Patients With Compensated Hepatitis B Virus-Related Cirrhosis and Low-Level Viremia: Treat or Not to Treat?

ABSTRACT: Patients with hepatitis B virus-related cirrhosis and low-level viremia represent a special group that might benefit from treatment because of their higher risk of complications. Evidence for the benefit of treatment in this population is lacking. The current study, which analyzed data of a historical cohort of 627 patients from a single Korean center with hepatitis B virus-related compensated cirrhosis, reported a 2.4-fold increased hepatocellular carcinoma risk among patients with low-level viremia compared with those with undetectable viremia provides indirect evidence in support of treatment for this population. The study underscores the importance of treating patients before the development of cirrhosis and the need for finite duration curative therapy.

Childhood pancreatic trauma: Clinical presentation, natural history and outcome.

OBJECTIVES: To study the presentation, management strategies and long-term natural history of children with pancreatic trauma. METHODS: Children admitted with pancreatic trauma were analyzed for their presentation, management and outcome. Management included nasojejunal feeds, total parenteral nutrition (TPN), octreotide, drainage (radiological and endoscopic), endoscopic retrograde cholangiopancreatography (ERCP) and surgery. Patients were assessed in follow-up for development of chronic pancreatitis (CP). RESULTS: 36 children [29 boys, age 144 (13-194) months] presented at 30 (3-210) days after trauma. Most common cause of trauma was bicycle handle bar injury [n = 18,50%]. Presenting features were abdominal pain [n = 26,72%], lump [n = 16, 44.4%], ascites [n = 13,36%], pleural effusion [n = 9,25%] and anasarca [n = 3,8.3%]. All presented with sequelae of ductal disruption with pseudocyst, ascites or pleural effusion. Fifteen (41.6%) patients each had Grade III and IV injury, 4 (11%) had grade V, and grading was unavailable in 2. Other organs were injured in 4 (11%) cases. Management consisted of various combinations of nasojejunal feeds [n = 17,47.2%], TPN [n = 5,13.8%], octreotide [n = 13,36%], pseudocyst drainage [radiological (n = 18,50%), endoscopic (n = 3,8.3%)] and ERCP [n = 12,33.3%]. Surgical intervention was done in 2 (5.5%) cases [cystojejunostomy and peritoneal lavage in 1 each]. Two (5.5%) patients died due to sepsis. Of the 32 cases in follow-up, 19 (59.3%) recovered and 13 (40.6%) developed CP, with half (6/13) of them being symptomatic with recurrent pain. CONCLUSION: Multi-disciplinary non-operative management is effective for managing pancreatic trauma in 94.4% of children, with 75% requiring radiological or endoscopic intervention. 40% developed structural changes later but only half were symptomatic.

Correction to: Utility and accuracy of transient elastography in determining liver fibrosis: a case-control study.

The author regrets that one of the author's name was incorrectly presented in the published version of this article. The third author's name original read as "Tajwar Singh Negi" this should have been "Tajwer Singh Negi".

Utility and accuracy of transient elastography in determining liver fibrosis: a case-control study.

The objectives of this prospective case-control study were to determine liver stiffness (LSM) by transient elastography (TE) in children with newly diagnosed chronic liver disease (CLD) and to find out normal values in healthy Indian children. Two groups (A: 50 CLD who underwent liver biopsy and B: 50 healthy) aged 5-18 years were recruited prospectively. Liver biopsies were scored as per Metavir scoring and compared with TE. The median age of 100 recruited children was 13.6 years. In group B, normal LSM was 4.9 (2.5-7.3) kPa with significantly higher LSM in adolescent males (5.6 (4.1-7.3) kPa) as compared with females (4.3 (3.7-4.9) kPa), p = 0.001. In group A, TE was excellent in discriminating significant fibrosis (≥ F2) (P = 0.001) at a cut-off value of 10.6 kPa with area under receiver operating characteristic curve of 0.96. Metavir fibrosis stage (ß = 0.611; R2 = 0.586) and age (ß = 0.230; R2 = 0.586) were independent variables associated with higher LSM in stepwise multiple logistic regression analysis.Conclusions: TE is an excellent non-invasive tool to assess significant liver fibrosis and can be used as an alternative to liver biopsy. Normative value of TE in adolescent males is higher than in females.What is Known:• Transient elastography is a good non-invasive test for liver fibrosis assessment.• Normal liver stiffness depends on race, gender, and age.What is New:• This is the first study from India to show the normative data of transient elastography in healthy Indian children.• We have documented that liver stiffness measurement by fibroscan in treatment naïve chronic liver disease has excellent correlation in significant fibrosis, severe fibrosis, and cirrhosis.

Drug-Induced Acute-on-Chronic Liver Failure in Asian Patients.

OBJECTIVES: Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF. METHODS: We identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation. RESULTS: Of the 3,132 patients with ACLF, drugs were implicated as a cause in 329 (10.5%, mean age 47 years, 65% men) and other nondrug causes in 2,803 (89.5%) (group B). Complementary and alternative medications (71.7%) were the commonest insult, followed by combination antituberculosis therapy drugs (27.3%). Alcoholic liver disease (28.6%), cryptogenic liver disease (25.5%), and non-alcoholic steatohepatitis (NASH) (16.7%) were common causes of underlying liver diseases. Patients with drug-induced ACLF had jaundice (100%), ascites (88%), encephalopathy (46.5%), high Model for End-Stage Liver Disease (MELD) (30.2), and Child-Turcotte-Pugh score (12.1). The overall 90-day mortality was higher in drug-induced (46.5%) than in non-drug-induced ACLF (38.8%) (P = 0.007). The Cox regression model identified arterial lactate (P < 0.001) and total bilirubin (P = 0.008) as predictors of mortality. DISCUSSION: Drugs are important identifiable causes of ACLF in Asia-Pacific countries, predominantly from complementary and alternative medications, followed by antituberculosis drugs. Encephalopathy, bilirubin, blood urea, lactate, and international normalized ratio (INR) predict mortality in drug-induced ACLF.

Development of predisposition, injury, response, organ failure model for predicting acute kidney injury in acute on chronic liver failure.

BACKGROUND AND AIM: There is limited data on predictors of acute kidney injury in acute on chronic liver failure. We developed a PIRO model (Predisposition, Injury, Response, Organ failure) for predicting acute kidney injury in a multicentric cohort of acute on chronic liver failure patients. PATIENTS AND METHODS: Data of 2360 patients from APASL-ACLF Research Consortium (AARC) was analysed. Multivariate logistic regression model (PIRO score) was developed from a derivation cohort (n=1363) which was validated in another prospective multicentric cohort of acute on chronic liver failure patients (n=997). RESULTS: Factors significant for P component were serum creatinine[(≥2 mg/dL)OR 4.52, 95% CI (3.67-5.30)], bilirubin [(<12 mg/dL,OR 1) vs (12-30 mg/dL,OR 1.45, 95% 1.1-2.63) vs (≥30 mg/dL,OR 2.6, 95% CI 1.3-5.2)], serum potassium [(<3 mmol/LOR-1) vs (3-4.9 mmol/L,OR 2.7, 95% CI 1.05-1.97) vs (≥5 mmol/L,OR 4.34, 95% CI 1.67-11.3)] and blood urea (OR 3.73, 95% CI 2.5-5.5); for I component nephrotoxic medications (OR-9.86, 95% CI 3.2-30.8); for R component,Systemic Inflammatory Response Syndrome,(OR-2.14, 95% CI 1.4-3.3); for O component, Circulatory failure (OR-3.5, 95% CI 2.2-5.5). The PIRO score predicted acute kidney injury with C-index of 0.95 and 0.96 in the derivation and validation cohort. The increasing PIRO score was also associated with mortality (P<.001) in both the derivation and validation cohorts. CONCLUSIONS: The PIRO model identifies and stratifies acute on chronic liver failure patients at risk of developing acute kidney injury. It reliably predicts mortality in these patients, underscoring the prognostic significance of acute kidney injury in patients with acute on chronic liver failure.

Clinical profile and treatment outcome of chronic pancreatitis in children: a long-term follow-up study of 156 cases.

AIM: There is a paucity of literature in pediatric chronic pancreatitis (CP) and most information is derived from adult literature. We, therefore, analyzed our experience of CP to look for clinical profile and long-term outcome. METHODS: From January 2003 to December 2015, 156 consecutive children (≤18 years) diagnosed as CP were included. Their clinical profile, management, and follow-up data were retrieved. Genetic markers (PRSS1, SPINK1, and CFTR) were studied in 40 idiopathic cases. RESULTS: The median age of the patients was 13 [inter-quartile range (IQR): 10-14] years (93 males) and 134 (86%) were idiopathic. Genetic mutations were found in 22/40 (55%) idiopathic cases. All but two presented with pain abdomen (episodic pain in 93.6%) and symptom duration was 12 (IQR: 6-24) months. There were two subsets; calcific (CCP) 68 (43.5%) and non-calcific (NCCP) 88 (56.5%). In CCP group, significantly more children had Cambridge grade 5 magnetic resonance cholangiopancreatography changes, low weight Z-score, and had continuous pain more compared to NCCP group. Over a median follow-up of 23 (IQR: 8-45.5) months, more children in CCP group had complications. Endoscopic therapy (done for persistent pain in 40) relieved pain in 52.5% of cases while medical therapy did so in 36% of cases. CONCLUSION: Pediatric CP in Asia presents with episodic pain and genetic predisposition seems to be a major cause. There are two subsets; CCP and NCCP with former showing marked imaging changes, more often associated with malnutrition and complications. Endoscopic therapy for pain relief gives modest benefit but medical therapy is not encouraging.

Evaluation of cognitivity, proinflammatory cytokines, and brain magnetic resonance imaging in minimal hepatic encephalopathy induced by cirrhosis and extrahepatic portal vein obstruction.

BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is the mildest form of hepatic encephalopathy (HE) and is characterized by deficits in neurocognitive performance without any clinical symptoms of HE. In the current study, we aim to evaluate and compare the neurocognitive, biochemical, and brain magnetic resonance (MR) imaging changes between patients with cirrhotic MHE and extrahepatic portal vein obstruction (EHPVO) MHE. METHODS: Thirty-three cirrhotic and 14 EHPVO patients were diagnosed with MHE and were included in the analysis along with 24 normal healthy volunteers. All subjects underwent MR imaging including diffusion tensor imaging and proton MR spectroscopy (1 H-MRS) followed by cognitive assessments, critical flicker frequency (CFF) measurements, quantification of blood ammonia, and serum proinflammatory cytokine levels. RESULTS: We observed abnormal neurocognitive functions and CFF measurements in both cirrhotic MHE and EHPVO MHE patients as compared with controls. Significantly increased blood ammonia, serum proinflammatory cytokines (IL-6, TNF-α) level, mean diffusivity in multiple brain sites, 1 H-MRS derived glutamate/glutamine (Glx)/creatine (Cr), and significantly decreased 1 H-MRS derived myo-inositol/Cr were observed in both cirrhotic MHE and EHPVO MHE compared with those of controls. Choline/Cr level was significantly decreased in cirrhotic MHE as compared with controls and EHPVO MHE. CONCLUSIONS: Cirrhotic MHE showed more severe changes on mean diffusivity in multiple brain sites and inflammation as compared with EHPVO MHE. This study confirms that there are significant difference in neurocognitive, biochemical, and MR profile between cirrhotic MHE and EHPVO MHE, which may help to understand the pathophysiologies of these two types of MHE and may contribute to improve their clinical managements.

Reduced cortical thickness in patients with acute-on-chronic liver failure due to non-alcoholic etiology.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a form of liver disease with high short-term mortality. ACLF offers considerable potential to affect the cortical areas by significant tissue injury due to loss of neurons and other supporting cells. We measured changes in cortical thickness and metabolites profile in ACLF patients following treatment, and compared it with those of age matched healthy volunteers. METHODS: For the cortical thickness analysis we performed whole brain high resolution T1-weighted magnetic resonance imaging (MRI) on 15 ACLF and 10 healthy volunteers at 3T clinical MR scanner. Proton MR Spectroscopy ((1)H MRS) was also performed to measure level of altered metabolites. Out of 15 ACLF patients 10 survived and underwent follow-up study after clinical recovery at 3 weeks. FreeSurfer program was used to quantify cortical thickness and LC- Model software was used to quantify absolute metabolites concentrations. Neuropsychological (NP) test was performed to assess the cognitive performance in follow-up ACLF patients compared to controls. RESULTS: Significantly reduced cortical thicknesses in multiple brain sites, and significantly decreased N-acetyl aspartate (NAA), myo-inositol (mI) and significantly increased glutamate/glutamine (glx) metabolites were observed in ACLF compared to those of controls at baseline study. Follow-up patients showed significant recovery in cortical thickness and Glx level, while NAA and mI were partially recovered compared to baseline study. When compared to controls, follow-up patients still showed reduced cortical thickness and altered metabolites level. Follow-up patients had abnormal neuropsychological (NP) scores compared to controls. CONCLUSIONS: Neuronal loss as suggested by the reduced NAA, decreased cellular density due to increased cerebral hyperammonemia as supported by the increased glx level, and increased proinflammatory cytokines and free radicals may account for the reduced cortical thickness in ACLF patients. Presence of reduced cortical thickness, altered metabolites and abnormal NP test scores in post recovery subjects as compared to those of controls is associated with incomplete clinical recovery. The current imaging protocol can be easily implemented in clinical settings to evaluate and monitor brain tissue changes in patients with ACLF during the course of treatment.

Respiratory dysfunction is common in patients with achalasia and improves after pneumatic dilation.

BACKGROUND: Dysphagia, regurgitation, and chest pain are common achalasia, with a variable report of pulmonary symptoms possibly due to micro-aspiration. Pneumatic dilation (PD) may improve pulmonary function. Data on pulmonary dysfunction among achalasia patients are scanty, and the effect of PD is unknown. AIM: To evaluate pulmonary dysfunction in patients with achalasia based on clinical and radiologic evaluation and spirometry and to study the effect of PD at 1-month follow-up. METHODS: Patients with achalasia (diagnosed using high-resolution manometry and the Chicago classification) were evaluated prospectively by spirometry before (n = 38) and 1 month after PD (n = 31). All patients received a chest X-ray, and patients with respiratory abnormality before PD received high-resolution computed tomography of the thorax. RESULTS: Of the 38 patients, 17 and 21 had type I and II achalasia, respectively. The respiratory symptoms, such as pharyngeal symptoms [27/38 (71 %) vs. 8/31 (26 %); P = 0.0001], cough [23/38 (60.5 %) vs. 5/31 (16 %), P = 0.0001], and dyspnea [8/38 (21 %) vs. 0/31 (0 %), P = 0.006], improved after treatment with PD. Spirometry showed abnormalities in 17/38 (45 %) patients before and in 8/15 (53 %) after PD. Median FEV(1), FVC, PEFR, and percentage of predicted MEF(25-75), improved from 78 % (36-85), 74 % (48-100), 62 % (18-72), and 48 % (15-66) before to 83 % (58-94), 86 % (55-99), 69 % (38-81), and 59 % (33-78) after PD, respectively (P < 0.05 for all). CONCLUSION: Respiratory symptoms and spirometry abnormalities are common in patients with achalasia and improved after successful PD.

2023 Update of Indian National Association for Study of the Liver Consensus on Management of Intermediate and Advanced Hepatocellular Carcinoma: The Puri III Recommendations.

Hepatocellular carcinoma (HCC) presents significant treatment challenges despite considerable advancements in its management. The Indian National Association for the Study of the Liver (INASL) first published its guidelines to aid healthcare professionals in the diagnosis and treatment of HCC in 2014. These guidelines were subsequently updated in 2019. However, INASL has recognized the need to revise its guidelines in 2023 due to recent rapid advancements in the diagnosis and management of HCC, particularly for intermediate and advanced stages. The aim is to provide healthcare professionals with evidence-based recommendations tailored to the Indian context. To accomplish this, a task force was formed, and a two-day round table discussion was held in Puri, Odisha. During this event, experts in their respective fields deliberated and finalized consensus statements to develop these updated guidelines. The 2023 INASL guidelines offer a comprehensive framework for the diagnosis, staging, and management of intermediate and advanced HCC in India. They represent a significant step forward in standardizing clinical practices nationwide, with the primary objective of ensuring that patients with HCC receive the best possible care based on the latest evidence. The guidelines cover various topics related to intermediate and advanced HCC, including biomarkers of aggressive behavior, staging, treatment options, and follow-up care.

Frequency and factors associated with increased small intestinal permeability in patients with portal hypertension.

AIM: Cirrhosis with portal hypertension (PHT) may be associated with increased small intestinal permeability (SIP), predisposing to malnutrition and bacterial translocation causing septicaemia, endotoxaemia and spontaneous bacterial peritonitis. However, data on SIP in extrahepatic portal venous obstruction (EHPVO), in which PHT occurs without hepatic dysfunction, are scanty. Such studies would help to know the effect of PHT on SIP independent of hepatic dysfunction; hence, we undertook this study. METHODS: A total of 96 patients with PHT (cirrhosis 71, EHPVO 25) underwent evaluation of SIP using urinary lactulose/mannitol excretion ratio over 6 hours after oral administration of 15 mL (10 g) lactulose and 5 g mannitol using 1H-NMR spectroscopy by a method described by us previously. RESULTS: Gender of patients with EHPVO and cirrhosis was comparable but patients with EHPVO were younger in age. The causes of cirrhosis were cryptogenic (n = 22), alcohol (n = 20), post-viral (n = 21) and others (n = 8). Twenty-seven (38%) patients with cirrhosis had ascites. Abnormal SIP was detected in 47 (49%) patients (40/71,56% with cirrhosis vs. 7/25, 28% with EHPVO, p = 0.01). Patients with cirrhosis had a higher urinary lactulose/mannitol excretion ratio than those with EHPVO (0.09, range 0-0.87 mmol vs. 0.05, 0-0.19 mmol; p = 0.008). Patients with abnormal SIP had a higher Child score, and more often had cirrhosis than EHPVO, ascites and deranged liver function. On multivariate analysis, presence of cirrhosis, ascites, high serum bilirubin level and prothrombin time were associated with abnormal SIP. CONCLUSIONS: Cirrhosis was associated with abnormal SIP, which was related to liver dysfunction. However, SIP was normal in patients with EHPVO.

Safety and Efficacy of Atezolizumab-Bevacizumab in Real World: The First Indian Experience.

Background: Atezolizumab-bevacizumab (atezo/bev) combination is a recommended first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC). There are no studies from India reporting the safety and efficacy of this drug in real-world settings where most patients present in an advanced stage. Methods: In this retrospective study from two centers in India, we included patients with uHCC who received atezo/bev as first-line systemic therapy. Comparison of overall survival (OS) among the different Child-Turcotte-Pugh (CTP) classes was the primary objective, while progression-free survival (PFS), radiologic response, and adverse events to the therapy were secondary objectives. Results: The median age of the 67 patients who received atezo/bev therapy was 61 (29-82) years, and 86% were males. Nonalcoholic steatohepatitis (55.2%) was the commonest cause of cirrhosis, and most patients belonged to BCLC-C (74.6%%). There were 24 patients in CTP A, 36 in CTP B, and 7 in CTP C. The median OS was 12 (95%CI, 8.16-15.83) months in the cohort. The median OS in CTP class A, B, and C was 21 (95%CI, 0-42.06) months, 9 (95%CI, 5.46-12.53) months, and 4 (95%CI, 2.14-5.85) months, respectively (P < 0.001). The median PFS in the whole cohort was 8 (95%CI, 6.03-9.96) months. The median PFS in Child A, B, and C was 18 (95%CI, 0.16-35.84) months, 8 (95%CI, 6.14-9.85) months, and 2 (95%CI, 1.77-2.23) months (P < 0.001). On mRECIST evaluation, 12.9% had achieved a complete response, 25.8% had a partial response, 27.41% had stable disease, and the rest had progressed. The objective response rate was 38.7%, and the disease control rate was 66.12%. Of the 64% who developed adverse events, 13.43% discontinued the drug. The incidence of grade ≥3 events was significantly higher in CTP C (85.7%) compared to CTP A (12.5%) and CTP B (14%) (P < 0.001). Conclusions: Atezolizumab-bevacizumab is safe and effective in uHCC in real-world settings. Candidate selection is of utmost importance in treating uHCC with atezolizumab-bevacizumab to achieve a good response. Current evidence strongly suggests limited use of atezolizumab-bevacizumab in patients with CTP C, and such individuals should not be considered for this combination therapy.

Position statement from the Indian Society of Gastroenterology, Cardiological Society of India, Indian Academy of Neurology and Vascular Society of India on gastrointestinal bleeding and endoscopic procedures in patients on antiplatelet and/or anticoagulant therapy.

Antiplatelet and/or anticoagulant agents (collectively known as antithrombotic agents) are used to reduce the risk of thromboembolic events in patients with conditions such as atrial fibrillation, acute coronary syndrome, recurrent stroke prevention, deep vein thrombosis, hypercoagulable states and endoprostheses. Antithrombotic-associated gastrointestinal (GI) bleeding is an increasing burden due to the growing population of advanced age with multiple comorbidities and the expanding indications for the use of antiplatelet agents and anticoagulants. GI bleeding in antithrombotic users is associated with an increase in short-term and long-term mortality. In addition, in recent decades, there has been an exponential increase in the use of diagnostic and therapeutic GI endoscopic procedures. Since endoscopic procedures hold an inherent risk of bleeding that depends on the type of endoscopy and patients' comorbidities, in patients already on antithrombotic therapies, the risk of procedure-related bleeding is further increased. Interrupting or modifying doses of these agents prior to any invasive procedures put these patients at increased risk of thromboembolic events. Although many international GI societies have published guidelines for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures, no Indian guidelines exist that cater to Indian gastroenterologists and their patients. In this regard, the Indian Society of Gastroenterology (ISG), in association with the Cardiological Society of India (CSI), Indian Academy of Neurology (IAN) and Vascular Society of India (VSI), have developed a "Guidance Document" for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures.

Indian National Association for Study of the Liver (INASL) Guidance Paper on Nomenclature, Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease (NAFLD).

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and in India. The already high burden of NAFLD in India is expected to further increase in the future in parallel with the ongoing epidemics of obesity and type 2 diabetes mellitus. Given the high prevalence of NAFLD in the community, it is crucial to identify those at risk of progressive liver disease to streamline referral and guide proper management. Existing guidelines on NAFLD by various international societies fail to capture the entire landscape of NAFLD in India and are often difficult to incorporate in clinical practice due to fundamental differences in sociocultural aspects and health infrastructure available in India. A lot of progress has been made in the field of NAFLD in the 7 years since the initial position paper by the Indian National Association for the Study of Liver on NAFLD in 2015. Further, the ongoing debate on the nomenclature of NAFLD is creating undue confusion among clinical practitioners. The ensuing comprehensive review provides consensus-based, guidance statements on the nomenclature, diagnosis, and treatment of NAFLD that are practically implementable in the Indian setting.

Erratum to 'Indian National Association for the Study of Liver Consensus Statement on Acute Liver Failure (Part-2): Management of Acute Liver Failure' [J Clin Exp Hepatol 10 (2020) 477-517].

[This corrects the article DOI: 10.1016/j.jceh.2020.04.011.].

Capsule endoscopy for obscure gastrointestinal bleeding in the tropics: report from India.

BACKGROUND: Capsule endoscopy (CE) is useful in patients with obscure gastrointestinal bleeding (OGIB). Experience in CE in OGIB in the tropics is limited. METHODS: Eighty-six patients with OGIB were evaluated clinically and using CE (Given Imaging, Yoqneam, Israel) 89 times (twice in three patients) during a 64-month period. Images were downloaded and examined by a single investigator using software (Rapid Reader; Given Imaging, Yoqneam, Israel). Patients received specific treatment and were followed up. Intraoperative findings, response to specific treatment and outcome on follow up (10.3±14.1 months) were considered to confirm CE findings. RESULTS: Of 86 patients (aged 54.5±16.3 years, 63 males), 64 and 22 had OGIB-overt and OGIB-occult, respectively. Lesions were equally detected in OGIB-overt and OGIB-occult patients (48/64, 75% vs 18/22, 81.8%, P= ns). Lesions were detected in 64 of 86 (74.4%) patients [vascular malformations with or without fresh bleeding in 24 (37.5%), tumors in 12 (18.8%), strictures in 15 (23.4%), ulcers in five (7.8%), hookworm in five (7.8%), and more than one lesion in three patients (4.7%)]. Endoscopic insertion of the capsule was required in four patients, and in six it was retained, although none developed intestinal obstruction (surgical removal in two). The sensitivity, specificity, positive and negative predictive values of CE to detect the lesion(s) were 92.9%, 68.2%, 84.8%, and 83.3%, respectively. CONCLUSION: CE is safe and is equally effective in detecting lesion(s) in occult and overt OGIB. Worm infestation and small bowel tuberculosis are unique and important causes of OGIB in the tropics.

Serum Metabolic Disturbances Associated with Acute-on-chronic Liver Failure in Patients with Underlying Alcoholic Liver Diseases: An Elaborative NMR-based Metabolomics Study.

OBJECTIVES: Acute-on-chronic liver failure (ACLF), which develops in patients with underlying alcoholic liver disease (ALD), is characterized by acute deterioration of liver function and organ failures are secondary to that. The clear understanding of metabolic pathways perturbed in ALD-ACLF patients can greatly decrease the mortality and morbidity of patients through predicting outcome, guiding treatment, and monitoring response to treatment. The purpose of this study was to investigate the metabolic disturbances associated with ACLF using nuclear magnetic resonance (NMR)-based serum metabolomics approach and further to assess if the serum metabolic alterations are affected by the severity of hepatic impairment. MATERIALS AND METHODS: The serum-metabolic profiles of 40 ALD-ACLF patients were compared to those of 49 age and sex-matched normal-control (NC) subjects making composite use of both multivariate and univariate statistical tests. RESULTS: Compared to NC, the sera of ACLF patients were characterized by significantly decreased serum levels of several amino acids (except methionine and tyrosine), lipid, and membrane metabolites suggesting a kind of nutritional deficiency and disturbed metabolic homeostasis in ACLF. Twelve serum metabolic entities (including BCAA, histidine, alanine, threonine, and glutamine) were found with AUROC (i.e., area under ROC curve) value >0.9 suggesting their potential in clinical diagnosis and surveillance. CONCLUSION: Overall, the study revealed important metabolic changes underlying the pathophysiology of ACLF and those related to disease progression would add value to standard clinical scores of severity to predict outcome and may serve as surrogate endpoints for evaluating treatment response.