Decentralised same day test and treatment of hepatitis C levering existing peer support networks among men who inject drugs: feasibility and effectiveness.

BACKGROUND: Prevalence of hepatitis C virus (HCV) infection among people who inject drugs in the state of Manipur, India, is 43%; however, access to care is poor. We piloted a Community-led and comprehensive hepatitis care model that included same-day HCV treatment at drug treatment centres. METHODS: Screening was conducted through venipuncture samples collected by community peer PWID, using HCV antibody (HCV Ab) rapid screening and hepatitis B virus (HBV) surface antigen (HBsAg) rapid diagnostic tests. Reactive HCV Ab samples were tested for HCV RNA using near point-of-care Truenat® HCV on Truelab® Quattro. Eligible HCV RNA-positive participants were treated on the same day using direct-acting antivirals and followed for sustained virologic response (SVR). HBsAg-negative participants received rapid HBV vaccination regimen while those positive for HBsAg were tested for DNA and referred for treatment. RESULTS: Between November 2021 and August 2022, 643 individuals were approached and 503 consented and were screened. All screened were males with history of injection drug use, and a median age of 27 years (IQR 23-32). Of the 241 (47.9%) HCV Ab reactive all underwent RNA testing and 156 (64.7%) were RNA detectable. Of those with viraemia, 155 (99.4%) were initiated on treatment with 153 (98.1%) on same day, with 2 (1.2%) HBsAg positive and waiting for HBV DNA results. Among those 153, median time from HCV Ab screening to treatment was 6 h 38 min (IQR 5 h 42 min-8 h 23 min). In total 155 (100%) completed HCV treatment, of those 148 (95.5%) completed SVR testing and 130 (87.8%) achieved SVR12. 27 (5%) participants were HBsAg-positive, 3 (11.1%) were also living with HCV viraemia; 443 (97.6%) were eligible for vaccination and 436 (98.4%) received all 3 vaccine doses. CONCLUSION: Community-led hepatitis care incorporating same day "test and treat" for HCV was feasible and effective. HBV screening identified a large proportion who were unvaccinated. Peer support extended resulted in ensuring compliance to care and treatment cascade and completing all the three doses of HBV vaccination. As the screening, diagnostics infrastructure and vaccine are available in most countries with national viral hepatitis programs also in place, our model can be adapted or replicated to progress towards global elimination targets.

Definitions, etiologies and outcomes of acute on chronic liver failure: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a major public health concern. We aimed to assess the definitions, etiological spectrum, organ failure (OF), and outcomes of ACLF globally. METHODS: Three databases were searched for studies on ACLF from 1990 till September 2022. Information regarding definitions, acute precipitants, underlying chronic liver disease (CLD), OF, and mortality were extracted. Meta-analyses were performed for pooled prevalence rates (95% confidence interval, CI) using random effects model for each definition of ACLF. RESULTS: Of the 11,451 studies identified, 114 articles (142 cohorts encompassing 210,239 patients) met the eligibility criteria. Most studies (53.2%) used the European Association for the Study of the Liver (EASL) definition, followed by Asia-Pacific Association for the Study of the Liver (APASL) (33.3%). Systemic infection was the major acute precipitant and alcohol use was the major cause of CLD in EASL-defined studies while alcohol was both, the major acute precipitant and cause of CLD in APASL-defined studies. Liver failure was the major OF in APASL-based studies, while renal failure was predominant in EASL-based studies. Thirty-day mortality varied across definitions: APASL: 38.9% [95%CI 31.2-46.9], EASL: 47.9% [95%CI 42.2-53.5] and NACSELD: 52.2% [95%CI 51.9-52.5]. Diagnostic overlap between definitions ranged from 7.7% to 80.2%. Meta-regression suggested that the WHO region influenced 30-day mortality in studies using EASL definition. CONCLUSION: Heterogeneity in the definition of ACLF proposed by different expert societies and regional preferences in its use result in differences in clinical phenotype and outcomes. A uniform definition would enhance the comparability and interpretation of global data.

Etiological Spectrum of Cirrhosis in India: A Systematic Review and Meta-analysis.

Background: Cirrhosis is a significant cause of morbidity and mortality globally and in India. This systematic review and meta-analysis aimed to ascertain the etiological spectrum and changing trends of cirrhosis in India. Methods: We searched electronic databases, including Pubmed/Medline, Scopus, and Embase. We included original studies that reported the etiology of cirrhosis in the Indian population. Results: We included 158 studies (adults: 147, children: 11). The overall pooled estimate of alcohol as a cause of cirrhosis in adults was 43.2% (95% confidence interval (CI) 39.8-46.6%; I2 = 97.8%), followed by nonalcoholic fatty liver disease (NAFLD)/cryptogenic in 14.4%, 95% CI (11.7-17.3%; I2 = 98.4%), hepatitis B virus (HBV) in 11.5%, 95% CI (9.8-13.3%; I2 = 96.6%), and hepatitis C virus (HCV) in 6.2%, 95% CI (4.8-7.8%; I2 = 97.2%) of the included patients. The most common cause of cirrhosis in all zones was alcohol-related. Comparison of etiologies over time revealed a reduction in the viral hepatitis-related and an increase in the proportion of alcohol-related and NAFLD/cryptogenic-related cirrhosis. The overall pooled estimates of various etiologies in children were: HBV in 10.7%, 95% CI (4.6-18.7%; I2 = 91.0%), NAFLD/Cryptogenic in 22.3%, 95% CI (9.0-39.2%; I2 = 96.7%), and HCV in 2.0%, 95% CI (0.0-8.5%; I2 = 94.6%). Conclusions: Alcohol is the most common etiology of cirrhosis in adults in India. The proportions of alcohol and NAFLD-related cirrhosis are increasing, and those of viral hepatitis-related cirrhosis are reducing. The results of our meta-analysis will help formulate health policies and the allocation of resources.

Sofosbuvir/Velpatasvir/Voxilaprevir for Hepatitis C Virus Retreatment in Difficult-to-treat Patients: A Real-life Observational Study from India.

Background and aim: Hepatitis C virus (HCV) treatment fails to achieve sustained virological response at 12 weeks (SVR12) in 5-10 % and requires retreatment with second-line drugs. We report our experience of sofosbuvir/velpatasvir/voxilaprevir use for HCV retreatment in a small cohort of difficult-to-treat Indian patients. Methods: We reviewed our HCV databases to identify the patients who had failed to achieve SVR12 after treatment with sofosbuvir in combination with either daclatasvir, ledipasvir, or velpatasvir with/without ribavirin on one or more occasions. Participants were excluded if they had (i) decompensated cirrhosis, (ii) HIV coinfection or (iii) chronic kidney disease, or (iv) prior organ transplantation. All the participants were treated with sofosbuvir/velpatasvir/voxilaprevir plus ribavirin for 12 weeks. Treatment outcome was categorized as successful or failure if HCV RNA was undetectable or detectable at SVR12, respectively. Results: Fifteen patients (male 67 %; genotype-3 80 %) were included in the analysis. Ten (67 %) had cirrhosis. Five, eight, and two participants had previously failed one, two, and three courses of pegylated-interferon free, sofosbuvir containing direct acting antiviral (DAA) regimens respectively. Fourteen participants had failed to at least one course of the sofosbuvir/velpatasvir combination. Fourteen patients achieved SVR12, and one patient was lost to follow-up. Treatment was successful in 100 % and 93.3 % of per-protocol (PP) and intention to treat (ITT) analyses, respectively. Conclusion: Sofosbuvir/velpatasvir/voxilaprevir combination is an effective second-line therapy in India for difficult-to-treat HCV patients.

Humoral and cellular immune response in patients of liver cirrhosis and immunocompetent recipient of ChAdOx1nCoV-19 Vaccine (Covishield).

Despite the effectiveness of COVID-19 vaccination in reducing the severity of the disease, the demand for booster is increasing in vulnerable populations like elderly and immunocompromised individuals especially with each new wave of COVID-19 in different countries. There is limited data on the sustained immunity against COVID-19 in patients with liver cirrhosis. The study was aimed to compare the T cell and humoral immune response after 1 year of ChAdOx1nCoV-19 Vaccine in patients with liver cirrhosis and healthy health care workers (HCW). This was a prospective observational study including 36 HCW, 19 liver cirrhosis patients and 10 unvaccinated individuals. Anti-SARS-CoV-2S antibody, neutralizing antibody and memory T cell subsets were evaluated by ELISA and flow cytometry, respectively, in all three groups after 1 year of initial vaccination. Compared to HCW and unvaccinated individuals, liver cirrhosis patients had significantly depleted T cells, although CD4:CD8 + T cell ratio was normal. Both cirrhotic patients and HCW developed memory T cell subset [effector memory RA (P = 0.141, P < 0.001), effector memory (P < 0.001, P < 0.001), central memory (P < 0.001, P < 0.01), stem cell memory (P = 0.009, P = 0.08) and naïve (P < 0.001, P = 0.02)] compared to unvaccinated unexposed individuals of CD4 + T and CD8 + T, respectively. However, among HCW and cirrhotic group no difference was noted on central memory and stem cell memory cells on T cells. Patients with liver cirrhosis developed comparable memory T cells after vaccination which can evoke sustainable immune response on reinfection. Therefore, additional vaccine doses may not be necessary for cirrhosis patients.

The metabolic fingerprint of chronic hepatitis C progression: Metabolome shifts and cutting-edge diagnostic options.

Hepatitis C virus infection causes chronic diseases such as cirrhosis and hepatocellular carcinoma. Metabolomics research has been shown to be linked to pathophysiologic pathways in liver illnesses. The aim of this study was to investigate the serum metabolic profile of patients with chronic hepatitis C (CHC) infection and to identify underlying mechanisms as well as potential biomarkers associated with the disease. Nuclear magnetic resonance (NMR) was used to evaluate the sera of 83 patients with CHC virus and 52 healthy control volunteers (NMR). Then, multivariate statistical analysis was used to find distinguishing metabolites between the two groups. Sixteen out of 40 metabolites including include 3-HB, betaine, carnitine, creatinine, fucose, glutamine, glycerol, isopropanol, lysine, mannose, methanol, methionine, ornithine, proline, serine, and valine-were shown to be significantly different between the CHC and normal control (NC) groups (variable importance in projection >1 and p < 0.05). All the metabolic perturbations in this disease are associated with pathways of Glycine, serine, and threonine metabolism, glycerolipid metabolism, arginine and proline metabolism, aminoacyl-tRNA biosynthesis, cysteine and methionine metabolism, alanine, aspartate, and glutamate metabolism. Multivariate statistical analysis constructed using these expressed metabolites showed CHC patients can be discriminated from NCs with high sensitivity (90%) and specificity (99%). The metabolomics approach may expand the diagnostic armamentarium for patients with CHC while contributing to a comprehensive understanding of disease mechanisms.

Comparison between presepsin, procalcitonin, and CRP as biomarkers to diagnose sepsis in critically ill patients.

Background and Aims: Mortality associated with sepsis continues to remain high. Early diagnosis and aggressive management may improve outcomes. Biomarkers may help in early diagnosis, but the search for an ideal biomarker continues. Presepsin has been introduced as a new biomarker, however, it still needs validation before its use becomes routine. In this study, we aimed to compare the efficacy of various biomarkers in patients with suspected sepsis. Material and Methods: A retrospective analysis of 100 patients with suspected infection, admitted in the medical intensive care unit (ICU) was conducted. Diagnosis of sepsis was made on the basis of the current surviving sepsis guidelines criteria. Results: Out of 100 patients, 70 were diagnosed to have sepsis, and overall ICU mortality was 22%. Overall, C-reactive protein (CRP) was positive in 98, procalcitonin in 75, and presepsin in 64 patients. For diagnosis of sepsis the sensitivity, specificity, and AUC, respectively, for CRP was 98.6%, 3.3%, and 0.725. For procalcitonin (>0.5 ng/ml) it was 87.1%, 53.3%, and 0.776, and for procalcitonin (>1 ng/ml) 70%, 70%, and 0.816, respectively. For presepsin sensitivity, specificity, and AUC, respectively, for diagnosis of sepsis was 77.1%, 66.7%, and 0.734. For ICU mortality, sensitivity and specificity for CRP was 95.5% and 1.3%, for procalcitonin (>0.5) 72.7% and 24.4.%, for procalcitonin (>1) 59.1% and 42.3%, and for presepsin 61.5% and 27.3%, respectively. Conclusion: Inflammatory markers may be raised in a large proportion of ICU patients, even in those without sepsis. Procalcitnonin and presepsin had similar efficacy in diagnosing sepsis. However, none of the three biomarkers studied were accurate in predicting ICU mortality.

Acute myocardial infarction complicating acute ulcerative colitis: A clinical conundrum.

Inflammatory bowel disease (IBD) is an immune-mediated multisystem inflammatory disease that primarily affects the gastrointestinal tract, but it also has various extraintestinal manifestations like cardiovascular, dermatological, musculoskeletal, or hepatobiliary tract involvement. Herein, we describe a case of a 46-year-old female, who presented with acute coronary syndrome on the background of acute relapse of ulcerative colitis (UC), requiring a pragmatic clinical approach due to a labile balance between hemorrhagic and ischemic risk.

Hepatitis C Retreatment With First-Line Direct Acting Antiviral Drugs.

Background and Aims: Sofosbuvir (S), daclatasvir (D), ledipasvir, or velpatasvir (V) containing first-line hepatitis C virus (HCV) treatment regimens fail to cure viremia in 5-10%. We report our experience of HCV retreatment using these first-line drugs, in a setting where second-line anti-HCV drugs are not available. Methods: Adults, who had relapsed after first complete course of a sofosbuvir-containing first-line, pegylated interferon free, anti-HCV treatment regimen with or without ribavirin (Riba) were included. Retreatment regimen, tailored to the failed anti-HCV regimen, was based on principle of using first-line drugs for 24 weeks with ribavirin and swapping between pangenotypic and genotype-specific regimens. Retreatment outcome was categorized as successful (achieved undetectable HCV RNA at the end of treatment [ETR] and sustained viral response at week 12 [SVR12]), non-responder (failed to achieve ETR), or relapse (achieved ETR but not achieved SVR12). Results: Twelve patients (9 male; 7 cirrhosis; all genotype 3) who had relapsed to prior anti-HCV treatment (4 SD12, 4 SD24, 1 SDRiba12, 1 SDRiba24, 2 SV12) were included. Following retreatment (2 SDRiba24, 10 SVRiba24), all achieved ETR but only 9 (75%) achieved SVR12. Two among three, in whom retreatment failed, achieved SVR12 following another course of sofosbuvir/velpatasvir/ribavirin for 24 weeks. Overall, 11/12 (92%) patients achieved SVR12 following retreatment with the first-line anti-HCV drugs. Conclusion: HCV retreatment could be a treatment option if second-line anti-HCV drugs are not available. Successful retreatment could be achieved, in a large proportion, with the use of first-line drugs for 24 weeks with ribavirin and swapping of pangenotypic/genotype-specific regimens (NCT03483987).

Dysregulated metabolites and lipids in serum of patients with acute hepatitis E: A longitudinal study.

Hepatitis E is a disease associated with acute inflammation of the liver. It is related to several dysregulated metabolic pathways and alterations in the concentration of several metabolites. However, longitudinal analysis of the alterations in metabolites and lipids is generally lacking. This study investigated the changes in levels of metabolites and lipids over time in sera from men with acute hepatitis E compared to healthy controls similar in age and gender. Untargeted measurement of levels of various metabolites and lipids was done using mass spectrometry on 65 sera sequentially sampled from 14 patients with acute hepatitis E and 25 serum samples from five controls. Temporal changes in intensities of metabolites and lipids were determined over different times at 3-day periods for the hepatitis E virus (HEV) group. In carbohydrate metabolism, glucose levels, fructose 1-6-bisphosphate and ribulose-5-phosphate were increased in the HEV-infected persons compared to the healthy controls. HEV infection is significantly associated with decreased levels of inosine, guanosine, adenosine and urate in purine metabolism and thymine, uracil and ß-aminoisobutyrate in pyrimidine metabolism. Glutamate, alanine and valine levels were significantly lower in the HEV group than in healthy individuals. Homogentisate of tyrosine metabolism and cystathionine of serine metabolism were increased, whereas kynurenate of tryptophan metabolism decreased in the HEV group. Metabolites of the bile acid biosynthesis, urea cycle (arginine and citrulline) and ammonia recycling (urocanate) were significantly altered. Co-enzymes, pantothenate and pyridoxal, and co-factors, lipoamide and FAD, were elevated in the HEV group. The acylcarnitines, sphingomyelins, phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysoPC and lysoPE tended to be lower in the HEV group. In conclusion, acute hepatitis E is associated with altered metabolite and lipid profiles, significantly increased catabolism of carbohydrates, purines/pyrimidines and amino acids, and decreased levels of several glycerophospholipids.

Hepatic Venous Pressure Gradient Predicts Further Decompensation in Cirrhosis Patients with Acute Esophageal Variceal Bleeding.

BACKGROUND: The role of hepatic venous pressure gradient (HVPG) in predicting further decompensation in cirrhosis patients with acute variceal bleeding (AVB) is not known. We aimed to evaluate the role of HVPG in predicting further decompensation in cirrhosis patients with AVB Methods: In this prospective study, 145 patients with cirrhosis with esophageal or gastric AVB were included. HVPG was measured on the day of the AVB. Decompensating events occurring after 42-days of AVB were considered further decompensation. RESULTS: The median age of the study cohort was 44 years; 88.3% males. The predominant etiology of cirrhosis was alcohol (46.2%). Overall, 40 (27.6%) patients developed further decompensation during median follow-up of 296 days following AVB. Gastro intestinal bleeding n = 27 (18.6%) and new-onset/worsening ascites n = 20 (13.8%) were the most common decompensating events. According to the multivariate model, HVPG was an independent predictor of any further decompensation in esophageal AVB patients but not in gastric variceal bleeding patients. HVPG cut-off of ≥16 mmHg predicted further decompensation in the esophageal AVB. However, HVPG was not an independent predictor of mortality. CONCLUSION: HVPG measured during an episode of acute variceal hemorrhage from esophageal varices predicts further decompensating events in cirrhosis patients.

KGHeBTA (King George's Medical University Hepatitis B Therapeutic Algorithm): A New Diagnostic and Therapeutic Algorithm and Clinico-epidemiological Spectrum of Hepatitis B.

Background: Diagnostic and therapeutic algorithms given by various societies for hepatitis B are fragmented and complex. The clinico-epidemiologic spectrum of hepatitis B is not studied with large-scale data from our region. We aimed to develop a comprehensive algorithm for the treatment of hepatitis B and study its clinico-epidemiological spectrum. Methods: From 2014-2019, the clinico-laboratory data of hepatitis B surface antigen (HbsAg)-positive patients were prospectively recorded. King George's Medical University hepatitis B therapeutic algorithm (KGHeBTA) was developed on the basis of the standard existing guidelines. The prevalence of different clinical stages of HBsAg-positive patients was calculated and their treatment records reviewed. Testing circumstances and risk factors were noted. Results: Among 1,508 data record sheets, 421 were complete. According to the KGHeBTA algorithm, 221 had detectable hepatitis B virus DNA. 21% were cirrhotic and 79% non-cirrhotic. 72% were incidentally detected asymptomatic hepatitis B, 7% were hepatitis B with acute symptoms, 0.7% were acute hepatitis B, and 22% were chronic hepatitis B. 20% patients were eligible for antivirals and 80% patients were not eligible. 32% patients were actually treated with antivirals due to the inclusion of some special indications as pregnancy and family history. Screening during various medical illnesses (40%) was the most common and during health camps (0.2%), the least common testing approach. Road-side shaving (52%) was the most common and intravenous drug abuse (0.2%) and the least common risk factor for the detection of hepatitis B in our data pool. Conclusions: HBsAg-positive patients can be easily worked up and treated based on the proposed algorithm (KGHeBTA). About one fourth to one fifth of all HBsAg-positive patients were eligible and treated with oral antivirals. Most of the patients were incidentally detected asymptomatic hepatitis B screened during medical illnesses. Roadside shaving and intravenous drug abuse were the most and the least common risk factors.

Impact of body mass index on disease progression and outcomes in patients with nonalcoholic fatty liver disease.

BACKGROUND: The relationship between body mass index (BMI) and outcomes in patients with nonalcoholic fatty liver disease (NAFLD) is not well defined. This study aimed to assess the presentations, outcomes, and development of liver-related events (LREs) and non-LREs in patients with NAFLD stratified by BMI. METHODS: Records of NAFLD patients from 2000-2022 were reviewed. Patients were categorized as lean (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), and obese (>25 kg/m2) based on BMI. Stage of steatosis, fibrosis, and NAFLD activity score were noted in the patients undergoing liver biopsy in each group. RESULTS: Out of 1051 NAFLD patients, 127 (12.1%) had normal BMI, 177 (16.8%) and 747 (71.1%) were overweight and obese, respectively. Median [interquartile range] BMI was 21.9 [20.6-22.5], 24.2 [23.7-24.6], and 28.3 [26.6-30.6] kg/m2 in each group, respectively. Prevalence of metabolic syndrome and dyslipidemia were significantly higher in the obese. Obese patients had significantly higher median [interquartile range] liver stiffness (6.4 [4.9-9.4] kPa) than overweight and lean subjects. A higher proportion of obese patients had significant and advanced liver fibrosis. At follow-up, there were no significant differences in the progression of liver disease, new LREs, coronary artery disease, or hypertension across the BMI groups. Overweight and obese patients were more likely to develop new-onset diabetes by follow-up. The mortality rates in the three groups were comparable (0.47, 0.68, and 0.49 per 100 person-years, respectively), with similar causes of death (liver-related vs non-liver-related). CONCLUSIONS: Patients with lean NAFLD have similar disease severity and rates of progression as the obese. BMI is not a reliable determinant of outcomes in NAFLD patients.

Hypoperfusion context as a predictor of 28-d all-cause mortality in septic shock patients: A comparative observational study.

BACKGROUND: As per the latest Surviving Sepsis Campaign guidelines, fluid resuscitation should be guided by repeated measurements of blood lactate levels until normalization. Nevertheless, raised lactate levels should be interpreted in the clinical context, as there may be other causes of elevated lactate levels. Thus, it may not be the best tool for real-time assessment of the effect of hemodynamic resuscitation, and exploring alternative resuscitation targets should be an essential research priority in sepsis. AIM: To compare the 28-d mortality in two clinical patterns of septic shock: hyperlactatemic patients with hypoperfusion context and hyperlactatemic patients without hypoperfusion context. METHODS: This prospective comparative observational study carried out on 135 adult patients with septic shock that met Sepsis-3 definitions compared patients with hyperlactatemia in a hypoperfusion context (Group 1, n = 95) and patients with hyperlactatemia in a non-hypoperfusion context (Group 2, n = 40). Hypoperfusion context was defined by a central venous saturation less than 70%, central venous-arterial PCO2 gradient [P(cv-a)CO2] ≥ 6 mmHg, and capillary refilling time (CRT) ≥ 4 s. The patients were observed for various macro and micro hemodynamic parameters at regular intervals of 0 h, 3 h, and 6 h. All-cause 28-d mortality and all other secondary objective parameters were observed at specified intervals. Nominal categorical data were compared using the χ2 or Fisher's exact test. Non-normally distributed continuous variables were compared using the Mann-Whitney U test. Receiver operating characteristic curve analysis with the Youden index determined the cutoff values of lactate, CRT, and metabolic perfusion parameters to predict the 28-d all-cause mortality. A P value of < 0.05 was considered significant. RESULTS: Patient demographics, comorbidities, baseline laboratory, vital parameters, source of infection, baseline lactate levels, and lactate clearance at 3 h and 6 h, Sequential Organ Failure scores, need for invasive mechanical ventilation, days on mechanical ventilation, and renal replacement therapy-free days within 28 d, duration of intensive care unit stay, and hospital stay were comparable between the two groups. The stratification of patients into hypoperfusion and non-hypoperfusion context did not result in a significantly different 28-d mortality (24% vs 15%, respectively; P = 0.234). However, the patients within the hypoperfusion context with high P(cv-a)CO2 and CRT (P = 0.022) at baseline had significantly higher mortality than Group 2. The norepinephrine dose was higher in Group 1 but did not achieve statistical significance with a P > 0.05 at all measured intervals. Group 1 had a higher proportion of patients requiring vasopressin and the mean vasopressor-free days out of the total 28 d were lower in patients with hypoperfusion (18.88 ± 9.04 vs 21.08 ± 8.76; P = 0.011). The mean lactate levels and lactate clearance at 3 h and 6 h, CRT, P(cv-a)CO2 at 0 h, 3 h, and 6 h were found to be associated with 28-d mortality in patients with septic shock, with lactate levels at 6 h having the best predictive value (area under the curve lactate at 6 h: 0.845). CONCLUSION: Septic shock patients fulfilling the hypoperfusion and non-hypoperfusion context exhibited similar 28-d all-cause hospital mortality, although patients with hypoperfusion displayed a more severe circulatory dysfunction. Lactate levels at 6 h had a better predictive value in predicting 28-d mortality than other parameters. Persistently high P(cv-a)CO2 (> 6 mmHg) or increased CRT (> 4 s) at 3 h and 6 h during early resuscitation can be a valuable additional aid for prognostication of septic shock patients.

Eight versus twelve weeks of sofosbuvir-velpatasvir in treatment-naïve non-cirrhotic patients with chronic hepatitis C virus infection: Study protocol for a multicentric, open labelled, randomized, non-inferiority trial (RESOLVE trial).

BACKGROUND: Hepatitis C virus (HCV) is a common cause of liver cirrhosis and hepatocellular carcinoma. Globally, nearly 71 million people have chronic HCV infection, and approximately 399,000 dies annually. In patients without cirrhosis, HCV infection is treated with 12 weeks of sofosbuvir/velpatasvir combination. Results from available small, single-centre observational studies suggest that the sofosbuvir/velpatasvir combination given for 8 weeks may be as effective as the standard 12 weeks of treatment. We propose to compare the treatment response of 12 weeks versus 8 weeks of sofosbuvir/velpatasvir in non-cirrhotic people with chronic HCV infection. METHODS: This multicentric, randomized, open-label, non-inferiority trial will include 880 (2 arms x 440) treatment naïve, viraemic (HCV RNA >10,000 IU/mL), non-cirrhotic adults (age >18 years) with chronic hepatitis C. People who are at high-risk for HCV reinfection such as haemophiliacs, people who inject drugs, those on maintenance hemodialysis or having HIV will be excluded. The presence or absence of cirrhosis will be determined with a combination of history, examination, ultrasound, liver stiffness measured with transient elastography, APRI, FIB-4, and esophagogastroduodenoscopy. Participants will be randomized to receive either 8- or 12-week sofosbuvir/velpatasvir treatment. A blood specimen will be collected before starting the treatment (to determine the HCV genotype), after 4 weeks of treatment (for early virological response), and at 12 weeks after treatment discontinuation for SVR12. DISCUSSION: The study will provide data on the efficacy of 8 weeks of treatment as compared to the standard of care (12 weeks) in non-cirrhotic patients with chronic HCV infection. Treatment for a shorter duration may improve treatment compliance, reduce the cost of treatment, and ease the treatment implementation from a public health perspective. TRIAL REGISTRATION: Registered with Clinical Trial Registry of India (http://ctri.nic.in) Registration No. CTRI/2022/03/041368 [Registered on: 24/03/2022]-Trial Registered Prospectively.

Endoscopic ultrasound-guided liver biopsy using a single-pass, slow-pull technique with a 19-G Franseen tip fine-needle biopsy needle: A prospective study.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided liver biopsy (EUS-LB) is considered to be safe and effective. Commonly a 19-G fine-needle aspiration or biopsy needle is used. But, the results vary with different techniques that are used. Herein, we report the results of liver biopsy with a single-pass, three actuations (1:3) using the slow-pull technique. METHODS: In this prospective study, 50 consecutive patients with indications for liver biopsy underwent EUS-LB with a 19-gauge fine-needle biopsy (FNB) needle from both right and left lobes. The primary outcome was the adequacy of the specimen for histological diagnosis. Total specimen length (TSL), longest specimen length (LSL), complete portal tracts (CPTs) and comparison of these outcomes between the left lobe and right lobe specimens were secondary outcomes. Adverse events (AEs) were also measured during this study. RESULTS: Adequate tissue for histological diagnosis was obtained in all 50 patients (100%). The median number of CPTs was 32.5 (range, 11-58), while the median of TSL was 58 mm (range, 35-190) and the median LSL was 15 mm (range, 5-40). There was no significant difference in CPTs, TSL and LSL between left and right lobe biopsies. There was no major complication; one of the patients (2%) had bleed from the duodenal puncture site, which was managed endoscopically without the need for blood transfusion. CONCLUSIONS: Endoscopic ultrasound-guided liver biopsy using a 19-gauge Franseen tip needle with a single pass, three actuation (1:3) and slow-pull technique provides adequate tissue yield and has a good safety profile.

Acute Liver Failure Prognostic Criteria: It's Time to Revisit.

INTRODUCTION: Acute liver failure (ALF) is a devastating disease, and patients are at a higher risk of death without liver transplantation. Indicators are needed to identify the risk of death in ALF, which will help in the timely referral of patients to specialized centers. Clichy criteriaand King's College Hospital (KCH) criteria are the most widely used prognostic criteria. Real-life application of Clichy criteria is limited due to the non-availability of factor V level measurement. KCH criteria have good specificity but low sensitivity to predict outcomes. Therefore, we attempted to use the model for end-stage liver disease (MELD) score and chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score in ALF patients as prognostic indicators and need for liver transplantation. METHODS: Forty-one patients with ALF were enrolled in the study. On the day of admission, MELD and CLIF-SOFA scores were calculated for each patient. Area under receiver operating characteristics (AUROC) curve, sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and diagnostic accuracy (DA) of MELD and CLIF-SOFA score were calculated to predict the outcome of the patients. RESULTS: Out of 41 patients, nine patients left against medical advice. The sensitivity, specificity, PPV, NPV, and DA for the MELD score of enrolled patients in the study were 81.5%, 62.5%, 59.5%, 83.3%, 70.1%, and for the CLIF-SOFA score of enrolled patients in the study were 88.9%, 90.0%, 85.7%, 92.3%, 89.6% respectively. Patients who did not survive had higher INR, MELD, CLIF-SOFA scores, and hepatic encephalopathy (HE) grades. Five patients who had a combination of MELD ≥30 and CLIF-SOFA ≥10, expired. CONCLUSION:  In our study, we used MELD score and CLIF-SOFA as prognostic markers, and we concluded that CLIF-SOFA is a better predictor of mortality than MELD score in terms of sensitivity, specificity, NPV, PPV, and diagnostic accuracy. AUROC for CLIF-SOFA score is higher when compared to the MELD score.

Antibody response to ChAdOx1 nCoV-19 (Covishield®) vaccine in people on maintenance hemodialysis.

INTRODUCTION: People on renal replacement therapy (RRT) have a high risk of COVID-19 infection and subsequent death. COVID-19 vaccination is strongly recommended for those on RRT. Data are limited on the immune response of the ChAdOx1 nCoV-19/AZD1222 (Covishield®) vaccine in patients on RRT. METHODS: A prospective cohort of adult (age > 18 years), on RRT in the form of hemodialysis were included and received two intramuscular doses of Covishield®. A blood specimen of 5.0 mL was collected at two time points, within a few days before administering the first dose of the vaccine and at 4-16 weeks after the second dose. According to their prior COVID-19 infection status, the participants were grouped as (i) prior symptomatic COVID-19 infection, (ii) prior asymptomatic COVID-19 infection, and (iii) no prior COVID-19 infection. RESULTS: A large proportion (81%) of participants had anti-spike antibodies (ASAb) before vaccination, and a reasonable proportion (30%) also had neutralizing antibodies (NAb). The titer of ASAb was relatively low (207 U/mL) before vaccination. The ASAb titer (9405 [1635-25,000] U/mL) and percentage of NAb (96.4% [59.6-98.1%]) were markedly increased following the administration of two doses of the vaccine. The participants' prior COVID-19 exposure status did not influence the rise in ASAb titer and NAb percentage. Further, administering two doses of the Covishield vaccine helps them achieve a high ASAb titer. CONCLUSION: Two doses of ChAdOx1 nCoV-19/AZD1222 (Covishield®) vaccine, given 12 weeks apart, achieve a high titer of ASAb and a high percentage of NAb in people on hemodialysis.

Performance analysis of multiple input single layer neural network hardware chip.

An artificial neural network (ANN) is a computational system that is designed to replicate and process the behavior of the human brain using neuron nodes. ANNs are made up of thousands of processing neurons with input and output modules that self-learn and compute data to offer the best results. The hardware realization of the massive neuron system is a difficult task. The research article emphasizes the design and realization of multiple input perceptron chips in Xilinx integrated system environment (ISE) 14.7 software. The proposed single-layer ANN architecture is scalable and accepts variable 64 inputs. The design is distributed in eight parallel blocks of ANN in which one block consists of eight neurons. The performance of the chip is analyzed based on the hardware utilization, memory, combinational delay, and different processing elements with targeted hardware Virtex-5 field-programmable gate array (FPGA). The chip simulation is performed in Modelsim 10.0 software. Artificial intelligence has a wide range of applications, and cutting-edge computing technology has a vast market. Hardware processors that are fast, affordable, and suited for ANN applications and accelerators are being developed by the industries. The novelty of the work is that it provides a parallel and scalable design platform on FPGA for fast switching, which is the current need in the forthcoming neuromorphic hardware.