Shinichi Fujioka

High prevalence of TT virus in human bile juice samples: importance of secretion through bile into feces.

TT virus (TTV) is much more prevalent than we once imagined. With the use of primers designed from the noncoding regions, a more than 90% rate of TTV infection in the general population by polymerase chain reaction (PCR) has been reported, showing that nonparenteral transmission must play an important role to its epidemiology. We considered that TTV may be secreted through bile juice into feces to establish nonparenteral infection. Paired bile juice and serum samples were obtained from 26 patients who were receiving bile drainage. Feces were also recovered after the drainage tube was removed. TTV DNA was detected from 22 patients in serum (84.6%), and they were all TTV DNA positive in bile juice. Most feces samples recovered from TTV-positive patients were also TTV DNA positive. Secretion of TTV into bile juice appears to be common, and this could play an important role to its transmission and its epidemiology.

Early Clearance of Circulating Hepatitis C Virus Enhanced by Induction Therapy with Twice-a-Day Intravenous Injection of IFN-β

To improve the long-term efficacy of interferon (IFN) for treatment of chronic hepatitis C virus (HCV) infection, we proposed induction therapy with twice-a-day IFN-beta injection. This study was intended to clarify the antiviral mechanism. Thirty patients were randomly assigned to two groups: group A (twice-a-day therapy) received 3 MU IFN-beta intravenously (i.v.) twice a day for 2 weeks; group B (once-a-day therapy) received 6 MU of IFN-beta daily. HCV RNA, IFN-beta, alanine aminotransferase (ALT), 25-oligoadenylate synthetase (25-AS) activity, and beta2-microglobulin in serum were compared between the two groups during the first 2 weeks of IFN therapy. The clearance rate of serum HCV RNA in group A (86.7%) was significantly higher than that in group B (13.3%) at day 3 (p = 0.0006). No accumulation of IFN-beta was shown in serum throughout the therapy. The ratio (day 3/day 1) of 25-AS activity was significantly higher in group A. Multivariate analysis indicated twice-a-day IFN-beta injection therapy led to significantly early clearance of circulating HCV. Twice-a-day IFN-beta injection therapy could induce biologically enhanced antiviral activities and be an efficient induction therapy for eradication of HCV.

Fibrosis progression rates between chronic hepatitis B and C patients with elevated alanine aminotransferase levels

BackgroundWe evaluated the annual rate of fibrosis progression in chronic hepatitis B and C patients with elevated alanine aminotransferase (ALT) levels.MethodsForty-nine chronic hepatitis B patients and 21 chronic hepatitis C patients, each of whom had undergone two or more liver biopsies at an interval of more than 1 year, were enrolled in this retrospective clinical research protocol. The annual rate of fibrosis progression was calculated by dividing the change in fibrosis stage between the first and second liver biopsies by the interval in years between them.ResultsThe median interval in chronic hepatitis B and C was 3.4 (first and third quartiles, 1.8–4.7) and 3.2 (2.1–6.5) years, respectively. Overall, the mean fibrosis progression rate was 0.21 ± 0.31 (mean ± SD) fibrosis units (FU) per year in 49 patients with chronic hepatitis B, and 0.13 ± 0.18 FU/year in 21 patients with chronic hepatitis C. The ALT level was an independent variable correlating with fibrosis progression. In patients whose median ALT level was 70 IU/l or more, the mean fibrosis progression rate was 0.28 ± 0.32 FU/year in 36 patients with chronic hepatitis B, and 0.22 ± 0.23 FU/year in eight patients with chronic hepatitis C.ConclusionThis paired-biopsy study of untreated chronic hepatitis B or C demonstrated that fibrosis progression occurred largely in patients with continuously elevated ALT levels even over a relatively short period, and that liver fibrosis might progress by one stage within an average of 4–5 years of follow-up in patients with elevated ALT of 70 IU/l or more.

Diagnostic Accuracy of Laparoscopic Liver Biopsy in Chronic Liver Diseases, Comparison of Laparoscopic and US‐Guided Liver Biopsy Results

Liver biopsies were carried out using three different needles, a Vim‐Silverman needle 2.5 mm in outer caliber, an 18‐Gauge (18G) Majima needle, and a 17‐Gauge (17G) Majima needle. The biopsies were obtained from nearby locations on the liver surface under laparoscopic observation, to ascertain differences in histological diagnosis according to the size of the biopsy specimen. The biopsy specimens obtained with the Vim‐Silverman needle were wider than those obtained with the other two needles. The agreement in histological diagnoses of the liver, obtained with the Vim‐Silverman needle versus the 18G Majima needle, was 26.0%, while that between the Vim‐Silverman needle and the 17G Majima needle was 40.0%. Histological diagnosis tended to be underestimated in small biopsy specimens in advanced chronic liver diseases. A questionnaire survey, conducted in 92 hospitals affiliated with Okayama University Medical School, revealed US‐guided liver biopsy to be the practice of choice in 57 of 92 (62.0%) hospitals, and 18G needles were used in US‐guided liver biopsy in 35 of 78 (45.2%) hospitals.

Real-world virological efficacy and safety of elbasvir and grazoprevir in patients with chronic hepatitis C virus genotype 1 infection in Japan

BackgroundThe real-world virological efficacy and safety of an interferon (IFN)-free direct-acting antiviral (DAA) therapy with elbasvir (EBR) and grazoprevir (GZR) were evaluated in Japanese patients chronically infected with hepatitis C virus (HCV) genotype 1.MethodsThe rate of sustained virologic response (SVR) and safety were analyzed in patients who started the EBR/GZR regimen between November 2016 and July 2017. SVR rates were compared based on patient baseline characteristics.ResultsOverall, 371 of 381 patients (97.4%) achieved SVR. Multivariate analysis identified a history of failure to IFN-free DAA therapy and the presence of double resistance-associated substitutions (RASs) in HCV non-structural protein 5A (NS5A) as factors significantly associated with failure to EBR/GZR treatment. The SVR rates of patients with a history of IFN-free DAA therapy and those with double RASs were 55.6 and 63.6%, respectively. In all other subpopulations, the SVR rates were more than 90%. There were no severe adverse events associated with the treatment.ConclusionsThe EBR/GZR regimen yielded high virological efficacy with acceptable safety. Patients with a history of failure to IFN-free DAA therapy or with double RASs in HCV-NS5A remained difficult to treat with this regimen.

Efficacy and safety of elbasvir/grazoprevir for Japanese patients with genotype 1b chronic hepatitis C complicated by chronic kidney disease, including those undergoing hemodialysis: A post-hoc analysis of a multicenter study.

This study aimed to evaluate the efficacy and safety of elbasvir/grazoprevir in genotype 1b chronic hepatitis C Japanese patients with chronic kidney disease (CKD), including those undergoing hemodialysis.

Characteristics and Prognosis of Hepatocellular Carcinoma in Japanese Patients Undergoing Dialysis

Patients with end‐stage renal disease who are undergoing dialysis may be at high risk of developing hepatocellular carcinoma (HCC). We investigated the characteristics and prognosis of HCC in patients undergoing dialysis in Japan. Patients characteristics, progression of HCC at diagnosis, and survival rates after diagnosis were compared between 108 HCC patients undergoing dialysis and 526 non‐dialysis patients followed up at liver center. The comparisons were also performed after adjusting for patient age, gender, platelet count, and etiology using propensity‐score matching. HCC was more advanced in patients undergoing dialysis than in non‐dialysis controls. The 3‐ and 5‐year survival rates of patients undergoing dialysis were 56.3% and 38.3%, respectively, which were lower than those of non‐dialysis controls (66.5% and 52.7%, respectively, P = 0.0026). The results were the same after propensity score matching (P = 0.0014). In Japan, HCC was more advanced at diagnosis in patients undergoing dialysis in comparison to HCC in patients at liver centers, resulting in a lower survival rate after diagnosis.

Clinical features of hemodialysis patients treated for hepatocellular carcinoma: Comparison between resection and radiofrequency ablation

There is no consensus regarding which therapeutic option is better and/or safer for treating hemodialysis (HD) patients with hepatocellular carcinoma (HCC). The present study compared surgical resection (Hx) and radiofrequency ablation (RFA) with regard to therapeutic efficacy in HD patients with HCC. Of 108 HD patients with naïve HCC treated at 15 institutions between 1988 and 2014 enrolled in the present study, 58 fulfilled the up-to-7 criteria [7 as the sum of the size of the largest tumor (cm) and the number of tumors] and were treated with Hx (n=23) or RFA (n=35); their clinical features, complications and prognosis were assessed. The frequency of hepatitis C virus was higher in the RFA group compared with that in the Hx group (P=0.002), whereas there were no differences between the groups with regard to the average time from the first HD (P=0.953), tumor-nodes-metastasis (TNM) stage (Union for International Cancer Control 7th edition) (P=0.588), TNM stage (Liver Cancer Study Group of Japan 5th edition) (P=0.095), Child-Pugh classification (P=0.094), and Japan Integrated Scoring system (P=0.489). There were no significant differences in overall survival (OS) and disease-free survival (DFS) rates between the Hx and RFA groups [1-, 3- and 5-year OS rates: 81.7, 55.6 and 43.3% vs. 89.9, 67.1 and 56.3%, respectively (P=0.454); 1-, 3- and 5-year DFS rates: 71.1, 30.5 and 18.3% vs. 63.8, 31.6 and 21.1%, respectively (P=0.911)] Complications were observed in 4 patients (11.4%) in the RFA group (2 with subcapsular hemorrhage, 1 with intraperitoneal bleeding and 1 with tardive intrahepatic hematoma) and in 4 patients (17.4%) in the Hx group (2 with postoperative infection, 1 with liver failure and 1 with pleural effusion) (P=0.700). In conclusion, Hx and RFA have a similar therapeutic efficacy in HD patients with naïve HCC who fulfilled the up-to-7 criteria.

Endoscopy is one of the valuable diagnostic methods for primary aorto-enteric fistula

The present report describes a case of primary aorto‐enteric fistula (PAEF) in an 81‐year‐old man with no previous abdominal surgery. The patient was admitted to Teraoka Memorial Hospital in shock with repeated episodes of melena and hematemesis. We performed emergency endoscopy to establish a diagnosis and identified a ruptured aortic aneurysm visualized through a fistula in the second portion of the duodenum. As most PAEF cause massive gastrointestinal hemorrhage, prompt diagnosis is critical to ensure a successful outcome. Although the patient and his family refused surgery and the patient died, we were able to make the diagnosis at an early stage by endoscopy. While PAEF is usually very difficult to diagnose by a single modality, endoscopy can be one of the modalities to identify the source of gastrointestinal hemorrhages, even in cases of PAEF.