Identification of the suitable candidates for EOB-MRI with the high risk of the presence of non-hypervascular hypointense nodules in patients with HCV infection.

OBJECTIVES: Non-hypervascular hypointense nodules (NHHNs) depicted by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) have a high likelihood of progressing to hepatocellular carcinoma (HCC). The presence of NHHNs is a strong risk factor for HCC development in patients with chronic hepatitis C virus (HCV) infection after the achievement of sustained virologic response (SVR). However, it is difficult for all patients with HCV infection to undergo EOB-MRI for NHHN detection. We therefore explored serum markers that potentially indicate the presence of NHHNs. METHODS: Three serum markers, alpha-fetoprotein (AFP), FIB-4 index, and Wisteria floribunda agglutinin-positive Mac-2 binding protein glycan isomer (M2BPGi), were measured in 481 patients with HCV infection and no history of HCC who underwent EOB-MRI. The associations between these serum marker levels and the presence of NHHNs were investigated. RESULTS: All three markers were associated with the presence of NHHNs. M2BPGi predicted the presence of NHHNs more accurately than AFP and FBB-4 index; M2BPGi had the highest area under the receiver operating characteristic curve. Multivariate analysis identified male gender and high M2BPGi as factors associated with the presence of NHHNs. When patients were stratified by the degree of liver fibrosis, M2BPGi increased with the progression of fibrosis. In addition, NHHNs were more prevalently detected in patients with higher M2BPGi (COI > 3.46) in patients with similar fibrosis degree. CONCLUSIONS: M2BPGi is a serum marker that potentially identifies HCV patients with high risk of the presence of NHHNs, for whom EOB-MRI should be considered. KEY POINTS: • Non-hypervascular hypointense nodule on EOB-DTPA-enhanced MRI is pre-HCC nodule with high likelihood of progressing to HCC, which is a strong predictor for HCC that develops after the eradication of HCV in patients with HCV infection. • It is difficult for all patients with HCV infection to undergo EOB-MRI for NHHN detection due to limited access, limited availability of MRI equipment, and high costs. • Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein glycan isomer (M2BPGi) levels effectively indicate the presence of NHHNs and can be used to identify patients with high risk of their presence, for whom EOB-DTPA-enhanced MRI should be considered.

Functional expansion of a TCA cycle operon mRNA by a 3' end-derived small RNA.

Global RNA profiling studies in bacteria have predicted the existence of many of small noncoding RNAs (sRNAs) that are processed off mRNA 3' ends to regulate other mRNAs via the RNA chaperones Hfq and ProQ. Here, we present targets of SdhX (RybD), an Hfq-dependent sRNA that is generated by RNase E mediated 3' processing of the ∼10 000-nt mRNA of the TCA cycle operon sdhCDAB-sucABCD in enteric bacteria. An in silico search predicted ackA mRNA, which encodes acetate kinase, as a conserved primary target of SdhX. Through base pairing, SdhX represses AckA synthesis during growth of Salmonella on acetate. Repression can be achieved by a naturally occurring 38-nucleotide SdhX variant, revealing the shortest functional Hfq-associated sRNA yet. Salmonella SdhX also targets the mRNAs of fumB (anaerobic fumarase) and yfbV, a gene of unknown function adjacent to ackA. Instead, through a slightly different seed sequence, SdhX can repress other targets in Escherichia coli, namely katG (catalase) and fdoG (aerobic formate dehydrogenase). This study illustrates how a key operon from central metabolism is functionally connected to other metabolic pathways through a 3' appended sRNA, and supports the notion that mRNA 3'UTRs are a playground for the evolution of regulatory RNA networks in bacteria.

Texture Analysis Using Preoperative Positron Emission Tomography Images May Predict the Prognosis of Patients With Resectable Oral Squamous Cell Carcinoma.

PURPOSE: Texture analysis is a computer-assisted technique used to measure intratumoral heterogeneity, which is known to have important roles in cancer research. This study aimed to assess the potential prognostic values of textural features extracted from preoperative 18F-fluorodeoxyglucose positron emission tomography images in patients with resectable oral squamous cell carcinoma. PATIENTS AND METHODS: This retrospective cohort study included patients with oral squamous cell carcinoma who underwent resection surgery. We extracted 31 textural indices from preoperative positron emission tomography images. Overall survival (OS) and disease-free survival (DFS) were chosen as the primary outcome variables, and the primary predictor variables were age, sex, primary tumor location, pathological T and N classification, histologic differentiation, resected margin, perineural and lymphovascular invasion, maximum standardized uptake value, and the 14 textural indices selected in the factor analysis. We analyzed OS and DFS using Kaplan-Meier curves, and the differences between survival curves were determined using a log-rank test. The independent prognostic factors were assessed using the Cox-proportional hazards model. RESULTS: We enrolled 81 patients (median age, 67.3 years; range, 32 to 88 years). The median follow-up duration was 50.1 months (range, 6.3 to 133.7 months). The univariable and multivariable analyses revealed that higher entropy values (≥1.91) were associated with worse OS (hazard ratio, 21.49; 95% confidence interval, 1.36 to 340.71; P = .03) and DFS (hazard ratio, 50.69; 95% confidence interval, 5.23 to 491.18; P = .001). CONCLUSIONS: This study showed that entropy is a statistically significant prognostic factor of both OS and DFS. Texture analysis using preoperative positron emission tomography images may contribute to risk stratification.

Liver stiffness does not affect ultrasound-guided attenuation coefficient measurement in the evaluation of hepatic steatosis.

AIM: Recently, a new method has been developed to diagnose hepatic steatosis with attenuation coefficients based on the ultrasound-guided attenuation parameter (UGAP). We investigated whether fibrosis identified by hepatic stiffness measurements based on magnetic resonance elastography (MRE) affects attenuation coefficient measurement using UGAP for the evaluation of hepatic steatosis. METHODS: A total of 608 patients with chronic liver disease were analyzed. Correlations between magnetic resonance imaging-determined proton density fat fraction (PDFF) or MRE value and attenuation coefficients were evaluated. In addition, the interaction between hepatic fibrosis and the attenuation coefficient was analyzed. RESULTS: The correlation coefficient (r) between PDFF values and attenuation coefficient values was 0.724, indicating a strong relationship. Conversely, the r between MRE values and attenuation coefficient values was -0.187, indicating almost no relationship. In the multiple regression assessment of the effect of PDFF and MRE on the attenuation coefficient based on UGAP, the P-values for PDFF, MRE, and PDFF × MRE were < 0.001, 0.277, and 0.903, respectively. In patients with non-alcoholic fatty liver disease (n = 169), the r between PDFF values and attenuation coefficient values was 0.695, indicating a moderate relationship. Conversely, the r between MRE values and attenuation coefficient values was -0.068, indicating almost no relationship. In the multiple regression assessment of the effect of PDFF and MRE on the attenuation coefficient based on UGAP, the P-values for PDFF, MRE, and PDFF × MRE were <0.001, 0.948, and 0.706, respectively. CONCLUSION: UGAP-determined attenuation coefficient was weakly affected by liver stiffness, an indicator of hepatic fibrosis.

The impact of HCV eradication by direct-acting antivirals on the transition of precancerous hepatic nodules to HCC: A prospective observational study.

BACKGROUND & AIMS: It remains controversial whether the eradication of hepatitis C virus (HCV) by interferon (IFN)-free anti-HCV therapy using direct-acting antivirals (DAAs) suppresses or promotes hepatocellular carcinoma (HCC) development. We investigated the influence of HCV eradication by DAA therapy on HCC development, by observing changes of non-hypervascular hypointense nodules (NHHNs) by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI). METHODS: A total of 401 patients treated with DAA therapy who did not have a history of HCC were enrolled in this prospective cohort study. All patients underwent EOB-MRI prior to the start of DAA therapy and were followed up periodically after therapy. The progression of NHHNs detected at baseline to typical HCC, as indicated by hypervascularization and the incidence of newly emergent NHHNs, was analyzed. RESULTS: In comparison of patients who achieved sustained virologic response (SVR) with propensity score-matched patients with persistent HCV infection, there was no difference in the incidence of hypervascularization of NHHNs to typical HCC among patients who had NHHNs at baseline. Among patients who did not have NHHNs at baseline, the incidence of the new emergence of NHHNs did not differ between study patients and propensity score-matched patients with persistent HCV infection. CONCLUSIONS: During a 2-year observation period after SVR, the eradication of HCV by IFN-free DAA therapy did not suppress or enhance HCC development. (UMIN000017020).

Utility of Attenuation Coefficient Measurement Using an Ultrasound-Guided Attenuation Parameter for Evaluation of Hepatic Steatosis: Comparison With MRI-Determined Proton Density Fat Fraction.

OBJECTIVE: Recently, a new method was developed to diagnose hepatic steatosis by measuring attenuation coefficients that are based on the ultrasound-guided attenuation parameter (UGAP). We investigated the diagnostic ability of these coefficients to detect steatosis that was identified using the proton density fat fraction (PDFF) on MRI in patients with chronic liver disease. MATERIALS AND METHODS: A total of 126 patients with chronic liver disease (non-hepatitis B, non-hepatitis C) were analyzed. The diagnostic ability of UGAP-determined attenuation coefficients was evaluated using ROC curve analysis, and the correlation between MRI-determined PDFF values and attenuation coefficient values was determined. RESULTS: The correlation coefficient (r) between PDFF values and attenuation coefficient values was 0.746 (95% CI, 0.657-0.815) (p < 0.001), corresponding to a strong relationship. The diagnostic ability of attenuation coefficients for steatosis grades ≥ 1, ≥ 2, and 3 as determined by PDFF were 0.922 (95% CI, 0.870-0.973), 0.874 (95% CI, 0.814-0.934), and 0.892 (95% CI, 0.835-0.949), respectively. The r between PDFF values and attenuation coefficient values was 0.559 (95% CI, 0.391-0.705) (p < 0.001) in patients with mild or no steatosis (grade ≤ 1). In addition, the r between PDFF values and attenuation coefficient values was 0.773 (95% CI, 0.657-0.853) (p < 0.001) in obese patients (body mass index [weight in kilograms divided by the square of height in meters] ≥ 25). The diagnostic ability of attenuation coefficients for patients with steatosis grades ≥ 1, ≥ 2, and 3 as determined by PDFF were 0.884 (95% CI, 0.792-0.976), 0.863 (95% CI, 0.778-0.947), and 0.889 (95% CI, 0.813-0.965), respectively. CONCLUSION: UGAP-determined attenuation coefficient values had a good diagnostic ability to detect hepatic steatosis.

Type 2 diabetes mellitus: A risk factor for progression of liver fibrosis in middle-aged patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIM: The severity of liver fibrosis is strongly associated with prognosis in patients with non-alcoholic fatty liver disease (NAFLD). We evaluated clinical risk factors for progression of liver fibrosis in patients with NAFLD. METHODS: This study included 1562 middle-aged (36-64 years) patients with NAFLD and less severe liver fibrosis (fibrosis-4 index < 1.3). RESULTS: During follow-up, 186 patients progressed to advanced fibrosis (fibrosis-4 index > 2.67). The 3-, 5-, 7-, and 10-year cumulative incidence of progression to advanced fibrosis was 4.4%, 6.7%, 11.0%, and 16.7%, respectively. In the univariate analysis, age, albumin concentration, and type 2 diabetes mellitus (T2DM) were significantly associated with progression to advanced fibrosis. Multivariate analysis with adjustment for age, smoking, body mass index, albumin, estimated glomerular filtration rate, dyslipidemia, T2DM, and steatosis showed that age ≥ 50 years (hazard ratio [HR], 2.121; 95% confidence interval [CI], 1.462-3.076; P < 0.001), albumin concentration < 4.2 g/dL (HR, 1.802; 95% CI, 1.285-2.528; P < 0.001), and the presence of T2DM (HR, 1.879; 95% CI, 1.401-2.520; P < 0.001) were independently associated with progression to advanced fibrosis. Conversely, degree of steatosis was not associated with progression to advanced fibrosis. The respective 3-, 5-, 7-, and 10-year cumulative incidence of progression to advanced fibrosis was 3.6%, 5.0%, 8.2%, and 12.9% in patients without T2DM (n = 1077) and 6.1%, 10.4%, 16.7%, and 24.0% in patients with T2DM (n = 485) (P < 0.001). CONCLUSIONS: Type 2 diabetes mellitus is associated with progression to advanced liver fibrosis in middle-aged NAFLD patients, even those with less severe liver fibrosis.

Differences in the impact of prognostic factors for hepatocellular carcinoma over time.

The aim of the present study was to evaluate the prognostic significance of serum markers that reflect tumor progression, liver function, or liver fibrosis in patients with hepatocellular carcinoma (HCC), focusing on how their impact changes over time after diagnosis. Alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), albumin-bilirubin (ALBI) score, aspartate aminotransferase to platelet ratio index (APRI), and FIB-4 index were measured at the time of initial non-recurrent HCC diagnosis in 1669 patients between 1997 and 2016. Survival rates after diagnosis were compared after stratifying patients by these markers. Time-dependent receiver-operating characteristics (ROC) analysis was carried out to assess how these markers predict patient survival or death. Serum AFP and DCP levels, ALBI score, and APRI and FIB-4 index were strongly correlated with HCC progression, liver function, and degree of liver fibrosis, respectively. Survival rates after diagnosis were significantly different when patients were stratified by these markers. In the time-dependent ROC analysis, AFP and DCP had a high prognostic impact within 3 years of diagnosis but the impact decreased thereafter. In contrast, APRI and FIB-4 index had higher prognostic impact 10 years after diagnosis. ALBI score had a high prognostic impact throughout the study period. Time-dependent ROC analysis clearly showed changes in the prognostic importance of serum markers based on the duration after diagnosis. Whereas the prognostic impact of tumor progression markers was strong in the short term, liver fibrosis markers had higher prognostic impact long after diagnosis. Liver function had constant prognostic impact on patient survival after diagnosis.

Improvement of liver stiffness in patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response.

BACKGROUND AND AIM: There is insufficient research on whether direct-acting antiviral (DAA) therapy can improve liver fibrosis in patients with chronic hepatitis C virus (HCV). We evaluated sequential changes in liver stiffness using shear wave elastography in patients with HCV who received DAA therapy. METHODS: A total of 210 patients with HCV who received daclatasvir and asunaprevir therapy and achieved sustained virological response (SVR) were analyzed. Liver stiffness, as evaluated by shear wave elastography, and laboratory data were assessed before treatment (baseline), at end of treatment (EOT), and at 24 weeks after EOT (SVR24). RESULTS: Alanine aminotransferase levels (ALT) decreased over time, and there were significant differences between baseline and EOT and between EOT and SVR24. Although platelet counts did not significantly differ between baseline and EOT, they increased significantly from EOT to SVR24. The median (interquartile range) liver stiffness values at baseline, EOT, and SVR24 were 10.2 (7.7-14.7), 8.8 (7.1-12.1), and 7.6 (6.3-10.3) kPa, respectively (P < 0.001, baseline vs EOT; P < 0.001, EOT vs SVR24). Additionally, in patients with ALT ≤ 30 (indicating low necroinflammatory activity in the liver) and Fibrosis-4 index > 2.0 (n = 75), the liver stiffness values at baseline, EOT, and SVR24 were 9.6 (7.7-15.2), 9.2 (7.3-12.1), and 7.7 (6.3-10.1) kPa, respectively (P < 0.001, baseline vs EOT; P < 0.001, EOT vs SVR24). CONCLUSION: These results suggest that early improvement of liver stiffness starts during the administration of DAAs in patients who achieve SVR, and this effect is particularly pronounced in patients with progressive liver fibrosis.

Utility of combined gray-scale and perflubutane contrast-enhanced ultrasound for diagnosing early hepatocellular carcinomas: Comparison of well differentiated and distinctly nodular types.

AIM: To clarify the value of gray-scale ultrasound (US) combined with contrast-enhanced US (CEUS) with perflubutane in diagnosing early hepatocellular carcinoma (HCC). METHODS: A total of 57 surgically resected, well differentiated HCCs were analyzed. Hepatocellular carcinomas were macroscopically diagnosed as vaguely nodular or distinctly nodular types, which correspond to early HCC or progressed HCC, respectively. Gray-scale US findings were evaluated in terms of shape (round or roundish, or irregular), border and contour (well-defined and smooth, or poorly defined), and intratumor echo levels (hyper, hypo, iso, heterogeneous, or mosaic). Contrast-enhanced US findings were evaluated during the arterial phase (vascularity [finely homogeneous, dendritic, or chaotic] and perfusion enhancement [homogeneous or heterogeneous]), portal phase (presence or absence of washout), and post-vascular phase (echo intensity level [defect, incomplete defect, or iso-enhancing]). RESULTS: Eighteen HCCs were categorized as early HCCs and the remaining 39 were categorized as progressed HCCs. Receiver operating characteristic curve analysis for the diagnosis of early HCC yielded area under the receiver operating characteristic curve (Az ) values for border and contour on gray-scale US and echo intensity level in the CEUS post-vascular phase of 0.782 and 0.828, respectively. Multiple logistic regression analysis also indicated that both of these gray-scale US and CEUS findings were independently associated with early HCC. The Az value for the combination of border and contour and echo intensity for the diagnosis of early HCC was 0.907, corresponding to a high diagnostic value. CONCLUSION: The combination of gray-scale US and CEUS can provide high-quality imaging assessment for diagnosing early HCC.

Utility of real-time shear wave elastography for assessing liver fibrosis in patients with chronic hepatitis C infection without cirrhosis: Comparison of liver fibrosis indices.

AIM: To clarify the diagnostic impact of liver fibrosis except for cirrhosis identified using shear wave elastography (SWE) in chronic hepatitis C (CHC) patients, and to compare the performance in diagnosing liver fibrosis among SWE and liver fibrosis indices. METHODS: A total of 55 CHC patients who underwent liver biopsy were analyzed. The diagnostic performance for identifying significant liver fibrosis (F2-F3) for SWE, FIB-4 index, aspartate aminotransferase-to-platelet ratio index (APRI) and Forns' index was assessed using receiver-operator curve (ROC) analysis. RESULTS: The median SWE elasticity value, FIB-4 index, APRI and Forns' index in the F0-F1 and F2-F3 groups were 6.3 kPa and 13.1 kPa; 1.52 and 4.45; 0.41 and 1.43; and 7.69 and 8.85, respectively (P < 0.001 for all four methods). Multivariate analysis showed that SWE was independently associated with the presence of significant liver fibrosis (odds ratio, 2.52; 95% confidence interval, 1.49-4.28; P < 0.001). The area under the ROC curve for SWE in diagnosing significant liver fibrosis was 0.94, indicating high diagnostic value, compared with 0.86, 0.88 and 0.83, for the FIB-4 index, APRI and Forns' index, respectively, which corresponds to moderate diagnostic value. The accuracy of SWE, FIB-4 index, APRI and Forns' index for diagnosing significant liver fibrosis was 90.9%, 76.4%, 74.5% and 67.2%, respectively. CONCLUSION: SWE has excellent ability for diagnosing significant liver fibrosis in CHC even when patients with cirrhosis are excluded. The diagnostic performance of SWE is superior to that of three liver fibrosis indices.

Utility of contrast-enhanced ultrasound with perflubutane for diagnosing the macroscopic type of small nodular hepatocellular carcinomas.

OBJECTIVE: To clarify the diagnostic value of contrast-enhanced ultrasound (CEUS) with perflubutane in the macroscopic classification of small nodular hepatocellular carcinomas (HCCs). METHODS: A total of 99 surgically resected nodular HCCs with a maximum diameter of 3 cm or less were analysed. HCCs were macroscopically categorized as simple nodular (SN) and non-SN. CEUS findings were evaluated during the arterial phase (vascularity, level and shape of enhancement), portal phase (presence or absence of washout) and post-vascular phase (echo intensity and shape). RESULTS: Sixty-eight HCCs were categorized as SN and the remaining 31 were categorized as non-SN. For diagnosis of non-SN HCC, the areas under the receiver operating characteristic curve (A z) value for the shape of enhancement in the late arterial phase and the shape of the post-vascular image were 0.824 (95 % confidence interval [CI] 0.721-0.895) and 0.878 (95 % CI 0.788-0.933), respectively. The A z value for the combination of the shape of enhancement in the late arterial phase and the shape of the post-vascular image for the diagnosis of non-SN HCC was 0.907 (95 % CI 0.815-0.956), corresponding to a high diagnostic value. CONCLUSION: CEUS can provide high-quality imaging assessment for determining the macroscopic classification of small nodular HCCs. KEY POINTS: • Non-SN is one of the poor prognostic factors in patients with HCC • Assessment of macroscopic type provides valuable information for the management of HCC • CEUS can provide high-quality imaging assessment for macroscopic classification of HCC • For non-SN HCC diagnosed using CEUS, hepatectomy is preferred as curative treatment.

[Case of small bowel angioectasia in which the resection site was angiographically detected using intraoperative dye infusion].

A 37-year-old Japanese man undergoing treatment for dilated cardiomyopathy was presented with weakness and melena. He had conjunctival pallor and difficulty in standing;his blood pressure was 81/62 mmHg. Abdominal computed tomography revealed contrast dye leakage into the small intestine. He was diagnosed with hemorrhagic shock secondary to intestinal bleeding;we administered large volumes of intravenous fluid along with performing a blood transfusion. We then performed angiography to determine the site of bleeding angioectasia and placed a catheter into the affected artery. We identified the resection site using an intraoperative dye infusion via the catheter, and successfully performed small bowel resection. He was subsequently discharged without complications.

Non-hypervascular hypointense nodules detected by Gd-EOB-DTPA-enhanced MRI are a risk factor for recurrence of HCC after hepatectomy.

BACKGROUND & AIMS: The gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) often depicts non-hypervascular hypointense hepatic nodules during the hepatobiliary phase in patients with hepatocellular carcinoma (HCC). It is unclear whether the presence of these nodules is associated with HCC recurrence after hepatectomy. We conducted a prospective observational study to investigate the impact of the presence of non-hypervascular hypointense hepatic nodules on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI on the recurrence of HCC after hepatectomy. METHODS: A total of 77 patients who underwent hepatectomy for primary, non-recurrent, hypervascular HCC were prospectively followed up after hepatectomy. Post-operative recurrence rates were compared according to the presence of non-hypervascular hypointense nodules on preoperative Gd-EOB-DTPA-enhanced MRI. RESULTS: Recurrence rates after hepatectomy were higher in patients with non-hypervascular hypointense nodules (risk ratio 1.9396 [1.3615-2.7222]) and the presence of non-hypervascular hypointense nodules was an independent factor associated with postoperative recurrence (risk ratio 2.1767 [1.5089-3.1105]) along with HCC differentiation and portal vein invasion. While no differences were found in the rate of intrahepatic metastasis recurrence based on the preoperative presence of non-hypervascular hypointense hepatic nodules, the rate of multicentric recurrence was significantly higher in patients with preoperative non-hypervascular hypointense hepatic nodules. CONCLUSIONS: Patients with preoperative non-hypervascular hypointense hepatic nodules detected during the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI are at higher risk of HCC recurrence after hepatectomy, mainly due to multicentric recurrence.

Transarterial chemoembolization for hepatitis B virus-associated hepatocellular carcinoma: improved survival after concomitant treatment with nucleoside analogues.

PURPOSE: To determine whether nucleoside analogue therapy is associated with improved survival in patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) who are treated solely with transarterial chemoembolization. MATERIALS AND METHODS: A retrospective chart review of patients diagnosed with HBV-associated HCC was performed to identify patients treated solely with chemoembolization. Relevant demographic and clinical data were extracted and recorded. The influence of therapy with nucleoside analogues (lamivudine, adefovir dipivoxil, or entecavir) was determined by estimating the survival function using the Kaplan-Meier product-limit method. RESULTS: The inclusion criteria for chemoembolization were met by 81 patients (67 men and 14 women, mean age 60.6 years ± 9.2); 21 (25.9%) of these patients had been treated with nucleoside analogues. The number of chemoembolization treatments was significantly greater in the patients who were treated with nucleoside analogues (3.43 ± 2.32) than in the patients who did not receive nucleoside analogues (1.82 ± 0.95; P = .0022). The 1-year, 3-year, and 5-year survival rates were 89.5%, 66.8%, and 40.5% in the patients treated with nucleoside analogues and 72.6%, 27.5%, and 14.3% in the patients not treated with nucleoside analogues. The survival rate was significantly higher in the patients who received nucleoside analogues (P = .0051). Nucleoside analogue intake was an independent factor that was associated with increased survival (P = .0063). CONCLUSIONS: Administration of nucleoside analogues was associated with longer survival in patients with HBV-associated HCC who were treated with transarterial chemoembolization.

Evolution of hypointense hepatocellular nodules observed only in the hepatobiliary phase of gadoxetate disodium-enhanced MRI.

OBJECTIVE: We sought to determine whether hypointense hepatocellular nodules observed in the hepatobiliary phase of MRI enhanced with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (gadoxetate disodium) progress to hypervascular hepatocellular carcinoma. MATERIALS AND METHODS: Gadoxetate disodium-enhanced MRI was repeated for 30 patients with 49 nodules determined to be hypointense in the hepatobiliary phase but nonenhancing in the arterial phase of dynamic MRI. The correlation between characteristics of hypointense nodules with slightly or markedly low signal intensity relative to surrounding liver parenchyma and their progression to hypervascular hepatocellular carcinoma was analyzed in cirrhotic livers. All patients underwent angiography-assisted CT before MRI. The rate of progression to classic hepatocellular carcinoma was calculated by the Kaplan-Meier method. RESULTS: The overall 6- and 12-month cumulative incidences of vascularization were 27.6% and 43.5%. The 6- and 12-month cumulative incidences of vascularized nodules with a maximum diameter 15 mm or greater were 43.3% and 77.3% and a maximum diameter less than 15 mm were 16.9% and 16.9%. The difference between these incidences was significant (p = 0.0147). CONCLUSION: Hypointense nodules with a maximum diameter of at least 15 mm often become hypervascular. Therefore, patients with hypointense nodules characterized by a maximum diameter of 15 mm or greater should be observed carefully because of the high incidence of vascularization.

Characteristics and prognosis of patients with hepatocellular carcinoma after the year 2000 in Japan.

BACKGROUND AND AIM: The survival rate of patients with hepatocellular carcinoma (HCC) improved through the 1990s in Japan, primarily due to advances in the detection of small HCC under the establishment of surveillance systems. We investigated how the characteristics of patients with HCC changed and whether this trend is continuing after the year 2000. METHODS: The characteristics and survival rates of patients with initial HCC (not a recurrence) who were diagnosed after the year 2000 until 2008 were analyzed and compared with those of patients in whom HCC was diagnosed in the 1990s or before. RESULTS: In comparison to 8 years before the year 2000, the percentage of patients with better liver function at diagnosis of HCC increased after the year 2000, whereas the size of maximal HCC tumors did not change in comparison to patients before the year 2000. The survival rate of patients continued increasing after the year 2000. CONCLUSIONS: The prognosis of patients with HCC continues to improve after the year 2000. This is not due to further improvements in the detection of small-sized HCC; the detection of small HCC had reached a plateau in the 1990s. Rather, this improvement appears to be due in part from the continued increase in the distribution of patients with better liver function at diagnosis.

Prediction of Hepatocellular Carcinoma by Liver Stiffness Measurements Using Magnetic Resonance Elastography After Eradicating Hepatitis C Virus.

INTRODUCTION: Liver fibrosis stage is one of the most important factors in stratifying the risk of developing hepatocellular carcinoma (HCC). We evaluated the usefulness of liver stiffness measured by magnetic resonance elastography (MRE) to stratify the risk of developing HCC in patients who underwent MRE before receiving direct-acting antivirals (DAAs) and subsequently achieved sustained virological response (SVR). METHODS: A total of 537 consecutive patients with persistent hepatitis C virus who underwent initial MRE before DAA therapy and achieved SVR were enrolled. Factors associated with HCC development were analyzed by univariate and multivariate Cox proportional hazards models. RESULTS: Albumin-bilirubin score ≥ -2.60 (adjusted hazard ratio [aHR] 6.303), fibrosis-4 (FIB-4) score >3.25 (aHR 7.676), and MRE value ≥4.5 kPa (aHR 13.190) were associated with HCC development according to a univariate Cox proportional hazards model. A multivariate Cox proportional hazards model showed that an MRE value ≥4.5 kPa (aHR 7.301) was the only factor independently associated with HCC development. Even in patients with an FIB-4 score >3.25, the cumulative incidence rate of HCC development in those with an MRE value <4.5 kPa was significantly lower than that in patients with an MRE value ≥4.5 kPa. DISCUSSION: Liver stiffness measured by MRE before DAA therapy was an excellent marker for predicting subsequent HCC development in patients with hepatitis C virus infection who achieved SVR. The same results were observed in patients with high FIB-4 scores.

Pretreatment non-hypervascular hypointense nodules on Gd-EOB-DTPA-enhanced MRI as a predictor of hepatocellular carcinoma development after sustained virologic response in HCV infection.

BACKGROUND: Identification of risk factors for the development of hepatocellular carcinoma (HCC) after a sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection is urgently needed for HCC surveillance. AIMS: To evaluate whether the presence of non-hypervascular hypointense nodules (NHHNs) depicted by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) before direct-acting antivirals (DAAs) therapy is a risk factor for de novo HCC development after SVR. METHODS: The presence of NHHNs was examined with EOB-MRI before the start of DAA therapy in 383 patients with HCV infection who achieved SVR. The incidence of de novo HCC after SVR was compared between patients with versus without NHHNs. RESULTS: NHHNs were detected before DAA therapy in 32 patients (8.4%). The incidence of de novo HCC after SVR was significantly higher in patients with NHHNs than in those without (1-, 3-, 5-year incidence, 9.8%, 24.2% and 41.6% vs. 0%, 1.2% and 4.4%, P < 0.0001). The presence of NHHNs before DAA therapy (adjusted HR, 10.86; 95% CI, 4.03-31.64) and cirrhosis (adjusted HR, 7.23; 95% CI, 1.88-35.85) were independently associated with a higher incidence of HCC after SVR. A higher incidence of de novo HCC after SVR remained after adjustment for age, gender, regular alcohol intake, diabetes, cirrhosis, FIB-4 index and serum alpha-foetoprotein with inverse probability of treatment weighting. CONCLUSIONS: This study confirmed that the presence of NHHNs before DAA therapy is a strong risk factor for the development of de novo HCC after SVR.

Incidence of hepatocellular carcinoma in patients with chronic hepatitis B virus infection who have normal alanine aminotransferase values.

The importance of alanine aminotransferase (ALT) levels in the progression of hepatitis B virus (HBV) infection remains a subject of debate. This study sought to identify independent risk factors involved in development of hepatocellular carcinoma (HCC), particularly in patients with chronic HBV infection who have normal ALT values. Data from 381 consecutive hepatitis B patients were analyzed with average ALT integration values < or = 40 IU/L and follow-up periods of > 3 years. Integration values were calculated from biochemical tests, and serological markers associated with the cumulative incidence of HCC were analyzed. HCC developed in 17 of the 381 patients (4.5%) during the follow-up period. Male sex (hazard ratio, 6.011 [95% confidence interval: 1.353-26.710], P = 0.018), high HBV-DNA levels (> or = 5.0 log copies/ml; 5.125 [1.880-13.973], P = 0.001), low platelet counts (< 15.0 x 10(4)/mm(3); 4.803 [1.690-13.647], P = 0.003), and low total cholesterol levels (< 130 mg/dl; 5.983 [1.558-22.979], P = 0.009) were significantly associated with greater incidence of HCC development. High HBV-DNA levels and low platelet counts are associated with the development of HCC in patients infected with hepatitis B who have normal ALT values. Therefore, maintenance of low HBV-DNA levels is important for the prevention of HCC in patients with low platelet counts, particularly in patients whose ALT values fall within the current normal range.