Prognostic markers in hepatitis A-related pediatric acute liver failure and validation of the Peds-hepatitis A virus prognostic model.

OBJECTIVES: Hepatitis A virus (HAV) is the commonest cause for pediatric acute liver failure (PALF) in India. The objective of the study was to identify the predictors of mortality and to evaluate the utility of Peds-HAV model in a cohort of non-LT HAV-PALF. METHODS: The study included HAV-related PALF from two non-transplant centers. The predictors of outcome were identified by univariate analysis followed by Cox regression analysis. The prognostic accuracy of Peds-HAV model, King's College Hospital (KCH) criteria and pediatric end-stage liver disease score (PELD) were evaluated. RESULTS: As many as 140 children with PALF were included, of whom 96 (68.6%) children had HAV-PALF. On Cox regression analysis, international normalized ratio (INR) (p < 0.001), jaundice to encephalopathy (JE) interval (p < 0.001) and hepatic encephalopathy (HE) grade 3/4 (p = 0.01) were independent predictors of mortality. The mortality rates were 0% (0/42), 14.3% (3/21), 60% (9/15) and 94.4% (17/18) when none, 1, 2 or 3 criteria of the Peds-HAV were met, respectively. Peds-HAV model at a listing cut-off of  ≥ 2 criteria predicted death with 89.7% sensitivity and 89.6% specificity. In contrast, KCH criteria had a lower sensitivity of 62.1%. PELD score had a sensitivity of 89.7% and specificity of 85.1% at a cut-off of 30. The overall prognostic accuracy of Peds-HAV model (89.6%) was higher than those of KCH (83.3%) and PELD (86.5%). CONCLUSION: INR, HE grade and JE interval were independent predictors of mortality. The study provides an external validation of Peds-HAV model as a prognostic score in HAV-PALF. CLINICAL TRIAL REGISTRY NUMBER: Not applicable as this is a retrospective study.

Size and Number of Gastric Varices Decide Amount of Glue Injected during Endoscopic Therapy.

INTRODUCTION: Cyanoacrylate glue injection has become standard of care for acutely bleeding as well as for primary and secondary prophylaxis of high risk gastric varices. There is limited data on safe and effective amount of glue injected. Our study was aimed to fulfill the gap. MATERIALS: It was retrospective analysis of endoscopy laboratory chart, videos and corresponding case sheets of all consecutive endoscopies January to September 2022. Number, type and size of gastric varices, amount of glue injected and outcomes (technical success, intra procedural and post-procedural complications) were noted. RESULT: Among 337 upper gastrointestinal endoscopies performed during the study period, 12 patients had gastric varices. 3 had GOV1F1, 2 had GOV1F2, 8 had GOV2F2, 1 had GOV2F3 and one had isolated gastric varices, IGV2F1. 4 patients had history of upper GI bleed. 3 had one, 4 had two and 3 had three varices. 3 patients had <0.5 cm and 8 had >0.5 cm size varices. Cyanoacrylate glue was injected in 4 patients. Technical success was achieved in all (100%) patients. The amount of Cyanoacrylate glue injected was decided by the size and number of varices and varied between 1-4 ml depending on the above factors. Two patients had intra-procedural, self subsiding bleeding, one patient had severe abdominal pain needing intramuscular analgesic. None had fatal complication. CONCLUSION: Size and numbers of gastric varices are deciding factors for amount of glue injected during endotherapy. References Kumar A, Singh S, Madan K, et al. Undiluted N-butyl cyanoacrylate is safe and effective for gastric variceal bleeding. Gastrointest Endosc 2010;72(4):721-727. Saraswat VA, Verma A. Gluing gastric varices in 2012: lessons learnt over 25 years. J Clin Exp Hepatol 2012;2(1):55-69.

Serum kallistatin as a marker of severity of liver fibrosis in cirrhosis: A cross-sectional observational study.

Background: Liver cirrhosis is among the leading causes of morbidity and mortality worldwide. Although liver biopsy is the gold standard for the assessment of liver fibrosis in cirrhosis, it has its own limitations. Therefore, noninvasive methods to detect liver fibrosis are widely preferred. However, they also have their own limitations. Thus, there is always a need to extend the battery of serum-based assays. Kallistatin is a protein synthesized primarily in the liver. As it is a negative acute-phase protein, its blood level decreases with a decline in liver function. In our study, we explored the relationship between serum kallistatin and radiological evidence of liver fibrosis by transient elastography to determine if kallistatin levels can be used as a diagnostic marker of liver fibrosis. Materials and Methods: A cross-sectional study of 1-year duration was conducted at a leading tertiary care hospital in northern India. Patients between 15 and 75 years of age having evidence of chronic liver disease were enrolled. All enrolled patients were evaluated by detailed history, physical examination, and relevant investigations. Serum kallistatin levels were quantified using the ELISA method. Grading of liver fibrosis was done using transient elastography. A FibroScan scoring card was used to convert FibroScan results measured in kPa into the Metavir scale F1-F4. Results: A total of 128 subjects, including 64 patients with cirrhosis and 64 healthy controls, were enrolled. Our study suggested that FibroScan values were significantly higher in cases as compared to controls. The kallistatin level of cases was significantly lower than that of controls. An inverse correlation was found between FibroScan value and kallistatin level among cases. Conclusion: We conclude that serum kallistatin levels are low in patients with liver fibrosis and can be used as a potential marker of liver fibrosis.

A comparative study of novel fibrosis index and transient elastography for predicting fibrosis in patients of chronic liver disease.

Progressive deterioration of liver functions for more than 6 months is considered Chronic liver disease (CLD). Hepatic fibrosis occurs in response to chronic liver injury. The gold standard for assessment of hepatic fibrosis is Liver biopsy, which is an invasive and painful procedure. and rarely can pass on potential life-threatening complications. Thus non-invasive tests that can correctly indicate the severity of liver fibrosis is essential. A number of non-invasive markers have been developed which are useful supplements to assess stages of fibrosis. These are biomarkers (aspartate transaminase (AST) to alanine transaminase (ALT) ratio (AAR), AST to Platelet Ratio Index (APRI), fibrosis index (FI), fibrosis-4 (FIB-4), Age Platelet Index (API), Pohl score, Fibrosis Cirrhosis Index (FCI)) and transient elastography. In our study, we will compare Novel Fibrosis Index (NFI) with other available noninvasive serum indices and transient elastography in predicting Liver Fibrosis Stages. NFI=[(bilirubin×(ALP)2)/ (platelet count (albumin)2)]-n, where n=2000 is a constant. MATERIAL: In this study, a total of 142 cases of confirmed Chronic liver disease were included. All the patients underwent transient elastography and routine hematological and biochemical investigations. Fibrosis staging was done according to Metavir staging (F0-F4) using the fibroscan score. Then the serum indices for predicting liver fibrosis were calculated and compared for various fibrosis stages with Novel Fibrosis index. OBSERVATION: Out of 142 patients, the majority of the patients belonged to age above 40 years and were males(65%). The majority of the patients belonged to F4 fibrosis stage(77.4%) and the most common etiology of Chronic liver disease was Viral hepatitis(47%), the most common being Hepatitis B.The optimum cutoff of NFI for F4 stage was ≥6670 with a sensitivity of 75.8% and specificity of 81.8%. The optimum cutoff of NFI for F3 stage was ≥2112 with a sensitivity of 63.6% and specificity of 72.7%.%. The optimum cutoff of NFI for F2 stage was ≥1334 with a sensitivity of 100% and specificity of 5.3%.The NFI had maximum area under the curve compared to other indices in predicting F2,F3 and F4 stage. CONCLUSION: NFI was the best index in predicting various fibrosis stages in chronic liver disease patients compared to other available serum indices and had maximum accuracy in predicting F4 stage.

Tinospora Cordifolia (Giloy)-Induced Liver Injury During the COVID-19 Pandemic-Multicenter Nationwide Study From India.

Tinospora cordifolia (Giloy) is an herbal supplement commonly used in the Indian alternative medicine system Ayurveda. This herb has been promoted to the public in India as an immune booster to prevent novel coronavirus disease 2019. However, small reports have recently shown an association between Giloy use and the development of herb-induced liver injury (HILI) with autoimmune features in some patients. This large retrospective Indian multicenter study spanning 13 centers at nine locations was designed to identify features and outcomes of HILI temporally associated with Giloy use. Chemical and toxicological analyses of retrieved Giloy samples using state-of-the-art methods were also performed. We report 43 patients, of whom more than half were female, with a median time from initial Giloy consumption to symptom onset of 46 days. Patients presented with acute hepatitis, acute worsening of chronic liver disease (CLD, the most common clinical presentation), or acute liver failure. Causality assessment revealed probable liver injury in 67.4%. The most common autoantibody detected was anti-nuclear antibody. Liver biopsy in a subset revealed HILI associated with autoimmune features and hepatocyte and canalicular cholestasis and neutrophilic and eosinophilic infiltration. Conclusion: Giloy is associated with acute hepatitis with autoimmune features and can unmask autoimmune hepatitis (AIH) in people with silent AIH-related CLD. Further studies on the safety (and efficacy) of untested but heavily promoted herbals in alternative systems of medicine are an unmet need in the interests of public health and are especially important during this global health emergency.

Fulminant acute fatty liver of pregnancy presenting with multi-organ failure: A case series.

Liver disease in pregnancy can be classified into pregnancy-related, liver disease coincident with pregnancy or preexisting liver disease. Acute fatty liver of pregnancy (AFLP) is a rare liver disorder that is caused by defects in mitochondrial beta (ß) oxidation of fatty acids. In view of its fulminant presentation and rapid progression to multiple organ failure (MOF), AFLP carries high maternal and fetal mortality. These patients are commonly present in the third trimester of pregnancy with gastrointestinal symptoms and complications such as hypoglycemia, lactic acidosis, hyperammonemia, leukocytosis, liver dysfunction, coagulopathy, and renal dysfunction. Diagnosis is mostly based on the Swansea diagnostic criteria and by excluding other etiologies of liver dysfunction. Liver biopsy is rarely performed owing to underlying coagulopathy and thrombocytopenia. In this case series, we intend to share our experience of managing four cases of AFLP that were admitted to the intensive care unit with fetal demise and MOF.

Previous history of surgery in females and roadside shaving in males are the commonest risk factors for hepatitis C infection: A cross-sectional retrospective study.

BACKGROUND AND OBJECTIVES: Hepatitis C virus (HCV) is a causative agent of hepatitis C disease of the liver. We have analysed the major risk factors including demographic, clinical and genotypic distribution among HCV seropositive patients and their distribution in Uttar Pradesh, India. METHODS: This study was conducted by a questionnaire-based proforma, filled in Hepatobiliary Clinic, Department of Medicine, King Georg's Medical University, Lucknow, from 2014 to 2017. Demographic, clinical and laboratory data were recorded. Seropositivity was demonstrated through an anti-HCV IgG ELISA kit. Positive patients were further examined for HCV RNA by RT-PCR. RESULTS: A total of 31,440 patients attended the hepatobiliary clinic. Among these, 310 (0.99%) patients were confirmed for HCV infection and there was no significant difference between males and females (50.3% vs. 49.7%). Previous surgery (49.0%), dental extraction (41.0%) and roadside shaving (38.1%) were the major risk factors for HCV infection. We also observed that previous surgery 143/154 (92.9%) in female and roadside shaving 118/156 (75.6%) in male was the commonest factor for HCV, however; dental extraction was comparable among male and female (65 [51.8%] vs 62 [48.2%], P value = 0.818). HCV RNA genotype 3 (81.6%) was the most frequent followed by 3a (11.3%), 3b (5.8%), 1 (0.7%) and 4 (0.7%). In the district-wise analysis, frequent cases were included from Lucknow with previous surgery and dental extraction as the commonest risk factor. INTERPRETATION AND CONCLUSIONS: Previous surgery among female and roadside shaving among males are the commonest risk factors for HCV. This study suggests a powerful and strict guideline, to avoid HCV infection.