Non-hypervascular Hypointense Nodules Research Articles

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.

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. 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. 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. 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. • 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.

Risk stratification of hepatocellular carcinoma in patients with chronic liver disease by combining gadolinium‐ethoxybenzyl diethylenetriamine‐pentaacetic acid–enhanced magnetic resonance imaging and magnetic resonance elastography

Background Liver stiffness (LS) as measured by magnetic resonance elastography (MRE) and the presence of intrahepatic nonhypervascular hypointense nodules (NHHNs) during the hepatobiliary phase of gadolinium-ethoxybenzyl diethylenetriamine-pentaacetic acid–enhanced magnetic resonance imaging are non-invasive MR-based biomarkers of hepatocarcinogenesis. Methods We retrospectively evaluated the ability of these two MR-based biomarkers to stratify the risk of hepatocellular carcinoma (HCC) development in patients with chronic liver disease. Between September 2013 and April 2020, 868 consecutive patients underwent MRE and gadolinium-ethoxybenzyl diethylenetriamine-pentaacetic acid–enhanced magnetic resonance imaging, among whom 487 were enrolled in this study. Factors associated with hepatocarcinogenesis were analysed by a Cox proportional hazard model. Results Thirty-two patients developed hypervascular HCC. According to the time-dependent receiver operating characteristic analysis, an LS value of 3.94 kPa was selected as the optimal cut-off value for predicting HCC development. Multivariate analyses identified high LS (≥3.94 kPa) and the presence of NHHN as independent predictive factors for HCC development. Patients were classified as follows: high LS/NHHN+ (Group 1), high LS/NHHN− (Group 2), low LS/NHHN+ (Group 3) and low LS/NHHN− (Group 4). The 5-year incidence rates of HCC in Groups 1, 2, 3 and 4 were 49.0%, 16.3%, 10.0% and 2.5% respectively. The HCC development rate was highest in Group 1 and lowest in Group 4 (P < 0.01). Conclusion MRE-based LS measurements and the presence of NHHN are useful biomarkers to stratify the risk of HCC development among chronic liver disease patients. Combining these biomarkers can provide a detailed classification of the risk of HCC development.

Long-term persistence of hepatocarcinogenic potential of a non-hypervascular hypointense nodule on EOB-MRI after the eradication of hepatitis C virus.

Non-hypervascular hypointense nodules (NHHNs) on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) have a high likelihood of hypervascularization progressing to typical hypervascular hepatocellular carcinoma (HCC). NHHNs that were present before the start of anti-hepatitis C virus (HCV) therapy is a risk marker for HCC development after achieving sustained virologic response (SVR). In this report, we show a patient without a previous history of HCC in whom HCC developed by hypervascularization of NHHN after SVR. This patient achieved SVR more than 8years before NHHN developed into HCC, and during this time NHHN had been present but had remained unchanged in size and imaging features as shown by repeated EOB-MRI. Hepatocarcinogenic potential of NHHNs persist for a long time after SVR, despite the eradication of HCV.

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.

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. 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. 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. 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. 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.

Surgical Indications for Hepatocellular Carcinoma with Non-hypervascular Hypointense Nodules Detected by Gd-EOB-DTPA-Enhanced MRI.

The surgical indication for non-hypervascular hypointense nodules (NHVN) detected incidentally on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) for classical hepatocellular carcinoma (HCC) is unknown. Our aim is to clarify the long-term outcomes in patients with this finding. We reviewed the cases of 290 HCC patients, including 66 patients with NHVN, who underwent Gd-EOB-MRI prior to hepatectomy, between October 2008 and December 2017 at our center. We divided the patients into three groups: a no-NHVN group, a treated NHVN group, and an untreated NHVN group. There was no significant difference in (RFS) or overall survival (OS) between the no-NHVN and untreated NHVN groups (p = 0.103 and 0.103, respectively). There was no significant difference between these two groups after propensity score matching. Multivariate analyses showed that microscopic intrahepatic metastases and the size of the main classical HCC, the target tumor, were independent prognostic factors of overall survival, but the presence of non-hypervascular hypointense nodules was not. There was no significant difference in RFS or OS between the treated NHVN and untreated NHVN groups (p = 0.158 and 0.109, respectively). Non-hypervascular hypointense nodules detected incidentally on Gd-EOB-MRI associated with targeted hypervascular HCC did not reflect prognosis of HCC after hepatectomy. Surgical procedures for classical enhancing HCC may be performed even if non-hypervascular hypointense nodules adjacent to the targeted HCC cannot be removed completely.

The emergence of non-hypervascular hypointense nodules on Gd-EOB-DTPA-enhanced MRI in patients with chronic hepatitis C.

Intrahepatic non-hypervascular hypointense nodules (NHHNs) detected during the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) have the potential to transition into typical hypervascular hepatocellular carcinoma (HCC). However, the incidence and risk factors for the emergence of these nodules in patients with chronic hepatitis C virus (HCV) infection are unknown. To investigate the incidence and risk factors for NHHNs in patients with chronic HCV infection in a longitudinal follow-up study METHODS: EOB-MRI was performed in 608 patients with chronic HCV infection and no history of HCC. The characteristics of patients with and without NHHNs were compared. In patients without NHHNs at baseline, the incidence of NHHN emergence and associated risk factors were analysed. NHHNs were detected at baseline in 93 of 608 patients (15.3%). Among 515 patients without NHHNs at baseline, the 1-year, 3-year and 5-year incidence of NHHN emergence was 1.8%, 9.8% and 16.4%, respectively. Only FIB-4 index was independently associated with the emergence of NHHNs in multivariate analyses. Whereas NHHNs emerged in 24.1% of patients with FIB-4 index≥3.25 at 5years, none emerged in patients with FIB-4 index<1.45. In patients with chronic HCV infection, advanced liver fibrosis is an important risk factor for the presence or emergence of NHHNs.

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

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). 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. 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. 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).

Prognosis after curative treatments of additional non-hypervascular hypointense nodules detected by EOB-MRI in a resectable hepatocellular carcinoma

Prognosis after curative treatments of additional non-hypervascular hypointense nodules detected by EOB-MRI in a resectable hepatocellular carcinoma

Impact of previously cured hepatocellular carcinoma (HCC) on new development of HCC after eradication of hepatitis C infection with non-interferon-based treatments.

The incidence of hepatocellular carcinoma (HCC) in patients with a history of curatively-treated HCC is higher than in patients with no history of HCC even after sustained virologic response (SVR). To investigate differences in the patterns of HCC development after SVR in patients with a history of curatively-treated HCC and those with no history of HCC, based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) findings. EOB-MRI was performed in 164 patients with HCV cirrhosis who achieved SVR by interferon-free direct-acting antiviral (DAA) therapy just before the start of therapy. Changes in EOB-MRI findings after SVR were compared prospectively between patients with (n = 62) and without (n = 102) a history of HCC. The incidence of HCC after SVR was higher in patients with a history of HCC (P < 0.0001). The prevalence of nonhypervascular hypointense nodules (NHHNs) by EOB-MRI was significantly higher in patients with a history of HCC at baseline (P = 0.05). Although there was no difference in the incidence of the hypervascularisation of baseline NHHNs to typical hypervascular HCC between patients with and without a history of HCC, the incidence of direct emergence of hypervascular HCC despite the absence of NHHNs at baseline was significantly higher in patients with a history of HCC (P < 0.0001). Direct emergence of hypervascular HCC and a higher prevalence of NHHNs before DD therapy contributed to the higher incidence of HCC after SVR. (UMIN000017020).

T1 mapping on gadoxetic acid-enhanced MR imaging predicts recurrence of hepatocellular carcinoma after hepatectomy

PurposeOur purpose was to demonstrate the prognostic significance of T1 mapping on gadoxetic acid-enhanced MR imaging in prediction of recurrence of single HCC after hepatectomy. Materials and methodsOne hundred and seven patients with single nodular HCC (≤3 cm) who underwent preoperative gadoxetic acid-enhanced MRI were included in the study. T1 mapping with syngo MapIt was obtained on a 1.5 T scanner. Radiological features and reduction rate of T1 relaxation time (Δ%) of tumors were assessed by two radiologists. Cumulative recurrence rates were compared between groups of low and high reduction rate of T1 relaxation time. A further classified cumulative recurrence rate of the overall cohort was based on the numbers of independent predictive factors. ResultsReduction rate of T1 relaxation time (P = 0.001) and non-hypervascular hypointense nodules (P = 0.042) in preoperative gadoxetic acid-enhanced MRI were independently related to recurrence of HCC after hepatectomy. Patients of lower reduction rates group had higher cumulative recurrence rates (P < 0.0001) than patients of higher reduction rates group. A combination of the two risk factors in patients with single HCC had significantly higher recurrence rates compared to those with either or none of the two risk factors. ConclusionsReduction rate of T1 relaxation time combined with non-hypervascular hypointense nodules can be reliable biomarkers in the preoperative prediction of recurrence of HCC after hepatectomy.

Non-Hypervascular Hypointense Hepatic Nodules during the Hepatobiliary Phase of Gadolinium-Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid-Enhanced MRI as a Risk Factor of Intrahepatic Distant Recurrence after Radiofrequency Ablation of Hepatocellular Carcinoma

Background: Non-hypervascular hypointense hepatic nodules during the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI have been reported to be associated with intrahepatic distant recurrence (IDR) after hepatectomy or radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). IDR is categorized into hypervascular transformation of non-hypervascular hypointense hepatic nodules and new intrahepatic recurrence. The aim of this study was to evaluate the relationship between non-hypervascular hypointense hepatic nodules on Gd-EOB-DTPA-enhanced MRI and IDR after RFA, focusing on new intrahepatic recurrence. Methods: Ninety-one consecutive patients with 115 HCCs undergoing pretreatment Gd-EOB-DTPA-enhanced MRI and RFA for treatment of HCC were enrolled. Results: Of the 91 patients who underwent RFA for HCC, 24 had non-hypervascular hypointense hepatic nodules on pretreatment Gd-EOB-DTPA-enhanced MRI. Recurrences were observed in 15 and 19 patients with and without non-hypervascular hypointense hepatic nodules, respectively. Of the 15 recurrences in patients with non-hypervascular hypointense hepatic nodules, 10 patients had new intrahepatic recurrences. The cumulative incidence of new intrahepatic recurrence was significantly higher in patients with non-hypervascular hypointense hepatic nodules than in those without non-hypervascular hypointense hepatic nodules (p < 0.0001). Multivariate analysis revealed that the presence of non-hypervascular hypointense hepatic nodules and Child-Pugh score were independent risk factors for new intrahepatic recurrence. Conclusions: Non-hypervascular hypointense hepatic nodules during the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were a useful predictive factor for IDR, particularly for new intrahepatic recurrence, after RFA.

Association between non-hypervascular hypointense nodules on gadoxetic acid-enhanced MRI and liver stiffness or hepatocellular carcinoma

PurposeTo assess the association between non-hypervascular hypointense nodules (NHHNs) on gadoxetic acid-enhanced magnetic resonance imaging (MRI) and liver stiffness (LS) in patients with chronic liver disease, and analyzed their progression to overt hepatocellular carcinoma (HCC). MethodsBetween August 2012 and March 2016, a total of 714 consecutive patients who had undergone transient elastography for LS measurement and gadoxetic acid-enhanced MRI were investigated. The association between the presence of NHHNs on the hepatobiliary phase and LS, and the patient’s HCC status [none, presence of treatment-naïve HCC, or a history of previous HCC treatment] was assessed. In patients with these nodules, cumulative progression rates of nodules to overt HCC were compared with rates of new HCC development in other parts of the liver. ResultsThe prevalence of NHHNs was 16.8% (120/714). The presence of these nodules was significantly associated with the log LS (Odds ratio [OR], 1.48, p=0.002) and hepatitis B virus infection (OR, 3.14, p=0.017), regardless of the patient’s HCC status. The two year cumulative progression rate of overt HCC from corresponding nodules and rate of progression to HCC in other parts of the liver were 34.1% and 18.3%, respectively (p=0.071). ConclusionThe presence of NHHNs on gadoxetic acid-enhanced MRI was associated with higher LS and hepatitis B virus infection. Furthermore, these lesions frequently progressed to overt HCC.

Non-hypervascular Hypointense Nodules on Hepatocyte Phase Gadoxetic Acid-Enhanced MR Images: Transformation of MR Hepatobiliary Hypointense Nodules into Hypervascular Hepatocellular Carcinomas.

Background/AimsThe annual risk of transformation of non-hypervascular magnetic resonance (MR) hepatobiliary phase imaging (HBPI) hypointense nodules into hypervascular hepatocellular carcinomas (HCCs) was evaluated.MethodsCirrhotic patients with non-hypervascular HBPI hypointense nodules were retrospectively analyzed if they were diagnosed as HCC and MR followed up longer than 1 year during the period from January 2010 to October 2016 with regular intervals of 3 to 6 months. Risk factors for transformation into hypervascular HCCs were analyzed using the Cox proportional hazard model.ResultsAmong the 103 non-hypervascular HBPI hypointense nodules meeting the inclusion criteria, transformation into hypervascular HCCs occurred in 44 tumors (42.7%). The median follow-up period was 24 months. Multivariate analysis revealed that hyperintensity on T2-weighted images (T2WI) and diffusion-weighted images (DWI) were the two independent predictors of transformation into hypervascular HCCs (p=0.036 and p=0.041, respectively). Most tumors with hyperintensity on T2WI or DWI on the initial or follow-up MR were transformed into hypervascular HCCs within the first year. Among the 22 nodules (21.3%) showing a new change in dynamic phases during follow-up, 14 nodules (13.6%) showed malignant transformations.ConclusionsThe transformation rates of HBPI hypointense nodules into hypervascular HCCs could be predicted according to the initial or serial MRI findings.

Presence of non‐hypervascular hypointense nodules on Gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid‐enhanced magnetic resonance imaging in patients with hepatocellular carcinoma

Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) performed before curative therapy for hepatocellular carcinoma (HCC) can distinguish between intrahepatic distant recurrence and hypervascularization. This study aimed to retrospectively evaluate the presence of non-hypervascular hypointense nodules on hepatobiliary phase images from Gd-EOB-DTPA-enhanced MRI as a risk factor of the intrahepatic distant recurrence of early stage HCC following radiofrequency ablation (RFA). A total of 132 patients who underwent preprocedural Gd-EOB-DTPA-enhanced MRI followed by initial RFA were retrospectively analyzed. Post-RFA intrahepatic distant recurrence, which excluded the hypervascularization of non-hypervascular hypointense nodules detected by preprocedural Gd-EOB-DTPA-enhanced MRI, was evaluated according to the presence of non-hypervascular hypointense nodules on preprocedural Gd-EOB-DTPA-enhanced MRI. Intrahepatic distant recurrence rates following RFA were higher in patients with non-hypervascular hypointense nodules (1-year: 22.5%, 2-year: 52.1%, 5-year: 89.1%) compared with in patients without non-hypervascular hypointense nodules (1-year: 7.0%, 2-year: 28.8%, 5-year: 48.7%). The presence of non-hypervascular hypointense nodules was associated with markedly increased cumulative recurrence rates of both identical and different subsegment intrahepatic distant recurrence, being an independent risk factor for post-RFA identical and different subsegment intrahepatic distant recurrence (identical: HR=2.365, P=0.027; different: HR=3.276, P<0.001). The presence of non-hypervascular hypointense nodules on hepatobiliary phase images from Gd-EOB-DTPA-enhanced MRI obtained prior to RFA is an important predictive factor of intrahepatic distant recurrence following RFA of HCC.

Non-hypervascular hepatobiliary phase hypointense nodules on gadoxetic acid-enhanced MRI: Risk of HCC recurrence after radiofrequency ablation

Hepatobiliary phase images (HBPI) of gadoxetic acid-enhanced MRI can depict borderline hepatocellular nodules that have the potential to progress into hypervascular hepatocellular carcinomas (HCCs), as non-hypervascular hypointense nodules. We retrospectively evaluated the impact of the presence of non-hypervascular hypointense nodules at HBPI of gadoxetic acid-enhanced MRI on the patient's prognosis after radiofrequency ablation (RFA) for early stage HCCs. A total of 139 patients who underwent pre-procedural gadoxetic acid-enhanced MRI followed by RFA were included. After a mean follow-up of 44.6±13.2 months, we compared the results of tumor recurrence as well as overall and recurrence-free survival (RFS) with the presence of non-hypervascular hypointense nodules on HBPI. The presence of non-hypervascular hypointense nodules on HBPI did not affect overall survival (p=0.136). However, the estimated 5-year RFS rate was 71.3% in 29 patients without non-hypervascular hypointense nodules on HBPI compared to 27.9% in 110 patients with non-hypervascular hypointense nodules on HBPI, indicating a significant difference (hazard ratio=2.84 [1.39-5.98], p=0.006). When we classified recurrence into local tumor progression [LTP], intrahepatic distant recurrence [IDR], and extra-hepatic metastasis [EM], five-year cumulative incidences (CI) of IDR in patients with non-hypervascular hypointense nodules on HBPI were significantly higher than those in patients without non-hypervascular hypointense nodules on HBPI (17.9% vs. 67.5%, p<0.001). Five-year CIs of LTP and EM showed no significant difference (p>0.05). The presence of non-hypervascular hypointense hepatocellular nodules on HBPI of gadoxetic acid-enhanced MRI taken prior to RFA is a significant predictive factor of recurrence after RFA of early stage HCCs, particularly IDR.

Non-hypervascular hypointense nodules on Gd-EOB-DTPA-enhanced MRI as a predictor of outcomes for early-stage HCC.

In patients with hepatocellular carcinoma (HCC), gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) often identifies non-hypervascular hypointense hepatic nodules during the hepatobiliary phase, but their prognostic significance is unclear. We conducted a prospective observational study to investigate the impact of non-hypervascular hypointense hepatic nodules detected by Gd-EOB-DTPA-enhanced MRI on the outcome of patients with early-stage HCC. Post-treatment recurrence and survival rates were analyzed in 138 patients with non-recurrent, early-stage HCC [Barcelona Clinic Liver Cancer (BCLC) stage 0 or A] and Child-Pugh A liver function according to the presence of non-hypervascular hypointense nodules on pretreatment Gd-EOB-DTPA-enhanced MRI. Non-hypervascular hypointense hepatic nodules were detected in 51 (37.0%) patients with early-stage HCC on pretreatment Gd-EOB-DTPA-enhanced MRI. Recurrence rates were significantly higher in patients with non-hypervascular hypointense nodules (p < 0.0001). Based on a multivariate analysis, the presence of non-hypervascular hypointense hepatic nodules on Gd-EOB-DTPA-enhanced MRI was independently associated with an increased recurrence rate, independent of tumor progression or treatment (p = 0.0005). The survival rate was significantly lower in patients with non-hypervascular hypointense nodules on Gd-EOB-DTPA-enhanced MRI (p = 0.0108). In patients with early-stage typical HCC (BCLC 0 or A), the presence of concurrent non-hypervascular hypointense hepatic nodules in the hepatobiliary phase of pretreatment Gd-EOB-DTPA-enhanced MRI is an indicator of higher likelihood of recurrence after treatment and may be a marker for unfavorable outcome.

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

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. 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. 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. 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.