Showing papers in "Journal of Gastroenterology and Hepatology in 2014"

Guidelines for the diagnosis and treatment of Helicobacter pylori infection in Korea, 2013 revised edition

Abstract: The Korean College of Helicobacter and Upper Gastrointestinal Research first developed guidelines for the diagnosis and treatment of Helicobacter pylori (H. pylori) infection in 1998, and revised guidelines were proposed in 2009 by the same group. Although the revised guidelines were based on a comprehensive review of published articles and the consensus of expert opinions, the revised guidelines were not developed using an evidence-based process. The new guidelines presented in this study include specific changes regarding indication and treatment of H. pylori infection in Korea, and were developed through the adaptation process using an evidence-based approach. After systematic review of the literature, six guidelines were selected using the Appraisal of Guidelines for Research and Evaluation (AGREE) II process. A total of 21 statements were proposed with the grading system and revised using the modified Delphi method. After the guideline revisions, 11 statements about indication of test and treatment, four statements about diagnosis, and four statements about treatment of H. pylori infection were developed. The revised guidelines were reviewed by external experts before receiving official endorsement from the Korean College of Helicobacter and Upper Gastrointestinal Research, and disseminated to physicians and other medical professionals for use in clinical practice in Korea. The guidelines will continue to be updated and revised periodically.

Prevalence of nonalcoholic fatty liver disease in mainland of China: A meta‐analysis of published studies

Abstract: Background and Aim Nonalcoholic fatty liver disease (NAFLD) is becoming an increasingly important health issue. However, there are no data on the change in prevalence of NAFLD within a population over time, especially in the mainland of China. The goal of this study was to estimate the pooled prevalence of NAFLD in the mainland of China. Methods Systematic literature searches were conducted in PubMed, Web of Knowledge, Chinese Web of Knowledge, Wangfang, Weipu, and SinoMed databases, as well as relevant articles published from 1997 to 2013, reporting prevalence estimates of NAFLD in the mainland of China. Summary estimates of prevalence were calculated with a random effects model. The effects of research methodology on the prevalence estimates were assessed using a meta-regression model. Results Forty-eight studies were identified with of a total of 356 367 subjects. The overall pooled prevalence of NAFLD was 20.09% (17.95–22.31%). Subgroup analyses showed the following results: male: 24.81% (21.88–27.87%), female: 13.16% (11.33–15.11%), for 18–30: 9.22% (6.93–11.81%), for 40: 16.77% (13.22–20.66%), for 50: 23.50% (19.57–27.66%), for 60: 26.89% (21.11–33.09%), for urban: 21.83% (18.00–25.92%), for rural: 20.43% (8.01–36.74%); study years in 2000–2006: 18.22% (14.32–22.48%), 20.00% (16.84–23.36%) for 2007–2009, and 18.93% (15.41–22.72%) for 2010–2013. Conclusions The prevalence of NAFLD is lower than the estimates from developed countries. But it still reaches the epidemic proportions, and its prevalence is increasing. Meanwhile, a nationwide prevalence investigation should be conducted to confirm the estimates and determine more accurate rates for specific populations.

Post-liver transplantation sarcopenia in cirrhosis: A prospective evaluation

Abstract: Background and Aim Pre-transplant sarcopenia (reduced skeletal muscle mass) predicts poor outcome in cirrhosis In contrast, whether muscle mass increases post orthotopic liver transplantation (OLT) is not known and was studied prospectively

Controlled attenuation parameter for the detection and quantification of hepatic steatosis in nonalcoholic fatty liver disease

Abstract: Background and Aim Controlled attenuation parameter (CAP) has been suggested as a noninvasive method for detection and quantification of hepatic steatosis. We aim to study the diagnostic performance of CAP in nonalcoholic fatty liver disease (NAFLD) patients. Methods Transient elastography was performed in consecutive NAFLD patients undergoing liver biopsy and non-NAFLD controls. The accuracy of CAP for the detection and quantification of hepatic steatosis was assessed based on histological findings according to the Nonalcoholic Steatohepatitis Clinical Research Network Scoring System. Results Data for 101 NAFLD patients (mean age 50.3 ± 11.3 years old, 51.5% male) and 60 non-NAFLD controls were analyzed. CAP was associated with steatosis grade (odds ratio [OR] = 29.16, P < 0.001), body mass index (BMI; OR = 4.34, P < 0.001) and serum triglyceride (OR = 13.59, P = 0.037) on multivariate analysis. The median CAP for steatosis grades S0, S1, S2, and S3 were 184 dB/m, 305 dB/m, 320 dB/m, and 324 dB/m, respectively. The areas under receiver operating characteristics curves (AUROC) for estimation of steatosis grades ≥ S1, S2, and S3 were 0.97, 0.86, and 0.75, respectively. The optimal CAP cutoffs for estimation of steatosis grades ≥ S1, S2, and S3 were 263 dB/m, 281 dB/m, and 283 dB/m, respectively. Among non-obese patients, the AUROC for estimation of steatosis grades ≥ S1 and S2 were 0.99 and 0.99, respectively. Among obese patients, the AUROC for estimation of steatosis grades ≥ S1, S2, and S3 were 0.92, 0.64, and 0.58, respectively. Conclusions CAP is excellent for the detection of significant hepatic steatosis. However, its accuracy is impaired by an increased BMI, and it is less accurate to distinguish between the different grades of hepatic steatosis.

Anti-inflammatory mechanism of metformin and its effects in intestinal inflammation and colitis-associated colon cancer.

Abstract: Background and Aim The aim of this study is to evaluate the effect of metformin on intestinal inflammation. Methods COLO205 cells were pretreated with metformin and stimulated with tumor necrosis factor (TNF)-α. Expression of interleukin (IL)-8 was determined by luciferase assay and real-time PCR. Inhibitor of kappaB (IκB) phosphorylation/degradation and adenosine monohosphate-activated protein kinase (AMPK) activity were evaluated by Western blotting. DNA-binding activity of transcription factor nuclear factor-kappaB (NF-κB) was assessed by electrophoretic mobility shift assay. In an acute colitis model, mice were given 4% dextran sulfate sodium (DSS) for 5 days. IL-10−/− mice were used to evaluate the effect of metformin on chronic colitis. In an inflamation-associated tumor model, mice were given a single intraperitoneal injection of azoxymethane followed by three cycles of 2% DSS for 5 days and 2 weeks of free water consumption. Results Metformin significantly inhibited IL-8 induction in COLO 205 cells stimulated with TNF-α. Metformin attenuated IκBα phosphorylation and NF-κB DNA-binding activity. Administration of metformin significantly reduced the severity of DSS-induced colitis. In addition, DSS-induced IκB kinase (IKK) activation was significantly reduced in mice treated with metformin. Metformin significantly attenuated the severity of colitis in IL-10−/− mice, induced AMPK activity in intestinal epithelial cells, and inhibited the development of colitic cancer in mice. Conclusions These results indicate that metformin suppresses NF-κB activation in intestinal epithelial cells and ameliorates murine colitis and colitis-associated tumorigenesis in mice, suggesting that metformin could be a potential therapeutic agent for the treatment of inflammatory bowel disease.

Effect of multispecies probiotics on irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial.

Abstract: Background and Aim The efficacy of treatment with multispecies probiotics on irritable bowel syndrome (IBS) symptoms and the alterations of gut microbiota in patients who have taken probiotics were investigated. Methods This randomized, double-blind, placebo-controlled trial involved 49 IBS patients (probiotics: 25, placebo: 24) diagnosed according to the Rome III criteria. Patients were randomly assigned to two groups: either to receive multispecies probiotics (a mixture of Bifidobacterium longum, B. bifidum, B. lactis, Lactobacillus acidophilus, L. rhamnosus, and Streptococcus thermophilus) twice a day for 4 weeks or to receive a placebo twice a day for 4 weeks. The primary efficacy end-point was the proportion of participants whose IBS symptoms were substantially relieved at week 4. Secondary end-points were the intensity of abdominal pain/discomfort, bloating, stool frequency/consistency, alterations in fecal microflora over the 4 weeks. Fecal microflora were analyzed in 34 patients (probiotics: 17, placebo: 17) by quantitative real-time polymerase chain reaction assays. Results The proportion of patients whose IBS symptoms were substantially relieved at week 4 was significantly higher in the probiotics group than in the placebo group: 68.0% (17/25) versus 37.5% (9/24) (P < 0.05). Secondary end-points such as improvement in abdominal pain/discomfort and bloating occurred in the probiotics group but not in the placebo group. Fecal analysis revealed that B. lactis, L. rhamnosus, and S. thermophilus had increased significantly in the probiotics group after 4 weeks and that B. lactis had increased in the placebo group. Conclusions Multispecies probiotics are effective in IBS patients and induce the alterations in the composition of intestinal microbiota.

Controlled attenuation parameter for the detection of steatosis severity in chronic liver disease: a meta-analysis of diagnostic accuracy.

Abstract: Background and Aim Controlled attenuation parameter (CAP) is a novel ultrasound-based elastography method for detection of steatosis severity. This meta-analysis aimed to assess the performance of CAP. Methods PubMed, the Cochrane Library, and the Web of Knowledge were searched to find studies, published in English, relating to accuracy evaluations of CAP for detecting stage 1 (S1), stage 2 (S2), or stage 3 (S3) hepatic steatosis which was diagnosed by liver biopsy. Sensitivities, specificities, and hierarchical summary receiver operating characteristic (HSROC) curves were used to examine CAP performance. The clinical utility of CAP was also evaluated. Results Nine studies, with 11 cohorts were analyzed. The summary sensitivities and specificities values were 0.78 (95% confidence interval [CI], 0.69–0.84) and 0.79 (95% CI, 0.68–0.86) for ≥ S1, 0.85 (95% CI, 0.74–0.92) and 0.79 (95% CI, 0.71–0.85) for ≥ S2, and 0.83 (95% CI, 0.76–0.89) and 0.79 (95% CI, 0.68–0.87) for ≥ S3. The HSROCs were 0.85 (95% CI, 0.81–88) for ≥ S1, 0.88 (95% CI, 0.85–0.91) for ≥ S2, and 0.87 (95% CI, 0.84–0.90) for ≥ S3. Following a “positive” measurement (over the threshold value) for ≥ S1, ≥ S2, and ≥ S3, the corresponding post-test probabilities for the presence of steatosis (pretest probability was 50%) were 78%, 80% and 80%, respectively; if the values were below these thresholds (“negative” results), the post-test probabilities were 22%, 16%, and 17%, respectively. Conclusions CAP has good sensitivity and specificity for detecting hepatic steatosis; however, based on a meta-analysis, CAP was limited in their accuracy of steatosis, which precluded widespread use in clinical practice.

Comparison of long-term effectiveness and complications of radiofrequency ablation with hepatectomy for small hepatocellular carcinoma

Abstract: Background and Aim To determine and compare the adverse events and long-term effectiveness for patients with small hepatocellular carcinoma (HCC) (≤ 3 cm) treated by percutaneous radiofrequency ablation (RFA) or hepatectomy Methods Small HCC from 120 patients were randomized into either percutaneous RFA therapy or hepatectomy group, and the effectiveness and complications of two treatment modalities were analyzed The complications of post-RFA or hepatectomy, the complete treatment rate, treatment-related mortality, and disease-free and overall survival rate were followed up and conducted Results In patients with small HCC, complete remission rates were achieved in 95% and 967% in the percutaneus RFA and hepatectomy groups, respectively (P > 005) Hepatic function at day-7 status post-treatment, including albumin and bilirubin levels, were significantly worse in the hepatectomy group (P 005) There was no significant difference of the disease-free and overall survival rates at 1, 2, and 3 years between the RFA group and the surgical hepatectomy group (P = 0443 and P = 0207, respectively) Conclusions In patients with small HCC, percutaneous RFA showed similar local control and long-term survival compared with hepatectomy Importantly, percutaneous RFA are accompanied with a lower complication rate and shorter hospital stay day

Duodenal eosinophilia and early satiety in functional dyspepsia: Confirmation of a positive association in an Australian cohort

Abstract: Background and Aim Functional dyspepsia (FD), defined by unexplained pain or discomfort centered in the upper abdomen, is common. Diagnosis and treatment of FD based on the symptom-based Rome criteria remains challenging. Recently, eosinophilia in the duodenum has been implicated in the pathophysiology of FD in adults, specifically increased eosinophils in early satiety and postprandial distress, but the association remains controversial. The aim of this study was to characterize upper gastrointestinal (GI) tract pathology, specifically duodenal eosinophilia, in an Australian cohort of patients with FD. Methods Patients prospectively referred for an upper GI endoscopy (n = 55; mean age, 49.6 years; 61.8% female) were stratified to FD cases (n = 33) and controls (n = 22) using Rome II criteria. All subjects completed a validated bowel symptom questionnaire. The eosinophil count per square millimeter in the duodenal bulb (D1) and second part (D2) was assessed and Helicobacter pylori status determined by gastric histology. Associations with clinical symptoms were assessed. Results Cases and controls were demographically similar. Duodenal eosinophilia was significantly increased in subjects experiencing early satiety (P = 0.01) and postprandial fullness (P = 0.001). This association was seen in D2 but not D1. Abdominal pain was associated with eosinophilia in both D1 (P = 0.02) and D2 (P = 0.005). Smoking was also associated with higher eosinophil counts in D2 (P = 0.007) and symptoms of early satiety (P = 0.02). Conclusions Duodenal eosinophilia occurs in a subset of FD. The potential role of duodenal eosinophils in FD has implications for diagnosis and therapeutic trials.

Gut microbiota and liver disease

Abstract: Microbes are present in large numbers in each human being, in particularly in the gastrointestinal (GI) tract, and have long been believed to have some beneficial effects for their hosts. Till recently, however, we lacked tools for studying these organisms. Rapid technological advances in recent years have markedly improved our understanding of their role both in health and disease. Recent literature suggests that organisms in the GI tract, referred to collectively as gut microbiota, play an indispensable role in the maintenance of host's homeostasis. Alterations in the gut microbiota, that is in the nature and relative density of various constituent bacterial species, appear to have a role in pathogenesis and progression of several GI and hepatic diseases. This has also opened the vista for tinkering with gut flora in an attempt to treat or prevent such diseases. In this review, we have tried to summarize information on normal gut microbiota, laboratory techniques and animal models used to study it, and the role of its perturbations in some of the common hepatic disorders, such as non-alcoholic fatty liver disease (including obesity), non-alcoholic steatohepatitis, alcoholic liver disease, and liver cirrhosis and its complications.

Distribution and clinical correlates of viral and host genotypes in Chinese patients with chronic hepatitis C virus infection

Abstract: Background and Aim Chronic hepatitis C virus (HCV) infection is relatively frequent in China. This study investigated the clinical, demographic, and viral and host genetic characteristics that may influence disease manifestations and clinical management.

Mechanisms of isoniazid-induced idiosyncratic liver injury: Emerging role of mitochondrial stress

Abstract: Idiosyncratic drug-induced liver injury (DILI) is a significant adverse effect of antitubercular therapy with isoniazid (INH). Although the drug has been used for many decades, the underlying mode of action (both patient-specific and drug-specific mechanisms) leading to DILI are poorly understood. Among the patient-specific determinants of susceptibility to INH-associated DILI, the importance of HLA genetic variants has been increasingly recognized, whereas the role of polymorphisms of drug-metabolizing enzymes (NAT2 and CYP2E1) has become less important and remains controversial. However, these polymorphisms are merely correlative, and other molecular determinants of susceptibility have remained largely unknown. Regarding the drug-specific mechanisms underlying INH-induced liver injury, novel concepts have been emerging. Among these are covalent protein adduct formation via novel reactive intermediates, leading to hapten formation and a potential immune response, and interference with endogenous metabolism. Furthermore, INH and/or INH metabolites (e.g. hydrazine) can cause mitochondrial injury, which can lead to mitochondrial oxidant stress and impairment of energy homeostasis. Recent studies have revealed that underlying impairment of complex I function can trigger massive hepatocellular injury induced by otherwise nontoxic concentrations of INH superimposed on these mitochondrial deficiencies. This review discusses these emerging new paradigms of INH-induced DILI and highlights recent insights into the mechanisms, as well as points to the existing large gaps in our understanding of the pathogenesis.

Doxorubicin-eluting beads versus conventional transarterial chemoembolization for the treatment of hepatocellular carcinoma.

Abstract: Background and Aim Doxorubicin-eluting bead transarterial chemoembolization (DEB-TACE) is a novel locoregional treatment for unresectable hepatocellular carcinoma (HCC). However, to date, the benefits of DEB-TACE versus conventional transarterial chemoembolization (TACE) remain unclear. This meta-analysis was conducted to evaluate the efficacy and safety of the two treatments for patients with unresectable HCC. Methods We searched for relevant articles by means of computerized bibliographic search and complementary manual search. Objective tumor response, overall survival, and adverse events were then calculated and analyzed. Results A total of seven clinical studies with 700 participants were included in the current meta-analysis. Significantly better objective tumor response was found for DEB-TACE than for conventional TACE (OR = 1.92, 95% CI [1.34, 2.77]; P = 0.0004), with relative risk difference of 0.15 [0.07, 0.24] (P = 0.0003). One-year and 2-year survival rates were statistically significantly higher for DEB-TACE compared with conventional TACE (Peto OR, 95% CI: 0.64 [0.46, 0.89], P = 0.007; 0.61 [0.47, 0.80], P = 0.0003, respectively). Peto ORs of 6-month and 3-year survival were 0.72 [0.46, 1.14] (P = 0.16) and 0.77 [0.55, 1.06] (P = 0.11), respectively, showing no difference statistically. However, we could still find a tendency favoring DEB-TACE. Adverse side effects were similar in both groups, with postembolization syndrome occurring most commonly. Conclusions This meta-analysis shows that DEB-TACE provides significantly better tumor response compared with conventional TACE. One-year and 2-year survival are better with DEB-TACE. In addition, DEB-TACE is as safe as conventional TACE. Therefore, DEB-TACE is a better choice for HCC patients for whom curative treatments like liver transplantation and liver resection are not suitable.

Clinical association between non-alcoholic fatty liver disease and the development of hypertension.

Abstract: Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is getting an increas- ing attention for its clinical implications on cardiovascular disease (CVD). However, epidemiologic data are not so evident to sustain the causative association between NAFLD and hypertension, the major cause of CVD. Accordingly, we designed this study to investigate the clinical association between NAFLD and the development of hypertension. Methods: To assess the natural course of blood pressure according to degree of NAFLD (normal, mild, and moderate to severe), we conducted a prospective cohort study on the 22 090 Korean men without hypertension for 5 years. We serially checked the various metabolic factors including systolic and diastolic blood pressure in order to monitor the development of hypertension. Results: The incidence rate of hypertension increased according to the degree of NAFLD (normal: 14.4%, mild: 21.8%, moderate to severe: 30.1%, P < 0.001). Even after adjusting for other multiple covariates, the hazard ratios (95% confidence intervals) for hypertension were higher in the mild group (1.07; 1.00-1.15) and moderate to severe group (1.14; 1.00-1.30), compared with normal group, respectively (P for trend < 0.001). Conclusion: Development of hypertension is more potentially associated with the more progressive NAFLD than normal or milder state. In addition, NAFLD was an independent risk factor for hypertension.

Impact of rapid on-site evaluation on the adequacy of endoscopic-ultrasound guided fine-needle aspiration of solid pancreatic lesions: a systematic review and meta-analysis.

Abstract: Background Rapid on-site evaluation (ROSE) has the potential to improve adequacy rates for endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solid pancreatic lesions, but its impact is context-dependent. No studies exist that summarize the relationship between ROSE, number of needle passes, and resulting adequacy rates. Aims To analyze data from previous studies to establish if ROSE is associated with improved adequacy rates; to evaluate the relationship between ROSE, number of needle passes, and the resulting adequacy rates of EUS-FNA for solid pancreatic lesions. Methods Systematic review and meta-analysis of studies reporting the adequacy rates for EUS-FNA of solid pancreatic lesions. Results The search produced 3822 original studies, of which 70 studies met our inclusion criteria. The overall average adequacy rate was 96.2% (95% confidence interval: 95.5, 96.9). ROSE was associated with a statistically significant improvement of up to 3.5% in adequacy rates. There was heterogeneity in adequacy rates across all subgroups. No association between the assessor type and adequacy rates was found. Studies with ROSE have high per-case adequacy and a relatively high number of needle passes in contrast to non-ROSE studies. ROSE is an effect modifier of the relationship between number of needle passes and adequacy. Conclusions ROSE is associated with up to 3.5% improvement in adequacy rates for EUS-FNA of solid pancreatic lesions. ROSE assessor type has no impact on adequacy rates. ROSE is an effect modifier on the relationship between needle passes and per-case adequacy for EUS-FNA of solid pancreatic lesions.

Endoscopic resection for duodenal carcinoid tumors: A multicenter, retrospective study

Abstract: Background and Aim Gastrointestinal carcinoid tumors < 10 mm in diameter and limited to the submucosal layer demonstrate a low frequency of lymph node and distant metastasis, and are suitable for endoscopic treatment The aim of this study was to assess the efficacy, safety, and long-term prognosis of endoscopic resections for the treatment of duodenal carcinoid tumors Methods This study included a total of 41 duodenal carcinoid tumors in 38 patients between January 2006 and December 2011 The indications for endoscopic resection were lesions ≤ 10 mm in diameter, confined to the submucosal layer, and without lymph node or distant metastasis Endoscopic resection was accomplished using endoscopic mucosal resection (EMR), EMR with a ligation device (EMR-L), EMR after circumferential precutting, or endoscopic submucosal dissection (ESD) Results EMR was performed in 18 tumors, EMR-L in 16, EMR after circumferential precutting in 3, and ESD in 4 En-bloc resection was performed in 39 tumors (95%), and endoscopic complete resection was achieved in 40 (98%); pathological complete resection was achieved in 17 tumors (41%) The endoscopic complete resection rate did not differ according to the resection method, but the pathological complete resection rate was higher for ESD than for EMR and EMR-L Intraprocedural bleeding was noted in five cases, with no occurrence of perforation Recurrence was not observed during the mean follow-up period of 17 months (range 1–53 months) Conclusion Endoscopic resection appears to be a safe and effective treatment for duodenal carcinoid tumors measuring ≤ 10 mm in diameter and confined to the submucosal layer

Randomized trial of autologous bone marrow mesenchymal stem cells transplantation for hepatitis B virus cirrhosis: regulation of Treg/Th17 cells.

Abstract: Background and Aim Liver cirrhosis is one of the major consequences of hepatitis B virus (HBV) infection, and transplantation of autologous bone marrow mesenchymal stem cells (ABMSCs) is one of promising therapies for patients with HBV-related liver cirrhosis (HBV-LC). However, the mechanism is unclear. The aim of the current study was to explore the role of Treg/Th17 cells in ABMSCs transplantation in patients with HBV-LC. Methods In this prospective study, 56 patients were enrolled and randomly assigned to transplantation group and control group. After 24-week follow-up, 39 patients completed the study (20 cases in transplantation group and 19 cases in control group). The Model for End-Stage Liver Disease scores, liver function, changes of Treg/Th17 cells, as well as related transcription factors and serum cytokines, were determined. Results Although patients in both groups showed significant improvement after Entecavir treatment, ABMSC transplantation further improved patients' liver function. Moreover, there was a significant increase in Treg cells and a marked decrease in Th17 cells in the transplantation group compared with control, leading to an increased Treg/Th17 ratio. Furthermore, mRNA levels of Treg-related transcription factor (Foxp3) and Th17-related transcription factor (RORγt) were increased and decreased, respectively. In addition, serum transforming growth factor-β levels were significantly higher at early weeks of transplantation, while serum levels of interleukin-17, tumor necrosis factor-α, and interleukin-6 were significantly lower in patients in the transplantation group compared with control. Conclusion ABMSCs transplantation was effective in improving liver function in patients with HBV-LC, which was mediated, at least in part, through the regulation of Treg/Th17 cell balance.

miR‐224 promotion of cell migration and invasion by targeting Homeobox D 10 gene in human hepatocellular carcinoma

Abstract: Background and Aim MicroRNAs (miRNAs) are small noncoding RNA molecules that control target gene expression and are implicated in the regulation of diverse cellular pathways. In our previous research, we have demonstrated that miR-224 was overexpressed in liver cancer cells and tissues, which was an important factor in the regulation of cell migration and invasion. This study aimed to further explore the regulatory mechanism of miR-224 in the migration and invasion in liver cancer cells. Methods A luciferase reporter assay was used to confirm that the HOXD10 gene was a direct target of miR-224. Quantitative reverse transcriptase-polymerase chain reaction, Western blotting, Transwell migration, and Matrigel invasion assays were performed to clarify the molecular mechanism of miR-224 in the regulation of cell migration and invasion in human hepatocellular carcinoma (HCC). Results (i) The expression of miR-224 was strongly upregulated in MHHC97H and MHCC97L cells, and its expression level was significantly associated with cell invasive potential. (ii) The HOXD10 gene was confirmed to be a direct target of miR-224. Compared with normal liver tissues and cells, HOXD10 had lower expression in HCC tissues and cells and inversely regulated HCC cell invasion. (iii) miR-224 promoted expression of the tumor invasion-associated proteins p-PAK4 and MMP-9 by directly targeting HOXD10. Conclusion Our findings suggest a previously undescribed regulatory pathway in which the miR-224/HOXD10/p-PAK4/MMP-9 signaling pathway contributes to the regulation of cell migration and invasion and provides a new biotarget for HCC treatment.

Coffee and non-alcoholic fatty liver disease: brewing evidence for hepatoprotection?

Abstract: Coffee is one of the most popular beverages in the world. Several studies consistently show that coffee drinkers with chronic liver disease have a reduced risk of cirrhosis and a lower incidence of hepatocellular carcinoma regardless of primary etiology. With the increasing prevalence of non-alcoholic fatty liver disease (NAFLD) worldwide, there is renewed interest in the effect of coffee intake on NAFLD severity and positive clinical outcomes. This review gives an overview of growing epidemiological and clinical evidence which indicate that coffee consumption reduces severity of NAFLD. These studies vary in methodology, and potential confounding factors have not always been completely excluded. However, it does appear that coffee, and particular components other than caffeine, reduce NAFLD prevalence and inflammation of non-alcoholic steatohepatitis. Several possible mechanisms underlying coffee's hepatoprotective effects in NAFLD include antioxidative, anti-inflammatory, and antifibrotic effects, while a chemopreventive effect against hepatocarcinogenesis seems likely. The so-far limited data supporting such effects will be discussed, and the need for further study is highlighted.

Extrahepatic effects of nucleoside and nucleotide analogues in chronic hepatitis B treatment

Abstract: Oral nucleoside/nucleotide analogues (NAs) are the mainstay of therapy for patients with chronic hepatitis B and are generally well tolerated. Despite this, the safety profile of NAs is of paramount importance since the majority of patients will require long-term treatment. All NAs can potentially affect human DNA polymerase with decrease in mitochondrial DNA, leading to manifestations of mitochondrial toxicity. As a class effect, therefore, NAs can potentially cause extrahepatic conditions, such as myopathy, nephropathy, neuropathy, and lactic acidosis. Indeed, effects on muscles, including myopathy and creatine kinase elevations, have been described with clevudine and telbivudine use. Both adefovir and tenofovir are associated with dose-dependent nephropathy, predominantly affecting the proximal renal tubules. Neuropathy appears to be rare, and most commonly reported in patients receiving combination therapy with telbivudine and interferon. Increased risk of lactic acidosis has also been described for those with impaired liver and renal function taking entecavir. Loss of bone mineral density and hypophosphatemia have been described with the use of NAs, although the overwhelming studies have been with human immunodeficiency virus-infected patients. However, not all extrahepatic effects are detrimental. Recent evidence has suggested a potential renal beneficial effect with the use of telbivudine. The effect of NAs on pregnancy appears to be minimal for all NAs, with telbivudine and tenofovir having a more favorable category B rating. Ongoing pharmacovigilance is essential to identify new and monitor existing extrahepatic effects associated with NA use.

Primary hepatic angiosarcoma and potential treatment options.

Abstract: Angiosarcomas account for a mere 2-3% of adult soft tissue sarcomas, with an overall poor outcome. Depending on the primary site, angiosarcomas have distinct prognosis. Primary hepatic angiosarcomas (PHAs) are much rare tumors, with worse prognosis compared with other angiosarcomas. PHA is reported to be associated with vinyl chloride, but the majority of patients were still with unknown etiology. As PHA lacks specific symptoms, signs, or images, pathological diagnosis is necessary. The review summarizes 25 articles published from January 2000 to December 2012, including 64 cases of PHA with detailed information. Survival curves are estimated using the Kaplan-Meier method by SPSS 21.0. We find that the median survival time is 5 months; local excision alone or combination with adjuvant therapy is the optimal choice, with median survival time of 17 months. In addition, liver transplant is abandoned for high recurrence rate; emergent transcatheter arterial embolization is thought to be an efficient method for controlling intra-abdominal bleeding; and transcatheter arterial chemoembolization and chemotherapy may be helpful in improving survival.

Management of pancreatic ductal leaks and fistulae.

Abstract: Pancreatic duct leaks can occur as a result of both acute and chronic pancreatitis or in the setting of pancreatic trauma. Manifestations of leaks include pseudocysts, pancreatic ascites, high amylase pleural effusions, disconnected duct syndrome, and internal and external pancreatic fistulas. Patient presentations are highly variable and range from asymptomatic pancreatic cysts to patients with severe abdominal pain and sepsis from infected fluid collections. The diagnosis can often be made by high-quality cross-sectional imaging or during endoscopic retrograde cholangiopancreatography (ERCP). Because of their complexity, pancreatic leak patients are best managed by a multidisciplinary team comprised of therapeutic endoscopists, interventional radiologists, and surgeons in the field of pancreatic interventions. Minor leaks will often resolve with conservative management while severe leaks will frequently require interventions. Endoscopic treatments for pancreatic duct leaks have replaced surgical interventions in many situations. Interventional radiologists also have the ability to offer therapeutic interventions for many leak patients. The mainstay of endotherapy for pancreatic leaks is transpapillary pancreatic duct stenting with a stent that bridges the leak if possible, but varies based on the manifestation and clinical presentation. Fluid collections that result from leaks, such as pseudocysts, can often be treated by endoscopic transluminal drainage with or without endoscopic ultrasound or by percutaneous drainage. Endoscopic interventions have been shown to be effective and have an acceptable complication rate.

Associations between intakes of individual nutrients or whole food groups and non-alcoholic fatty liver disease among Korean adults

Abstract: Background and Aim Dietary factors are closely associated with the risk of non-alcoholic fatty liver disease (NAFLD). Asian and Western diets differ in energy-nutrient composition, fatty-acid composition, and main nutritional sources; therefore, the implications would be limited if the Western-oriented study results were applied to Asian patients. We aimed to identify the nutrient and food group intakes of a typical Asian diet and assess their effects on NAFLD risk. Methods In total, 348 subjects were recruited from 5 participating hospitals. Information on sociodemographic characteristics and health-related behaviors were obtained through face-to-face interviews. NAFLD was diagnosed by ultrasound. Dietary intakes were assessed with a 24-h recall applying a multiple-pass approach and 4-day food records that included 1 or 2 weekend days. Results There were no significant differences in health-related behaviors between the cases and controls except for smoking behavior. The cases had elevated triacylglycerol, fasting glucose, and low-density lipoprotein cholesterol levels compared with the controls. In men, after adjusting for variables, low intakes of vitamin C (odds ratio [OR], 4.23), vitamin K (OR, 3.93), folate (OR, 3.37), omega-3 fatty acids (OR, 2.16), and nuts and seeds (OR, 3.66) were associated with a significantly higher risk for developing NAFLD. In women, vitamin K (OR, 2.54) and vegetable (OR, 4.11) intakes showed a significant beneficial effect for lowering NAFLD risk. Conclusions Adequate intakes of vitamin C, vitamin K, folate, omega-3 fatty acids, nuts and seeds, and vegetables may help in preventing NAFLD in Korean adults.

Microvascular invasion in small hepatocellular carcinoma: is it predictable with preoperative diffusion-weighted imaging?

Abstract: Background and Aim The presence of microvascular invasion (MVI) is an independent risk factor affecting recurrence-free survival following surgical treatment for small hepatocellular carcinoma (HCC). Our aim in this study was to investigate whether diffusion-weighted imaging (DWI) could be useful in predicting MVI for small HCC. Methods Breath-hold DWI (b-value 0, 500 s/mm2) and gadopentate dimeglumine-enhanced dynamic imaging of preoperative magnetic resonance imaging of 109 surgically proven small HCCs from 92 patients were retrospectively analyzed. The signal intensity ratio on DWI and apparent diffusion coefficients (ADCs) for lesions were quantitatively measured. Signal intensity ratio and ADC of DWI, tumor size, tumor shape, tumor capsule, peritumoral enhancement on arterial phase images, and dynamic enhancement pattern were analyzed as radiological parameters reflecting MVI and were compared with histopathological references. The chi-square test, Fisher's exact test, Mann–Whitney U test, and the independent t-test were used for univariate analysis. To identify the independent predictors of MVI among these radiological parameters and to evaluate their diagnostic performance, multivariate logistic regression analysis and receiver operating characteristic curve analysis were performed, respectively. Results A univariate analysis showed that a lower ADC value (P = 0.005) and irregular circumferential enhancement (P = 0.020) showed statistically significant associations with MVI. A multiple logistic regression analysis showed that the ADC value and irregular circumferential enhancement were independent predictors of MVI. With a cut-off of 1.227 × 10−3 mm2/s, the ADC value provided a sensitivity of 66.7% and a specificity of 78.6% in the prediction of MVI with an odds ratio of 7.63 (P < 0.01). Conclusions Lower ADC values (< 1.227 × 10−3 mm2/s) on DWI with b-value of 0.500 s/mm2 can be a useful preoperative predictor of MVI for small HCCs.

Stereotactic ablative body radiotherapy for previously untreated solitary hepatocellular carcinoma

Abstract: Background and Aims Stereotactic ablative body radiotherapy (SABR) is a relatively new treatment for hepatocellular carcinoma (HCC). The outcomes of SABR for previously untreated solitary HCC unfit for ablation and surgical resection were evaluated. Methods Untreated solitary HCC patients treated with SABR were retrospectively studied. Between 2005 and 2012, 221 HCC patients underwent SABR. Among them, patients with untreated solitary HCC, treated with only SABR or SABR preceded by transarterial chemoembolization, were eligible. Based on baseline liver function and liver volume receiving ≥ 20 Gy, 35–40 Gy in five fractions was prescribed to the planning target volume surface. Results Sixty-three patients were eligible, with a median follow-up duration of 31.1 (range 12.0–88.1) months. No patients were lost to follow-up. Twenty patients were treated with only SABR. In 43 patients treated with SABR preceded by transarterial chemoembolization, accumulation of lipiodol in the tumor remained complete in five, a partial defect in 38 on pre-SABR computed tomography. The 1-, 2-, and 3-year local control rates were 100%, 95%, and 92%, respectively; the intrahepatic recurrence-free rates were 76%, 55%, and 36%, respectively; and the overall survival rates were 100%, 87%, and 73%, respectively. Grade 3 laboratory toxicities in the acute, subacute, and chronic phases were observed in 10, 9, and 13 patients, respectively, and ascites occurred in one patient. Conclusions Local control and overall survival after SABR for untreated solitary HCC were excellent despite the candidates being unfit for resection and ablation. SABR is safe and might be an alternative to resection and ablation.

Safety analysis of endoscopist-directed propofol sedation: a prospective, national multicenter study of 24 441 patients in German outpatient practices.

Abstract: Background and Aim Since 2008, there exists a German S3-guideline allowing non-anesthesiological administration of propofol for gastrointestinal endoscopy. In this prospective, national, multicenter study, we evaluated the safety of endoscopist-administered propofol sedation (EDP) in German outpatient practices of Gastroenterology. Methods In this multicenter survey of 53 ambulatory practices of Gastroenterology, we prospectively evaluated 24 441 patients that had received EDP. We recorded adverse events during the endoscopic procedure and additionally retrieved questionnaires investigating subjective parameters 24 h after the endoscopic procedure. Results In 24 441 patients 13 793 colonoscopies, 6467 esophagogastroduodenoscopies, and 4181 double examinations were performed. In this study, 52.1% of the patients received propofol mono-sedation, and 47.9% received a combination of midazolam and propofol. Major adverse events occurred in four patients (0.016%) enrolled to this study (three mask ventilations and one laryngospasm). Minor adverse events were observed in 112 patients (0.46%) with hypoxemia being the most common minor event. All patients with adverse events recovered without persistent impairment. Minor adverse events occurred more frequently in patients sedated with propofol mono compared to propofol and midazolam (P < 0.0001) and correlated with increasing propofol dosages (P < 0.001; Pearson correlation coefficient r = 0.044). Twenty-four hours after the endoscopy, patients sedated with propofol plus midazolam stated a significantly reduced sensation of pain (P < 0.01) and improved symptoms of dizziness, nausea and vomiting (P < 0.001) compared to patients having received propofol mono-sedation. Conclusion Four years after the implementation of a German S3-Guideline for endoscopic sedation, we demonstrated that EDP is a safe procedure.

Enhanced antiviral treatment efficacy and uptake in preventing the rising burden of hepatitis C-related liver disease and costs in Australia

Abstract: Background and Aim Chronic hepatitis C virus (HCV) infection is an important cause of advanced liver disease and liver-related deaths in Australia. Our aim was to describe the burden of HCV infection and consider treatment strategies to reduce HCV-related morbidity and mortality. Methods Baseline model parameters were based upon literature review and expert consensus with a focus on Australian data. Three treatment scenarios based on anticipated introduction of improved direct-acting antiviral regimens were considered to reduce HCV disease burden. Scenario 1 evaluated the impact of increased treatment efficacy alone (to 80–90% by 2016). Scenario 2 evaluated increased efficacy and increased treatment uptake (2550 to 13 500 by 2018) without treatment restriction, while Scenario 3 considered the same increases with treatment limited to ≥ F3 during 2015–2017. Results In 2013, there were an estimated 233 490 people with chronic HCV infection: 13 850 with cirrhosis, 590 with hepatocellular carcinoma (HCC) and 530 liver-related deaths. If the current HCV treatment setting is unchanged, threefold increases in the number of people with cirrhosis, HCC, and liver disease deaths will be seen by 2030. Scenario 1 resulted in modest impacts on disease burden (4% decrease in HCC, decompensated cirrhosis, and liver deaths) and costs. Scenario 3 had the greatest impact on disease burden (approximately 50% decrease in HCC, decompensated cirrhosis, and liver deaths) and costs, while Scenario 2 had slightly lesser impact. Conclusions Considerable increases in the burden of HCV-related advanced liver disease and its complications will be seen in Australia under current treatment levels and outcomes. Introduction of improved direct-acting antiviral regimens with enhanced efficacy at current treatment levels will lead to limited impacts on this disease burden. A combination of increased treatment efficacy and greater uptake is required to achieve major reductions in advanced liver disease and related costs.

Serum ferritin as a new prognostic factor in hepatocellular carcinoma patients treated with radiofrequency ablation

Abstract: Background and Aim Hepatic iron accumulation is considered to be a cofactor that influences liver injury and hepatocarcinogenesis. Aim of this study is to determine whether serum ferritin (SF) levels relate to overall survival (OS) and time to recurrence (TTR) in hepatocellular carcinoma (HCC) patients treated with percutaneous radiofrequency ablation (RFA). Methods We measured SF levels in 103 HCC patients (median age 70, M/F = 82.5%/17.5%) who underwent RFA between 2005 and 2010. Correlation between SF and other prognostic factors at baseline was analyzed. SF levels were entered into a Cox model and their influence on OS and TTR was evaluated in univariate and multivariate analyses. Results SF did not correlate with α-fetoprotein (rho: −0.12, P = 0.22), neutrophil/lymphocyte ratio (rho: −0.1020, P = 0.30), Model for End-Stage Liver Disease (rho: 0.18, P = 0.06), Child-Pugh score (P = 0.5), or Barcelona Cancer of the Liver Clinic stage (P = 0.16). A log-rank test found the value of 244 ng/mL as the optimal prognostic cut-off point for SF. Median OS was 62 months (54–78) and survival rate was 97%, 65%, and 52% at 1, 4, and 5 years, respectively. Performance status and SF were the only predictors of OS at multivariate analysis. Median TTR was 38 months (34–49) with a recurrence-free survival rate of 82.5%, 26.2%, and 23.3% at 1, 4, and 5 years, respectively, while SF and age were the only predictors of TTR. Conclusions SF level, possibly reflecting the degree of hepatic inflammation and fibrosis, is a negative risk factor for survival and recurrence after percutaneous RFA in HCC patients.

Comparison of microwave ablation and surgical resection for treatment of hepatocellular carcinomas conforming to Milan criteria.

Abstract: Background and Aim To compare the efficacy of microwave ablation (MWA) and surgical resection (RES) in the treatment of hepatocellular carcinoma (HCC) conforming to Milan criteria. Methods Two hundred twenty-four patients met the inclusion criteria and were enrolled in the study. One hundred and seventeen patients received MWA, and 107 patients underwent RES. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Results The 1-, 3-, and 5-year OS rates were 94%, 70%, 52% for the MWA group and 94%, 72%, 60% for the RES group (P = 0.513). The corresponding DFS rates for the two groups were 77%, 38%, 18% and 85%, 57%, 31% (P = 0.005). In subgroup analyses of patients with solitary HCC ≤ 3 cm, there were no significant differences in OS rates and DFS rates between the two groups (P = 0.577 and P = 0.140). For patients with solitary HCC 3 to 5 cm, there was no significant differences in OS rates between the two groups (P = 0.820), the DFS rates was significantly higher in the RES group than in the MWA group (P = 0.014). Conclusions MWA results in lower DFS rates than RES for HCC conforming to Milan criteria. However, the OS rates are comparable between the two therapies. For solitary HCC ≤ 3 cm, MWA is as effective as RES.

Analgesia for the cirrhotic patient: a literature review and recommendations.

Abstract: The choice of analgesic agent in cirrhotic patients is problematic and must be individualized taking into account several factors including severity of liver disease, history of opioid dependence, and potential drug interactions. With a cautious approach including slow dose up-titration and careful monitoring, effective analgesia can be achieved in most cirrhotic patients without significant side effects or decompensation of their liver disease. Paracetamol is safe in patients with chronic liver disease but reduced doses of 2-3 grams daily is recommended for long-term use. Non-steroidal anti-inflammatory drugs are best avoided because of risk of renal impairment, hepatorenal syndrome, and gastrointestinal hemorrhage. Opioids have an increased risk of toxicity particularly in patients with hypoalbuminaemia, and immediate-release as opposed to controlled-release formulations are advised. Co-prescription of laxatives is mandatory to avoid constipation and encephalopathy. Adjuvant analgesics such as tricyclic antidepressants and anti-convulsants may be used cautiously for cirrhotic patients with neuropathic pain. Gabapentin or pregabalin may be better tolerated in cirrhosis because of non-hepatic metabolism and a lack of anti-cholinergic side effects.