International Journal of Hepatology The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Randomized Controlled Study Comparing Use of Propofol Plus Fentanyl versus Midazolam Plus Fentanyl as Sedation in Diagnostic Endoscopy in Patients with Advanced Liver Disease Tue, 26 Sep 2017 00:00:00 +0000 Objectives. We aimed to investigate the safety and efficacy of propofol plus fentanyl versus midazolam plus fentanyl as sedative for patients with advanced liver disease presented for gastrointestinal endoscopy. Methods. A total of 100 patients with liver cirrhosis referred for upper endoscopy were enrolled and divided equally in two groups, midazolam plus fentanyl group and propofol plus fentanyl group. All patients were subjected to history taking, estimation of level of sedation, endoscopist rating, and hemodynamic parameters including oxygen saturation, heart rate, mean arterial pressure, incidence of side effect as (bradycardia, hypotension, hypoxia, nausea and vomiting, cough, shivering, or diplopia), time needed for complete recovery, and time needed for discharge. Results. There was no statistical significant difference between the studied groups regarding age, sex, weight, Child–Pugh classification score, type and duration of endoscopic intervention, time needed for complete recovery, or time needed for discharge. Complication rates were similar in both groups except for mean arterial blood pressure which was significantly lower in group of patients receiving propofol and fentanyl (). Conclusion. The use of either propofol or midazolam in combination to fentanyl is effective in sedation of patients with advanced liver diseases presented for upper GIT endoscope. The trial is registered with Identifier: NCT03063866. Sameh Abdelkhalik Ahmed, Amal Selim, Nehad Hawash, Ahmed Khaled Tawfik, Mohamed Yousef, Abdelrahman Kobtan, Rehab Badawi, Sally Elnawasany, Reham Abdelkader Elkhouly, Amr Shaaban Hanafy, Fatma H. Rizk, Loai Mansour, and Sherief Abd-Elsalam Copyright © 2017 Sameh Abdelkhalik Ahmed et al. All rights reserved. HCV Integrated Care: A Randomized Trial to Increase Treatment Initiation and SVR with Direct Acting Antivirals Thu, 27 Jul 2017 06:53:08 +0000 Background and Aims. Psychiatric or substance use disorders are barriers to successful HCV antiviral treatment. In a randomized, controlled trial (RCT), the effects of HCV Integrated Care (IC) for increasing treatment rates and sustained viral response (SVR) were studied with direct acting antivirals (DAA). Methods. In 2012-13, VA patients, whose screening was positive for depression, PTSD, or substance use (), were randomized to IC or Usual Care (UC). IC consisted of brief psychological interventions and case management. The primary endpoint was SVR among patients followed for an average of 16.6 months. Results. 42% of the study participants were previously homeless and 79% had HCV genotype 1. Twice as many IC participants (45%) initiated treatment compared with UC participants (23%) ( = 4.59, ). Among those treated, SVR rates did not significantly differ (IC: 12/18 = 67%; UC: 5/9 = 55%; ). Among all randomized participants, IC participants trended toward better SVR rates (30.0% versus 12.8% in UC; ). Conclusions. Although first-generation DAAs are no longer used, this smaller RCT helps confirm the results of a larger multisite RCT showing that Integrated Care results in higher treatment initiation and SVR rates among HCV-infected persons with comorbid psychological disorders. Integrated mental health services can facilitate treatment among the most challenging HCV patients, many of whom have not been successfully treated. This trial is registered with number NCT00722423. Erik J. Groessl, Lin Liu, Marisa Sklar, and Samuel B. Ho Copyright © 2017 Erik J. Groessl et al. All rights reserved. Shorter Leukocyte Telomere Length in Relation to Presumed Nonalcoholic Fatty Liver Disease in Mexican-American Men in NHANES 1999–2002 Tue, 27 Jun 2017 10:54:58 +0000 Leukocyte telomere length is shorter in response to chronic disease processes associated with inflammation such as diabetes mellitus and coronary artery disease. Data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002 was used to explore the relationship between leukocyte telomere length and presumed NAFLD, as indicated by elevated serum alanine aminotransferase (ALT) levels, obesity, or abdominal obesity. Logistic regression models were used to evaluate the relationship between telomere length and presumed markers of NAFLD adjusting for possible confounders. There was no relationship between elevated ALT levels, abdominal obesity, or obesity and telomere length in adjusted models in NHANES (OR 1.13, 95% CI 0.48–2.65; OR 1.17, 95% CI 0.52–2.62, resp.). Mexican-American men had shorter telomere length in relation to presumed NAFLD (OR 0.07, 95% CI 0.006–0.79) and using different indicators of NAFLD (OR 0.012, 95% CI 0.0006–0.24). Mexican origin with presumed NAFLD had shorter telomere length than men in other population groups. Longitudinal studies are necessary to evaluate the role of telomere length as a potential predictor to assess pathogenesis of NALFD in Mexicans. Janet M. Wojcicki, David Rehkopf, Elissa Epel, and Philip Rosenthal Copyright © 2017 Janet M. Wojcicki et al. All rights reserved. Imaging the Abdominal Manifestations of Cystic Fibrosis Sun, 29 Jan 2017 00:00:00 +0000 Cystic fibrosis (CF) is a multisystem disease with a range of abdominal manifestations including those involving the liver, pancreas, and kidneys. Recent advances in management of the respiratory complications of the disease has led to a greater life expectancy in patients with CF. Subsequently, there is increasing focus on the impact of abdominal disease on quality of life and survival. Liver cirrhosis is the most important extrapulmonary cause of death in CF, yet significant challenges remain in the diagnosis of CF related liver disease. The capacity to predict those patients at risk of developing cirrhosis remains a significant challenge. We review representative abdominal imaging findings in patients with CF selected from the records of two academic health centres, with a view to increasing familiarity with the abdominal manifestations of the disease. We review their presentation and expected imaging findings, with a focus on the challenges facing diagnosis of the hepatic manifestations of the disease. An increased familiarity with these abdominal manifestations will facilitate timely diagnosis and management, which is paramount to further improving outcomes for patients with cystic fibrosis. C. D. Gillespie, M. K. O’Reilly, G. N. Allen, S. McDermott, V. O. Chan, and C. A. Ridge Copyright © 2017 C. D. Gillespie et al. All rights reserved. Predictive Factors for a Long Hospital Stay in Patients Undergoing Laparoscopic Cholecystectomy Mon, 23 Jan 2017 00:00:00 +0000 Background. Although the advantages of laparoscopic cholecystectomy (LC) over open cholecystectomy are immediately obvious and appreciated, several patients need a postoperative hospital stay of more than 24 hours. Thus, the predictive factors for this longer stay need to be investigated. The aim of this study was to identify the causes of a long hospital stay after LC. Methods. This is a retrospective cohort study with 500 successful elective LC patients being included in the analysis. Short hospital stay was defined as being discharged within 24 hours after the operation, whereas long hospital stay was defined as the need for a stay of more than 24 hours after the operation. Results. Using multivariable analysis, ten independent predictive factors were identified for a long hospital stay. These included patients with cirrhosis, patients with a history of previous acute cholecystitis, cholangitis, or pancreatitis, patients on anticoagulation with warfarin, patients with standard-pressure pneumoperitoneum, patients who had been given metoclopramide as an intraoperative antiemetic drug, patients who had been using abdominal drain, patients who had numeric rating scale for pain > 3, patients with an oral analgesia requirement > 2 doses, complications, and private ward admission. Conclusions. LC difficulties were important predictive factors for a long hospital stay, as well as medication and operative factors. Wasana Ko-iam, Trichak Sandhu, Sahattaya Paiboonworachat, Paisal Pongchairerks, Anon Chotirosniramit, Narain Chotirosniramit, Kamtone Chandacham, Tidarat Jirapongcharoenlap, and Sunhawit Junrungsee Copyright © 2017 Wasana Ko-iam et al. All rights reserved. A Comprehensive Review of Portosystemic Collaterals in Cirrhosis: Historical Aspects, Anatomy, and Classifications Thu, 15 Dec 2016 09:54:46 +0000 Portosystemic collateral formation in cirrhosis plays an important part in events that define the natural history in affected patients. A detailed understanding of collateral anatomy and hemodynamics in cirrhotics is essential to envisage diagnosis, management, and outcomes of portal hypertension. In this review, we provide detailed insights into the historical, anatomical, and hemodynamic aspects to portal hypertension and collateral pathways in cirrhosis with emphasis on the various classification systems. Cyriac Abby Philips, Ankur Arora, Rajesh Shetty, and Vivek Kasana Copyright © 2016 Cyriac Abby Philips et al. All rights reserved. Cardiovascular Autonomic Dysfunction in Patients of Nonalcoholic Fatty Liver Disease Thu, 08 Dec 2016 07:20:36 +0000 Aim. The present study was designed to evaluate the heart rate variability (HRV) in nonalcoholic fatty liver disease (NAFLD) and to assess the effect of grade of NAFLD and diabetic status on HRV. Methods. This cross-sectional study included 75 subjects (25 NAFLD without diabetes, 25 NAFLD with diabetes, and 25 controls). Measurements included anthropometry, body composition analysis, estimation of plasma glucose, serum lipids, hsCRP, and serum insulin. HRV analysis was performed in both time and frequency domains. Results. The time and frequency domain indices of overall variability (SDNN, total power) were significantly lower in NAFLD with diabetes as compared to the controls. However, the LF : HF ratio did not differ among the three groups. The variables related to obesity, lipid profile, and glucose metabolism were also higher in NAFLD with diabetes and those with Grade II NAFLD without diabetes, as compared to controls. Multivariate stepwise regression analysis showed a negative correlation between HRV and total cholesterol and fat percentage. Conclusion. The grade of NAFLD as well as diabetic status contributes to the decrease in the cardiovascular autonomic function, with diabetic status rather than grade of NAFLD playing a critical role. Serum lipids and adiposity may also contribute to cardiac autonomic dysfunction. Mavidi Sunil Kumar, Akanksha Singh, Ashok Kumar Jaryal, Piyush Ranjan, K. K. Deepak, Sanjay Sharma, R. Lakshmy, R. M. Pandey, and Naval K. Vikram Copyright © 2016 Mavidi Sunil Kumar et al. All rights reserved. A Combination of Leucine, Metformin, and Sildenafil Treats Nonalcoholic Fatty Liver Disease and Steatohepatitis in Mice Wed, 30 Nov 2016 13:18:18 +0000 Sirt1, AMPK, and eNOS modulate hepatic energy metabolism and inflammation and are key players in the development of NASH. L-leucine, an allosteric Sirt1 activator, synergizes with low doses of metformin or sildenafil on the AMPK-eNOS-Sirt1 pathway to reverse mild NAFLD in preclinical mouse models. Here we tested a possible multicomponent synergy to yield greater therapeutic efficacy in NAFLD/NASH. Liver cells and macrophages or an atherogenic diet induced NASH mouse model was treated with two-way and three-way combinations. The three-way combination Sild-Met-Leu increased hepatic fatty acid oxidation and reduced lipogenic gene expression and inflammatory marker in vitro. In mice, Sild-Met-Leu reduced the diet induced increases of ALT, TGFβ, PAI-1, IL1β, and TNFα, hepatic collagen expression, and nearly completely reversed hepatocyte ballooning and triglyceride accumulation, while all two-way combinations had only modest effects. Therefore, these data provide preclinical evidence for therapeutic efficacy of Sild-Met-Leu in the treatment of NAFLD and NASH. Antje Bruckbauer, Jheelam Banerjee, Lizhi Fu, Fenfen Li, Qiang Cao, Xin Cui, Rui Wu, Hang Shi, Bingzhong Xue, and Michael B. Zemel Copyright © 2016 Antje Bruckbauer et al. All rights reserved. Hyperammonemia Is Associated with Increasing Severity of Both Liver Cirrhosis and Hepatic Encephalopathy Tue, 25 Oct 2016 12:32:32 +0000 Background. Hyperammonemia resulting from chronic liver disease (CLD) can potentially challenge and damage any organ system of the body, particularly the brain. However, there is still some controversy regarding the diagnostic or prognostic values of serum ammonia in patients with over hepatic encephalopathy, especially in the setting of acute-on-chronic or chronic liver failure. Moreover, the association of serum ammonia with worsening Child-Pugh grade of liver cirrhosis has not been studied. Objective. This study was conducted to solve the controversy regarding the association between hyperammonemia and cirrhosis, especially hepatic encephalopathy in chronically failed liver. Material and Methods. In this study, 171 cirrhotic patients had their serum ammonia measured and analyzed by SPSS version 16. Chi-squared test and one-way ANOVA were applied. Results. The study had 110 male and 61 female participants. The mean age of all the participants in years was . The mean duration (years) of CLD was while the mean Child-Pugh (CP) score was . Chronic viral hepatitis alone was responsible for 71.3% of the cases. Moreover, 86.5% of participants had hepatic encephalopathy (HE). The frequency of hyperammonemia was 67.3%, more frequent in males (, -score = 2.4, and ) than in females (, -score = 2.4, and ), and had a statistically significant relationship with increasing CP grade of cirrhosis ( = 27.46, , Phi = 0.40, and ). Furthermore, serum ammonia level was higher in patients with hepatic encephalopathy than in those without it; . Conclusion. Hyperammonemia is associated with both increasing Child-Pugh grade of liver cirrhosis and hepatic encephalopathy. Abidullah Khan, Maimoona Ayub, and Wazir Mohammad Khan Copyright © 2016 Abidullah Khan et al. All rights reserved. The Use of Thrombopoietin Receptor Agonists for Correction of Thrombocytopenia prior to Elective Procedures in Chronic Liver Diseases: Review of Current Evidence Sun, 09 Oct 2016 10:06:04 +0000 Patients with chronic liver diseases (CLD) undergo a range of invasive procedures during their clinical lifetime. Various hemostatic abnormalities are frequently identified during the periprocedural work-up; including thrombocytopenia. Thrombocytopenia of cirrhosis is multifactorial in origin, and decreased activity of thrombopoietin has been identified to be a major cause. Liver is an important site of thrombopoietin production and its levels are decreased in patients with cirrhosis. Severe thrombocytopenia (platelet counts < 60–75,000/µL) is associated with increased risk of bleeding with invasive procedures. In recent years, compounds with thrombopoietin receptor agonist activity have been studied as therapeutic options to raise platelet counts in CLD. We reviewed the use of Eltrombopag, Romiplostim, and Avatrombopag prior to various invasive procedures in patients with CLD. These agents seem promising in raising platelet counts before elective procedures resulting in reduction in platelet transfusions, and they also enabled more patients to undergo the procedures. However, these studies were not primarily aimed at comparing bleeding episodes among groups. Use of these agents had some adverse consequences, importantly being the occurrence of portal vein thrombosis. This review highlights the need of further studies to identify reliable methods of safely reducing the provoked bleeding risk linked to thrombocytopenia in CLD. Kamran Qureshi, Shyam Patel, and Andrew Meillier Copyright © 2016 Kamran Qureshi et al. All rights reserved. Prognostication of Learning Curve on Surgical Management of Vasculobiliary Injuries after Cholecystectomy Wed, 20 Jul 2016 13:44:20 +0000 Background. Concomitant vascular injury might adversely impact outcomes after iatrogenic bile duct injury (IBDI). Whether a new HPB center should embark upon repair of complex biliary injuries with associated vascular injuries during learning curve is unknown. The objective of this study was to determine outcome of surgical management of IBDI with and without vascular injuries in a new HPB center during its learning curve. Methods. We retrospectively reviewed patients who underwent surgical management of IBDI at our center. A total of 39 patients were included. Patients without (Group 1) and with vascular injuries (Group 2) were compared. Outcome was defined as 90-day morbidity and mortality. Results. Median age was 39 (20–80) years. There were 10 (25.6%) vascular injuries. E2 injuries were associated significantly with high frequency of vascular injuries (66% versus 15.1%) (). Right hepatectomy was performed in three patients. Out of these, two had a right hepatic duct stricture and one patient had combined right arterial and portal venous injury. The number of patients who developed postoperative complications was not significantly different between the two groups (11.1% versus 23.4%) (). Conclusion. Learning curve is not a negative prognostic variable in the surgical management of iatrogenic vasculobiliary injuries after cholecystectomy. Abu Bakar Hafeez Bhatti, Faisal Saud Dar, Haseeb Zia, Muhammad Salman Rafique, Nusrat Yar Khan, Mohammad Salih, and Najmul Hassan Shah Copyright © 2016 Abu Bakar Hafeez Bhatti et al. All rights reserved. Different Nodules Identified during Liver Explant Gross Examination: Relevance and Need for Sectioning—Experience from India Wed, 22 Jun 2016 08:45:45 +0000 Objective. The goal of this study was to determine the etiopathological association of various hepatic nodules identified during gross examination of liver explants specimen and the grossing aspects of these abnormal nodules especially those smaller than 1 cm in diameter. Our aim was to analyze whether there is any association of macroregenerative and dysplastic nodule with hepatocellular carcinoma. Materials and Methods. Fifty consecutive liver explants specimens were analyzed for the presence of any abnormal nodule (abnormal nodule defined as any nodule different in color, texture, and appearance from adjacent liver tissue). Results. Of the total 40 abnormal nodules identified in 50 liver explant specimens, there were 12 (30%) HCC [including 5 small HCC (41% of total HCC) and 1 steatohepatitic HCC (8% of total HCC)], 11 (27%) MRNs, 8 (20%) dysplastic nodules, and 9 (22%) necrotic nodules. Most cases (72%) of MRN are seen in hepatitis C virus related cirrhosis with only 2 cases having associated HCC. Most cases of HCC were seen in cases of HBV associated cirrhosis (60%). The association of MRN was not found to be significantly associated with HCC with a value of 1.0. Dysplastic nodules were found to be significantly associated with HCC with a value of 0.02. Conclusion. In hepatic carcinogenesis, the role of MRN does not appear to be significant. However, the presence of dysplastic nodules is significantly associated with HCC. The study identified another variant of cirrhotic nodules herein called necrotic nodules that are mostly tan greenish in color and <0.5 cm in diameter. No dysplastic changes were identified in any of these nodules disqualifying the need of sectioning in such nodules. Nalini Bansal, Vivek Vij, and Mukul Rastogi Copyright © 2016 Nalini Bansal et al. All rights reserved. Elbasvir/Grazoprevir: A Review of the Latest Agent in the Fight against Hepatitis C Wed, 15 Jun 2016 13:50:48 +0000 Hepatitis C virus (HCV) is estimated to affect up to 150 million people worldwide. Despite worldwide prevalence, treatment modalities prior to 2011 remained suboptimal, with low virologic response rates and intolerable side effect profiles. Fortunately, the landscape of treatment for chronic hepatitis C has rapidly evolved since the introduction of HCV NS3/4 protease inhibitors in 2011. Elbasvir, a NS5A inhibitor, combined with grazoprevir, a NS3/4A protease inhibitor, is the latest FDA-approved therapy for patients with genotype 1 or 4 chronic hepatitis C, with or without compensated cirrhosis. This review will focus on the current literature and clinical evidence supporting elbasvir/grazoprevir as first-line therapy in patients with genotypes 1 and 4 chronic hepatitis C. Allison M. Bell, Jamie L. Wagner, Katie E. Barber, and Kayla R. Stover Copyright © 2016 Allison M. Bell et al. All rights reserved. The Effect of Artichoke Leaf Extract on Alanine Aminotransferase and Aspartate Aminotransferase in the Patients with Nonalcoholic Steatohepatitis Wed, 11 May 2016 07:08:14 +0000 Background. Based on recent basic and clinical investigations, the extract of artichoke (Cynara scolymus) leaf has been revealed to be used for hepatoprotective and cholesterol reducing purposes. We aimed to assess the therapeutic effects of artichoke on biochemical and liver biomarkers in patients with nonalcoholic steatohepatitis (NASH). Methods. In a randomized double blind clinical trial, 60 consecutive patients suffering NASH were randomly assigned to receive Cynara scolymus extract (as 6 tablets per day consisting of 2700 mg extract of the herb) as the intervention group or placebo as the control group for two months. Results. Comparing changes in study markers following interventions showed improvement in liver enzymes. The levels of triglycerides and cholesterol were significantly reduced in the group treated with Cynara scolymus when compared to placebo group. To compare the role of Cynara scolymus use with placebo in changes in study parameters, multivariate linear regression models were employed indicating higher improvement in liver enzymes and also lipid profile particularly triglycerides and total cholesterol following administration of Cynara scolymus in comparison with placebo use. Conclusion. This study sheds light on the potential hepatoprotective activity and hypolipidemic effect of Cynara scolymus in management of NASH. This clinical trial is registered in the IRCT, Iranian Registry of Clinical Trials, by number IRCT2014070218321N1. Vajiheh Rangboo, Mostafa Noroozi, Roza Zavoshy, Seyed Amirmansoor Rezadoost, and Asghar Mohammadpoorasl Copyright © 2016 Vajiheh Rangboo et al. All rights reserved. Therapeutic Potential of HGF-Expressing Human Umbilical Cord Mesenchymal Stem Cells in Mice with Acute Liver Failure Sun, 28 Feb 2016 14:29:40 +0000 Human umbilical cord-derived mesenchymal stem cells (UCMSCs) are particularly attractive cells for cellular and gene therapy in acute liver failure (ALF). However, the efficacy of this cell therapy in animal studies needs to be significantly improved before it can be translated into clinics. In this study, we investigated the therapeutic potential of UCMSCs that overexpress hepatocyte growth factor (HGF) in an acetaminophen-induced acute liver failure mouse model. We found that the HGF-UCMSC cell therapy protected animals from acute liver failure by reducing liver damage and prolonging animal survival. The therapeutic effect of HGF-UCMSCs was associated with the increment in serum glutathione (GSH) and hepatic enzymes that maintain redox homeostasis, including γ-glutamylcysteine synthetase (γ-GCS), superoxide dismutase (SOD), and catalase (CAT). Immunohistochemical staining confirmed that HGF-UCMSCs were mobilized to the injured areas of the liver. Additionally, HGF-UCMSCs modulated apoptosis by upregulating the antiapoptotic Bcl2 and downregulating proapoptotic genes, including Bax and TNFα. Taken together, these data suggest that ectopic expression of HGF in UCMSCs protects animals from acetaminophen-induced acute liver failure through antiapoptosis and antioxidation mechanisms. Yunxia Tang, Qiongshu Li, Fanwei Meng, Xingyu Huang, Chan Li, Xin Zhou, Xiaoping Zeng, Yixin He, Jia Liu, Xiang Hu, Ji-Fan Hu, and Tao Li Copyright © 2016 Yunxia Tang et al. All rights reserved. Outcome following Resection of Biliary Cystadenoma: A Single Centre Experience and Literature Review Tue, 29 Dec 2015 12:37:33 +0000 Background. Biliary cystadenomas (BCAs) are rare, benign, potentially malignant cystic lesions of the liver, accounting for less than 5% of cystic liver tumours. We report the outcome following resection of biliary cystadenoma from a single tertiary centre. Methods. Data of patients who had resection of BCA between January 1993 and July 2014 were obtained from liver surgical database. Patient demographics, clinicopathological characteristics, operative data, and postoperative outcome were analysed. Results. 29 patients had surgery for BCA. Male : female ratio was 1 : 28. Clinical presentation was abdominal pain (74%), jaundice (20%), abdominal mass (14%), and deranged liver function tests (3%). Cyst characteristics included septations (48%), wall thickening (31%), wall irregularity (38%), papillary projections (10%), and mural nodule (3%). Surgical procedures included atypical liver resection (52%), left hemihepatectomy (34%), right hemihepatectomy (10%), and left lateral segmentectomy (3%). Median length of stay was 7 (IQ 6.5–8.5) days. Two patients developed postoperative bile leak. No patients had malignancy on final histology. Median follow-up was 13 (IQ 6.5–15.7) years. One patient developed delayed biliary stricture and one died of cholangiocarcinoma 11 years later. Conclusion. Biliary cystadenomas can be resected safely with significantly low morbidity. Malignant transformation and recurrence are rare. Complete surgical resection provides a cure. M. Pitchaimuthu, G. Aidoo-Micah, C. Coldham, R. Sutcliffe, J. K. Roberts, P. Muiesan, J. Isaac, D. Mirza, and R. Marudanayagam Copyright © 2015 M. Pitchaimuthu et al. All rights reserved. Factors That Could Impact on Liver Fibrosis Staging by Transient Elastography Sun, 06 Dec 2015 11:47:44 +0000 Transient elastography (TE) based on liver stiffness measurement (LSM) is one of the most validated noninvasive methods for liver fibrosis staging in patients with chronic liver diseases. This method is painless, has no potential complications, is rapid (<10 min), and can be performed at the patient’s bedside. However, several points should be considered when interpreting TE results. This review aims to discuss the critical points that might influence liver stiffness and TE results. Spectrum bias and the impact of the prevalence of fibrosis stages should be taken into account when interpreting the studies that validated this method using liver biopsy as a gold-standard. LSM might be influenced by nonfasting status, flare of transaminases, heart failure, extrahepatic cholestasis, presence of steatosis, aetiology of liver disease, type and position of probe, and operator’s experience. In addition, interobserver variability can impact on the management of patients with chronic liver diseases. TE should be performed by an experienced operator (>100 exams), in a 3-hour fasting status, and its results should be handled by specialist clinicians that are aware of the limitations of this method. Hugo Perazzo, Valdilea G. Veloso, Beatriz Grinsztejn, Chris Hyde, and Rodolfo Castro Copyright © 2015 Hugo Perazzo et al. All rights reserved. Chronic Hepatitis C: An Overview of Evidence on Epidemiology and Management from a Brazilian Perspective Sun, 29 Nov 2015 08:02:23 +0000 Chronic hepatitis C remains one of the main causes of chronic liver disease worldwide and presents a variable natural history ranging from minimal changes to advanced fibrosis and cirrhosis and its complications, such as development of hepatocellular carcinoma. Approximately, 1.45 million people are estimated to be infected by HCV in Brazil representing a major public health issue. The aim of this paper was to review the epidemiology and management of chronic hepatitis C from a Brazilian perspective. The management of chronic hepatitis C has been challenged by the use of noninvasive methods to stage liver fibrosis as an alternative to liver biopsy and the high cost of new interferon-free antiviral treatments. Moreover, the need of cost-effectiveness analysis in hepatitis C and the recent changes in treatment protocols were discussed. Rodolfo Castro, Hugo Perazzo, Beatriz Grinsztejn, Valdilea G. Veloso, and Chris Hyde Copyright © 2015 Rodolfo Castro et al. All rights reserved. Growing Up: Not an Easy Transition—Perspectives of Patients and Parents regarding Transfer from a Pediatric Liver Transplant Center to Adult Care Sun, 22 Nov 2015 14:32:20 +0000 The transition from pediatric to adult care is a critical time when children with chronic illness sustain high morbidity and mortality. Transition services need to be focused on the adolescents’ needs, which may differ from those perceived by healthcare providers. In this study, a survey of 31 patients with chronic liver disease and/or liver transplant who were “transferred” to adult services within the last 3 years was conducted. Patients were asked about their current health status and their perceptions of the overall transfer process. The mean age at transfer was 19.81 (18–21) years. Almost half the patients (47%) were not seen at the adult facility until 2–6 months after leaving the Children’s hospital and 20% were not seen until 6–12 months. About 20% had their first contact with adult services through an emergency room visit. About 19% reported being out of medication during transition. Of the transplanted patients, 19% were being evaluated for a retransplant. The majority (82%) felt that an increased emphasis on promoting independence and “letting go” both by parents and by pediatric care providers was critical in their transition to independence and adult care services. This study provides thought-provoking insights, which are critical in designing the ideal transition program for children with chronic diseases. Sona Chandra, Shannon Luetkemeyer, Rene Romero, and Nitika Arora Gupta Copyright © 2015 Sona Chandra et al. All rights reserved. Acalculous Acute Cholecystitis in Previously Healthy Children: General Overview and Analysis of Pediatric Infectious Cases Wed, 11 Nov 2015 12:03:12 +0000 Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder, which does not appear to be associated with the presence of gallstones. AAC is estimated to represent more than 50% of cases of acute cholecystitis in the pediatric population. Although this pathology was initially described in critically ill patients, actually most pediatric cases have been observed during several infectious diseases. Particularly, here we reviewed pediatric infectious acute acalculous cholecystitis and analyzed the pathophysiological and clinical aspects of bacterial and viral forms. Dimitri Poddighe, Matteo Tresoldi, Amelia Licari, and Gian Luigi Marseglia Copyright © 2015 Dimitri Poddighe et al. All rights reserved. Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response? Tue, 10 Nov 2015 09:03:31 +0000 Background & Aims. The currently available treatment for chronic hepatitis C (CHC) in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP) were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (, , and , resp.). In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders () and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, and , respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (). Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy. Mohamed Ahmed Khedr, Ahmad Mohamed Sira, Magdy Anwar Saber, and Gamal Yousef Raia Copyright © 2015 Mohamed Ahmed Khedr et al. All rights reserved. Evaluation of Serum Cystatin C as a Marker of Early Renal Impairment in Patients with Liver Cirrhosis Tue, 13 Oct 2015 12:05:31 +0000 Background. Serum cystatin C (CysC) was proposed as an effective reflection of the glomerular filtration rate (GFR). However, its role in patients with liver cirrhosis has not been extensively verified especially in the detection of early RI. Patients and Methods. Seventy consecutive potential candidates for living donor liver transplantation with serum creatinine (Cr) <1.5 mg/dL were included. CysC, Cr, and estimated GFR [creatinine clearance (CCr), Cockcroft-Gault formula (C-G), MDRD equations with 4 and 6 variables, CKD-EPI-Cr, CKD-EPI-CysC, and CKD-EPI-Cr-CysC] were all correlated to isotopic GFR. Early RI was defined as GFR of 60–89 mL/min/1.73 m2. Results. Patients were 25.7% and 74.3% Child-Pugh classes B and C, respectively. GFR was ≥90, 60–89, and 30–59 mL/min/1.73 m2 in 31.4%, 64.3%, and 4.3% of the patients, respectively. All markers and equations, except C-G, were significantly correlated to GFR with CKD-EPI-Cr-CysC formula having the highest correlation (r = 0.474) and the largest area under the ROC curve (0.808) for discriminating early RI. At a cutoff value of 1.2 mg/L, CysC was 89.6% sensitive and 63.6% specific in detecting early RI. Conclusion. In patients with liver cirrhosis, CysC and CysC-based equations showed the highest significant correlation to GFR and were measures that best discriminated early RI. Mahmoud Omar, Wael Abdel-Razek, Gamal Abo-Raia, Medhat Assem, and Gasser El-Azab Copyright © 2015 Mahmoud Omar et al. All rights reserved. The Value of Serum Midkine Level in Diagnosis of Hepatocellular Carcinoma Sun, 08 Feb 2015 06:30:23 +0000 Background and Aim. Identification of sensitive biomarkers to improve early diagnosis of HCC is needed. We aimed to evaluate serum midkine (MDK) as a biomarker for HCC diagnosis. Patients and Methods. 40 HCCs, 30 liver cirrhosis patients, and 30 healthy subjects were enrolled. Serum MDK using ELISA was measured in all included subjects. Results. Serum MDK was significantly elevated in HCC group compared to cirrhotic and healthy control groups (0.625 versus 0.15 and 0.125 ng/mL), respectively. No significant association was found between MDK and either BCLC stage, tumor diameter, tumor number, or AFP level. Receiver operating characteristic curve showed that best cutoff for MDK and AFP was 0.387 and 88.5 ng/mL, respectively. Area under the curve of MDK was significantly larger than that of AFP (0.941 versus 0.671). The sensitivity of MDK at 0.387 ng/mL for HCC diagnosis was significantly higher than that of AFP at cutoffs 20, 88.5, and 200 ng/mL (92.5 versus 62.5, 40, and 25%), respectively. Sensitivity of MDK reached 93.3% in patients with AFP <20 ng/mL. Moreover, MDK at 0.387 ng/mL had significant better sensitivity than AFP at 20 ng/mL in distinguishing HCC from BCLC 0/A (90 versus 40%). Conclusion. Serum MDK might be a potential diagnostic marker for HCC particularity in its early stages. Karim Y. A. Shaheen, Abeer I. Abdel-Mageed, Eslam Safwat, and Ashraf M. AlBreedy Copyright © 2015 Karim Y. A. Shaheen et al. All rights reserved. Mystery of Hepatitis E Virus: Recent Advances in Its Diagnosis and Management Mon, 19 Jan 2015 12:30:19 +0000 Mysterious aspects of the long presumed to be well-known hepatitis E virus (HEV) have recently surfaced that distinguish it from other hepatotropic viruses. It is a cause of chronic hepatitis in immunosuppressed patients. It has human to human transmission through blood and mantains high seroprevalence in blood donors. HEV has also been found to occur more frequently in the West in those without a history of travel to endemic countries. It has varied extrahepatic manifestations and has multiple non-human reservoirs including pigs and rats. Considering these recent discoveries, it appears odd that HEV is not sought more frequently when working up acute and chronic hepatitis patients. The disease is particularly severe among pregnant women and has a high attack rate in young adults. What adds to its ambiguity is the absence of a well-established diagnostic criteria for its detection and that there is no specific antiviral drug for hepatitis E, except for isolated cases where ribavirin or pegylated interferon alpha has been used with occasional success. This review paper discusses the recent advances in the knowledge of the virus itself, its epidemiology, diagnostic approach and prevention, and the treatment options available. Aftab Ahmed, Ijlal Akbar Ali, Hira Ghazal, Javid Fazili, and Salman Nusrat Copyright © 2015 Aftab Ahmed et al. All rights reserved. Circulating MicroRNAs in Plasma of Hepatitis B e Antigen Positive Children Reveal Liver-Specific Target Genes Wed, 17 Dec 2014 07:45:33 +0000 Background and Aim. Hepatitis B e antigen positive (HBeAg-positive) children are at high risk of severe complications such as hepatocellular carcinoma and cirrhosis. Liver damage is caused by the host immune response to infected hepatocytes, and we hypothesise that specific microRNAs play a role in this complex interaction between virus and host. The study aimed to identify microRNAs with aberrant plasma expressions in HBeAg-positive children and with liver-specific target genes. Methods. By revisiting our previous screen of microRNA plasma levels in HBeAg-positive and HBeAg-negative children with chronic hepatitis B (CHB) and in healthy controls, candidate microRNAs with aberrant plasma expressions in HBeAg-positive children were identified. MicroRNAs targeting liver-specific genes were selected based on bioinformatics analysis and validated by qRT-PCR using plasma samples from 34 HBeAg-positive, 26 HBeAg-negative, and 60 healthy control children. Results. Thirteen microRNAs showed aberrant plasma expressions in HBeAg-positive children and targeted liver-specific genes. In particular, three microRNAs were upregulated and one was downregulated in HBeAg-positive children compared to HBeAg-negative and healthy control children, which showed equal levels. Conclusion. The identified microRNAs might impact the progression of CHB in children. Functional studies are warranted, however, to elucidate the microRNAs’ role in the immunopathogenesis of childhood CHB. Thilde Nordmann Winther, Kari Stougaard Jacobsen, Aashiq Hussain Mirza, Ida Louise Heiberg, Claus Heiner Bang-Berthelsen, Flemming Pociot, and Birthe Hogh Copyright © 2014 Thilde Nordmann Winther et al. All rights reserved. E. coli Induced Experimental Model of Primary Biliary Cirrhosis: At Last Tue, 16 Dec 2014 11:28:17 +0000 Recurrent urinary tract infections (UTI) have been considered potential triggers of primary biliary cirrhosis (PBC), an autoimmune cholestatic liver disease characterised by progressive destruction of intrahepatic bile ducts. Additional support for the link made between PBC and UTI was based on early observations of recurrent episodes of bacteriuria in female patients with PBC. A series of large epidemiological studies demonstrated a strong correlation between recurrent UTI and PBC, initiating a series of studies investigating the role of Escherichia coli (E. coli, the most prevalent organism isolated in women with UTI) as a trigger of PBC. Immunological evidence of B- and T-cell cross-reactive responses implicating PBC-specific autoantigens and E. coli mimics have been clearly demonstrated, adding support to the notion that E. coli is a potential infectious inducer of PBC in susceptible individuals. One of the major limitations in proving the E. coli/PBC association was the lack of reliable E. coli-infected animal models of PBC. This review provides an overview of the evidence linking this infectious agent with PBC and discusses the pros and cons of a recently developed E. coli-infected animal model of PBC. Andreas L. Koutsoumpas, Daniel S. Smyk, and Dimitrios P. Bogdanos Copyright © 2014 Andreas L. Koutsoumpas et al. All rights reserved. The Mind and Liver Test: A New Approach to the Diagnosis of Minimal Hepatic Encephalopathy in Resource-Poor Settings Mon, 08 Dec 2014 12:52:14 +0000 Background and Aims. Minimal hepatic encephalopathy (MHE) is diagnosed using neuropsychometric tests or neurophysiological tests that are either inapplicable to illiterate patient population in resource-poor settings or require sophisticated and expensive equipment. The available tests assess discrete domains of mental impairment. Our aim was (a) to design a neuropsychometric test that measures all domains of mental impairment in MHE using one metric; (b) to evaluate its sensitivity, specificity, and reproducibility. Methods. The mind and liver test (MALT), a psychometric test assessing cognition, memory, and psychometric impairment, each on a scale of 20, was designed keeping in mind the requirements of a universal test. 40 cirrhotics and 36 controls were subjected to critical flicker frequency (CFF) and MALT in same sitting. ROC curve was plotted for MALT using CFF as gold standard. Bland-Altman plot was used to find test-retest agreement. Results. CFF values and MALT scores varied significantly between the cases and the controls . MALT was 94% sensitive and 83% specific. Using ROC with CFF as gold standard, the AUC for diagnosis of MHE using MALT score was 0.89. Test-retest agreement was high (ICC = 0.89). Conclusion. In this pilot study, MALT proved to be highly sensitive, specific, inexpensive, and reproducible. Saurav Das, Sajjadh M. J. Ali, James Seward, and Jayanthi Venkataraman Copyright © 2014 Saurav Das et al. All rights reserved. IFNL4 ss469415590 Variant Is Associated with Treatment Response in Japanese HCV Genotype 1 Infected Individuals Treated with IFN-Including Regimens Mon, 08 Dec 2014 12:36:41 +0000 Aim. Eradication of hepatitis C virus (HCV) is still challenging even if interferon- (IFN-) free regimens with direct-acting antiviral agents (DAAs) for HCV-infected individuals are available in clinical practice. IFNL4 is a newly described protein, associated with human antiviral defenses. We investigated whether IFNL4 ss469415590 variant has an effect on the prediction of treatment response in HCV-infected patients treated with IFN-including regimens. Patients and Methods. In all, 185 patients infected with HCV genotype 1 treated with peg-IFN plus ribavirin, with or without telaprevir, were genotyped for IFNL4 ss469415590. We retrospectively investigated whether the role of IFNL4 ss469415590 variant and other factors could predict sustained virological response (SVR) in Japanese patients infected with HCV genotype 1. Results. There were 65.7%, 31.5%, and 2.8% patients in the IFNL4 ss469415590 TT/TT, TT/-G, and -G/-G groups, respectively. SVR rates were 82.1% or 49.3% in patients treated with peg-IFN plus ribavirin with or without telaprevir, respectively. IFNL4 ss469415590 variant and HCV viral loads or IFNL4 ss469415590 variant and early virological response were better predictors of SVR in patients treated with peg-IFN plus ribavirin with or without telaprevir, respectively. Conclusion. In the era of DAAs, measurement of IFNL4 ss469415590 variant could help the prediction of SVR in Japanese HCV genotype 1 infected individuals treated with IFN-including regimens. Tatsuo Miyamura, Tatsuo Kanda, Shingo Nakamoto, Makoto Arai, Masato Nakamura, Shuang Wu, Xia Jiang, Reina Sasaki, Yuki Haga, Shin Yasui, Yoshihiko Ooka, Tetsuhiro Chiba, Fumio Imazeki, Shigeru Mikami, and Osamu Yokosuka Copyright © 2014 Tatsuo Miyamura et al. All rights reserved. Central Portalization Correlates with Fibrosis but Not with Risk Factors for Nonalcoholic Steatohepatitis in Steatotic Chronic Hepatitis C Sun, 30 Nov 2014 00:10:09 +0000 Concomitant steatosis in chronic hepatitis C is associated with fibrosis and unfavorable treatment outcome. Central zone injury in nonalcoholic steatohepatitis (NASH) manifests as central portalization, with centrizonal microvessels and ductular reaction. We investigated whether central portalization in steatotic HCV biopsies would identify patients with metabolic risk factors for NASH. Liver biopsies with chronic hepatitis C and >10% steatosis were evaluated for the degree of steatosis, zonation of steatosis, fibrosis, and nonalcoholic fatty liver disease (NAFLD) activity score. The presence of centrizonal microvessels, sinusoidal capillarization, ductular reaction, and CK7 positive intermediate-phenotype hepatocytes were evaluated by CD34 and CK7 immunostain. The degree of steatosis and fibrosis showed a positive correlation. Additional positive correlations were noted between centrizonal angiogenesis and NAFLD activity score and central portalization and fibrosis. However, neither central portalization nor zonation of steatosis identified patients with metabolic risk factors for NASH. Therefore, central portalization cannot be used as a surrogate marker to identify patients with metabolic risk factors for NASH in steatotic HCV biopsies. The mechanism of centrizonal injury in steatotic HCV hepatitis is not solely attributable to the metabolic risk factors for NASH. Hwajeong Lee, Sanaz Ainechi, Karen Dresser, and Elizabeth M. Kurian Copyright © 2014 Hwajeong Lee et al. All rights reserved. Clinical Features of Adult Patients with Acute Hepatitis B Virus Infection Progressing to Chronic Infection Thu, 02 Oct 2014 12:49:09 +0000 Background. Information regarding the progression of acute hepatitis B virus (HBV) infection to chronic infection in adults is scarce. Methods. Twenty-five adult patients with acute HBV infection (14 men and 11 women, 18–84 years old), whose clinical features progressed to those of chronic infection (group A) or did not (group B), were studied retrospectively. Results. There were 3 and 22 patients in groups A and B, respectively. Two of the 3 patients of group A lacked the typical symptoms of acute hepatitis. No differences were found between groups with respect to age, sex, or HBV genotypes. However, total bilirubin and alanine aminotransaminase levels were significantly lower in group A. Conclusions. Three of the 25 adult patients with acute HBV infection progressed to chronic infection. Hepatitis was mild in these patients. Patients with mild acute hepatitis B or unapparent HBV infection may have a higher risk of progressing to chronic infection. Kojiro Michitaka, Atsushi Hiraoka, Yoshio Tokumoto, Keiko Ninomiya, Tomoyuki Ninomiya, Norio Horiike, Masanori Abe, and Yoichi Hiasa Copyright © 2014 Kojiro Michitaka et al. All rights reserved.