Takeshi Fukuda

Effects of terlipressin on systemic, hepatic and renal hemodynamics in patients with cirrhosis

Background and Aim:  Terlipressin has been shown to be effective in the management of hepatorenal syndrome. However, how terlipressin exerts its effect on the renal artery is unknown. The aim of the present study was to assess the effects of terlipressin on systemic, hepatic and renal hemodynamics in cirrhosis.

An open-label randomized controlled study of pegylated interferon/ribavirin combination therapy for chronic hepatitis C with versus without fluvastatin.

Summary.  Pegylated interferon (PEG‐IFN)/ribavirin combination therapy is the standard‐of‐care (SOC) treatment for chronic hepatitis C patients infected with hepatitis C virus (HCV) genotype 1b and high viral load. The addition of fluvastatin to SOC treatment has been suggested to be effective for better outcome in retrospective pilot analyses. We investigated whether the combination of fluvastatin with PEG‐IFN/ribavirin could actually improve sustained viral response (SVR) in patients with HCV genotype 1b and high viral load. A randomized, open‐labeled, controlled study was conducted between July 2008 and December 2009 in 101 chronic hepatitis C patients allocated to PEG‐IFN/ribavirin combination therapy with or without fluvastatin. SVR rates were calculated in groups, stratifying host and viral factors. We also analyzed predictive factors for SVR among patients on fluvastatin with multivariate regression analysis. Rapid and early virological, and end of treatment response rates in the fluvastatin group were not significantly different from those in the non‐fluvastatin group. Notwithstanding, SVR rate was significantly higher in the fluvastatin group than in the non‐fluvastatin group (63.0%vs 41.7%, P = 0.0422). Comparison of the two groups stratifying demographic data and HCV characteristics showed significantly higher SVR rates to more than 80% in males, more than two mutations in the interferon sensitivity determining region (ISDR), and a history of relapse among the fluvastatin group than the non‐fluvastatin group. Being male and major genotype IL28B single nucleotide polymorphisms (SNPs) were independent predictive factors for SVR among patients on fluvastatin with multivariate analysis. Fluvastatin‐combined with PEG‐IFN/ribavirin therapy significantly improves SVR rates in patients with HCV genotype 1b and high viral load. Male and major genotype IL28B SNPs were independent predictors for SVR among patients on fluvastatin combination therapy.

Combination of fluvastatin with pegylated interferon/ribavirin therapy reduces viral relapse in chronic hepatitis C infected with HCV genotype 1b

Although the anti‐hepatitis C virus (HCV) effect of statins in vitro and clinical efficacy of fluvastatin combined with Pegylated interferon (PEG‐IFN)/ribavirin therapy for chronic hepatitis C (CHC) have been reported, the details of clinical presentation are largely unknown. We focused on viral relapse that influences treatment outcome, and performed a post‐hoc analysis by using data from a randomized controlled trial.

Small Intestinal Edema Had the Strongest Correlation with Portal Venous Pressure amongst Capsule Endoscopy Findings

Background/Aim: Previous studies have reported small intestinal lesions in patients with portal hypertensive disease. However, the etiology of these lesions is not clear, as portal venous pressure was not measured in any of these studies. The aim of this study is to clarify the association between small intestinal lesions and hepatic venous pressure gradient (HVPG), which correlates well with portal venous pressure. Methods: Thirty-five patients with liver cirrhosis were evaluated by capsule endoscopy for small intestinal lesions. HVPG was measured within 3 days of capsule endoscopy. Blood tests, clinical symptoms, Child-Pugh classification and HVPG were analyzed against small intestinal lesions such as edemas, red spots, angiodysplasia and varices. Lesions were categorized according to their location in the duodenum, jejunum or ileum. Edema was evaluated using a 4-grade capsule endoscopy scoring index. Results: HVPG and edema scores increased with Child-Pugh scores. Red spots and angiodysplasia did not correlate with HVPG. Varices were detected in only 5 patients. The edema score was the factor which most strongly correlated with HVPG by multivariate analysis (p = 0.0008). There was also a strong linear relation between edema scores and HVPG (R = 0.75, p < 0.0001). Conclusion: Small intestinal edemas showed the strongest correlation with HVPG among all small intestinal lesions.

Serum 25-hydroxyvitamin D3 levels affect treatment outcome in pegylated interferon/ribavirin combination therapy for compensated cirrhotic patients with hepatitis C virus genotype 1b and high viral load

Much is unknown about the effect of 25‐hydroxyvitamin D3 levels on the outcome of pegylated interferon/ribavirin (PEG IFN/RBV) therapy for hepatitis C virus‐related cirrhosis. The purpose of the present study was to analyze and elucidate factors, including 25‐hydroxyvitamin D3, that contribute to a sustained virological response (SVR) in patients with cirrhosis.

EFFICACY OF ALFACALCIDOL ON PEG-IFN/ RIBAVIRIN COMBINATION THERAPY FOR ELDERLY PATIENTS WITH CHRONIC HEPATITIS C: A PILOT STUDY

Background Serum vitamin D concentration is reported to show a decrease in older age. Patients with chronic hepatitis C (CHC) in Japan are older on average than those in Western countries. Moreover, the outcome of pegylated-interferon (PEG-IFN)/ ribavirin therapy combined with vitamin D in elderly patients is unclear. Objectives This pilot study explored the efficacy and safety of alfacalcidol as vitamin D source in PEG-IFN/ ribavirin combination therapy for elderly CHC patients infected with hepatitis C virus genotype 1b. Patients and Methods Consecutive twenty CHC patients aged ≥ 65 years were enrolled in this pilot study. Fifteen patients met the inclusion criteria and received PEG-IFN/ ribavirin therapy combined with alfacalcidol. Four-week lead-in of oral alfacalcidol was conducted, and it was subsequently and concurrently administered in PEG-IFN/ ribavirin combination therapy (vitamin D group). Age, gender, and IL28B genotype-matched patients, who received PEG-IFN/ ribavirin alone, were saved as control group (n = 15) to compare the treatment outcome with the vitamin D group. Results Subjects consisted of 14 males and 16 females, with a median age of 70 years (65-78). The serum 25 (OH) D3 concentration in females (20 ng/ml, 11-37) was significantly lower than males (27 ng/mL, 13-49) (P = 0.004). Sustained virological response (SVR) rates were 33.3% (5/15) in the control group and 80.0% (12/15) in the vitamin D group, respectively (P = 0.025). While no significant difference was shown in the (SVR) rate between the two groups among males (P = 0.592), in females the SVR rate was significantly higher in the vitamin D group (87.5%, 7/8) than the control group (25.0%, 2/8) (P = 0.041). The relapse rates in the groups with and without alfacalcidol were 7.7% (1/13) and 61.5% (8/13), respectively (P = 0.011). Interestingly, in females, the relapse in the control group was shown in 5 of 7 (71.4%), whereas in the vitamin D group the relapse rate was decreased (1/8, 12.5%) (P = 0.041). No specific adverse events were observed in the vitamin D group. Conclusions PEG-IFN/ ribavirin combined with alfacalcidol may be effective and safe in elderly CHC patients. In particular, concomitant administration of alfacalcidol may lead to a reduced relapse rate, and consequently improving the SVR rate in elderly females.

Predictive factors for improvement of ascites after transjugular intrahepatic portosystemic shunt in patients with refractory ascites

The aim of this study was to investigate the predictive factors for the response of ascites to a transjugular intrahepatic portosystemic shunt (TIPS) and the impact of improvement of ascites on the overall prognosis of patients with cirrhosis and refractory ascites.

Effects of fasudil on the portal and systemic hemodynamics of patients with cirrhosis.

Fasudil, a Rho‐kinase inhibitor, has been shown to reduce portal venous pressure in cirrhotic rats. However, its effects on portal and systemic hemodynamics have not been investigated in cirrhotic patients with portal hypertension. The aim of this study was to assess the effects of fasudil on the portal and systemic hemodynamics of cirrhotic patients with portal hypertension.

Effect of fluvastatin on 24-week telaprevir-based combination therapy for hepatitis C virus genotype 1b-infected chronic hepatitis C.

Objectives The addition of fluvastatin significantly improves sustained virological response (SVR) in pegylated interferon and ribavirin (peg-IFN/RBV) combination therapy for patients infected with the hepatitis C virus. However, the add-on effect on telaprevir-based triple combination therapy remains unknown. The aim of this study was to investigate the effect of fluvastatin on telaprevir-based combination therapy by conducting a prospective, open-label, randomized, controlled trial. Patients and methods Among 124 genotype 1b-infected chronic hepatitis C patients recruited, 116 eligible patients were allocated randomly to two study arms; they received 12 weeks of telaprevir/peg-IFN/RBV, followed by 12 weeks of peg-IFN/RBV with or without 24 weeks of fluvastatin (fluvastatin group and control group, respectively). Treatment outcomes and adverse effects were compared between the two groups. Results There were 56 men and 60 women, median age 60 years (range, 28–71 years). Rapid virological response and end of treatment response rates were 87.9% (51/58) and 96.6% (56/58) in the control group and 75.9% (44/58) and 98.3% (57/58) in the fluvastatin group, respectively. SVR rates in the control group and the fluvastatin group were 84.5% (49/58) and 81.0% (47/58), respectively; there was no significant difference (P=0.806). Stratified analysis showed that no factors associated with the SVR rate were found between the two groups. No adverse events were associated with fluvastatin. Conclusion In this trial, administration of fluvastatin with telaprevir/peg-IFN/RBV was a safe combination. However, fluvastatin had no add-on effect on 24-week telaprevir-based combination therapy for chronic hepatitis C genotype 1b-infected patients.

Lead-in treatment with interferon-β/ribavirin may modify the early hepatitis C virus dynamics in pegylated interferon alpha-2b/ribavirin combination for chronic hepatitis C patients with the IL28B minor genotype

The most important factor influencing the effect of pegylated interferon (PEG‐IFN)/ribavirin therapy (PEG) for chronic hepatitis C genotype 1b with high viral load is the interleukin 28B (IL28B) genotype. We investigated the usefulness of lead‐in twice‐daily interferon (IFN)‐β/ribavirin therapy (IFN‐β), and the early hepatitis C virus RNA (HCV‐RNA) dynamics was compared between PEG and IFN‐β groups according to the IL28B genotype.