Takatoshi Kitamura

Imaging Study of Early Hepatocellular Carcinoma: Usefulness of Gadoxetic Acid–enhanced MR Imaging

PURPOSE To describe imaging findings of early hepatocellular carcinoma (HCC) at gadoxetic acid-enhanced magnetic resonance (MR) imaging, dynamic contrast material-enhanced computed tomography (CT), CT during arterial portography (CTAP), and CT during hepatic arteriography (CTHA) and to compare the diagnostic performance of each modality for small (≤ 2 cm) HCC. MATERIALS AND METHODS The institute ethics committee deemed study approval unnecessary. One hundred eight resected small lesions in 64 patients were diagnosed as a dysplastic nodule (DN) (n = 12), progressed HCC (n = 66), or early HCC (n = 30). All but two patients underwent all imaging examinations. The imaging characteristics of the lesions with each modality were determined. To evaluate the diagnostic performance of the modalities, two radiologists graded the presence of HCC with use of a five-point confidence scale. The area under the receiver operating characteristic curve (A(z)), sensitivity, and specificity of each modality were compared. RESULTS The imaging features that are statistically significant for differentiating an early HCC from a DN include fat-containing lesions at dual-echo T1-weighted MR imaging (seen in 16 of the 30 early HCCs and none of the DNs), low attenuation at unenhanced CT (seen in 13 of the 30 early HCCs and none of the DNs), low attenuation at CTAP (seen in 11 of the 30 early HCCs and none of the DNs), and low signal intensity at hepatocyte phase gadoxetic acid-enhanced MR imaging (seen in 29 of the 30 early HCCs and none of the DNs). The diagnostic performance of gadoxetic acid-enhanced MR imaging (A(z), 0.98 and 0.99) was significantly greater than that of contrast-enhanced CT (A(z), 0.87) and CTHA-CTAP (A(z), 0.85 and 0.86) owing to its significantly higher sensitivity (P < .001). CONCLUSION Gadoxetic acid-enhanced MR imaging is the most useful imaging technique for evaluating small HCC, including early HCC.

Liver parenchymal enhancement of hepatocyte-phase images in Gd-EOB-DTPA-enhanced MR imaging: which biological markers of the liver function affect the enhancement?

To clarify the factors that predict enhancement of the liver parenchyma in hepatocyte‐phase of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd‐EOB‐DTPA)‐enhanced MR imaging.

High-b-value diffusion-weighted MR imaging of hepatocellular lesions: Estimation of grade of malignancy of hepatocellular carcinoma

To evaluate the effectiveness of diffusion‐weighted magnetic resonance imaging (DWI) in estimating the grade of malignancy of hepatocellular carcinoma.

Diagnosis of colorectal hepatic metastases: Comparison of contrast‐enhanced CT, contrast‐enhanced US, superparamagnetic iron oxide‐enhanced MRI, and gadoxetic acid‐enhanced MRI

To compare the diagnostic accuracy of contrast‐enhanced computed tomography (CE‐CT), contrast‐enhanced ultrasonography (CE‐US), superparamagnetic iron oxide‐enhanced magnetic resonance imaging (SPIO‐MRI), and gadoxetic acid‐enhanced MRI (Gd‐EOB‐MRI) in the evaluation of colorectal hepatic metastases.

Double-dose gadoxetic Acid-enhanced magnetic resonance imaging in patients with chronic liver disease.

Objectives:To determine the effect of double-dose gadoxetic-acid (Gd-EOB-DTPA) on lesion-liver contrast ratio in arterial- and hepatocyte-phase images and arterial-phase image quality in patients with chronic liver disease. Materials and Methods:The ethics committee at our institute approved this study. This study included 28 patients (13 with Child-Pugh class A and 15 with class B) with 54 hepatocellular carcinomas. All patients received the standard Gd-EOB-DTPA dose (0.025 mmol/kg bodyweight) and double dose (0.050 mmol/kg bodyweight). The lesion-liver contrast ratio was evaluated in arterial- and hepatocyte-phase images. The artifacts in arterial-phase images were evaluated with a 4-point scale. Wilcoxon signed-rank test were used for comparisons. Results:The hepatocyte-phase lesion-liver contrast ratio after the double dose was significantly higher than that after the standard dose in patients with Child-Pugh class B disease(standard dose vs. double dose; 0.20 ± 0.16 vs. 0.25 ± 0.17; P < 0.0001); however, the ratio after both the standard and double doses was equivalent in patients with Child-Pugh class A disease (0.35 ± 0.18 vs. 0.35 ± 0.14; P = 0.3038). The double dose significantly increased the arterial-phase lesion-liver contrast ratio (0.34 ± 0.19 vs. 0.58 ± 0.33; P < 0.0001). The artifacts in the arterial-phase images were more prominent after the standard dose (2.7 vs. 2.4 for reader 1, 2.8 vs. 2.4 for reader 2; P = 0.0195 and 0.0010). Conclusions:Administration of double dose of Gd-EOB-DTPA provided better arterial enhancement of hepatocellular carcinomas in patients with chronic liver disease, and also improved the lesion-liver contrast in hepatocyte-phase images in patients with Child-Pugh class B disease.

Higher prevalence and viral load of TT virus in saliva than in the corresponding serum: Another possible transmission route and replication site of TT virus

Although TT virus (TTV) is transmissible by blood or blood products, many patients with no history of transfusion of blood and blood products have been shown to be infected, suggesting other possible routes of transmission. To investigate the transmission routes and replication sites of TTV, 85 paired saliva and serum samples were studied by semi‐nested polymerase chain reaction. The prevalence of TTV DNA was 38% (32/85 samples) and 21% (18/85) in saliva and serum, respectively. Fifteen patients had TTV DNA both in saliva and serum. Six out of fifteen patients had significantly higher viral titers in saliva than in serum, but none had higher titer in serum than in saliva. When the 222 base‐pair nucleotide sequences of PCR products amplified from the samples were analyzed, 12 patients had the same genotype/subtype in saliva and serum and exhibited high homology (96–100%). The other 3 had different genotypes/subtypes in saliva and serum, and the homology was 61.9–87.2%. Mixed infection was observed both in saliva and serum. Further studies are required to determine if a subgroup of TTV has tropism to saliva. The high prevalence and viral load of TTV in saliva suggest that salivary fluid may be a possible route of transmission of TTV and that TTV might replicate not only in liver tissue but also in other tissues such as oropharyngeal tissues and/or salivary glands. J. Med. Virol. 62:531–537, 2000.

Comprehensive analysis for viral elements and interleukin‐28B polymorphisms in response to pegylated interferon plus ribavirin therapy in hepatitis C virus 1B infection

To comprehensively characterize the contribution of virological factors as well as interleukin‐28B (IL28B) single‐nucleotide polymorphisms (SNPs) in determining treatment responses in pegylated‐interferon plus ribavirin (Peg‐IFN/RBV) therapy for chronic hepatitis C virus (HCV)‐1b infection, we undertook a retrospective cohort analysis for the pretreatment dominant complete HCV open reading frame (ORF) amino‐acid (aa) sequence study in 103 consecutive HCV‐1b Japanese patients. The dominant HCV sequences classified by the response were subjected to systematic sliding‐window comparison analysis to characterize response‐specific viral sequences, along with IL28B SNP analyses (rs8099917). In each comparison of the patients between with and without rapid viral response (RVR), nonearly viral response (nEVR), sustained virological response (SVR), or relapse, the following regions were extracted as most significantly associated with the different responses respectively: nonstructural protein 5A (NS5A) aa.2224‐2248 (P = 1.2E‐07); core aa.70 (P = 4E‐04); NS5A aa.2340‐2382 (P = 7.0E‐08); and NS5A aa.2360‐2377 (P = 1.1E‐05). Those NS5A regions nearly coincided with the interferon (IFN) sensitivity‐determining region (NS5A aa.2209‐2248) and the IFN/RBV resistance‐determining region (NS5A aa.2339‐2379). In a multivariate analysis, the IL28B SNP (odds ratio [OR] = 16.8; P = 0.009) and NS5A aa.2340‐2382 (OR = 13.8; P = 0.0003) were extracted as the two most‐significant independent variables contributing to the final outcome. Conclusion: In Peg‐IFN/RBV therapy, polymorphisms in IL28B, NS5A aa.2224‐2248, core aa.70, and, most important, NS5A aa.2340‐2382 have a tremendous influence on treatment response in association with viral kinetics, resulting in significantly different outcomes in chronic HCV‐1b infection. (HEPATOLOGY 2012;56:1611–1621)

Diagnosis of colorectal hepatic metastases: Contrast-enhanced ultrasonography versus contrast-enhanced computed tomography versus superparamagnetic iron oxide-enhanced magnetic resonance imaging with diffusion-weighted imaging

To compare the diagnostic accuracy of contrast‐enhanced ultrasonography (CE‐US), contrast‐enhanced CT (CE‐CT), and superparamagnetic iron oxide‐enhanced MRI (SPIO‐MRI) with diffusion‐weighted imaging (DWI) in the evaluation of colorectal hepatic metastases.

Persistence of hepatitis B viremia after recovery from acute hepatitis B: correlation between anti-HBc titer and HBV DNA in serum

During the follow-up of 19 patients with self-limited acute hepatitis B for more than 2 years, clearance of hepatitis B surface antigen from the sera was observed in all patients within 6 months after disease onset, and the corresponding antibody (anti-HBs) appeared in 17 of the 19 patients within 12 months. However, upon performing nested polymerase chain reaction with the estimated sensitivity of 120-200 copies/ml, using two independent pairs of primers derived from the well-conserved sequences in the S gene or C gene region of the hepatitis B virus (HBV) genomes of all seven genotypes, HBV DNA was detected over a period of at least 12 months in serum samples obtained from five (26%) of the 19 patients, although it became undetectable in all five patients at 2-3 years after disease onset. The titer of antibody against hepatitis B core antigen (anti-HBc), assayed by the hemagglutination inhibition (HI, 2(N)) test, was significantly lower at the initial examination in the five patients who remained viremic for at least 12 months, than in the remaining 14 patients who cleared HBV DNA from their sera within 12 months after disease onset (10.6+/-2.7 vs. 13.6+/-0.7, P<0.02). Furthermore, these five patients showed a significantly lower rate of decrease of anti-HBc titer during the 12-month period after disease onset than the remaining 14 patients (55.0+/-32.6 vs. 91.0+/-7.9%, P<0.01). These results indicate that the initial titer and dynamics of anti-HBc may reflect the evolution of HBV viremia after clinical recovery from acute hepatitis B.

Polymerase domain B mutation is associated with hepatitis relapse during long-term lamivudine therapy for chronic hepatitis B.

Breakthrough hepatitis remains the major issue in long-term lamivudine therapy for chronic hepatitis B. However, the emergence of drug-resistant hepatitis B virus (HBV) is not always accompanied by a relapse of hepatitis. To elucidate factors predictive of breakthrough hepatitis, 53 patients with genotype C of HBV on long-term lamivudine therapy were analyzed. HBV reappeared during therapy in 19 patients with a cumulative incidence of 15% at 1 year, 34% at 2 years, and 60% at 3 years. Within this group, breakthrough hepatitis developed in 12 patients (63%). A polymerase gene domain B mutation (rt180M) emerged in 13 patients, and domain C mutations (rt204I, rt204V) were found in 19 patients. The rt180M mutation was associated with breakthrough hepatitis (p < 0.05) with a positive predictive value of 85% and a negative predictive value of 83%. Patients with the rt180M mutation had higher HBV-DNA levels during viral breakthrough compared to patients with rt180wt (p < 0.05). The mutational pattern of rt204 was not associated with breakthrough hepatitis. In conclusion, genotypic assays for the rt180M mutation after viral breakthrough may be useful in predicting the risk of breakthrough hepatitis and in deciding when to initiate alternative or additive nucleoside analogue therapy.