The clinical features of patients with a Y93H variant of hepatitis C virus detected by a PCR invader assay.

BACKGROUND: Resistance-associated variants (RAVs) reduce the efficacy of interferon (IFN)-free therapy with asunaprevir and daclatasvir for patients infected with hepatitis C virus (HCV) genotype 1b. The characteristics of patients with an L31 or a Y93 variant in the nonstructural 5A region detected by a polymerase chain reaction invader assay were investigated. METHODS: In total, 201 patients with HCV genotype 1b were examined for L31F/M/V variants or a Y93H variant by the polymerase chain reaction invader assay. RESULTS: L31M and Y93H variants were detected in 4.6 and 21.4 % of patients, respectively. Patients with an L31M variant had no significant characteristics. Patients with a Y93H variant had significantly higher HCV RNA levels (6.5 ± 0.5 log copies per milliliter vs 6.1 ± 0.7 log copies per milliliter, p = 0.0002), higher frequency of mutant type of the IFN-sensitivity-determining region (88.4 % vs 71.7 %, p = 0.0251), and higher frequency of TT genotype at rs8099917 of IL28B (91.7 % vs 54.3 %, p < 0.0001) than those with Y93 wild-type strains. Multivariate analysis identified HCV RNA levels [odds ratio (OR) 3.72, 95 % confidence interval (CI) 1.71-8.06, p = 0.0009] and TT genotype at rs8099917 (OR 7.45, 95 % CI 2.11-26.4, p = 0.0018) as factors associated with the presence of a Y93H variant. CONCLUSION: The presence of a Y93H variant was associated with higher HCV RNA levels and TT genotype at rs8099917 of IL28B. Thus, patients with a Y93H variant may be ideal candidates for IFN-based therapy rather than IFN-free therapy, although the high viral load of these patients may reduce the response rate of IFN-based therapy.

Vitamin E reduces liver stiffness in nonalcoholic fatty liver disease.

AIM: To evaluate the efficacy of vitamin E treatment on liver stiffness in nonalcoholic fatty liver disease (NAFLD). METHODS: Thirty-eight NAFLD patients were administered vitamin E for > 1 year. The doses of vitamin E were 150, 300, or 600 mg; three times per day after each meal. Responses were assessed by liver enzyme levels [aspartate aminotransferase (AST), alanine aminotranferease (ALT), and γ-glutamyl transpeptidase (γ-GTP)], noninvasive scoring systems of hepatic fibrosis-4 [FIB-4 index and aspartate aminotransferase-to-platelet index (APRI)], and liver stiffness [velocity of shear wave (Vs)] measured by acoustic radiation force impulse elastography. Vs measurements were performed at baseline and 12 mo after baseline. The patients were genotyped for the patatin-like phospholipase domain containing 3 (PNPLA3) polymorphisms and then divided into either the CC/CG or GG group to examine each group's responses to vitamin E treatment. RESULTS: We found marked differences in the platelet count, serum albumin levels, alkaline phosphatase levels, FIB-4 index, APRI, and Vs at baseline depending on the PNPLA3 polymorphism. AST, ALT, and γ-GTP levels (all P < 0.001); FIB-4 index (P = 0.035); APRI (P < 0.001); and Vs (P < 0.001) significantly decreased from baseline to 12 mo in the analysis of all patients. In the subset analyses of PNPLA3 genotypes, AST levels (P = 0.011), ALT levels (P < 0.001), γ-GTP levels (P = 0.005), APRI (P = 0.036), and Vs (P = 0.029) in genotype GG patients significantly improved, and AST and ALT levels (both P < 0.001), γ-GTP levels (P = 0.003), FIB-4 index (P = 0.017), and APRI (P < 0.001) in genotype CC/CG patients. CONCLUSION: One year of vitamin E treatment improved noninvasive fibrosis scores and liver stiffness in NAFLD patients. The responses were similar between different PNPLA3 genotypes.

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.

Additional BCAA-enriched nutrient mixture improves the nutritional condition in cirrhotic patients with hypoalbuminemia despite treatment with regular BCAA granules: A pilot study.

BACKGROUND/AIMS: To elucidate the effect of adding branched-chain amino acid (BCAA)-enriched nutrient mixtures in cirrhotic patients with hypoalbuminemia despite the use of BCAA granules. MATERIALS AND METHODS: A BCAA-enriched nutrient mixture containing 5.6 g of BCAA and 210 kcal was additionally administered in 40 cirrhotic patients with hypoalbuminemia despite their treatment with BCAA granules containing 12 g of BCAA. Laboratory data were assessed at 6 months before beginning additional therapy, at baseline, and at 6 months after baseline. RESULTS: Serum albumin levels significantly decreased from 6 months before baseline (3.14±0.47 g/dL) to baseline (2.83±0.46 g/dL), despite the treatment with BCAA granules (p<0.001), and tended to increase from baseline to 6 months after baseline (2.95±0.42 g/dL) (p=0.084). In the subset of 23 patients without hepatocellular carcinoma treatments, upper gastrointestinal tract bleeding, or albumin infusion, serum albumin levels significantly increased from baseline (2.93±0.38 g/dL) to 6 months after baseline (3.15±0.34 g/dL) (p=0.014). CONCLUSION: Additional therapy with BCAA-enriched nutrient mixtures increased serum albumin levels of the cirrhotic patients with hypoalbuminemia despite the treatment with BCAA granules and without hepatocellular carcinoma treatment, upper gastrointestinal tract bleeding, or albumin infusion.

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

AIM: To investigate associations between patatin-like phospholipase domain-containing 3 (PNPLA3) genotypes and fibrosis and hepatocarcinogenesis in Japanese chronic hepatitis C (CHC) patients. METHODS: Two 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. RESULTS: PNPLA3 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. CONCLUSION: PNPLA3 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.

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 (ß = 0.1865, P < 0.0001) and hyaluronic acid levels (ß = 0.0008, P = 0.0039) in all patients by multiple regression analysis. Fibrosis area correlated significantly with ARFI by Spearman's rank correlation test but not by multiple regression analysis. ARFI correlated significantly with body mass index (BMI) (ß = -0.0334, P = 0.0001) in F 0 or F 1, with γ-glutamyltranspeptidase levels (ß = 0.0048, P = 0.0012) in F 2, and with fibrosis stage (ß = 0.2921, P = 0.0044) and hyaluronic acid levels (ß = 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.