aims: Although important, clinically significant liver fibrosis is often overlooked in the general population. We aimed to examine the prevalence of clinically significant liver fibrosis using noninvasive tests (NITs) in the general population. Methods: We collected data from four databases (MEDLINE, Embase, Cochrane Library, and KoreaMed) from inception to June 13, 2023. Original articles reporting the prevalence of clinically significant liver fibrosis in the general population were included. The Stata metaprop function was used to obtain the pooled prevalence of liver fibrosis with NITs in the general population. Results: We screened 6,429 articles and included 45 eligible studies that reported the prevalence of clinically significant liver fibrosis in the general population. The prevalence of advanced liver fibrosis, using the high probability cutoff of the fibrosis-4 (FIB-4) index, was 2.3% (95% confidence interval [CI], 1.2-3.7%). The prevalence of significant liver fibrosis, advanced liver fibrosis, and liver cirrhosis, assessed using vibration-controlled transient elastography (VCTE) among the general population, was 7.3% (95% CI, 5.9-8.8%), 3.5% (95% CI, 2.7-4.5), and 1.2% (95% CI, 0.8-1.8%), respectively. Region-based subgroup analysis revealed that the highest prevalence of advanced fibrosis using the high probability cutoff of the FIB-4 index was observed in the American region. Furthermore, the American region exhibits the highest prevalence of significant liver fibrosis, advanced liver fibrosis, and liver cirrhosis, using VCTE. Conclusions: Previously undiagnosed clinically significant liver fibrosis is found in the general population through NITs. Future research is necessary to stratify the risk in the general population.

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.

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.