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Labor analgesia (LA) is associated with the potential hazard of high-risk delivery, such as cesarean section (CS) and instrumental vaginal delivery (IVD), and adverse neonatal outcomes such as neonatal asphyxia and respiratory distress. The objective was to examine the impact of LA on mode of delivery and neonatal outcomes and to counsel pregnant women about a potentially higher risk and allow them to decide LA or non-LA. This retrospective cohort study containing 5,184 pregnant women analyzed the association between LA and both mode of delivery and neonatal outcomes. LA increased the risk of IVD (Adjusted Odds Ratio [AOR] 3.25, 95% confidence interval [95%CI] 2.51–4.20) but decreased that of CS (AOR 0.52, 95%CI 0.44–0.60). Two factors (advanced maternal age [AOR 1.70, 95%CI 1.33–2.17] and primipara [AOR 4.72, 95%CI 3.30–6.75]) increased the risk of IVD. We should carefully consider the indication of LA for cases with these two factors since LA can increase the risk of IVD and adverse neonatal outcomes.

Background and aimsThe risk factors in the progression of nonalcoholic fatty liver disease (NAFLD) have not been fully clarified. Porphyromonas gingivalis (P.g) has been considered to be a confounding risk factor for systemic diseases. We aimed to evaluate the effect of P.g infection on risk of progression to NASH.Methods(1) Serum IgG antibody titers against P.g fimbriae (fimA) in 200 biopsy-proven NAFLD patients were measured by ELISA and compared with histological findings. (2) C57BL/6J mice were fed a control diet (CD) or high-fat diet (HFD) with or without P.g-odontogenic infection and analyzed histologically. Mouse livers were analyzed using CE–TOFMS and LC–TOFMS.Results(1) A significant correlation between fibrosis progression and antibody titers against P.g possessing fimA type 4 was identified (P = 0.0081). Multivariate analysis identified older age and type 4 P.g-positivity as risk factors for advanced fibrosis. (2) Fibrosis and steatosis were more severe in HFD P.g(+) mice compared with HFD P.g(−) mice. In metabolome analysis, fatty acid metabolism was significantly disrupted with HFD in P.g-infected mouse livers. Monounsaturated/saturated fatty acid ratios were significantly higher in the HFD P.g(+) group than in the HFD P.g(−) group (P < 0.05). Moreover, expression levels of SCD1 and ELOVL6 were significantly reduced.ConclusionsThese results suggest that P.g infection is an important risk factor for pathological progression in NAFLD. Increase in the monounsaturated/saturated fatty acid ratio may be an important change that facilitates progression of NAFLD.

BackgroundThe current status of Helicobacter pylori infection in Japan has not been investigated. We evaluated the status of H. pylori infection in a Japanese general population using large-scale resident-register-based sampling.MethodsAll 6069 adults in a rural town and 6000 adults in two urban cities (3000 each), selected by register-based random sampling, were enrolled in our health check-up program. Antibody titers against Helicobacter pylori (cut-off value was 3 U/mL by Eiken E-plate) were evaluated, and subjects with a positive result were encouraged to undergo further examinations.ResultsA total of 1586 subjects participated in serum sampling. The overall prevalence of H. pylori infection was 40.0% (634/1586), and it increased with age both in rural and urban areas. Although the overall positive rate was higher in the rural area (49.4%) than in the urban areas (35.6 and 32.3%), there was no difference in H. pylori status of younger subjects between the two areas. Among 634 patients with a positive titer, 374 (59.0%) underwent further examinations including endoscopic examination, and 180/634 (28.4%) patients received eradication therapy. Gastric neoplasms (three adenocarcinomas and one adenoma) were found in our screening program.ConclusionWe clarified population-based random sampling data of H. pylori infection in a Japanese general population. In younger subjects, a decrease in the prevalence of H. pylori infection was confirmed both in rural and urban areas. This provides basic information for establishing a strategy to reduce gastric cancer deaths.

Aims Hepatitis C virus (HCV) infection among drug users presents an important public health problem; however, little recognition and few approaches to address this issue in Japan. This study was conducted to investigate the current disease status by assessing anti‐HCV antibody (Ab) seroprevalence among people who inject drugs (PWIDs) and people who use drugs (PWUDs) in Hiroshima, Japan. Methods This study was a psychiatric single‐site chart review in patients with drug abuse problems in the Hiroshima region. The primary outcome was anti‐HCV Ab prevalence among PWIDs who underwent anti‐HCV Ab testing. The secondary outcomes included the prevalence of anti‐HCV Ab among PWUDs who underwent anti‐HCV Ab testing and the proportion of patients who underwent anti‐HCV Ab examination. Results A total of 222 PWUD patients were enrolled. Among these, 16 patients (7.2%) had records of injection drug use (PWIDs). Eleven (68.8%) of the 16 PWIDs received anti‐HCV Ab tests, and 4 (36.4%, 4/11) were anti‐HCV Ab‐positive. Among 222 PWUDs, 126 (56.8%) patients received anti‐HCV Ab tests, and 57 of these patients (45.2%, 57/126) were anti‐HCV Ab‐positive. Conclusion The prevalence of anti‐HCV Ab among PWIDs and PWUDs who visited the study site was higher than the general population, which was 2.2% among hospitalized patients between May 2018 and November 2019. Considering the World Health Organization's (WHO) elimination goal and recent advances in HCV treatment, patients with drug abuse experience should be encouraged to take HCV tests and consult hepatologists for further investigations and treatment if they are positive for anti‐HCV Ab. This study was conducted to investigate the prevalence of Hepatitis C virus (HCV) infection by assessing anti‐HCV antibody (Ab) seroprevalence among people who inject drugs (PWIDs) and people who use drugs (PWUDs) in Hiroshima, Japan. In the results, the prevalence of anti‐HCV Ab among PWIDs and PWUDs who visited the study site was substantially higher than the general population. Considering the World Health Organization's (WHO) HCV elimination goal, patients with drug abuse experience should be encouraged to take HCV tests and consult hepatologists for further investigations and treatment if they are positive for anti‐HCV Ab.

The risk of hepatocellular carcinoma (HCC) development is reduced following viral elimination by interferon therapy in chronic hepatitis C patients. However, the risk in patients treated with interferon-free direct-acting antivirals (DAAs) is unknown. We evaluated chronic hepatitis C patients who achieved viral eradication by pegylated-interferon plus ribavirin (PEG-IFN/RBV, n = 244) or daclatasvir plus asunaprevir (DCV/ASV, n = 154) therapy. None of the patients had prior history of HCC or antiviral therapy. The median observation period after the end of treatment for the PEG-IFN/RBV and DCV/ASV groups were 96 (range 10-196) and 23 (range 4-78) months, respectively. During the observation period, HCC developed in 13 (5.3%) and 7 (4.5%) patients in the PEG-IFN/RBV and DCV/ASV groups, respectively. The cumulative HCC development rate after 1-, 3- and 5-years (0.4%, 3% and 5% for the PEG-IFN/RBV group and 0.6%, 9% and 9% for the DAA group, respectively) were similar between the two groups. Propensity score matching analysis also showed no significant difference in HCC development rates between the two groups. Serum AFP levels decreased to similar levels between PEG-IFN/RBV and DCV/ASV groups following the achievement of viral eradication. The risk for HCC development following viral eradication by IFN-free DAA therapy may be similar to that in IFN-based therapy.

Background We previously reported on the trends in the etiologies of hepatocellular carcinoma (HCC) diagnosed in patients between 1995 and 2009. The aims of our updated study were to evaluate the incidence, nonhepatitis B and nonhepatitis C viral (NBNC) etiologies, and clinical characteristics of HCCs occurring in patients between 1992 and 2018. Methods The study enrolled 2171 consecutive patients with HCC between 1992 and 2018. Their medical records were reviewed. The patients were divided into two groups, patients with early diagnoses from 1992 to 2009 and those with late diagnoses from 2010 to 2018. Results NBNC-HCC occurred in 514 patients (23.6%). The percentage of patients with HCC who had NBNC-HCC increased from 26.5% in 2009 to 46.3% in 2018. Patients with NBNC-HCC were older (median ages from 67 to 73 years). Type 2 diabetes mellitus (48.5–60.3%: P  = 0.008), hypertension (48.5–57.4%: P  = 0.047), and hyperlipidemia (39.2–53.8%: P  = 0.001) increased significantly in recent years. The median FIB-4 index decreased (4.37–3.61: P  = 0.026) and the median platelet count increased (15.1–17.9 × 10 4 /μL: P  = 0.013). Among the 514 patients with NBNC-HCC, 194 underwent hepatic resection for nonalcoholic steatohepatitis (NASH) (15%), alcoholic liver disease (ALD) (29%), and cryptogenic hepatitis (56%). Cirrhosis was detected in 72%, 39%, and 16% of patients with NASH, ALD, and cryptogenic hepatitis, respectively. The prevalence of cirrhosis in patients with NASH was significantly higher than the prevalence of cirrhosis in the other groups ( P  < 0.001). Overall, 70% of the non-malignant liver tissue of patients with NBNC-HCC was not involved with cirrhosis. On the other hand, the median FIB-4 index in patients with cryptogenic HCC was 2.56, which was a significantly lower value than those values in the other groups of patients. The FIB-4 index considered as one of useful screening of HCC. Conclusions The prevalence of NBNC-HCC has increased rapidly even in a regional university hospital. Metabolic syndrome may be an important risk factor for HCC. HCC was also found in patients with non-cirrhotic livers. The FIB-4 index may be a useful screening method for HCC in patients with NBNC.

The feature of blood glucose dynamics in patients with chronic liver disease (CLD) is marked blood glucose fluctuations. However, the detail of blood glucose dynamics is not well known. The aim of the present study was to evaluate glycemic fluctuations by continuous glucose monitoring (CGM). A total of 105 CLD patients with type 2 diabetes mellitus (T2DM) were enrolled in this study. Various parameters of glycemic variability were evaluated. The association of these parameters with liver functional reserve was examined. The parameters were also evaluated according to glycated hemoglobin A1c (HbA1c) levels. Data of all patients showed that mean blood glucose (MBG) levels and the difference between highest and lowest blood glucose (ΔBG) increased significantly with worsening of liver functional reserve (P < 0.001 and P = 0.005, respectively). Although many of the cases were being treated for diabetes, postprandial hyperglycemia was seen in 92% of patients. Nocturnal hypoglycemia was seen in 22% of patients. In non-anemic patients with HbA1c levels of < 7.0%, the percentage of patients with mean amplitude of glycemic excursion (MAGE) of ≥ 77.4 mg/dL and that of MBG levels of > 145 mg/dL were higher in liver cirrhosis (LC) patients than in chronic hepatitis (CH) patients. In them, homeostasis model assessment for insulin resistance (HOMA-IR) of > 2.5 and LC were significantly associated with the increase in MAGE. LC was also significantly associated with increased MBG levels. The CGM systems were useful in finding hidden abnormalities of blood glucose fluctuations in CLD patients with T2DM, especially in non-anemic CLD patients with HbA1c levels of < 7.0%.

It is not clear that antiviral therapy for hepatitis C virus (HCV) after recovery from curative treatment for hepatocellular carcinoma (HCC) has an effect on suppressing recurrence or improving survival rates. We analyzed the impact of eradication by interferon (IFN)-free direct-acting antiviral (DAA) therapy on clinical outcomes of patients with HCV-associated HCC who underwent curative treatment. This was a retrospective study. We retrospectively reviewed 109 consecutive patients with sustained virologic response with DAA therapy after HCC treatment and analyzed HCC recurrence and overall survival (OS). Among these patients are those with a history of HCC recurrence and curative HCC treatments administered as definitive HCC treatments prior to initiation of DAA therapy. Among 109 patients, 64 received DAA therapy after curative treatment for HCC; the remaining 45 received ⩾2 subsequent treatments for HCC. Cumulative HCC recurrence rates at 1, 3, and 5 years were 23%, 47%, and 56%, respectively. Multivariate analysis identified predictive factors for suppression of HCC recurrence as tumor number (hazard ratio (HR) 2.293 for multiple;  = 0.006) and number of HCC treatments before DAA therapy (HR 2.928 for ⩾2;  = 0.001). Among 64 patients who received curative treatment for HCC, cumulative first HCC recurrence rates at 1, 3, and 5 years were 12%, 34%, and 44%, respectively, second recurrence rates were 11%, 28%, and 39%, and third recurrence rates were 0%, 22%, and 53%, respectively; recurrence tended to be suppressed until 3 years. Cumulative OS rates at 3 and 5 years were 87% and 75%, respectively. On multivariate analysis, tumor number (HR 2.452 for single;  = 0.026) was the only independent predictor of OS. DAA therapy after curative treatment for HCC suppresses HCC recurrence in the long term, but recurrence was higher in patients with a history of many HCC treatments.

Introduction: Portal hypertensive enteropathy (PHE) is a well-known small-bowel lesion that occurs with liver cirrhosis (LC) and is associated with increased hepatic venous pressure. However, it is unclear how esophageal varices (EV) treatment actually affects PHE. We aimed to analyze the effects of EV treatment on PHE. Methods: Among LC patients who underwent capsule endoscopy (CE) more than twice to confirm PHE at our hospital from February 2009 to September 2018, we targeted those with no change in the Child-Pugh classification after EV treatment for the prevention of bleeding. Patients were assigned to groups based on the EV treatment method (endoscopic injection sclerotherapy [EIS] group or endoscopic variceal ligation [EVL] group). We analyzed the PHE findings before and after treatment, and we investigated changes in the collateral vein using computed tomography imaging. Results: We analyzed 42 LC patients (27 men; mean age, 65.3 years); 20 were in the EIS group and 22 were in the EVL group. Exacerbation of PHE was significantly prevalent in the EIS group (90%) compared to that in the EVL group (50%). CE of PHE showed significantly prevalent exacerbation of villous edema in the EIS group (65%) compared to that in the EVL group (23%). Stenosis or disappearance of the feeding vessel (55%) and exacerbation of the hepatofugal collateral vein (35%) were significantly prevalent in the EIS group. Conclusions: EIS exacerbates PHE, especially villous edema, in LC patients with changes in collateral circulation.

Background Wisteria floribunda agglutinin positive human Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel serum glycomarker for liver fibrosis. However, it is not known whether or not M2BPGi reflects only liver fibrosis. We measured serum M2BPGi levels in patients with acute liver injury. Methods Fifty-one patients with acute liver injury were enrolled. M2BPGi levels were measured at the initial visit and at achievement of recovery. The relationship between M2BPGi values at the initial visit and clinical outcomes was analyzed. Results Serum M2BPGi levels at the initial visit were elevated in 47 of 51 acute liver injury patients (8.33 ± 7.56 cutoff index). M2BPGi values were associated with prothrombin activity ( r  = −0.600, P  = 0.001), total bilirubin level ( r  = 0.588, P  = 0.001), and Model for End-Stage Liver Disease score ( r  = 0.490, P  = 0.001) but not with aspartate aminotransferase ( r  = −0.070) and alanine aminotransferase ( r  = −0.073) levels. M2BPGi values at the initial visit were significantly higher in patients with acute liver failure (diagnosed by prothrombin activity of 40% or less; P  < 0.001), subsequent development of hepatic coma ( P  = 0.036), and subsequent requirement of liver transplant ( P  = 0.014), and in a patient who died ( P  = 0.045). M2BPGi values decreased after aminotransferase level normalization in patients who recovered from acute liver injury; however, M2BPGi level was not a predictive factor for recovery with medical therapy. Conclusions Serum M2BPGi values increased in patients with acute liver injury and decreased following recovery. The marker seems to reflect not only liver fibrosis but also other factors, such as liver inflammation, liver damage, and hepatocyte regeneration.