UNASSIGNED: Severe alcoholic hepatitis (SAH) is a grave condition, and the presence of acute kidney injury (AKI) further jeopardizes patient survival. However, the impact of AKI on survival in SAH has not been assessed from this region of Asia.
UNASSIGNED: This study was conducted on consecutive alcohol-associated liver disease (ALD) patients hospitalized in Gastroenterology Department, SCB Medical College, Cuttack, India, between October 2016 and December 2018. On diagnosis of SAH (mDF score ≥32), demographic, clinical, and laboratory parameters were recorded, and survival was compared between patients with and without AKI (AKIN criteria). In addition, survival was compared among SAH patients defined by other criteria and prognostic models in the presence and absence of AKI.
UNASSIGNED: 309 (70.71%) of ALD patients had SAH, and 201 (65%) of them had AKI. SAH patients with AKI had higher total leucocyte count, total bilirubin, serum creatinine, serum urea, INR, MELD (UNOS), MELD (Na+), CTP score, mDF score, Glasgow score, ABIC score, and increased prevalence of acute on chronic liver failure (ACLF) as per EASL-CLIF Consortium criteria (P < 0.001). Further, they had prolonged hospital stay, and increased death during hospitalization, at 28 days as well as 90 days (P < 0.001). Significant differences in survival were also seen in SAH (as per MELD, ABIC, and GAHS criteria) patients above the marked cut offs in respect to AKI.
UNASSIGNED: Over two-thirds of ALD patients had SAH, and about two-thirds had AKI. Patients with SAH and AKI had an increased prevalence of ACLF, longer hospital stay, and increased mortality during hospitalization at 28 days and 90 days.
UNASSIGNED: SAH is a critical condition, and the presence of AKI negatively affects their survival. Hence, early identification of SAH and AKI, as well as early initiation of treatment, is crucial for better survival. Our study from the coastal part of eastern India is the first to demonstrate the prevalence of SAH among patients with ALD along with the prevalence of AKI among SAH patients in this region. This knowledge will be helpful in managing these patients from this region of world.

Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease.

UNASSIGNED: Development of sepsis is a major contributor to poor outcomes after liver transplant. The neutrophil-lymphocyte ratio (NLR) is an easily calculable inflammatory biomarker. We aim to utilize NLR to diagnose and predict the onset of sepsis in patients undergoing living donor liver transplants (LDLT).
UNASSIGNED: Analysis of the perioperative course of 314 consecutive adult patients who underwent elective ABO compatible LDLT was done. Patients were divided into two cohorts; those who developed sepsis and a control group. Sepsis was defined by the combination of SIRS and clinical/radiological suspicion of infection. NLR was calculated by dividing the percentage of neutrophils by the percentage of lymphocytes in peripheral blood.
UNASSIGNED: ostoperatively, 127 out of 314 patients (40.5%) having at least one episode of sepsis were included in the septic cohort and were compared to the 187 (59.5%) patients in the control group. Demographic and baseline characteristics, including NLR (13.74 ± 0.99 vs. 12.65 ± 0.57, P = 0.294) were comparable preoperatively. The NLR of the septic cohort was significantly higher than the control cohort (15.01 ± 1.67 vs. 9.98 ± 0.63, P = 0.001) 3 days prior to sepsis and remained significantly higher till the day of sepsis. The area under the cover was maximum for NLR 1 day prior to the development of sepsis (r = 0.707) with a sensitivity, specificity, positive predictive value, and negative predictive value of 62.4%, 62.2%, 51.4%, and 72.0%, respectively, at a cutoff of 8.5.
UNASSIGNED: NLR is a useful tool in diagnosing and pre-empting development of sepsis in LDLT.

Coronavirus disease is caused by the SARS-CoV-2 virus. The virus first appeared in Wuhan (China) in December 2019 and has spread globally. Till now, it affected 269 million people with 5.3 million deaths in 224 countries and territories. With the emergence of variants like Omicron, the COVID-19 cases grew exponentially, with thousands of deaths. The general symptoms of COVID-19 include fever, sore throat, cough, lung infections, and, in severe cases, acute respiratory distress syndrome, sepsis, and death. SARS-CoV-2 predominantly affects the lung, but it can also affect other organs such as the brain, heart, and gastrointestinal system. It is observed that 75 % of hospitalized COVID-19 patients have at least one COVID-19 associated comorbidity. The most common reported comorbidities are hypertension, NDs, diabetes, cancer, endothelial dysfunction, and CVDs. Moreover, older and pre-existing polypharmacy patients have worsened COVID-19 associated complications. SARS-CoV-2 also results in the hypercoagulability issues like gangrene, stroke, pulmonary embolism, and other associated complications. This review aims to provide the latest information on the impact of the COVID-19 on pre-existing comorbidities such as CVDs, NDs, COPD, and other complications. This review will help us to understand the current scenario of COVID-19 and comorbidities; thus, it will play an important role in the management and decision-making efforts to tackle such complications.

BACKGROUND: Single-session endoscopic stone extraction (ESE) and laparoscopic cholecystectomy (LC) has the best outcome in managing concomitant cholelithiasis (gallstone disease [GSD]) and choledocholithiasis (common bile duct stone [CBDS]). Traditional rendezvous technique with an intraoperative cholangiogram is associated with various technical (bowel distention, frozen Calot\'s triangle, limitation of intraoperative cholangiogram and so on) and logistical difficulties (lack of trained personnel and equipment for ESE in the operating room). We modified our approach of ESE-LC (tandem ESE-LC) to study the safety of the approach and overcome these disadvantages of the traditional rendezvous approach.
METHODS: A prospective study of patients with GSD and suspected CBDS from January 2017 to December 2019 was conducted. Tandem ESE-LC involves ESE and LC under the same general anaesthesia in a single day, while ESE is performed in the endoscopic suite using carbon dioxide insufflation, a balloon/basket was used for achieving bile duct clearance and the same was confirmed with an occlusion cholangiogram. Patients were then shifted to the operating room for LC. The primary outcome included bile duct clearance and safety of the procedure.
RESULTS: Of 56 patients assessed for eligibility, 42 were included in the study (median age: 53 years, 25 [60%] women). Biliary colic was the most common presenting symptom (n = 24, 57%), followed by acute cholecystitis (n = 11, 26%). The median number of stones and stone size was 1 (1-6) and 4 mm (3-10), respectively. All patients had successful bile duct clearance. Stenting was performed in 5 (12%) patients. Intraoperatively, Calot\'s dissection was difficult and frozen in 10 and 11 patients respectively. The cystic duct was short and wide in 13 (31%) patients. Subtotal cholecystectomy was performed in 6 (14%) patients. The median duration of postprocedural hospital stay was 1 (0-13) day. Three patients had tandem ESE-LC on a day-care basis. One patient had post-endoscopic retrograde cholangiopancretography pancreatitis, and another required percutaneous drainage for gall bladder fossa collection. No patient had retained CBDS at a median follow-up of 18 (3-28) months.
CONCLUSIONS: Tandem ESE-LC is safe and effective method in managing concomitant GSD and CBDS.

BACKGROUND: Gastrointestinal candidiasis is often neglected and potentially serious infection in cirrhosis patients. Therefore, we evaluated the prevalence, risk factors, and outcomes of esophageal candidiasis (EC) in cirrhotics and did a systematic review to summarize EC\'s available evidence in cirrhosis.
METHODS: Consecutive patients with cirrhosis posted for esophagogastroduodenoscopy (EGD) at a tertiary care institute were screened for EC (cases) between January 2019 and March 2020. EC was diagnosed on EGD findings and/or brush cytology. Controls (without EC) were recruited randomly, and EC\'s risk factors and outcomes were compared between cases and controls.Four electronic databases were searched for studies describing EC in cirrhosis. Prevalence estimates of EC were pooled on random-effects meta-analysis, and heterogeneity was assessed by I2. A checklist for prevalence studies was used to evaluate the risk of bias in studies.
RESULTS: EC was diagnosed in 100 of 2762 patients with cirrhosis (3.6%). Patients with EC had a higher model for end-stage liver disease (MELD) (12.4 vs. 11.2; P = 0.007), acute-on-chronic liver failure (ACLF) (26% vs. 10%; P = 0.003) and concomitant bacterial infections (24% vs. 7%; P = 0.001), as compared with controls. A multivariable model, including recent alcohol binge, hepatocellular carcinoma (HCC), upper gastrointestinal (UGI) bleed, ACLF, diabetes, and MELD, predicted EC\'s development in cirrhosis with excellent discrimination (C-index: 0.918). Six percent of cases developed the invasive disease and worsened with multiorgan failures, and four patients with EC died on follow-up.Of 236 articles identified, EC\'s pooled prevalence from 8 studies (all with low-risk of bias) was 2.1% (95% CI: 0.8-5.8). Risk factors and outcomes of EC in cirrhosis were not reported in the literature.
CONCLUSIONS: EC is not a rare infection in cirrhosis patients, and it may predispose to invasive candidiasis and untimely deaths. Alcohol binge, HCC, UGI bleed, ACLF, diabetes, and higher MELD are the independent predictors of EC in cirrhosis. At-risk patients with cirrhosis or those with deglutition symptoms should be rapidly screened and treated for EC.

We sought to validate the Society for Cardiovascular Angiography and Interventions (SCAI) cardiogenic shock classification for mortality risk stratification in patients with sepsis and concomitant cardiovascular disease or mixed septic-cardiogenic shock. We conducted a single-center retropective cohort study of cardiac intensive care unit patients with an admission diagnosis of sepsis. We used clinical, vital sign, and laboratory data during the first 24 hours after admission to assign SCAI shock stage. We included 605 patients with a median age of 69.4 years (interquartile range, 57.9 to 79.8 years), 222 of whom (36.7%) were female. Acute coronary syndrome or heart failure was present in 480 patients (79.3%), and cardiogenic shock or cardiac arrest was present in 271 patients (44.8%). The median day 1 Sequential Organ Failure Assessment (SOFA) cardiovascular subscore was 1.5 (interquartile range, 1 to 4), and the admission SCAI shock stage distribution was stage B, 40.7% (246); stage C, 19.3% (117); stage D, 32.9% (199); and stage E, 7.1% (43). In-hospital mortality occurred in 177 of the 605 patients (29.3%) and increased incrementally with higher SCAI shock stage. After multivariable adjustment, admission SCAI shock stage was associated with in-hospital mortality (adjusted odds ratio per stage, 1.46; 95% CI, 1.14 to 1.88; P=.003). Admission SCAI shock stage had higher discrimination for in-hospital mortality than the day 1 SOFA cardiovascular subscore (area under the receiver operating characteristic curve, 0.68 vs 0.64; P=.04 by the DeLong test). Admission SCAI shock stage was associated with 1-year mortality (adjusted hazard ratio per stage, 1.19; 95% CI, 1.03 to 1.37; P=.02). The SCAI shock classification provides improved mortality risk stratification over the day 1 SOFA cardiovascular subscore in cardiac intensive care unit patients with sepsis and concomitant cardiovascular disease or mixed septic-cardiogenic shock.

UNASSIGNED: Spontaneous bacterial peritonitis (SBP) remains a major complication of cirrhosis. However, the incidence and the real impact of SBP in determining patient survival rates remain unclear. This study aims to evaluate the incidence and risk factors for SBP development and the role of SBP in predicting transplant-free survival.
UNASSIGNED: Two hundred two consecutive patients underwent 492 paracenteses with biochemical and microbiological analysis of the ascitic fluid. When multiple paracenteses had been performed on a given patient, the first SBP-positive paracentesis or the first paracentesis conducted when none was diagnostic for SBP was included in the study.
UNASSIGNED: SBP was detected in 28 of 202 (13.9%) patients; in 26 of 28 patients, the neutrophil count in the ascitic fluid was ≥250 cells/μl, and in 15 of 28 patients, the cultures were positive. Variables independently associated with SBP were as follows: a higher model of end-stage liver disease (MELD) score, the serum glucose value, elevated CRP serum levels, and higher potassium serum levels. Overall, the median (range) transplant-free survival was 289 (54-1253) days. One hundred (49.5%) patients died, whereas 35 patients (17.3%) underwent liver transplantation. Independent predictors of death or liver transplantation were a higher MELD score and the development of SBP, especially if it was antibiotic-resistant or recurrent SBP.
UNASSIGNED: The occurrence of SBP is associated with more severe liver dysfunction in conjunction with the presence of inflammation. Unlike the occurrence of SBP per se, failure of first-line antibiotic treatment and SBP recurrence appear to strongly influence the mortality rate.

Accidental or suicidal poisoning with yellow phosphorus or metal phosphides (YPMP) such as aluminum (AlP) zinc phosphide (Zn3P2) commonly cause acute liver failure (ALF) and cardiotoxicity. These are used as household, agricultural and industrial rodenticides and in production of ammunitions, firecrackers and fertilizers. In absence of a clinically available laboratory test for diagnosis or toxin measurement or an antidote, managing their poisoning is challenging even at a tertiary care center with a dedicated liver intensive care unit (LICU) and liver transplant facility.
METHODS: Patients with YPMP related ALF were monitored using standardized clinical, hemodynamic, biochemical, metabolic, neurological, electrocardiography (ECG) and SOFA score and managed using uniform intensive care, treatment and transplant protocols in LICU. Socio-demographic characteristics, clinical and biochemical parameters and scores were summarized and compared between 3 groups i.e. spontaneous survivors, transplanted patients and non-survivors. Predictors of spontaneous survival and the need for liver transplant are also evaluated.
RESULTS: Nineteen patients with YPMP related ALF were about 32 years old (63.2% females) and presented to us at a median of 3 (0 - 10) days after poisoning. YPMP related cardiotoxicity was rapidly progressive and fatal whereas liver transplant was therapeutic for ALF. Spontaneous survivors had lower dose ingestion (<17.5 grams), absence of cardiotoxicity, < grade 3 HE, lactate < 5.8, SOFA score < 14.5, and increase in SOFA score by < 5.5. Patients with renal failure need for CVVHDF and KCC positivity on account of PT-INR > 6.5 had higher mortality risk. Patients undergoing liver transplant and with spontaneous recovery required longer ICU and hospital stay. At median follow-up of 3.4 (2.6 - 5.5) years, all spontaneous survivors and transplanted patients are well with normal liver function.
CONCLUSIONS: Early transfer to a specialized center, pre-emptive close monitoring, and intensive care and organ support with ventilation, CVVHDF, plasmapheresis and others may maximize their chances of spontaneous recovery, allow accurate prognostication and a timely liver transplant.

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.