Changes in the gut microbiota after hepatitis C virus eradication.

The gut microbiota interacts with infectious diseases and affects host immunity. Liver disease is also reportedly associated with changes in the gut microbiota. To elucidate the changes in the gut microbiota before and after hepatitis C virus (HCV) eradication through direct-acting antiviral (DAA) treatment in patients with chronic hepatitis C (CHC), we investigated 42 samples from 14 patients who received DAA therapy for HCV. Fecal samples were obtained before treatment (Pre), when treatment ended (EOT), and 24 weeks after treatment ended (Post24). The target V3-4 region of the 16S rRNA gene from fecal samples was amplified using the Illumina Miseq sequencing platform. The diversity of the gut microbiota did not significantly differ between Pre, EOT, and Post24. Principal coordinates analysis showed that for each patient, the values at Pre, EOT, and Post24 were concentrated within a small area. The linear discriminant analysis of effect size showed that the relative abundances of Faecalibacterium and Bacillus increased at EOT, further increased at Post24, and were significantly increased at Post24 compared to Pre. These suggest that changes in the gut microbiota should be considered as among the various effects observed on living organisms after HCV eradication.

The Propagation Display Method Improves the Reproducibility of Pancreatic Shear Wave Elastography.

Evaluation of the pancreatic elastic modulus (PEM) using shear wave elastography (SWE) requires at least 5 measurements to ensure reproducibility. The aim of this study was to evaluate improvement in reproducibility of SWE, using the propagation display method in normal pancreas ([NP] phase 1) and to examine the differences in PEM between NP and chronic pancreatitis (CP), intraductal papillary mucinous neoplasm (IPMN) and autoimmune pancreatitis ([AIP] phase 2). In phase 1, the measurement success rate, median PEM in repeated measurements and appropriate number of SWE measurements were determined in 109 cases with NP. In phase 2, PEM was measured in CP (n = 10), IPMN (n = 31) and AIP (n = 5), using the required number of SWE measurements determined in phase 1. In phase 1, the measurement success rate was 93.9% (92/109 cases). The median PEM for NP was 14.6 kPa and the appropriate number of SWE measurements was at least 3. In phase 2, the median PEMs in CP, IPMN and AIP were 19.6, 18.1 and 17.2 kPa, respectively, with significant differences between NP and CP (p = 0.0133) and between NP and IPMN (p = 0.0436). Use of the propagation display method in SWE improves the reproducibility of measurement of PEM.

Influence of proton pump inhibitors on microbiota in chronic liver disease patients.

BACKGROUND: Current knowledge suggests that proton pump inhibitors (PPIs) are associated with an increased risk of hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP). These conditions and PPI use are related to gut microbiota. The aim of this study is to research the changes in gut microbiota caused by PPI in patients with chronic liver disease. METHODS: From 198 Japanese patients, 31 patients in the PPI and non-PPI groups were matched using propensity score matching (PSM) based on age, sex, and Child-Turcotte-Pugh class. We investigated the gut microbial composition of stool samples using the Illumina MiSeq sequencing platform and compared them using linear discriminant analysis effect size and phylogenetic investigation of communities by reconstruction of unobserved states. RESULTS: Before PSM, Child-Turcotte-Pugh score (p = 0.038), ascites (p = 0.049), encephalopathy (p = 0.023), and esophageal varices (p < 0.01) were significantly higher in the PPI group than in the non-PPI group. After PSM, six genera, consisting of Lactobacillus, Streptococcus, Selenomonas, Veillonella, Campylobacter, and Haemophilus were enriched in the PPI group. Eggerthella, Paraprevotella, Turicibacter, Dorea, Anaerotruncus, and Ruminococcus were less abundant in the PPI group. We identified five types of level 3 KEGG pathways predicted to be significantly different. CONCLUSIONS: Part of microbial changes caused by PPI use was common to the changes by progression of liver cirrhosis. Increases in oral bacterial flora and decreases in autochthonous flora may produce the intestinal environment which tends to make the risk factor for HE or SBP.

Objective evaluation of blood flow in the small-intestinal villous: quantification of findings from dynamic endoscopy with concomitant narrow-band imaging.

BACKGROUND AND AIMS: We have previously shown that the increase in blood flow volume in jejunum villi after spraying of 10 % dextrose solution correlates with pancreatic exocrine function (PEF). The aim of this study was to establish an objective method to evaluate the amount of jejunum villous blood flow using a novel image analysis system. PATIENTS AND METHODS: The subjects were 26 patients who underwent upper gastrointestinal endoscopy with a newly developed small intestine endoscope (SIF-Y0007, Olympus, Tokyo, Japan). By defining the ratio of capillary occupancy in each villus at levels from 1 to 5, villous blood flow was evaluated subjectively on the villous blood flow scale (VBFS). Objective evaluation was performed based on luminance analysis. The morphological opening process was used to make images with leveled brightness. A histogram was prepared from the luminance information and the standard deviation was determined and defined as SDOV (Standard Deviation calculated from a histogram made by luminance analysis Of Villi). PEF was evaluated by measuring the BT-PABA (N-benzoyl-L-tyrosyl-p-aminobenzoic acid) excretion rate. RESULTS: There was a significant positive correlation between VBFS and SDOV ( P  < 0.0001, ρ = 0.5882). SDOV was also positively correlated with PEF ( P  = 0.0004, ρ = 0.6421). CONCLUSIONS: SDOV is a new objective index for evaluation of blood flow volume in jejunum villi. SDOV may be useful in clinical practice to estimate PEF and for clarification of the mechanisms underlying the functional correlation between the pancreas and small intestine.

Increase in breath hydrogen concentration was correlated with the main pancreatic duct stenosis.

BACKGROUND: Hydrogen is produced from unabsorbed carbohydrates in the intestine through degradation and metabolism by hydrogenase of intestinal bacteria. The hydrogen is then partially diffused into blood flow and released and detected in exhaled breath. Pancreatic juice production is decreased in patients with reduced pancreatic exocrine function, including those with pancreatic cancer, thus decreasing digestion and absorption of nutrients including carbohydrates, which may increase undigested carbohydrates in the intestine and increase breath hydrogen concentration (BHC). The aim of this study was to investigate the association between BHC and pancreatic diseases. METHODS: A retrospective study was designed and 68 patients underwent morning fasting breath hydrogen test. Since there is no clear standard, normal BHC, the median of the measured values from the subjects (9 ppm) was adopted as the standard. The subjects were classified into those with a value exceeding the median (BHC high group: 32 patients) and a value equal to or below the median (BHC low group: 36 patients). Patients characteristics, blood test results and imaging findings characteristic of pancreatic diseases were compared between the groups. RESULTS: The age was significantly higher (P = 0.010) and the incidences of pancreatic ductal adenocarcinoma and autoimmune pancreatitis were significantly higher (P = 0.018 and P = 0.004, respectively) in the BHC high group. With respect to the blood test items, the Alb level was significantly lower in the BHC high group (P = 0.005). With respect to the characteristic imaging findings of pancreatic diseases, the proportions of patients with pancreatic enlargement, the main pancreatic duct (MPD) stenosis, and the MPD dilatation were significantly higher in the BHC high group (P = 0.022, P < 0.001, and P = 0.002, respectively). On univariate analysis, only the MPD stenosis was extracted as an independent factor (P = 0.014). CONCLUSION: It was suggested that the fasting BHC is associated with pancreatic diseases causing stenosis of the MPD, including pancreatic cancer (UMIN000020777).

Quantitative diagnosis of chronic pancreatitis using EUS elastography.

BACKGROUND: It is difficult to diagnose chronic pancreatitis (CP) objectively because of a lack of standard diagnostic criteria. Endoscopic ultrasonography (EUS) has been used to assess the severity of CP, but the diagnosis of CP using EUS depends on an endosnonographer. The aim of this study was to establish an objective diagnostic method for CP using EUS elastography (EUS-EG). METHODS: A retrospective study was designed and 96 patients underwent EUS-EG for follow-up of known CP, or who were clinically suspected as having CP. CP patients were categorized CP patients as 4 stages using the Rosemont classification (RC). EUS-EG was performed and the "Mean value", which was negatively correlated with pancreatic fibrosis, was calculated using histogram analysis. RESULTS: The "Mean value" of each RC stage (normal, indeterminate for CP, suggestive of CP, and consistent with CP) was 90.1 ± 19.3, 73.2 ± 10.6, 63.7 ± 14.2, and 56.1 ± 13.6, respectively, and showed significant differences for each stage (p < 0.001). There was a significant negative correlation between the "Mean value" and the number of EUS features (r s = -0.59, p < 0.001). Multiple linear regression analysis was used to assess the diagnostic finding of the "Mean value" and showed that hyperechoic foci with shadowing and lobularity with honeycombing maintained their independent diagnostic findings. CONCLUSIONS: EUS-EG was an objective diagnostic apparatus for CP and provided objective information to support EUS features.

Quantitative evaluation of pancreatic tumor fibrosis using shear wave elastography.

BACKGROUND & AIMS: There is no established non-invasive method for diagnosis of pancreatic fibrosis. Shear wave elastography (SW-EG) may be a candidate for this purpose. The aims of this study were to assess the reproducibility of SW-EG in the normal imaging pancreas (Phase 1) and to evaluate the diagnostic performance of SW-EG for pancreatic fibrosis classified histologically (Phase 2). METHODS: Phase 1: This included 127 cases that underwent SW-EG of the normal imaging pancreas. SW-EG was measured at least five times in the pancreatic parenchyma and the median of repeated measurements was defined as the pancreatic elastic modulus (PEM). Phase 2: This included 53 cases that underwent SW-EG of the pancreatic parenchyma preoperatively and in which pancreas parenchyma were evaluated histologically. Histological fibrosis was graded in 4 stages: normal, mild, moderate, and severe. RESULTS: Phase 1: Median PEM in the head, body, and tail of the pancreas were 3.23, 3.17, and 2.91 kPa, respectively, with no significant difference among regions (P = 0.554). The intraclass correlation coefficient showed good reproducibility (ρ = 0.71) after 5 measurements. Phase 2: There was a significant positive correlation between PEM and the histological pancreatic fibrosis stage (rs = 0.63, P < 0.001). Areas under the receiver operating characteristic curve for the accuracy of SW-EG for diagnosis of pancreatic fibrosis were 0.85 (≥mild), 0.84 (≥moderate), and 0.87 (severe). CONCLUSION: SW-EG can be used to determine the stage of pancreatic fibrosis non-invasively with high accuracy and reproducibility.

The prognostic factors and trajectory of HRQOL in patients with pancreatic cancer who received psychiatric intervention.

BACKGROUND AND AIM: Patients with advanced pancreatic cancer have severe pain, anxiety, and depression, and these symptoms deteriorate quality of life (QOL). Previous study reported that early psychiatric intervention for advanced cancer patients may improve QOL. We evaluated the trajectory of health-related QOL (HRQOL) in patients with pancreatic cancer after an early psychiatric intervention. METHODS: A prospective cohort study was performed in 108 pancreatic cancer patients who received consultation liaison psychiatry from November, 2011 to October, 2014 at Nagoya University Hospital. Longitudinal changes in HRQOL and the association between aspects of HRQOL and survival were evaluated using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 before treatment and every month after the start of treatment. RESULTS: Physical functioning significantly decreased after 1, 3, and 6 months of treatment compared with baseline, but global health status (GHS), role functioning, emotional functioning, and social functioning showed a tendency to improve. Severe impairment of GHS, fatigue, and appetite loss were apparent at 3 months prior to death. In multivariate analysis, pain was a significant prognostic factor for survival (hazard ratio [HR], 1.109; 95% confidence interval [CI], 1.021-1.204; P = 0.013), in addition to poor performance status (HR, 5.473; 95%CI, 2.338-12.816; P < .0001) and distant metastases at diagnosis (HR, 3.274; 95%CI, 1.872-5.725; P < .0001). CONCLUSIONS: Early psychiatric intervention in patients with pancreatic cancer may maintain HRQOL. More effective pain management and reduction of psychological distress are important for patients with pancreatic cancer.

[A case of successful treatment of granulocyte colony-stimulating factor producing hepatocellular carcinoma accompanying type B hepatitis with tegafur-uracil].

A 37-year-old man underwent lobectomy of the right liver for granulocyte colony-stimulating factor (G-CSF) producing hepatocellular carcinoma accompanying type B hepatitis. Within two months after the surgery, lung metastases were revealed and administration of sorafenib was begun, however, the lung metastases continued to enlarge. Changing the patient's medication to tegafur-uracil provided remarkable reduction of the lung metastases. The patient is alive two years after diagnosis and receives outpatient chemotherapy. We concluded that this case is valuable with regard to the extreme rarity of G-CSF producing hepatocellular carcinoma and its successful treatment in this case.