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.

Obstructive Jaundice with skin involvement - An unusual presentation of Myeloid Sarcoma.

Biliary obstruction secondary to malignancy is a common clinical problem. Rarely, biliary obstruction is due to leukemia, and obstructive jaundice in these patients usually presents late in the course of the disease. We present a rare case of a patient who presented with fever, jaundice, and pruritus with multiple nodular swellings in the left shoulder, left thigh, and lower back. Magnetic resonance cholangiopancreatography (MRCP) revealed periampullary mass lesion causing dilated common bile duct (CBD) and intrahepatic bile ducts; hence, endoscopic retrograde cholangiography with plastic stenting was done. Biopsy from the shoulder lesion revealed a mesenchymal tumor, and immunohistochemistry (IHC) confirmed the lesion as myeloid sarcoma. Myeloid sarcoma is an extramedullary tumor, a subtype of acute myeloid leukemia, and presentation as biliary lesions with multiple anatomical sites is very rare. The patient was started on chemotherapy after the normalization of bilirubin. The patient showed improvement of skin lesions and normalization of liver function test (LFT) after 3 weeks of chemotherapy.

Evaluating the Association of Genetic Polymorphism of Cytochrome p450 (CYP2C9*3) in Gastric Cancer Using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).

Background and aim As a distinguished system, the cytochrome P450 (CYP) enzyme superfamily is involved in the biotransformation of several endogenous and exogenous substances including drugs, toxins, and carcinogens. Reports on the role of CYP enzyme in gastric cancer (GC) from the Eastern region of India are scarce. The present study aimed to evaluate the effect of single nucleotide polymorphisms (SNP) in cytochrome P450 family 2 subfamily C member 9 (CYP2C9*3) among cases with gastric malignancy. Material and methods The current study is a cross-sectional observational study carried out among 113 GC cases attending the Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India, and Srirama Chandra Bhanja Medical College and Hospital, Cuttack, India. Two ml of venous blood was collected from the confirmed cases of GC. The samples were subjected to genomic DNA isolation followed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (PCR-RFLP). Results The prevalence of both homozygous and heterozygous mutation in GC cases is 4% and 8%, respectively. The overall association of cytochrome P450 family 2 subfamily C member 9 (CYP2C9) mutation in GC cases is 12% whereas 88% were detected as wild/standard type. The mutation CYP2C9 SNP has been seen in Helicobacter pylori-infected cases and as well as those without H. pylori infection. Conclusions The CYP2C9*3 genetic polymorphism might play a significant role as a risk factor for the development of gastric malignancy irrespective of H. pylori infection, among the eastern Indian population.

Plasmalyte-A Based del Nido Cardioplegia Versus Plain Ringer Based del Nido Cardioplegia: Double-Blind Randomized Trial.

Background: In this prospective randomized controlled trial, we compared the standard del Nido cardioplegia solution (SDN) with the modified del Nido cardioplegia solution (MDN) in which the base solution was the plain Ringer solution. Methods: A total of 80 patients aged < 12 years undergoing intracardiac repair of Tetralogy of Fallot were randomized into SDN (n = 39) or MDN (n = 41) groups. The primary outcome was a change in cardiac index (CI). Secondary outcomes were ventricular arrhythmias after the release of aortic-cross clamp, postoperative inotropic score (IS), time to peripheral rewarming, duration of mechanical ventilation, intensive care unit (ICU) length of stay, and hospital length of stay, and electron microscopic differences between the 2 groups. Cardiac Troponin-I, inflammatory markers tumor necrosis factor-α (TNF-α), and interleukin-L (IL-6) were measured. Results: Applying the noninferiority confidence interval approach, the difference between the changes in CI between the 2 groups was -0.093 L/min/m2 (95% CI: -0.46-0.27 L/min/m2) which was within the noninferiority threshold of -0.5 indicating that CI was similar in both SDN and MDN. Ventricular arrhythmias postclamp release (P = .91), IS (P = .09), duration of mechanical ventilation (P = .27), ICU length of stay (P = .50), hospital length of stay (P = .57), IL-6 (P = .19), TNF-α (P = .17), Troponin-I (P = .15), electron microscopy changes (P > .05) were not different between groups. Conclusion: MDN was shown to be noninferior to the SDN cardioplegia in terms of preservation of cardiac index. In addition, other metrics indicative of myocardial protection were similar between groups. In developing nations where SDN is not available or is expensive, MDN cardioplegia is an acceptable alternative.

Management of Helicobacter pylori infection: The Bhubaneswar Consensus Report of the Indian Society of Gastroenterology.

The Indian Society of Gastroenterology (ISG) felt the need to organize a consensus on Helicobacter pylori (H. pylori) infection and to update the current management of H. pylori infection; hence, ISG constituted the ISG's Task Force on Helicobacter pylori. The Task Force on H. pylori undertook an exercise to produce consensus statements on H. pylori infection. Twenty-five experts from different parts of India, including gastroenterologists, pathologists, surgeons, epidemiologists, pediatricians, and microbiologists participated in the meeting. The participants were allocated to one of following sections for the meeting: Epidemiology of H. pylori infection in India and H. pylori associated conditions; diagnosis; treatment and retreatment; H. pylori and gastric cancer, and H. pylori prevention/public health. Each group reviewed all published literature on H. pylori infection with special reference to the Indian scenario and prepared appropriate statements on different aspects for voting and consensus development. This consensus, which was produced through a modified Delphi process including two rounds of face-to-face meetings, reflects our current understanding and recommendations for the diagnosis and management of H. pylori infection. These consensus should serve as a reference for not only guiding treatment of H. pylori infection but also to guide future research on the subject.

Tenofovir is Superior to Entecavir in Patients with Treatment-naïve Hepatitis B e-Antigen-Positive Chronic Hepatitis B.

BACKGROUND AND AIM: Chronic Hepatitis B (CHB) is a global health problem affecting around 400 million of people worldwide. Two available first-line antiviral drugs are tenofovir disoproxil fumarate (TDF) and Entecavir (ETV). Till date,there are few published reports from India comparing efficacy of TDF and ETV in CHB cases. Therefore, this present study was carried out with an aim to compare the efficacy of ETV and TDF in patients with nucleos(t)ide naïve CHB. MATERIALS AND METHODS: This retrospective cohort study was carried out in 192 treatment naïve CHB cases, who completed 24 months of treatment with either TDF or ETV between March 2015 and August 2017. The primary end point of the study was undetectable hepatitis B virus DNA after 24 months of therapy. RESULTS: Of total 192 patients with CHB, 38 hepatitis B e-antigen (HBeAg)-positive and 53 HBeAg-negative patients were treated with tenofovir, whereas 40 HBeAg-positive and 61 HBeAg-negative patients were treated with ETV. Pretreatment characteristics at baseline were not statistically different between the TDF and ETV groups. Patients treated with TDF achieved significantly higher complete viral suppression as compared with ETV-treated patients (Log rank: 7.04, P = 0.008) in HBeAg-positive CHB during the 24 months follow-up time; whereas no significant difference in viral suppression rate could be noticed in HBeAg-negative patients (Log rank: 0.98, P = 0.38). Both univariate and multivariate analysis by cox proportional hazard model confirmed that tenofovir had significant rate of complete viral suppression in comparison with ETV in HBeAg-positive patients (P < 0.05); whereas complete viral suppression rates were similar in HBeAg-negative patients. CONCLUSION: In our study, tenofovir had more effective antiviral suppressive effect compared with ETV in HBeAg-positive, nucleos(t)ide-naïve CHB cases.

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.

Flare of Autoimmune Hepatitis Causing Acute on Chronic Liver Failure: Diagnosis and Response to Corticosteroid Therapy.

Autoimmune hepatitis (AIH) is considered less common in the Asia Pacific region. Due to this, AIH flare as a cause of acute on chronic liver failure (ACLF) is often overlooked and treatment delayed. We aimed at the defining clinical and histopathological spectrum and role of steroid therapy in AIH-ACLF. Patients with AIH-ACLF, prospectively recruited and followed between 2012 and 2017, were analyzed from the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) data base. Diagnosis of AIH was confirmed using International Autoimmune Hepatitis Group score or simplified AIH score with histopathological evidence. Of 2,825 ACLF patients, 82 (2.9%) fulfilled criteria of AIH (age 42.1 ± 18.1 years, 70% female). At baseline, mean bilirubin was 18.6 ± 8.2 mg/dL, Child-Turcotte-Pugh score was 11.7 ± 1.4, and Model for End-Stage Liver Disease (MELD) score was 27.6 ± 6.5. Mean immunoglobulin G was 21.61 ± 7.32 g/dL, and this was elevated ≥1.1 times in 97% of cases; 49% were seronegative. Liver histology was available in 90%, with median histological activity index of 10 (interquartile range, 7-12); 90% with moderate to severe interface activity; 56% showing significant parenchymal necrosis (bridging and confluent necrosis); and cirrhosis in 42%. Twenty-eight (34%) patients received steroid therapy and showed shorter intensive care unit (ICU) stay (median 1.5 versus 4 days, P < 0.001) and improved 90-day survival (75% versus 48.1%, P = 0.02) with comparable incidence of sepsis (P = 0.32) compared to those who did not. Patients of advanced age, more severe liver disease (MELD >27; 83.3% sensitivity, 78.9% specificity, area under the receiver operating characteristic curve 0.86), presence of hepatic encephalopathy, and fibrosis grade ≥F3 had an unfavorable response to corticosteroid therapy. Conclusion: AIH presenting as ACLF is not uncommon in Asian patients; a low threshold for liver biopsy is needed to confirm the diagnosis as nearly half the patients are seronegative; early stratification to steroid therapy or liver transplantation (MELD >27, hepatic encephalopathy in ≥F3) would reduce ICU stay and improve outcomes.

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.

Comparison of levosimendan and nitroglycerine in patients undergoing coronary artery bypass graft surgery.

BACKGROUND: Levosimendan a calcium ion sensitizer improves both systolic and diastolic functions. This novel lusitropic drug has predictable antiischemic properties which are mediated via the opening of mitochondrial adenosine triphosphate-sensitive potassium channels. This action of levosimendan is beneficial in cardiac surgical patients as it improves myocardial contractility, decreases systemic vascular resistance (SVR), and increases cardiac index (CI) and is thought to be cardioprotective. We decided to study whether levosimendan has any impact on the outcomes such as the duration of ventilation, the length of Intensive Care Unit (ICU) stay, and the hospital stay when compared with the nitroglycerine (NTG), which is the current standard of care at our center. MATERIALS AND METHODS: Forty-seven patients undergoing elective coronary artery bypass surgery were randomly assigned to two groups receiving either levosimendan or NTG. The medications were started before starting surgery and continued until 24 h in the postoperative period. Baseline hemodynamic parameters were evaluated before beginning of the operation and then postoperatively at 3 different time intervals. N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) levels were also measured in both groups. RESULTS: In comparison to the NTG group, the duration of ventilation and length of ICU stay were significantly less in levosimendan group (P < 0.05, P = 0.02). NT-proBNP level analysis showed a slow rising pattern in both groups and a statistically significant rise in the levels was observed in NTG group (P = 0.03, P = 0.02) in postoperative period when compared to levosimendan group of patients. CONCLUSION: Levosimendan treatment in patients undergoing surgical revascularization resulted in improved CI, decreased SVR and lower heart rate. And, thereby the duration of ventilation and length of ICU stay were significantly less in this group of patients when compared with NTG group.

Nutcracker syndrome in a young female with solitary functional left ovary: a surgical challenge.

Nutcracker syndrome (NCS), a rare clinical entity, when refractory to medical management warrants surgical intervention. In the following discussion, we present a case of NCS which was managed successfully by left renal vein transposition using a decompression shunt.