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Background and Aim: Endoscopic resection (ER) is widely performed to treat early colorectal cancer. However, additional surgery for pathological T1 colorectal cancer (pT1CRC) after ER is controversial because of the imprecise prediction of lymph node metastasis (LNM). Recently, several patients of pT1CRC with lymphoid follicular replacement (LFR) without LNM have been reported. This study aimed to investigate the clinicopathological features and risk of LNM in patients with pT1CRC with LFR., Methods: We retrospectively analyzed patients who underwent ER or surgical resection and were diagnosed with pT1CRC between January 2010 and December 2020. We defined pT1CRC with LFR as the replacement of a part of the lymphoid follicular component within the submucosal area by adenocarcinoma, with no invasion into other submucosal areas., Results: Among the 600 eligible patients, the incidence rate of pT1CRC with LFR was 6.7% (40/600). Patients with pT1CRC with LFR represented 14.3% (37/258) of the endoscopically treated patients and 0.9% (3/342) of the surgically treated patients. For patients with pT1CRC with LFR, 80.0% (32/40) had flat and depressed lesions, and 35.0% (14/40) had submucosal invasion depth ≥1000 μm. Patients with pT1CRC with LFR had negative lymphovascular invasion, differentiated type, and budding grade 1. In the median follow-up of 61 months, patients with pT1CRC with LFR had no LNM., Conclusions: The presence of LFR in pT1CRC may be associated with a low risk of LNM. In patients with pT1CRC with LFR, follow-up without additional surgery is possible even if the submucosal invasion depth is ≥1000 μm., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: New nomenclature of steatotic liver disease (SLD) including metabolic dysfunction-associated SLD (MASLD), MASLD and increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD) has recently been proposed. We investigated clustering analyses to decipher the complex landscape of SLD pathologies including the former nomenclature of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD)., Methods: Japanese individuals who received annual health checkups including abdominal ultrasonography (n = 15 788, men/women: 10 250/5538, mean age: 49 years) were recruited., Results: The numbers of individuals with SLD, MASLD, MetALD, ALD, NAFLD, and MAFLD were 5603 (35.5%), 4227 (26.8%), 795 (5.0%), 324 (2.1%), 3982 (25.8%), and 4946 (31.3%), respectively. Clustering analyses using t-distributed stochastic neighbor embedding and K-means to visually represent interconnections in SLDs uncovered five cluster formations. MASLD and NAFLD mainly shared three clusters including (i) low alcohol intake with relatively low-grade obesity; (ii) obesity with dyslipidemia; and (iii) dysfunction of glucose metabolism. Both MetALD and ALD displayed one distinct cluster intertwined with alcohol consumption. MAFLD widely shared all of the five clusters. In machine learning-based analyses using algorithms of random forest and extreme gradient boosting and receiver operating characteristic curve analyses, fatty liver index (FLI), calculated by body mass index, waist circumference, and levels of γ-glutamyl transferase and triglycerides, was selected as a useful feature for SLDs., Conclusions: The new nomenclature of SLDs is useful for obtaining a better understanding of liver pathologies and for providing valuable insights into predictive factors and the dynamic interplay of diseases. FLI may be a noninvasive predictive marker for detection of SLDs., (© 2024 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: There has been no report on a direct comparison between linked color imaging (LCI) and second-generation narrow-band imaging (2G-NBI) for surveillance of epithelial neoplasms in the upper gastrointestinal tract (UGIT). The aim of this study was to verify the superiority of LCI to 2G-NBI for surveillance esophagogastroduodenoscopy and to clarify how each endoscopic system should be used., Methods: This study was conducted as an open-label, two-arm-parallel (1:1), multicenter, randomized controlled trial at six institutions. Patients aged 20-85 years with a treatment history of epithelial neoplasms in the UGIT were recruited. Patients were assigned to a 2G-NBI group and an LCI group, and esophagogastroduodenoscopy was performed with primary image-enhanced endoscopy followed by white light imaging (WLI). The primary endpoint was the detection rate of one or more epithelial neoplasms in the primary image-enhanced endoscopy. A WLI-detected epithelial neoplasm was defined as a lesion that was detected in only WLI., Results: A total of 372 patients in the 2G-NBI group and 378 patients in the LCI group were analyzed. Epithelial neoplasms in the UGIT were detected by 2G-NBI in 18 patients (4.6%) and were detected by LCI in 20 patients (5.3%) (P = 0.87). WLI-detected epithelial neoplasms were in 11 patients in the 2G-NBI group (3.0%) and in 1 patient in the LCI group (0.27%) (P = 0.003)., Conclusions: Linked color imaging did not show superiority to 2G-NBI for the detection of epithelial neoplasms. Also, the percentage of WLI-detected epithelial neoplasms in primary NBI was significantly higher than that in primary LCI., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Optical biopsy using endocytoscopy for superficial nonampullary duodenal epithelial tumors (SNADETs) is practical; however, a diagnostic algorithm has not been established. The aim of this study was to determine correlations of endocytoscopic findings of SNADETs with histology using computer analysis and to establish an algorithm., Methods: Endocytoscopic images and histological images of duodenal lesions from 70 patients were retrospectively collected. The numbers of glands and densely stained areas with methylene blue (DSMs) per 1 mm 2 and the percentage of DSMs per screen in endocytoscopy were determined. Moreover, correlations in DSMs and glands between endocytoscopy and histological images were analyzed. Histopathological diagnoses were assessed according to the revised Vienna classification. The primary outcome was correlation between the number of glands in endocytoscopy and that in histology. Finally, a diagnostic algorithm for endoscopic intervention of SNADETs with a statistical program command was established., Results: The number of glands in endocytoscopic images was correlated with that in histopathological images (ρ 0.64, P < 0.001). There were significant differences in the mean number of glands between category 4/5 and category 3 (P = 0.03) and the mean percentage of DSMs between category 4/5 and category 1 (P < 0.001). When the cutoffs for the number of glands and percentage of DSMs were set at 47 per 1 mm 2 and 20.8% in one screen, respectively, the area under the ROC curve was 0.89., Conclusions: Endocytoscopic images of SNADETs reflect histopathological atypia, and computer analysis provides a practical diagnostic algorithm for endoscopic intervention., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Linked color imaging (LCI) is useful for screening in the gastrointestinal tract; however, its true clinical benefit has not been determined. The aim of this study was to determine the objective advantage of LCI for detection of upper gastrointestinal neoplasms., Methods: Nine endoscopists, including three novices, three trainees, and three experts, prospectively performed eye tracking. From 30 cases of esophageal or gastric neoplasm and 30 normal cases without neoplasms, a total of 120 images, including 60 pair images of white light imaging (WLI) and LCI taken at the same positions and angles, were randomly shown for 10 s. The sensitivity of tumor detection as a primary endpoint was evaluated and sensitivities by organ, size, and visual gaze pattern were also assessed. Color differences (ΔE using CIE1976 [L*a*b*]) between lesions and surrounding mucosa were measured and compared with detectability., Results: A total of 1080 experiments were completed. The sensitivities of tumor detection in WLI and LCI were 53.7% (50.1-56.8%) and 68.1% (64.8-70.8%), respectively (P = 0.002). LCI provided higher sensitivity than WLI for the novice and trainee groups (novice: 42.2% [WLI] vs 65.6% [LCI], P = 0.003; trainee: 54.4% vs 70.0%, P = 0.045). No significant correlations were found between sensitivity and visual gaze patterns. LCI significantly increased ΔE, and the diagnostic accuracy with WLI depended on ΔE., Conclusions: In conclusion, LCI significantly improved sensitivity in the detection of epithelial neoplasia and enabled epithelial neoplasia detection that is not possible with the small color difference in WLI. (UMIN000047944)., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Recently, dispersion imaging by shear wave elastography has been developed to visualize a tissue viscosity-related factor by measuring the dispersion slope. However, clinical significance of dispersion imaging in the field of pancreatic cancer is unknown. This study aimed to investigate the clinical significance of dispersion imaging in the treatment and diagnosis of pancreatic cancer., Methods: We measured shear wave dispersion slope (SWD) (m/s/kHz) and shear wave elasticity (SWE) (kPa) in patients with pancreatic ductal adenocarcinoma (PDA). The primary endpoint was the relationship between the changes in SWD and SWE values before and after chemotherapy and the response to chemotherapy. Secondary endpoints included SWD and SWE values in relation to differences between PDA and non-PDA sites and histopathological scores of stroma, inflammation, fibrosis, and necrosis in endoscopic ultrasound-guided fine-needle aspiration specimens., Results: Fifty-six patients were included, 30 of whom underwent chemotherapy. There was no relationship between the changes of SWD and SWE values and chemotherapy responses. In 56 patients, the median SWD value was 12.20 m/s/kHz (interquartile range [IQR]: 10.88-13.61) at PDA sites and 13.57 m/s/kHz (IQR: 12.28-16.20) at non-PDA sites (P = 0.005). The median SWE value was 8.18 kPa (IQR: 7.00-9.74) at PDA sites and 6.14 kPa (IQR: 5.40-6.77) at non-PDA sites (P < 0.001). Histopathological evaluation revealed that inflammation scores were correlated with SWD values (r s  = 0.42, P < 0.001)., Conclusions: Dispersion imaging in pancreatic cancer would be useful for diagnosis and assessing inflammation., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation (LT). The rate of HCV infection is high in patients on hemodialysis and in patients infected with human immunodeficiency virus (HIV). In liver transplant patients with HCV infection, recurrent HCV infection of the transplanted liver is universal and results in rapid liver fibrosis progression. In patients with HCV/HIV coinfection as well, liver fibrosis advances rapidly. Thus, there is an urgent need for prompt HCV infection treatment in these special populations (i.e. HIV/HCV coinfection, HCV infection after LT, and dialysis patients). Interferon (IFN)-based therapy for HCV infection could not achieve a high rate of sustained viral response and could cause severe adverse events in the aforementioned special populations. Direct-acting antivirals (DAAs) have recently been developed, and clinical trials have shown that IFN-free DAA-based therapies are associated with a significantly better safety and therapeutic profile than IFN-based therapies. However, the majority of the initial DAA trials excluded special populations; thus, the efficacy and safety of IFN-free DAA-based therapy in special populations remained to be clearly established. Although recent clinical trials and clinical studies have shown the high efficacy and safety of this therapy even in special populations, several unresolved problems, including emergence of resistance-associated variants after failure to respond to DAAs and HCC occurrence after DAA therapy, still exist. Hence, in this review, we discuss the recent advances in anti-HCV therapy for special populations and the remaining problems regarding this therapy., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Immune checkpoint inhibitors (ICI) have revolutionized anti-malignancy therapy and thus have been increasingly used. Although ICI may cause immune-related adverse events (irAE) in various organs, including the liver, the prevalence and predictive factors of irAE have not been clarified., Methods: In this retrospective study, consecutive patients who had malignancies and were treated with ICI without other chemotherapeutic agents at Hokkaido University Hospital between 2014 and 2019 were screened. Patients were excluded if they were < 20 years old and had insufficient clinical data., Results: Of the 233 patients screened, 202 patients met the inclusion criteria and were included in the analysis. The patients were aged 25-92 years, and 60.9% were male. The patients received nivolumab (n = 137), pembrolizumab (n = 45), ipilimumab (n = 17), atezolizumab (n = 2), and avelumab (n = 1). The prevalence of any grade and grade ≥ 3 irAE hepatitis was 8.4% (17/202) and 4.0% (8/202), respectively. irAE hepatitis occurred at a median duration of 42 days in any grade and 36 days in grade ≥ 3 after ICI initiation. The clinical course of grade ≥ 3 irAE hepatitis was generally favorable; however, 50% required corticosteroid treatment and two patients required additional mycophenolate mofetil. Female sex and history of ICI treatment were significantly associated with the incidence of grade ≥ 3 irAE hepatitis., Conclusions: Grade ≥ 3 irAE hepatitis was observed in 4.0% of the patients who were treated with ICI. Female sex and history of ICI treatment were significantly associated with the incidence of grade ≥ 3 irAE hepatitis., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in BRAF-mutated colorectal carcinomas with not only high levels of microsatellite instability but also microsatellite stable. SSA/Ps with advanced histology, including cytological dysplasia or minimally invasive carcinomas, are important lesions because SSA/Ps are considered major contributors to "interval cancers" and these lesions can rapidly become dysplastic or invasive carcinomas. Clinicopathologically, SSA/Ps with dysplasia or invasive carcinoma were associated with advanced age, female sex, and proximal colon. Although SSA/Ps with submucosal invasive carcinoma were smaller and invaded less deeply into the submucosal layer than conventional tubular adenomas with submucosal invasive carcinoma, SSA/Ps with submucosal invasive carcinoma frequently had a mucinous component and exhibited a higher potential for lymphatic invasion and lymph node metastasis. In an SSA/P series, endoscopic characteristics, including (semi)pedunculated morphology, double elevation, central depression, and reddishness, may help accurately diagnose SSA/Ps with advanced histology. Removal of SSA/Ps with dysplasia or invasive carcinoma was recommended. Endoscopic treatment such as endoscopic mucosal resection or endoscopic submucosal dissection is useful for those lesions. However, surgical resection with lymph node dissection might be indicated when SSA/Ps with invasive carcinoma are endoscopically suspected, because these have the high risk of lymph node metastasis. Greater awareness may promote further research into improving the detection, recognition, and complete resection rates of SSA/Ps with dysplasia or invasive carcinoma and reduce the interval cancer rates., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Data on long-term outcomes after therapeutic endoscopic retrograde cholangiopancreatography (ERCP) using balloon-assisted enteroscopy (BAE) for choledochojejunal anastomotic stenosis (CJS) or pancreaticojejunal anastomotic stenosis (PJS) remain limited. We retrospectively assessed the long-term results of patients who achieved clinical success using BAE for CJS and PJS., Methods: Patients who achieved technical and clinical success for CJS or PJS by BAE-ERCP and were followed up for more than 6 months after the initial BAE-ERCP therapy were retrospectively identified at 11 Japanese institutions. The primary end-point was CJS or PJS recurrence rates. The secondary end-points were initial therapy details, initial therapy complications, and CJS or PJS recurrence treatment details. We also evaluated restenosis-associated factors., Results: From September 2008 to December 2015, 67 patients (CJS, 61; PJS, six) were included. The overall CJS and PJS recurrence rates were 34.4% and 33.3%, respectively. The 1-year CJS recurrence rate was 18.5% (95% confidence interval, 10.7-31.0). Of all the patients, 88.1% underwent balloon dilation at the anastomotic stenosis site; stent placement was performed in 15 of 67 patients (22.4%). The complication rate was 8.2% in CJS and 0% in PJS. In patients who underwent balloon dilation, "remaining waist" was significantly associated with CJS recurrence after anastomotic balloon dilation (P = 0.001)., Conclusions: The long-term outcomes of BAE-ERCP were comparable with those of percutaneous transhepatic treatment or surgical re-anastomosis., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Interferon (IFN) λ plays an important role in innate immunity to protect against hepatitis C viral (HCV) infection. Single nucleotide polymorphisms (SNPs) near IL28B (IFNλ3) are strongly associated with treatment response to IFNα therapy in chronic hepatitis C (CHC) patients. Recently, IFNλ4 related to IL28B-unfavorable allele was discovered. However, the impact of IFNλs on CHC is unknown. We aimed to investigate the mechanism underlying responsiveness to IFN-based therapy in CHC associated with SNPs near IL28B., Methods: We evaluated the basal mRNA levels and ex-vivo induction of IFNλ expression including IFNλ4 in peripheral blood mononuclear cells (PBMCs) from 50 CHC patients treated with pegylated-IFNα/RBV. Furthermore, we investigated the effect of IFNλ4 on induction of IL28B in vitro., Results: When PBMCs were stimulated with IFNα and polyinosinic-polycytidylic acid, IL28B induction was significantly lower in patients with IL28B-unfavorable genotype (rs12979860 CT/TT) than those with IL28B-favorable genotype (rs12979860 CC; P=0.049). IL28B induction was lower in nonresponders than in relapsers (P = 0.04), and it was also lower in nonsustained virological responder patients for triple therapy including NS3 protease inhibitors. IFNλ4 mRNA was detected in 12 of 26 patients with IL28B-unfavorable SNP, and IFNλ4 expression was associated with lower IL28B induction in patients with IL28B-unfavorable genotype (P=0.04) and nonresponse to IFNα therapy (P=0.003). Overexpression of IFNλ4 suppressed IL28B induction and promoter activation., Conclusions: Impaired induction of IL28B, related to IFNλ4 expression in PBMCs of IL28B-unfavorable patients, is associated with nonresponse to IFNα-based therapy for hepatitis C viral infection., (© 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background and Aims: The serrated colorectal carcinoma (CRC) as proposed to arise from serrated adenoma (SA) is characterized by upregulation of HIF1α, suppression of PTCH or EphB2, loss of DNA repair proteins, and BRAF mutation. The aim of this study was to evaluate alterations of these candidates involved in the serrated pathway in colorectal polyps., Methods: We analyzed immunoreactivity of these proteins, methylation of PTCH and EphB2, and mutation of BRAF and Kras in sessile SAs (SSAs; n = 32), traditional SAs (n = 28), hyperplastic polyps (HPs; n = 24), and conventional adenomas (ADs; n = 21)., Results: Increase of nuclear HIF1α expression was more frequent in SA than HP, but less frequent in SA than AD (P < 0.001). Increase of PTCH expression was not found in SSA or HP, but was evident in about half of traditional SA and all AD (P < 0.001). Decrease of EphB2 expression was more prominent in SA than HP or AD (P ≤ 0.005). Loss of hMLH1 and MGMT expression were most frequent in SSA (P < 0.001). Loss of hMSH2 showed more pronounced in SA and HP than AD (P ≤ 0.004). Methylations of PTCH and EphB2 were rare in all categories. BRAF mutation harbored frequently in SA, but not AD; only AD harbored Kras mutation., Conclusions: This work provides evidence of similarity of HIF1α, EphB2 or DNA repair proteins expression, and BRAF mutation in serrated CRCs and their precursors, especially SSA, compared with AD and HP., (© 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background and Aim: It was previously reported that high-grade intraepithelial neoplasia of the esophagus turns pink within a few minutes after iodine staining (pink-color sign; PCS); however, iodine staining is uncomfortable. By using narrow band imaging (NBI), color change in the area between the intraepithelial papillary capillary loop (background coloration; BGC) is often observed within the brownish area. The diagnostic usefulness of BGC findings for differentiating high-grade intraepithelial neoplasia from low-grade intraepithelial neoplasia was evaluated., Methods: In a prospective observational study from September 2010 to August 2012, 285 patients who were in a high-risk group for esophageal squamous cell carcinoma underwent endoscopic examination. Lesions with both endoscopic findings of dilated intraepithelial papillary capillary loop on NBI and iodine-unstained areas were studied, in which endoscopic biopsy or endoscopic resection was subsequently performed. The esophageal background mucosa was also evaluated on the basis of the iodine staining pattern (uniform type: Group U, scattered type: Group S)., Results: One hundred three esophageal lesions in 87 patients were studied. When BGC was used as the differentiation index, sensitivity was 93.8%, specificity was 88.2%, and accuracy was 91.3%. When PCS was used, sensitivity was 97.9%, specificity was 88.2%, and accuracy was 93.2% (P = 0.79). In Group U (n = 54), BGC had an accuracy of 93.8%, and PCS had an accuracy of 92.3% (P = 1.0). On the other hand, in Group S (n = 33), BGC had an accuracy of 86.8%, while PCS had an accuracy of 94.7% (P = 0.27)., Conclusions: Diagnosis using BGC on NBI may substitute for diagnosis based on PCS in many patients., (© 2013 The Author. Journal of Gastroenterology and Hepatology published by Wiley Publishing Asia Pty Ltd and Journal of Gastroenterology and Hepatology Foundation.)

Background and Aims: The change of therapeutic strategy for large colorectal tumors after the introduction of endoscopic submucosal dissection (ESD) has not yet been clarified. The aim of this study was to estimate the impact of ESD as an initial treatment strategy., Methods: A questionnaire was administered to nine expert panelists in colorectal ESD. The questionnaire used retrospective data from consecutive case series. Forty-seven cases of early colorectal tumors (≥ 20 mm) were included. Endoscopic growth types were 25 laterally-spreading tumors (LST) of granular type (G), 15 LST of non-granular types (NG), and seven protruded types. Pathological diagnoses included 15 adenomas (Ad), 18 intramucosal cancers (M), three submucosally-shallow invasive cancers (< 1000 µm) (SMs), and 11 submucosally-deep invasive cancers (≥ 1000 µm) (SMd). The expert panelists completed questionnaires about recommended initial treatment under suppositions of before and after the introduction of ESD. Over-surgery was defined as surgery for Ad, M, and SMs. Non-curative endoscopic resection (ER) was defined as ER for SMd., Results: After the introduction of ESD, the reduction in the over-surgery rate was estimated at 10.8% for Ad, M, and SMs, and the increase in the non-curative ER rate was estimated at 27.2% for SMd. By endoscopic growth type, the reduction of over-surgery rates for LST-NG, LST-G, and protruded type was 15.5%, 10.5%, and 2.2%, respectively., Conclusions: The endoscopists changed their therapeutic strategy for large colorectal tumors to reduce over-surgery, especially in LST-NG, demonstrating the impact of ESD., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background and Aims: Identifying the invasive depth of cancers less than 10 mm in diameter remains a challenge. This study examines the clinicopathological characteristics of colorectal cancers less than 10 mm in diameter and invading submucosal layer (SM)3 and below, which require surgery and must never be treated by endoscopic mucosal resection., Methods: We studied 54 cases of colorectal cancer less than 10 mm in diameter and invading the submucosa and deeper tissues, by dividing them into two groups: those invading SM1 and SM2 versus those invading SM3 and below. We investigated the clinicopathological characteristics of cancers invading SM3 and below by comparing them with cancers invading SM1 and SM2. Similarly, 38 cases, whose endoscopic findings could be analyzed, were selected and examined., Results: In cases invading SM3 and below, the rates of moderately to poorly differentiated adenocarcinoma, lymphatic and venous permeation and lymph node metastasis were significantly higher than those invading SM1 and SM2. Among cases invading SM3 and below, the presence of endoscopic findings-including white spots of the protruded type, and fullness, white spots, hardness and protruded lesions in the depressed area of the depressed type-was significantly higher than among those invading SM1 and SM2., Conclusion: Colorectal cancers less than 10 mm in diameter and invading SM3 and below have high malignant potential. Cancers of this invasive depth can be identified by looking for characteristics such as white spots, fullness, hardness and protruded lesions in the depressed area. Careful endoscopic observation for these signs aids in determining the appropriate treatment.

Background: Coexistence of primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) is referred to as PBC-AIH overlap. Pathogenesis of PBC-AIH is not well understood and its diagnosis is challenging. We previously reported the clinical characteristics of 10 patients diagnosed with PBC-AIH overlap., Aims: The aim of the study was extend the earlier series and evaluate the diagnostic criteria, biological characteristics, potential therapy, and long-term outcomes of patients with PBC-AIH overlap., Methods and Results: We retrospectively analyzed clinical, biochemical, and histological characteristics of 144 patients diagnosed with PBC and 73 diagnosed with AIH. We identified 16 cases of PBC-AIH overlap, according to criteria established by Chazouillères et al. and other studies. PBC preceded AIH in 6 patients and both diseases occurred simultaneously in the remaining 10 patients. PBC-AIH overlap has clinical, biochemical, and histological characteristics of both PBC and AIH. Thirteen patients treated with both ursodeoxycholic acid (UDCA) and immunosuppressive therapy responded well, with normal alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels. The remaining three patients treated with either prednisolone (PSL) or UDCA alone developed cirrhosis, varices, ascites, encephalopathy, or died of liver-related causes at the 5, 12, and 14-year follow up., Conclusions: PBC-AIH overlap is not a rare entity; it was observed in 11% of PBC patients in this study. Further studies will be required to investigate whether PBC-AIH overlap is distinct from the two individual diseases in terms of long-term outcomes and therapeutic implications.

Background and Aim: Colonoscopy plays an integral role in the diagnosis, management and surveillance of ulcerative colitis (UC). In the present study we assessed the relationship between endoscopic and histological findings, clinical symptoms, and laboratory data., Methods: We performed total colonoscopy examinations in 54 consecutive patients with UC. Seven segments (appendiceal region, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum) were scored for endoscopic and histological activity. The patients were also evaluated using a symptom-activity index and laboratory markers: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell (WBC) and platelet (plt) counts., Results: There was a significant positive correlation between endoscopic and histological scores (r(s)=0.738), and between symptom activity score, endoscopic score (r(s)=0.444), and histological score (r(s)=0.557). Although the endoscopic and histological scores of distal colonic lesions (rectum-sigmoid, endoscopic: r(s)=0.515, histological: r(s)=0.624) correlated with clinical symptoms, there was no similar correlation for the proximal colon (appendiceal region-descending; endoscopic, r(s)=0.268, histological, r(s)=0.329). CRP, ESR, and WBC count also correlated with the sum of endoscopic and histological scores (CRP, r(s)=0.447, r(s)=0.369; ESR, r(s)=0.483, r(s)=0.589; WBC, r(s)=0.338, r(s)=0.330), whereas platelet count did not (r(s)=0.171, r(s)=0.210). In particular, CRP and ESR were well correlated with the activity of proximal colonic lesions (CRP, r(s) = 0.474, r(s)=0.480; ESR, r(s) = 0.423, r(s)=0.529) rather than with that of distal lesions (CRP, r(s)=0.236, r(s)=0.212; ESR, r(s)=0.368, r(s)=0.497)., Conclusions: In this study, clinical symptoms reflected the activity of distal colonic lesions, whereas CRP and ESR reflected the activity of proximal lesions. Therefore, total colonoscopy may be indicated when CRP or ESR is elevated in UC patients in clinical remission.

Background and Aim: We have reported previously that synthetic small interfering RNA (siRNA) and DNA-based siRNA expression vectors efficiently and specifically suppress hepatitis C virus (HCV) replication in vitro. In this study, we investigated the effects of the siRNA targeting HCV-RNA in vivo., Methods: We constructed recombinant retrovirus and adenovirus expressing short hairpin RNA (shRNA), and transfected into replicon-expressing cells in vitro and transgenic mice in vivo., Results: Retroviral transduction of Huh7 cells to express shRNA and subsequent transfection of an HCV replicon into the cells showed that the cells had acquired resistance to HCV replication. Infection of cells expressing the HCV replicon with an adenovirus expressing shRNA resulted in efficient vector delivery and expression of shRNA, leading to suppression of the replicon in the cells by approximately 10(-3). Intravenous delivery of the adenovirus expressing shRNA into transgenic mice that can be induced to express HCV structural proteins by the Cre/loxP switching system resulted in specific suppression of virus protein synthesis in the liver., Conclusion: Taken together, our results support the feasibility of utilizing gene targeting therapy based on siRNA and/or shRNA expression to counteract HCV replication, which might prove valuable in the treatment of hepatitis C.

Background and Aim: Combination treatments of interferon-alpha (IFN) and ribavirin (RBV) are more effective than those of IFN alone in hepatitis C virus (HCV) infection. However, mechanisms of the action of the combination regimen are not well understood. To elucidate the viral genetic basis of IFN plus RBV combination therapy, genetic variabilities of HCV-1b were analyzed., Methods: We performed pair-wise comparisons of full-length HCV genomic sequences in three patients' sera before and after initiation of IFN plus RBV treatment. Subsequently, we analyzed amino acid sequences of the NS5B region, which codes for the viral RNA-dependent RNA polymerase, and compared these with the outcomes of the therapy in 81 patients., Results: Analysis of the entire HCV sequence in patients who received IFN plus RBV therapy did not show consistent amino acid changes between before and after the initiation of the therapy. NS5B sequence analyses revealed that mutations at positions 300-358 of NS5B, including polymerase motif B to E, occurred more frequently in a group of patients exhibiting a sustained viral response (SVR) or an end-of-treatment response (ETR) compared with a group of patients exhibiting a non-response (NR). Closer examination revealed that mutations at aa 309, 333, 338 and 355 of NS5B occurred significantly more frequently in the SVR plus ETR group than in the NR group (P = 0.0004). Multivariate analysis showed that the number of mutations at these four sites was an independent predictor of SVR plus ETR versus NR., Conclusions: Particular amino acid changes in the NS5B region of HCV may correlate with outcomes of IFN plus RBV combination therapy., (Copyright 2005 Blackwell Publishing Asia Pty Ltd.)