gadoxetic-acid-disodium and Hepatitis-C

We conducted a prospective study using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) to determine whether sustained virological response (SVR) by direct-acting anti-viral (DAA) drugs suppresses hepatocarcinogenesis in patients with hepatitis C virus (HCV) infection.. To use serial Gd-EOB-MRI to assess the impact of DAAs on hepatocarcinogenesis.. Between February 2008 and December 2018, 1083 consecutive patients with HCV infection underwent Gd-EOB-MRI. Of these, 719 patients were enrolled, including 210 patients in the 'Non-DAA group', who did not receive DAAs before the introduction of DAAs, and 509 patients in the 'DAA group', who achieved SVR after the introduction of DDAs. Factors associated with hepatocarcinogenesis were analysed by a Cox proportional hazard model. In addition, hepatocarcinogenesis was classified into two types, 'multistep' and 'de novo', on the basis of Gd-EOB-MRI findings. Factors associated with each type were analysed by Fine and Gray proportional hazards models.. Hepatocarcinogenesis was observed in 67 of 719 (9.3%) patients. Factors associated with hepatocarcinogenesis were male gender, albumin-bilirubin (ALBI) grade 2 or 3, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) ≥5%, the presence of nonhypervascular hypointense nodules (NHHNs) and Non-DAA group. Of 67 patients, multistep hepatocarcinogenesis occurred in 58 patients (86.6%) and de novo hepatocarcinogenesis occurred in nine patients (13.4%). Factors associated with multistep hepatocarcinogenesis were male gender and Non-DAA group.. The eradication of HCV by DAA therapy reduces multistep hepatocarcinogenesis.

Topics: Aged; alpha-Fetoproteins; Antiviral Agents; Bilirubin; Carcinoma, Hepatocellular; Contrast Media; Female; Follow-Up Studies; Gadolinium DTPA; Hepatitis C; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Prospective Studies; Serum Albumin; Sex Characteristics; Sustained Virologic Response

To determine MR-imaging features for the differentiation between hepatocellular carcinoma (HCC) and benign hepatocellular tumors in the non-cirrhotic liver.. 107 consecutive patients without liver cirrhosis (46 male; 45 ± 14 years) who underwent liver resection due to suspicion of HCC were included in this multi-center study. The following imaging features were assessed: lesion diameter and demarcation, satellite-lesions, central-scar, capsule, fat-content, hemorrhage, vein-infiltration and signal-intensity (SI) on native T1-, T2- and dynamic-enhanced T1-weighted images (center versus periphery). In addition, contrast-media (CM) uptake in the liver specific phase was analyzed in a sub-group of 42 patients.. Significant differences between HCC (n=55) and benign lesions (n=52) were shown for native T1-, T2- and dynamic-enhanced T1-SI, fat-content, and satellite-lesions (all, P<.05). Independent predictors for HCC were T1-hypointensity (odds-ratio, 4.81), T2-hypo-/hyperintensity (5.07), lack of central tumor-enhancement (3.36), and satellite-lesions (5.78; all P<0.05). Sensitivity and specificity of HCC was 91% and 75% respectively for two out-of four independent predictors, whereas specificity reached 98% for all four predictors. Sub-analysis, showed significant differences in liver specific CM uptake between HCC (n=18) and benign lesions (n=24; P<0.001) and revealed lack of liver specific CM uptake (odds-ratio, 2.7) as additional independent feature for diagnosis of HCC.. Independent MRI features indicating HCC are T1-hypointensity, T2-hypo- or hyperintensity, lack of central tumor-enhancement, presence of satellite-lesions and lack of liver specific CM-uptake. These features may have the potential to improve the diagnosis of HCC in the non-cirrhotic liver.

Topics: Adenoma, Liver Cell; Adult; Aged; Carcinoma, Hepatocellular; Contrast Media; Diagnosis, Differential; Female; Focal Nodular Hyperplasia; Follow-Up Studies; Gadolinium DTPA; Hepatectomy; Hepatitis C; Humans; Image Enhancement; Liver; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Retrospective Studies; Sensitivity and Specificity

To identify the characteristic diagnostic features of hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH) in Fontan-associated liver disease (FALD) patients using dynamic gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI).. Thirty-one FALD patients (mean age, 28.3 ± 7.2 years) with liver nodules who underwent dynamic Gd-EOB-DTPA-enhanced MRI were enrolled prospectively. Twenty-five patients (mean age, 72.8 ± 11.4 years) with hepatitis C virus (HCV)-related HCC constituted the control group. The tumour-to-liver signal intensity (SI) ratio was measured at 30, 60, 100, 180 seconds and 15 minutes, and the SI ratio was compared among FALD-HCC, FALD-FNH, and HCV-HCC.. FALD-HCC exhibited weak early enhancement with mild washout in late phases. FALD-FNH exhibited marked early enhancement that continued until the late phases. The SI ratio was significantly lower for FALD-HCC than for FALD-FNH in all phases. The SI ratio was significantly lower for FALD-HCC than for HCV-HCC only at 30 seconds (p<0.05), whereas poorer washout was seen in FALD-HCC than HCV-HCC in other phases. In 15 minutes, FALD-HCC had a significantly lower SI ratio compared to FALD-FNH (p<0.001).. The time course of Gd-EOB-DTPA-enhanced MRI signal intensity in FALD-HCC was different from that in FALD-FNH or HCV-HCC. This imaging finding may be useful adjunctive information to distinguish FALD-HCC from FALD-FNH.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Contrast Media; Focal Nodular Hyperplasia; Gadolinium; Gadolinium DTPA; Hepatitis C; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Middle Aged; Retrospective Studies; Young Adult

Glecaprevir is a substrate for organic anion-transporting polypeptide (OATP) 1B1/1B3, which transports bilirubin. Hyperbilirubinemia is an adverse event during anti-hepatitis C virus treatment with glecaprevir and pibrentasvir. Gadoxetic acid is also transported by OATP1B1/1B3, and we aimed to evaluate whether gadoxetic acid-enhanced magnetic resonance (MR) imaging was associated with glecaprevir trough concentrations (C

Topics: Aminoisobutyric Acids; Bilirubin; Cyclopropanes; Gadolinium DTPA; Hepacivirus; Hepatitis C; Humans; Hyperbilirubinemia; Lactams, Macrocyclic; Leucine; Magnetic Resonance Imaging; Proline; Quinoxalines; Sulfonamides

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.

Topics: Antiviral Agents; Carcinoma, Hepatocellular; Contrast Media; Gadolinium DTPA; Hepatitis C; Hepatitis C, Chronic; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Sustained Virologic Response

Paritaprevir inhibits organic anion-transporting polypeptide (OATP)1B1 and OATP1B3, which transport bilirubin. Hyperbilirubinemia is an adverse event reported during hepatitis C treatment. Gadoxetic acid is also transported by OATP1B1/1B3. We evaluated whether the enhancement effect in gadoxetic acid-enhanced magnetic resonance (MR) imaging could predict the plasma concentration of paritaprevir and might anticipate the development of hyperbilirubinemia.. This prospective study evaluated 27 patients with hepatitis C who underwent gadoxetic acid-enhanced MR imaging prior to treatment with ombitasvir, paritaprevir, and ritonavir. The contrast enhancement index (CEI), a measure of liver enhancement during the hepatobiliary phase, was assessed. Plasma trough concentrations, and concentrations at 2, 4, and 6 h after dosing were determined 7 d after the start of treatment.. Seven patients (26%) developed hyperbilirubinemia (≥ 1.6 mg/dl). Paritaprevir trough concentration (Ctrough) was significantly higher in patients with hyperbilirubinemia than in those without (p = 0.022). We found an inverse relationship between CEI and Ctrough (r = 0.612, p = 0.001), while there was not a significantly weak inverse relationship between AUC0-6 h and CEI (r = -0.338, p = 0.085). The partial correlation coefficient between CEI and Ctrough was -0.425 (p = 0.034), while excluding the effects of albumin and the FIB-4 index. Receiver operating characteristic (ROC) curve analysis showed that the CEI was relatively accurate in predicting hyperbilirubinemia, with area under the ROC of 0.882. Multivariate analysis showed that the CEI < 1.61 was the only independent predictor related to the development of hyperbilirubinemia, with an odds ratio of 9.08 (95% confidence interval 1.05-78.86, p = 0.046).. Hepatic enhancement with gadoxetic acid was independently related to paritaprevir concentration and was an independent pretreatment factor in predicting hyperbilirubinemia. Gadoxetic acid-enhanced MR imaging can therefore be useful in determining the risk of paritaprevir-induced hyperbilirubinemia.

Topics: Adult; Aged; Aged, 80 and over; Contrast Media; Cyclopropanes; Female; Gadolinium DTPA; Hepatitis C; Humans; Hyperbilirubinemia; Lactams, Macrocyclic; Macrocyclic Compounds; Magnetic Resonance Imaging; Male; Middle Aged; Proline; Prospective Studies; Sulfonamides; Time Factors; Treatment Outcome

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).

Topics: Aged; Antiviral Agents; Carcinoma, Hepatocellular; Female; Gadolinium DTPA; Hepatitis C; Humans; Incidence; Liver Cirrhosis; Liver Neoplasms; Magnetic Resonance Imaging; Male; Neoplasm Recurrence, Local; Remission Induction; Risk Factors; Sustained Virologic Response

Topics: Biopsy; Carcinoma, Hepatocellular; Contrast Media; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Gadolinium DTPA; Hepatectomy; Hepatitis C; Humans; Liver; Liver Neoplasms; Male; Middle Aged; Peliosis Hepatis; Predictive Value of Tests; Tomography, X-Ray Computed

To clarify the correlation between hepatobiliary phase (HBP) images using gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) and albumin-bilirubin (ALBI) grading system.. We evaluated 220 consecutive patients who underwent liver magnetic resonance imaging with Gd-EOB-DTPA. Quantitative liver-spleen contrast ratio (Q-LSC) was calculated in HBP images approximately 20min after Gd-EOB-DTPA administration. To evaluate the degree of association between Q-LSC and ALBI grade, the Child-Pugh (C-P) score was used for comparison. Correlation coefficients were calculated, and median Q-LSC values were compared with the C-P scores and ALBI grades. The Steel-Dwass multiple comparison test was used for statistical analysis.. The correlation coefficient between Q-LSC and C-P score was -0.35, P<0.0001, and the ALBI grade was -0.61, P<0.0001. Q-LSC of overall median, C-P A, B, and C were 1.94, 1.91, 1.96, and 1.33, respectively. The differences between C-P A and C-P B, C-P B and C-P C, and C-P A and C-P C were P=0.999, 0.126, and 0.149, respectively. Q-LSC of the overall median, ALBI grade 1, 2, and 3 were 1.94, 2.12, 1.69, and 1.30, respectively. The differences between ALBI grades 1 and 2, 2 and 3, and 1 and 3 were P<0.0001, P=0.0466, and P=0.0035, respectively. Q-LSC was better correlated and discriminated by ALBI grade than C-P score.. A strong correlation was observed between Q-LSC of an HBP image with Gd-EOB-DTPA and ALBI grade; HBP imaging could be a surrogate for the ALBI grade.

Topics: Aged; Aged, 80 and over; Bile Ducts; Bilirubin; Contrast Media; Female; Gadolinium DTPA; Hepatitis B; Hepatitis C; Humans; Liver; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Retrospective Studies; Serum Albumin; Spleen

Topics: Ablation Techniques; Aged; Carcinoma, Hepatocellular; Contrast Media; Diagnosis, Differential; Electroporation; Ferric Compounds; Gadolinium DTPA; Hepatitis C; Humans; Iron; Liver; Liver Cirrhosis; Liver Neoplasms; Magnetic Resonance Imaging; Oxides; Tomography, X-Ray Computed; Ultrasonography, Interventional

The aim of this study was to examine liver stiffness value measured by magnetic resonance elastography (MRE) and laboratory test results to find the best method for predicting insufficient liver enhancement on gadoxetic acid-enhanced hepatocyte-phase images.. The institutional ethics committee approved this retrospective study with waiver of informed consent. In total, 118 patients with Child-Pugh class A disease and type C hepatitis underwent MRE and gadoxetic acid-enhanced magnetic resonance imaging. During MRE examination, a pneumatic passive driver was used to obtain liver stiffness in kPa. Liver enhancement was assessed using liver-to-spleen contrast ratio (LSR), calculated using signal intensities of the liver and spleen on hepatocyte-phase magnetic resonance images obtained 20 minutes after contrast administration of gadoxetic acid. Insufficient liver enhancement was defined as an LSR lower than 1.5. The following laboratory test results were used as possible predictors of insufficient liver enhancement as well as liver stiffness measured by MRE: albumin, total bilirubin, aspartate aminotransferase, percentage prothrombin time, and platelet count. Correlation coefficients were calculated between LSR and these variables. Logistic analysis was performed to determine independent predictors of insufficient liver enhancement.. All possible predictors investigated were significantly correlated with LSR. Logistic regression analysis revealed that MRE was the only variable to predict insufficient liver enhancement, with an odds ratio (95% confidence interval) of 2.03 (1.22-3.85) (P = 0.0138). A cutoff value of greater than 6.4 kPa yielded 95% specificity for predicting insufficient liver enhancement.. Gadoxetic acid is not recommended in patients with liver stiffness greater than 6.4 kPa (consistent with severe fibrosis) because of insufficient liver enhancement on hepatocyte-phase images.

Topics: Confidence Intervals; Elasticity Imaging Techniques; Gadolinium DTPA; Hepatitis C; Hepatocytes; Humans; Liver; Logistic Models; Odds Ratio; Radiography; Retrospective Studies