Munenori Itagaki

New Proposal for Response-Guided Peg-Interferon- Plus-Ribavirin Combination Therapy for Chronic Hepatitis C Virus Genotype 2 Infection

This study aimed to determine the most suitable duration of pegylated‐interferon (Peg‐IFN)‐plus‐ribavirin combination therapy in patients infected with hepatitis C virus (HCV) genotype 2 who had not achieved rapid virological response (serum HCV RNA disappearance after 4 weeks of therapy). HCV genotype 2 patients (n = 182) with a high viral load received >80% of the standard Peg‐IFN‐plus‐ribavirin dose for at least 24 weeks, and their final virological responses were studied. Patients were classified into “rapid virological response” and “non‐rapid virological response” groups. The non‐rapid virological response group was further divided into a “virological response at 8 weeks” (serum HCV RNA disappearance after 8 weeks of therapy) and a “non‐virological response at 8 weeks” group. Factors related to rapid virological response and optimal therapy duration in the non‐rapid virological response group were evaluated. Multivariate logistic regression analysis showed that subtype HCV genotype 2a (P = 0.0015) and low concentration of pretreatment serum HCV RNA (P = 0.0058) were independent factors in a rapid virological response. In the virological response at 8 weeks group, the sustained virological response rate after 24 weeks of therapy was significantly lower than after 36 weeks (P = 0.044) or after 48 weeks (P = 0.006), and was similar for 36‐ and 48‐weeks. The cost for achieving (CAS) one sustained virological response was lowest with 36‐week therapy. Prolongation of Peg‐IFN‐plus‐ribavirin combination therapy to 36 weeks is suitable for achieving virological response at 8 weeks, given the high, sustained virological response rate and cost benefit. J. Med. Virol. 85:1523–1533, 2013.

Impact of Chronic Hepatitis C Virus Genotype 1b Infection on Triglyceride Concentration in Serum Lipoprotein Fractions.

Reduced low-density lipoprotein (LDL) cholesterol level is a characteristic feature of dyslipidemia in chronic hepatitis C virus (HCV) infection. However, abnormality in serum triglyceride (TG) has not been fully investigated. To clarify the impact of HCV genotype 1b (G1b) infection and advanced fibrosis on serum TG profiles, TG concentrations in lipoprotein fractions were examined in fasting sera from 185 subjects with active or cleared HCV infection by high-performance liquid chromatography. Serum lipoproteins were fractionated into four classes: chylomicron, very low-density lipoprotein (VLDL), LDL, and high-density lipoprotein (HDL). Then, the significance of HCV G1b infection on TG levels in each lipoprotein fraction was determined using multiple regression models. We found that active HCV G1b infection was positively associated with high HDL-TG levels and low VLDL-TG levels, independent of other factors included in the regression model. In VLDL sub-fractions, active HCV infection was only found to be associated with low levels of large VLDL-TG. Similarly, advanced liver fibrosis in chronic HCV G1b infection was associated with high levels of LDL-TG, HDL-TG, and small VLDL-TG, independent of other clinical factors. These findings indicate that active HCV G1b infection and advanced fibrosis are closely associated with abnormal serum TG profiles.

Assessment of the features of serum apolipoprotein profiles in chronic HCV infection: difference between HCV genotypes 1b and 2

BackgroundThe life cycle of hepatitis C virus (HCV) is tightly associated with host lipoprotein metabolic pathways. Apolipoprotein is present on the outer surface of lipoprotein particles and plays an important role in lipoprotein metabolism. We aimed to elucidate the influence of chronic HCV infection on serum apolipoprotein profiles.MethodsFasting serum apolipoprotein profiles of 310 subjects with active or cleared HCV infection were examined. Subsequently, the association between chronic HCV infection and serum apolipoprotein levels was determined using multiple regression analysis.ResultsActive HCV infection was associated with high serum levels of apo A-II and low serum levels of apo C-II and C-III. HCV infection with both genotype 1b (G1b) and genotype 2 (G2) was associated with low serum levels of either apo C-II and C-III, whereas only HCV G1b infections caused elevated levels of apo A II and E. Among active HCV infections, HCV G1b was associated with an elevation in the serum apo E levels. Furthermore, IL28B non-major genotype (rs8099917 TG/GG) was associated with low levels of serum apo B and high levels of apoA-II, and advanced fibrosis was associated with low levels of apo B and C-II in G1b infection.ConclusionsActive HCV infection is distinctively associated with characteristic serum apolipoprotein profiles. The influence on apolipoprotein profiles varies with different HCV genotypes. Moreover, the genotype of IL28B and hepatic fibrosis affected serum apolipoproteins in G1b infection. Abnormalities in serum apolipoproteins may provide a clue to the elucidation of complex interactions between active HCV infection and lipid metabolism.

Acute Pancreatitis due to pH-Dependent Mesalazine That Occurred in the Course of Ulcerative Colitis

We report the case of a 26-year-old male who presented with acute pancreatitis during the course of treatment for pancolitic ulcerative colitis (UC) with a time-dependent mesalazine formulation, prednisolone and azathioprine (AZA). Despite a review of his clinical history and various tests, the cause of pancreatitis could not be determined. Since drug-induced pancreatitis was considered possible, administration of the time-dependent mesalazine preparation and AZA was discontinued, and conservative treatment for acute pancreatitis was performed. The pancreatitis promptly improved with these treatments, but drug lymphocyte stimulation test (DLST) for both the time-dependent mesalazine formulation and AZA was negative. A pH-dependent mesalazine formulation was given for maintenance therapy of UC. Subsequently, as the pancreatitis relapsed, drug-induced pancreatitis was strongly suspected. Administration of mesalazine was discontinued, and pancreatitis was smoothly in remission by conservative treatment. According to the positive DLST result for the pH-dependent mesalazine formulation and the clinical course, a diagnosis of pH-dependent mesalazine-induced pancreatitis due to this formulation was made. During the clinical course of UC, occurrence of drug-induced pancreatitis must always be considered.

High level of serum cholesteryl ester transfer protein in active hepatitis C virus infection

AIM To determine the significance of cholesteryl ester transfer protein (CETP) in lipoprotein abnormalities in chronic hepatitis C virus (HCV) infection. METHODS We evaluated the significance of the serum concentration of CETP in 110 Japanese patients with chronic HCV infection. Fifty-five patients had active HCV infection, and HCV eradication had been achieved in 55. The role of CETP in serum lipoprotein abnormalities, specifically, in triglyceride (TG) concentrations in the four major classes of lipoproteins, was investigated using Pearson correlations in conjunction with multiple regression analysis and compared them between those with active HCV infection and those in whom eradication had been achieved. RESULTS The serum CETP levels of patients with active HCV infection were significantly higher than those of patients in whom HCV eradication was achieved (mean ± SD, 2.84 ± 0.69 μg/mL vs 2.40 ± 1.00 μg/mL, P = 0.008). In multiple regression analysis, HCV infection status (active or eradicated) was an independent factor significantly associated with the serum CETP level. TG concentrations in low-density lipoprotein (mean ± SD, 36.25 ± 15.28 μg/mL vs 28.14 ± 9.94 μg/mL, P = 0.001) and high-density lipoprotein (HDL) (mean ± SD, 25.9 ± 7.34 μg/mL vs 17.17 ± 4.82 μg/mL, P < 0.001) were significantly higher in patients with active HCV infection than in those in whom HCV eradication was achieved. The CETP level was strongly correlated with HDL-TG in patients with active HCV infection (R = 0.557, P < 0.001), whereas CETP was not correlated with HDL-TG in patients in whom HCV eradication was achieved (R = -0.079, P = 0.56). CONCLUSION Our results indicate that CETP plays a role in abnormalities of lipoprotein metabolism in patients with chronic HCV infection.

Aldehyde dehydrogenase 2 polymorphism for development to hepatocellular carcinoma in East Asian alcoholic liver cirrhosis

We aimed to clarify the influences of aldehyde dehydrogenase 2 (ALDH2), alcohol dehydrogenase 1B (ADH1B) polymorphisms, and ethanol consumption profile to hepatocellular carcinoma (HCC) development in alcoholic liver cirrhosis without chronic hepatitis B and C virus infection (non‐B non‐C).

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

AIM To investigate how hepatitis C virus (HCV) G1b infection influences the particle number of lipoproteins. METHODS The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV G1b 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 LipoSEARCH. The number of lipoprotein particles in each fraction was calculated using a newly developed algorithm, and the relationship between chronic HCV G1b 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 high-density 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 G1b 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 G1b infection decreases the numbers of medium, small, and very small LDL particles.

Early syphilitic hepatitis concomitant with nephrotic syndrome followed by acute kidney injury

Although acute hepatitis and nephrotic syndrome are commonly reported as complications of tertiary syphilis, nephrotic syndrome concomitant with hepatitis in early-stage syphilis is rare. Here, we describe the case of a 46-year-old male who was diagnosed with acute liver dysfunction and nephrotic syndrome after presenting with general malaise, and who subsequently developed acute kidney injury. Laboratory examination showed alkaline phosphatase had a greater magnitude of elevation compared to alanine aminotransferase, suggesting the possibility of syphilitic hepatitis. The rapid plasmin regain test and Treponema pallidum hemagglutination assay were positive, supporting the presence of a syphilis infection. Additionally, liver biopsy examination showed infiltration of inflammatory cells into the portal area and epithelioid cell granulomas. Moreover, kidney biopsy examination by both optical and electron microscopy showed a congestion of neutrophils in the capillary vessels, structural collapse of the tubules, and subepithelial deposits under the epithelium of the glomerular endothelial cells. These pathological changes were consistent with those reported previously for early syphilitic hepatitis and nephrotic syndrome in early-stage syphilis. All the symptoms, including liver and renal dysfunction, resolved after benzyl penicillin treatment was initiated. Hence, we believe early-stage syphilis should be included in the differential diagnosis of unknown liver damage and/or nephrosis.

Infliximab- and immunosuppressant-resistant Crohn's disease successfully treated with adsorptive granulocyte apheresis combined with prednisolone.

Activated granulocytes, monocytes, and platelets appear to be closely involved in active Crohn’s disease (CD). Adsorptive granulocyte apheresis (GCAP) is a new treatment for inflammatory bowel disease. GCAP was used to treat a 23-year-old female patient with CD resistant to both infliximab (IFX) and azathioprine (AZA). At 16 years of age, the patient underwent a partial ileal resection for peritonitis caused by perforative ileitis. On pathological examination of the resected specimen, the diagnosis was CD. Mesalazine was started, but the patient did not comply with therapy. She was admitted to our hospital again in 2007 due to an acute exacerbation. IFX induction therapy was started. The combination of both AZA daily and IFX every 8 weeks was continued as maintenance therapy. However, she developed severe abdominal pain in September 2009. Computed tomography revealed ileitis and ascending colitis, and blood tests showed high inflammatory response marker levels. She was considered to have IFX- and AZA-resistant CD. Initial intravenous steroid therapy did not result in any improvement. Therefore, weekly GCAP therapy was given for 5 weeks, which immediately improved the inflammatory response markers. GCAP combined with prednisolone could be effective for IFX- and AZA-refractory CD.

Endoscopic submucosal dissection for an atypical small verrucous carcinoma: a case report.

BackgroundEsophageal verrucous carcinoma is a rare variant of esophageal squamous cell carcinoma. In most cases, verrucous carcinoma presents as an exophytic, slow-growing mass with an extensive superficial growth pattern. Symptoms often include an insidious onset of dysphagia resulting in weight loss. In a patient presenting with super early-stage verrucous carcinoma, we were able to eliminate the aberration using endoscopic submucosal dissection.Case presentationAn asymptomatic 68-year-old Asian man was found to have an abnormality in his esophagus. The abnormality was discovered, by chance, in a barium study for a health checkup. Esophagogastroduodenoscopy revealed a 1-centimeter polypoid lesion covered with squamous epithelium. Biopsies showed squamous high-grade intraepithelial neoplasia. An endoscopic submucosal dissection was performed and the histopathological findings showed a well-differentiated squamous cell carcinoma with hyperkeratosis with a church spire configuration. These features are consistent with the growth pattern of verrucous carcinoma.ConclusionsVerrucous carcinoma can manifest as a small mass with nonclinical symptoms and endoscopic submucosal dissection is useful as a curative treatment. We must consider that verrucous carcinoma can manifest as appearance of a polyp that is not papillary or warty-like with and without extensive superficial growth appearance.