Tomokatsu Miyaki

Pitavastatin inhibits hepatic steatosis and fibrosis in non‐alcoholic steatohepatitis model rats

Aim:  Non‐alcoholic steatohepatitis (NASH) may progress to liver cirrhosis, and NASH patients with liver cirrhosis are at risk of developing hepatocellular carcinoma. Statins, 3‐hydroxy‐3‐methyglutaryl‐coenzyme A reductase inhibitors, are well known to reduce low‐density lipoprotein cholesterol and reduce the incidence of coronary heart disease and other major vascular events by anti‐inflammatory and antifibrotic effects, and antiproliferative properties in colorectal cancers have also been reported. Recently, statins have been reported to improve hepatic steatosis; however, the effect on fibrosis is controversial.

Clinical Evaluation of Sofosbuvir/Ledipasvir in Chronic Hepatitis C Genotype 1 with and without Prior Daclatasvir/Asnaprevir Therapy.

This study explored treatment outcomes of sofosbuvir (SOF)/ledipasvir (LDV) therapy for chronic hepatitis C patients with and without prior daclatasvir (DCV)/asunaprevir (ASV) therapy.

Clinical evaluation of sofosbuvir/ledipasvir in patients with chronic hepatitis C genotype 1 with and without prior daclatasvir/asunaprevir therapy

This study explored treatment outcomes of sofosbuvir (SOF)/ledipasvir (LDV) therapy for chronic hepatitis C patients with and without prior daclatasvir (DCV)/asunaprevir (ASV) therapy.

Noninvasive evaluation of hepatic fibrosis in hepatitis C virus‐infected patients using ethoxybenzyl‐magnetic resonance imaging

Liver biopsy is the gold standard test to determine the grade of fibrosis, but there are associated problems. Because gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid is secreted partially in hepatocytes and bile, it is possible that ethoxybenzyl‐magnetic resonance imaging (EOB‐MRI) correlates with liver function and liver fibrosis. The aim of this study was to compare the fibrosis seen in liver biopsy samples to the signal intensity of the hepatobiliary phase measured on EOB‐MRI in hepatitis C virus (HCV)‐infected patients.

Serum interferon‐gamma‐inducible protein‐10 concentrations and IL28B genotype associated with responses to pegylated interferon plus ribavirin with and without telaprevir for chronic hepatitis C

Several studies have shown that high pretreatment concentrations of serum interferon‐γ‐inducible protein‐10 (IP‐10) are correlated with non‐response to pegylated interferon (PEG‐IFN) plus ribavirin (RBV) for chronic hepatitis C (CHC). However, there are few reports on their effect on the Asian population.

Familial occurrence of congenital bile duct cysts

Congenital bile duct cysts are now a well‐documented anomaly of the biliary tree, and have become more common in Japan. Familial occurrence of congenital bile duct cysts, however, is extremely rare, with only six reported cases in the literature. We report a familial pattern of congenital bile duct cysts in a mother and her daughter. A 33‐year‐old female was admitted for evaluation of right upper quadrant abdominal pain and fever 6 days after an uneventful delivery of her second child. A com‐ puted tomography (CT) and ultrasound scan (US) revealed an obstructed biliary tract. Percutaneous transhepatic biliary drainage was then performed, and a cholangiogram revealed a Scholtz type B choledochocele without an anomalous connection of the pancreaticobiliary ducts. Endoscopic US demonstrated that the choledochocele was associated with a stone in the cyst. A pylorus‐preserving pancreatoduodenal resection was performed, and a histological study revealed that the choledochocele was lined by biliary mucosa without evidence of malignancy. The newborn infant had an abdominal tumour. An US and CT revealed a congenital bile duct cyst. An operation was performed and the intraoperative cholangiogram showed an Alonso‐Lej type I congenital bile duct cyst with an anomalous connection of the pancreaticobiliary ducts. Whether congenital bile duct cysts are hereditary remains to be elucidated.

Factors influencing distant recurrence of hepatocellular carcinoma following combined radiofrequency ablation and transarterial chemoembolization therapy in patients with hepatitis C.

Background: The purpose of this study was to clarify important risk factors for distant recurrence of hepatocellular carcinoma in patients positive for hepatitis C and without local recurrence. Methods: A total of 212 patients (145 males and 67 females) underwent radiofrequency ablation and transcatheter arterial embolization or transcatheter arterial chemoembolization at initial development of hepatocellular carcinoma. All patients were positive for hepatitis C. Child–Pugh classification was A in 115 and B in 97. The indication for radiofrequency ablation was the presence of up to three tumors ≤ 3 cm. The distant recurrence rate was analyzed using the Kaplan–Meier method and tested by Wilcoxon’s method. Results: Cumulative distant recurrence rates at years 1, 3, and 5 were 19%, 62%, and 79%, respectively. On univariate analysis, a ≥ 3 cm tumor, ≥ 50 ng/mL α-fetoprotein level, and < 3.6 g/dL serum albumin level were significant risk factors for distant recurrence, but only a serum albumin level < 3.6 g/dL (P = 0.004) was identified as significant on multivariate analysis. In the group with a pretreatment albumin level ≥ 3.6 g/dL, the distant recurrence rate was compared between patients in whom the albumin level rose, remained unchanged, or decreased by < 0.3 g/dL, and those in whom the level decreased by ≥ 0.3 g/dL. The rate was significantly higher in the latter, with a one-year recurrence rate of 7% versus 15% (P = 0.04). Conclusion: Distant recurrence was significantly decreased in patients with a high serum albumin level. Distant recurrence was more likely to occur in patients with a decreased albumin level, although the pretreatment level was high. Thus, strict follow-up after treatment for hepatocellular carcinoma is necessary in patients with low serum albumin levels.

Influence of Genes Suppressing Interferon Effects in Peripheral Blood Mononuclear Cells during Triple Antiviral Therapy for Chronic Hepatitis C

The levels of expression of interferon-stimulated genes (ISGs) in liver are associated with response to treatment with pegylated interferon (PEG-IFN) plus ribavirin (RBV). However, associations between the responses of ISGs to IFN-based therapy and treatment efficacy or interleukin-28B (IL28B) genotype have not yet been determined. Therefore, we investigated the early responses of ISGs and interferon-lambdas (IFN-λs) in peripheral blood mononuclear cells (PBMCs) during PEG-IFN/RBV plus NS3/4 protease inhibitor (PI) therapy. We prospectively enrolled 50 chronic hepatitis C patients with HCV genotype 1, and collected PBMCs at baseline, 8 and 24 h after the initial administration of PEG-IFN/RBV/PI. Levels of mRNAs for selected ISGs and IFN-λs were evaluated by real-time PCR. All 31 patients with a favorable IL28B genotype and 13 of 19 with an unfavorable genotype achieved sustained virological responses (SVR). Levels of mRNA for A20, SOCS1, and SOCS3, known to suppress antiviral activity by interfering with the IFN signaling pathway, as well as IRF1 were significantly higher at 8 h in patients with an unfavorable IL28B genotype than in those with a favorable one (P = 0.007, 0.026, 0.0004, 0.0006, respectively), especially in the non-SVR group. Particularly, the fold-change of IRF1 at 8 h relative to baseline was significantly higher in non-SVR than in SVR cases with an unfavorable IL28B genotype (P = 0.035). In conclusion, levels of several mRNAs of genes suppressing antiviral activity in PBMCs during PEG-IFN/RBV/PI differed according to IL28B genotypes, paralleling treatment efficacy.

Clinical factors related to long-term administration of sorafenib in patients with hepatocellular carcinoma.

Background Sorafenib has been approved in the indication of unresectable hepatocellular carcinoma, but there are many cases in which administration of the drug is discontinued due to severe side effects. In this study, we compared the characteristics of patients who continued and discontinued sorafenib. Methods Ninety-six patients (75 men and 21 women) were initiated on sorafenib from July 2009 through September 2011. The patient characteristics of interest included gender, age, etiology, Child-Pugh classification, treatment history and frequency, and levels of α-fetoprotein, des- gamma-carboxy prothrombin, aspartate amino acid transferase, and alanine aminotransferase. Duration of administration of sorafenib and reasons for its discontinuation were compared. Results Median overall survival was 11.8 months. Discontinuation of sorafenib within 90 days was identified as an independent prognostic factor for overall survival on multivariate analysis (P < 0.0001). Transarterial chemoembolization performed six times or more (P = 0.013) was also identified as an independent factor contributing to discontinuation of sorafenib within 90 days in multivariate analysis. Patients who received sorafenib for ≥90 days had significantly longer overall survival than those who discontinued it (P < 0.0001). Conclusion Prolonged treatment with sorafenib is an important factor in achieving extended overall survival. We recommend starting sorafenib before latent liver damage has occurred as a result of too many transarterial chemoembolization procedures.

Percutaneous Transhepatic Self-expanding Metallic Stent Placement for the Treatment of Malignant Afferent Loop Obstruction

We report the case of a 71-year-old man with afferent loop obstruction (ALO) after Roux-en-Y reconstruction due to gastric cancer. Computed tomography showed a distended afferent loop and a dilatated bile duct. We could not reach the stricture site in the afferent loop using a gastroscope. We performed percutaneous transhepatic biliary drainage (PTBD) and placed a self-expanding metallic stent (SEMS) in the duodenal stricture through the PTBD route. Although an endoscopic approach is preferable, when PTBD can be performed, percutaneous transhepatic SEMS placement might be an alternative option for treating ALO in cases in which it is not possible to reach the site of stenosis with an endoscope.