Usefulness of portal vein pressure for predicting the effects of tolvaptan in cirrhotic patients

AIM: To elucidate influencing factors of treatment response, then tolvaptan has been approved in Japan for liquid retention.METHODS: We herein conducted this study to clarify the influencing factors in 40 patients with decompensated liver cirrhosis complicated by liquid retention. Tolvaptan was administered at a dosage of 7.5 mg once a day for patients with conventional diuretic-resistant hepatic edema for 7 d. At the initiation of tolvaptan, the estimated hepatic venous pressure gradient(HVPG) value which was estimated portal vein pressure was measured using hepatic venous catheterization. We analyzed the effects of tolvaptan and influencing factors associated with treatment response.RESULTS: Subjects comprised patients with a median age of 65(range, 40-82) years. According to the ChildPugh classification, class A was 3 patients, class B was 19, and class C was 18. Changes from the baseline in body weight were-1.0 kg(P = 2.04 × 10^(-6)) and-1.3 kg(P = 1.83 × 10^(-5)), respectively. The median HVPG value was 240(range, 105-580) mm H2 O. HVPG was only significant influencing factor of the weight loss effect. When patients with body weight loss of 2 kg or greater from the baseline was defined as responders, receiver operating characteristic curve analysis showed that the optimal HVPG cutoff value was 190 mm H_2 O in predicting treatment response. The response rate was 87.5%(7/8) in patients with HVPG of 190 mm H2 O or less, whereas it was only 12.5%(2/16) in those with HVPG of greater than 190 mm H2O(P = 7.46 × 10^(-4)). We compared each characteristics factors between responders and non-responders. As a result, HVPG(P = 0.045) and serum hyaluronic acid(P = 0.017) were detected as useful factors.CONCLUSION: The present study suggests that tolvaptan in the treatment of liquid retention could be more effective for patients with lower portal vein pressure.

Interferon-λ3 polymorphisms in pegylated-interferon-α plus ribavirin therapy for genotype-2 chronic hepatitis C

AIM: To evaluate interferon-λ3(IFNL3) polymorphisms in response-guided pegylated interferon-α plus ribavirin(Peg-IFNα/RBV) therapy for genotype 2(G2) chronic hepatitis C.METHODS: Between January 2006 and June 2012, a total of 180 patients with chronic infections of G2 hepatitis C virus(HCV) were treated with responseguided Peg-IFNα/RBV therapy. The treatment duration was 24 wk for patients who achieved rapid virologic response(RVR), and 36 or 48 wk for patients who did not. Then, the impact of the IFNL3 single nucleotide polymorphism genotype(TT/non-TT at rs8099917) on treatment outcomes was evaluated in the 180 patients, and between patients infected with either HCV subgenotype 2a or 2b.RESULTS: Of the 180 patients evaluated, 111 achieved RVR, while the remaining 69 patients did not. In RVR patients, the sustained virologic response(SVR) rate was 96.4%, and the IFNL3 genotype did not influence the SVR rate(96.6% vs 95.8% in IFNL3 genotype TT vs non-TT). However, in non-RVR patients, the SVR rate decreased to 72.5%(P < 0.0001), and this rate was significantly different between the IFNL3 genotype TT and non-TT groups(80.0% vs 42.9%, P = 0.0146). Multivariate regression analysis in non-RVR patients identified the IFNL3 genotype TT as the only baseline-significant factor associated with SVR(OR = 5.39, 95%CI: 1.29-22.62; P = 0.0189). In analysis according to HCV sub-genotype, no significant difference in the SVR rate was found between HCV sub-genotypes 2a and 2b.CONCLUSION: In response-guided Peg-IFNα/RBV combination therapy for chronically HCV G2-infected patients, the impact of the IFNL3 genotype on SVR was limited to non-RVR patients.

Hepatitis C virus G1b infection decreases the number of small low-density lipoprotein particles

AIM: To investigate how hepatitis C virus(HCV) G1 b infection influences the particle number of lipoproteins.METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV G1 b infection(active HCV group) and 91 with cleared HCV infection(SVR group), were examined. Serum lipoprotein was fractionated by high-performance liquid chromatography into twenty fractions. The cholesterol and triglyceride concentrations in each fraction were measured using Lipo SEARCH. The number of lipoprotein particles in each fraction was calculated using a newly developed algorithm, and the relationship between chronic HCV G1 b infection and the lipoprotein particle number was determined by multiple linear regression analysis.RESULTS: The median number of low-density lipoprotein(LDL) particles was significantly lower in the active HCV group [1182 nmol/L, interquartile range(IQR): 444 nmol/L] than in the SVR group(1363 nmol/L, IQR: 472 nmol/L, P < 0.001), as was that of highdensity lipoprotein(HDL) particles(14168 nmol/L vs 15054 nmol/L, IQR: 4114 nmol/L vs 3385 nmol/L, P = 0.042). The number of very low-density lipoprotein(VLDL) particles was similar between the two groups. Among the four LDL sub-fractions, the number of large LDL particles was similar between the two groups. However, the numbers of medium(median: 533.0 nmol/L, IQR: 214.7 nmol/L vs median: 633.5 nmol/L, IQR: 229.6 nmol/L, P < 0.001), small(median: 190.9 nmol/L, IQR: 152.4 nmol/L vs median: 263.2 nmol/L, IQR: 159.9 nmol/L; P < 0.001), and very small LDL particles(median: 103.5 nmol/L, IQR: 66.8 nmol/L vs median: 139.3 nmol/L, IQR: 67.3 nmol/L, P < 0.001) were significantly lower in the active HCV group than in the SVR group, respectively. Multiple linear regression analysis indicated an association between HCV G1 b infection and the decreased numbers of medium, small, and very small LDL particles. However, active HCV infection did not affect the number of large LDL particles or any sub-fractions of VLDL and HDL particles.CONCLUSION: HCV G1 b infection decreases the numbers of medium, small, and very small LDL particles.

Effect of Silica Nanoparticles on Cultured Central Nervous System Cells

Nanotechnology is developing rapidly and the production of novel man-made nanoparticles is increasing. However, the effects of these particles on human health are unevaluated. Depending on particle size and the surface properties, nanoparticles may have the potential to affect human health. In recent studies, several silica nanoparticles (<100 nm) were shown to be penetrating into the brain. Thus, it is important to understand the influence of these nanoparticles on the central nervous system. In this study, we investigated the toxicological influence of nanoparticles on cortical cultured neurons isolated from embryonic day 18 Wister rats. Cortical cultured neurons at 21 days in vitro (DIV) were treated with 30 nm silica nanoparticles for 1 hr. Many neurons were damaged immediately more than at 0.01 mg/ml concentration of silica. Cell damage was also assessed using the lactate dehydrogenase (LDH) assay and the reactive oxygen species (ROS) assay. We revealed that the Neuro-toxicological mechanisms were due to membrane permeability. It was suggested that cell membrane permeability was enhanced because of ROS generation. Given these results, it will be important to determine the effect of nano-silica particles in vivo and identify the extent of neuronal damage.