Toru Nishikawa

Liver stiffness measured by transient elastography correlates with fibrosis area in liver biopsy in patients with chronic hepatitis C

Aim:  Liver stiffness (LS) measured by transient elastography (TE) has been reported to correlate with liver fibrosis, which is usually semiquantitatively assessed. In the present study, the fibrosis area was measured by image analysis software in liver biopsy specimens and its correlation with LS was assessed.

Reduction of liver stiffness by interferon treatment in the patients with chronic hepatitis C

Aim:  To assess the regression of liver fibrosis after interferon (IFN) treatment in patients with chronic hepatitis C, liver stiffness (LS) was measured repeatedly and the factors associated with reduction of LS were assessed.

Liver stiffness in extrahepatic cholestasis correlates positively with bilirubin and negatively with alanine aminotransferase

Aim:  Transient elastography is a non‐invasive tool to measure liver stiffness (LS), which has been reported to correlate with stage of liver fibrosis. Extrahepatic cholestasis was reported to cause elevated LS, which is considered to be attributed to the increased hydrostatic pressure in the liver. In the present study, the correlation of LS with laboratory data was investigated in extrahepatic cholestasis. The change of LS after biliary drainage was also assessed.

Factors correlating with acoustic radiation force impulse elastography in chronic hepatitis C.

AIM To investigate the factors other than fibrosis stage correlating with acoustic radiation force impulse (ARFI) elastograpy in chronic hepatitis C. METHODS ARFI elastograpy was performed in 108 consecutive patients with chronic hepatitis C who underwent a liver biopsy. The proportion of fibrosis area in the biopsy specimens was measured by computer-assisted morphometric image analysis. RESULTS ARFI correlated significantly with fibrosis stage (β = 0.1865, P < 0.0001) and hyaluronic acid levels (β = 0.0008, P = 0.0039) in all patients by multiple regression analysis. Fibrosis area correlated significantly with ARFI by Spearmans rank correlation test but not by multiple regression analysis. ARFI correlated significantly with body mass index (BMI) (β = -0.0334, P = 0.0001) in F 0 or F 1, with γ-glutamyltranspeptidase levels (β = 0.0048, P = 0.0012) in F 2, and with fibrosis stage (β = 0.2921, P = 0.0044) and hyaluronic acid levels (β = 0.0012, P = 0.0025) in F 3 or F 4. The ARFI cutoff value was 1.28 m/s for F ≥ 2, 1.44 m/s for F ≥ 3, and 1.73 m/s for F 4. CONCLUSION ARFI correlated with fibrosis stage and hyaluronic acid but not with inflammation. ARFI was affected by BMI, γ-glutamyltranspeptidase, and hyaluronic acid in each fibrosis stage.

Changes of shear-wave velocity by interferon-based therapy in chronic hepatitis C

AIM To evaluate the changes of shear-wave velocity (Vs) by acoustic radiation force impulse after treatment in chronic hepatitis C. METHODS Eighty-seven patients with chronic hepatitis C were consecutively treated with combinations of interferon (IFN) plus ribavirin (RBV). Vs value (m/s) was measured with acoustic radiation force impulse before treatment, at end of treatment (EOT), 1 year after EOT, and 2 years after EOT. RESULTS In patients with a sustained virological response (SVR) (n = 41), Vs significantly decreased at EOT [1.19 (1.07-1.37), P = 0.0004], 1 year after EOT [1.10 (1.00-1.22), P = 0.0001], and 2 years after EOT [1.05 (0.95-1.16), P < 0.0001] compared with baseline [1.27 (1.11-1.49)]. In patients with a relapse (n = 26), Vs did not significantly decrease at EOT [1.23 (1.12-1.55)], 1 year after EOT [1.20 (1.12-1.80)], and 2 years after EOT [1.41 (1.08-2.01)] compared with baseline [1.39 (1.15-1.57)]. In patients with a nonvirological response (n = 20), Vs did not significantly decrease at EOT [1.64 (1.43-2.06)], 1 year after EOT [1.66 (1.30-1.95)], and 2 years after EOT [1.61 (1.36-2.37)] compared with baseline [1.80 (1.54-2.01)]. Among genotype 1 patients, baseline Vs was significantly lower in SVR patients [1.28 (1.04-1.40)] than in non-SVR patients [1.56 (1.20-1.83)] (P = 0.0142). CONCLUSION Reduction of Vs values was shown in SVR patients after IFN-plus-RBV therapy by acoustic radiation force impulse.

PNPLA3 I148M associations with liver carcinogenesis in Japanese chronic hepatitis C patients

AimTo investigate associations between patatin-like phospholipase domain-containing 3 (PNPLA3) genotypes and fibrosis and hepatocarcinogenesis in Japanese chronic hepatitis C (CHC) patients.MethodsTwo hundred and thirty-one patients with CHC were examined for PNPLA3 genotypes, liver stiffness measurements (LSM), and hepatocellular carcinoma (HCC) from May 2010 to October 2012 at Fujita Health University Hospital. The rs738409 single nucleotide polymorphism (SNP) encoding for a functional PNPLA3 I148M protein variant was genotyped using a TaqMan predesigned SNP genotyping assay. LSM was determined as the velocity of a shear wave (Vs) with an acoustic radiation force impulse. Vs cut-off values for cirrhosis were set at 1.55 m/s. We excluded CHC patients with a sustained virological response or relapse after interferon treatment.ResultsPNPLA3 genotypes were CC, CG, and GG for 118, 72, and 41 patients, respectively. Multivariable logistic regression analysis selected older age (OR = 1.06; 95% CI: 1.03–1.09; p < 0.0001), higher body mass index (BMI) (OR= 1.12; 95% CI: 1.03–1.22; p = 0.0082), and PNPLA3 genotype GG (OR = 2.07; 95% CI: 0.97–4.42; p = 0.0599) as the factors independently associated with cirrhosis. When 137 patients without past history of interferon treatment were separately assessed, multivariable logistic regression analysis selected older age (OR = 1.05; 95% CI: 1.02–1.09; p = 0.0034), and PNPLA3 genotype GG (OR = 3.35; 95% CI: 1.13–9.91; p = 0.0291) as the factors independently associated with cirrhosis. Multivariable logistic regression analysis selected older age (OR = 1.12; 95% CI: 1.07–1.17; p < 0.0001), PNPLA3 genotype GG (OR = 2.62; 95% CI: 1.15–5.96; p = 0.0218), and male gender (OR = 1.83; 95% CI: 0.90–3.71); p = 0.0936) as the factors independently associated with HCC.ConclusionPNPLA3 genotype I148M is one of risk factors for developing HCC in Japanese CHC patients, and is one of risk factors for progress to cirrhosis in the patients without past history of interferon treatment.

HLA-DQ gene polymorphisms are associated with hepatocellular carcinoma and hepatitis B surface antigen in chronic hepatitis B virus infection†

Genome‐wide association studies have revealed that single nucleotide polymorphism (SNP) of human leukocyte antigen (HLA)‐DQ is associated with the clearance of hepatitis B surface antigen (HBsAg) in acute hepatitis B virus (HBV) infection. We examined the effects of SNPs on the development of hepatocellular carcinoma (HCC) and markers of HBV in chronic HBV infection.

Drainage patterns of the cholecystic vein evaluated by power doppler imaging

Power Doppler imaging (PDI) is a new technique that enhances detection of low-velocity blood flow. We used this modality to assess gallbladder vasculature, especially drainage pattern and flow analysis of the cholecystic vein. The power Doppler equipment used in this study was the Acuson Sequoia 512 system (Mountain View, California). Subjects were 27 patients with acute cholecystitis, 9 with gallbladder polyps, 7 with adenomyomatosis, 6 with gallstones, 2 with gallbladder cancer, 8 with liver cirrhosis, 7 with fatty liver, 4 with portal occlusion resulting from tumor thrombus, and 2 with anomalous arrangement of the pancreatic-obiliary ductal system. Ninety vessels in 72 individuals were evaluated with PDI. Continuous wave-form signals (cystic veins) were delineated at the body of the gallbladder in 67% of 72 cases (90 vessels) and in the fundus in 22%. Vessels communicating with the cystic vein (drainage vessel) were then analyzed in 78 veins. The drainage vessel was assessed to be a portal branch of segment 5 of the liver (P 5) in 59%, a middle hepatic vein (MHV) in 38%, and the PV trunk in 3%. The cystic vein from the body drained into the P 5 in 74% and the fundus drained into the MHV in 75%. On fast Fourier transformation analysis of the cystic venous, flow, estimated maximal velocity (Vmax) was relatively high in patients with acute cholecystitis, gallbladder cancer and portal occlusion. Interestingly, the focal spared area in the fatty liver appeared to be perfused with cystic veins, in addition to having reduced portal blood flow. We conclude that power Doppler imaging may hold promise for assessing drainage pattern of the cystic vein.