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.

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.

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.

Indian National Association for the Study of Liver Consensus Statement on Acute Liver Failure (Part-2): Management of Acute Liver Failure.

Acute liver failure (ALF) is not an uncommon complication of a common disease such as acute hepatitis. Viral hepatitis followed by antituberculosis drug-induced hepatotoxicity are the commonest causes of ALF in India. Clinically, such patients present with appearance of jaundice, encephalopathy, and coagulopathy. Hepatic encephalopathy (HE) and cerebral edema are central and most important clinical event in the course of ALF, followed by superadded infections, and determine the outcome in these patients. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a crucial role in the pathogenesis, and several therapies aim to correct this abnormality. The role of newer ammonia-lowering agents is still evolving. These patients are best managed at a tertiary care hospital with facility for liver transplantation (LT). Aggressive intensive medical management has been documented to salvage a substantial proportion of patients. In those with poor prognostic factors, LT is the only effective therapy that has been shown to improve survival. However, recognizing suitable patients with poor prognosis has remained a challenge. Close monitoring, early identification and treatment of complications, and couseling for transplant form the first-line approach to manage such patients. Recent research shows that use of dynamic prognostic models is better for selecting patients undergoing liver transplantation and timely transplant can save life of patients with ALF with poor prognostic factors.

Indian National Association for the Study of the Liver Consensus Statement on Acute Liver Failure (Part 1): Epidemiology, Pathogenesis, Presentation and Prognosis.

Acute liver failure (ALF) is an infrequent, unpredictable, potentially fatal complication of acute liver injury (ALI) consequent to varied etiologies. Etiologies of ALF as reported in the literature have regional differences, which affects the clinical presentation and natural course. In this part of the consensus article designed to reflect the clinical practices in India, disease burden, epidemiology, clinical presentation, monitoring, and prognostication have been discussed. In India, viral hepatitis is the most frequent cause of ALF, with drug-induced hepatitis due to antituberculosis drugs being the second most frequent cause. The clinical presentation of ALF is characterized by jaundice, coagulopathy, and encephalopathy. It is important to differentiate ALF from other causes of liver failure, including acute on chronic liver failure, subacute liver failure, as well as certain tropical infections which can mimic this presentation. The disease often has a fulminant clinical course with high short-term mortality. Death is usually attributable to cerebral complications, infections, and resultant multiorgan failure. Timely liver transplantation (LT) can change the outcome, and hence, it is vital to provide intensive care to patients until LT can be arranged. It is equally important to assess prognosis to select patients who are suitable for LT. Several prognostic scores have been proposed, and their comparisons show that indigenously developed dynamic scores have an edge over scores described from the Western world. Management of ALF will be described in part 2 of this document.

2019 Update of Indian National Association for Study of the Liver Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri II Recommendations.

Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality, and healthcare expenditure in patients with chronic liver disease in India. The Indian National Association for Study of the Liver (INASL) had published its first guidelines on diagnosis and management of HCC (The Puri Recommendations) in 2014, and these guidelines were very well received by the healthcare community involved in diagnosis and management of HCC in India and neighboring countries. However, since 2014, many new developments have taken place in the field of HCC diagnosis and management, hence INASL endeavored to update its 2014 consensus guidelines. A new Task Force on HCC was constituted that reviewed the previous guidelines as well as the recent developments in various aspects of HCC that needed to be incorporated in the new guidelines. A 2-day round table discussion was held on 5th and 6th May 2018 at Puri, Odisha, to discuss, debate, and finalize the revised consensus statements. Each statement of the guideline was graded according to the Grading of Recommendations Assessment Development and Evaluation system with minor modifications. We present here the 2019 Update of INASL Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri-2 Recommendations.

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.

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.

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.

Palliation of malignant gastroduodenal obstruction with self-expandable metal stent using side- and forward-viewing endoscope: Feasibility and outcome.

BACKGROUND: The endoscopic placement of a self-expandable metal stent (SEMS), an alternative to surgical bypass for the palliation of malignant gastric outlet obstruction (GOO), is commonly performed using a forward-viewing endoscope with a wide therapeutic channel; however, due to limited availability, most Indian centers use a side-viewing duodenoscope. We studied the feasibility and outcome of SEMS placement using side- and forward-viewing endoscopes. METHOD: Data of patients undergoing SEMS placement using side- and forward-viewing endoscopes with a therapeutic channel for the palliation of malignant GOO presenting during a 5-year period were analyzed retrospectively. Follow-up data were obtained from records and telephonic interviews, and technical and clinical success, complications, and survival were evaluated. RESULTS: Of 114 patients (age 56.5 ± 11.6 years, 59 [52%] female), 90 (79%) and 24 (21%) underwent SEMS placement using side- and forward-viewing endoscopes, respectively. Technical (89, 98.9% vs. 24, 100%, P = ns) and clinical success (84, 93.3% vs. 23, 95.8%, P = ns) and complication rate (3, 3.3% vs. 0, P = ns) between side- and forward-viewing endoscopes were comparable. However, SEMS could be placed in a shorter time using a forward- rather than side-viewing endoscope (21 min [inter-quartile range 19.5-35] vs. 34 min [25-45], P = < 0.001). SEMS could be deployed successfully with a forward-viewing endoscope in two patients in whom an initial attempt using side-viewing endoscope failed. Gastric outlet obstruction scoring system (GOOSS) improved following stent placement (median 0, range 0-2 vs. 2, 0-3, P = 0.0001). The survival of patients undergoing SEMS placement using side- and forward-viewing endoscopes was comparable. CONCLUSION: Although side- and forward-viewing endoscopes are equally effective for antroduodenal SEMS placement, the procedure can be performed faster using the latter.

INASL Guidelines on Management of Hepatitis B Virus Infection in Patients receiving Chemotherapy, Biologicals, Immunosupressants, or Corticosteroids.

Hepatitis B Virus (HBV) reactivation in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids is emerging to be an important cause of morbidity and mortality in patients with current or prior exposure to HBV infection. These patients suffer a dual onslaught of illness: one from the primary disease for which they are receiving the culprit drug that led to HBV reactivation, and the other from HBV reactivation itself. The HBV reactivation not only leads to a compromised liver function, which may culminate into hepatic failure; it also adversely impacts the treatment outcome of the primary illness. Hence, identification of patients at risk of reactivation before starting these drugs, and starting treatment aimed at prevention of HBV reactivation is the best strategy of managing these patients. There are no Indian guidelines on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids for the treatment of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions, or solid-organ or bone marrow transplantation. The Indian National Association for Study of the Liver (INASL) had set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for management of various aspects of HBV infection, relevant to India. In 2017 the taskforce had published the first INASL guidelines on management of HBV infection in India. In the present guidelines, which are in continuation with the previous guidelines, the issues on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids are addressed.

Perforation following pneumatic dilation of achalasia cardia in a university hospital in northern India: A two-decade experience.

Pneumatic dilation (PD) is a cost-effective first-line treatment for achalasia. The most feared complication of PD is esophageal perforation (EP). As data on EP after PD for achalasia are not widely reported, we present the frequency, risk factors, and treatment-outcome of EP. Records of patients undergoing PD for achalasia (January 1995 to September 2015) were retrospectively reviewed. Of 433 patients (age 38 years, 13-88, 57% male), and 521 dilations, 12 were complicated by EP (2.7% of patients and 2.3% of PD). EP occurred in 7 (3.4%), 4 (1.7%), and 1 (4.1%) with use of balloon diameters 30, 35, and 40 mm, respectively. In most (11/12, 92%), EP occurred during the first PD. No risk factor for EP was identified (p = 0.65 for the first dilation vs. > 1 dilation, and 0.75 for balloon size of 30 mm vs. > 30 mm). Seven patients with contrast leak on esophagogram and/or computed tomography scan underwent surgery. One other with contrast leak was successfully treated with a fully covered self-expandable metal stent (FC-SEMS); the remaining four with small leak/pneumomediastinum were managed conservatively. The median duration of hospital stay following perforation was 13 days (7-26) and 8 days (6-10) in surgery and conservative groups, respectively. No mortality was observed in either group. The frequency of EP with PD was 2.3%. Though most EP (92%) occurred during the first dilation, neither the balloon size nor repeated dilations were identified as risk factors. Both surgical and conservative approaches had a favorable outcome in appropriate settings.

INASL Position Statements on Prevention, Diagnosis and Management of Hepatitis B Virus Infection in India: The Andaman Statements.

Hepatitis B Virus (HBV) infection is one of the major causes of morbidity, mortality and healthcare expenditure in India. There are no Indian consensus guidelines on prevention, diagnosis and management of HBV infection. The Indian National Association for Study of the Liver (INASL) set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for diagnosis and management of HBV infection, relevant to disease patterns and clinical practices in India. The taskforce first identified contentious issues on various aspects of HBV management, which were allotted to individual members of the taskforce who reviewed them in detail. A 2-day round table discussion was held on 11th and 12th February 2017 at Port Blair, Andaman & Nicobar Islands, to discuss, debate, and finalize the consensus statements. The members of the taskforce reviewed and discussed the existing literature threadbare at this meeting and formulated the 'INASL position statements' on each of the issues. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong: 1, weak: 2) thus reflects the quality (grade) of underlying evidence (A, B, C, D). We present here the INASL position statements on prevention, diagnosis and management of HBV in India.

Low-grade small intestinal bacterial overgrowth is common in patients with non-alcoholic steatohepatitis on quantitative jejunal aspirate culture.

BACKGROUND: Though pathogenesis of non-alcoholic steatohepatitis (NASH) is unclear, association with small intestinal bacterial overgrowth [SIBO] and fecal dysbiosis is suggested. We evaluated SIBO in NASH using quantitative jejunal aspirate culture (conventional criteria: ≥ 105 colony forming unit (CFU)/mL and newer cutoff ≥ 103 CFU/mL) and glucose hydrogen breath test. METHODS: Thirty-eight patients with NASH (age 37.5 years, range 20-54, 9, 24% female), diagnosed by ultrasonography, alanine aminotransferase >1.5 times normal and liver biopsy (in 27/38, 71%) and exclusion of other causes and 12 constipation-predominant irritable bowel syndrome as historical controls (age 39.5-y, 26-44; 3, 25% female) without fatty liver were studied. RESULTS: Jejunal aspirates, obtained in 35/38 patients, were sterile in 14/35 (40%) and bacteria isolated in 21 (60%) (all aerobic, in one anaerobe also; Gram positive 5, negative 13, both 3). In contrast, bacteria (two Gram negative) were isolated in 3/12 (25%) controls (odds ratio 4.5, 95% CI 1.0-19.5; p = 0.04); colony counts were higher in NASH than controls (median 380 CFU/mL, 0-200,000 vs. 0 CFU/mL, 0-1000; p = 0.02). Gram negative bacteria tended to be commoner in NASH than controls (16/35 vs. 2/12; p = 0.07). Seven out of 35 (20%) patients with NASH (≥ 105 CFU/mL in 5 and 2 other on glucose hydrogen breath test) and no control had SIBO (p = ns); low-grade SIBO (≥103 CFU/mL) was commoner in NASH than controls (14/35, 40%, vs. 1/12, 8.3%; p = 0.04). There was no correlation between bacterial colony count and bacterial type and anthropometric and biochemical parameters. CONCLUSION: Low-grade bacterial overgrowth, particularly with Gram negative bacteria, was commoner in NASH than controls.

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.

Gut microbiota: its role in hepatic encephalopathy.

Ammonia, a key factor in the pathogenesis of hepatic encephalopathy (HE), is predominantly derived from urea breakdown by urease producing large intestinal bacteria and from small intestine and kidneys, where the enzyme glutaminases releases ammonia from circulating glutamine. Non-culture techniques like pyrosequencing of bacterial 16S ribosomal ribonucleic acid are used to characterize fecal microbiota. Fecal microbiota in patients with cirrhosis have been shown to alter with increasing Child-Turcotte-Pugh (CTP) and Model for End stage Liver Disease (MELD) scores, and with development of covert or overt HE. Cirrhosis dysbiosis ratio (CDR), the ratio of autochthonous/good bacteria (e.g. Lachnospiraceae, Ruminococcaceae and Clostridiales) to non-autochthonous/pathogenic bacteria (e.g. Enterobacteriaceae and Streptococcaceae), is significantly higher in controls and patients with compensated cirrhosis than patients with decompensated cirrhosis. Although their stool microbiota do not differ, sigmoid colonic mucosal microbiota in liver cirrhosis patients with and without HE, are different. Linkage of pathogenic colonic mucosal bacteria with poor cognition and inflammation suggests that important processes at the mucosal interface, such as bacterial translocation and immune dysfunction, are involved in the pathogenesis of HE. Fecal microbiome composition does not change significantly when HE is treated with lactulose or when HE recurs after lactulose withdrawal. Despite improving cognition and endotoxemia as well as shifting positive correlation of pathogenic bacteria with metabolites, linked to ammonia, aromatic amino acids and oxidative stress, to a negative correlation, rifaximin changes gut microbiome composition only modestly. These observations suggest that the beneficial effects of lactulose and rifaximin could be associated with a change in microbial metabolic function as well as an improvement in dysbiosis.

Non-alcoholic Fatty Liver Disease and Metabolic Syndrome-Position Paper of the Indian National Association for the Study of the Liver, Endocrine Society of India, Indian College of Cardiology and Indian Society of Gastroenterology.

Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic syndrome. Prevalence of metabolic risk factors including diabetes mellitus, obesity, etc. is rapidly increasing in India putting this population at risk for NAFLD. Patients with NAFLD are at increased risk for liver-related morbidity and mortality and also cardiovascular disease risk and increased incidence of diabetes mellitus on long-term follow-up. Management of patients with NAFLD may require a multi-disciplinary approach involving not only the hepatologists but also the internists, cardiologists, and endocrinologists. This position paper which is a combined effort of the Indian National Association for Study of the Liver (INASL), Endocrine Society of India (ESI), Indian College of Cardiology (ICC) and the Indian Society of Gastroenterology (ISG) defines the spectrum of NAFLD and the association of NAFLD with insulin resistance and metabolic syndrome besides suggesting preferred approaches for the diagnosis and management of patients with NAFLD in the Indian context.

Portal cavernoma cholangiopathy: consensus statement of a working party of the Indian national association for study of the liver.

Portal cavernoma cholangiopathy (PCC) is defined as abnormalities in the extrahepatic biliary system including the cystic duct and gallbladder with or without abnormalities in the 1st and 2nd generation biliary ducts in a patient with portal cavernoma. Presence of a portal cavernoma, typical cholangiographic changes on endoscopic or magnetic resonance cholangiography and the absence of other causes of these biliary changes like bile duct injury, primary sclerosing cholangitis, cholangiocarcinoma etc are mandatory to arrive a diagnosis. Compression by porto-portal collateral veins involving the paracholedochal and epicholedochal venous plexuses and cholecystic veins and ischemic insult due to deficient portal blood supply or prolonged compression by collaterals bring about biliary changes. While the former are reversible after porto-systemic shunt surgery, the latter are not. Majority of the patients with PCC are asymptomatic and approximately 21% are symptomatic. Symptoms in PCC could be in the form of long standing jaundice due to chronic cholestasis, or biliary pain with or without cholangitis due to biliary stones. Endoscopic retrograde cholangiography has no diagnostic role because it is invasive and is associated with risk of complications, hence it is reserved for therapeutic procedures. Magnetic resonance cholangiography and portovenography is a noninvasive and comprehensive imaging technique, and is the modality of choice for mapping of the biliary and vascular abnormalities in these patients. PCC is a progressive condition and symptoms develop late in the course of portal hypertension only in patients with severe or advanced changes of cholangiopathy. Asymptomatic patients with PCC do not require any treatment. Treatment of symptomatic PCC can be approached in a phased manner, coping first with biliary clearance by nasobiliary or biliary stent placement for acute cholangitis and endoscopic biliary sphincterotomy for biliary stone removal; second, with portal decompression by creating portosystemic shunt; and third, with persistent biliary obstruction by performing second-stage biliary drainage surgery such as hepaticojejunostomy or choledochoduodenostomy. Patients with symptomatic PCC have good prognosis after successful endoscopic biliary drainage and after successful shunt surgery.