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Acute-on-chronic liver failure (ACLF) is a severe form of alcoholic hepatitis (SAH). We aimed to study the natural course, response to corticosteroids (CS), and the role of the Asian Pacific Association for the Study of Liver (APASL) research consortium (AARC) score in determining clinical outcomes in AH patients.Prospectively collected data from the AARC database were analyzed.Of the 1249 AH patients, (aged 43.8 ± 10.6 years, 96.9% male, AARC score 9.2 ± 1.9), 38.8% died on a 90 day follow-up. Of these, 150 (12.0%) had mild-moderate AH (MAH), 65 (5.2%) had SAH and 1034 (82.8%) had ACLF. Two hundred and eleven (16.9%) patients received CS, of which 101 (47.87%) were steroid responders by day 7 of Lille's model, which was associated with improved survival [Hazard ratio (HR) 0.15, 95% CI 0.12-0.19]. AARC-ACLF grade 3 [OR 0.28, 0.14-0.55] was an independent predictor of steroid non-response and mortality [HR 3.29, 2.63-4.11]. Complications increased with degree of liver failure [AARC grade III vs. II vs I], bacterial infections [48.6% vs. 37% vs. 34.7%; p 0.001); extrahepatic organ failure [66.9% vs. 41.8% vs. 35.4%; p 0.001] respectively. The AARC score better discriminated 90-day mortality. Harrell's C-index was 0.72 compared to other scores.Nearly 4 of 5 patients with AH present with ACLF. Such patients have a higher risk of infections, organ failures, lower response to CS, and higher mortality. Patients with AH and ACLF with AARC grade 3 should be considered for an early liver transplant.

BACKGROUND/AIM: Hormonal changes and hepatic osteodystrophy are less often studied complications of cirrhosis. This study describes the variance in hormones and osteodystrophy between Frail and Not frail patients with cirrhosis. METHODS: 116 outpatients with cirrhosis were prospectively enrolled in this study. Frailty assessment was done using Liver Frailty Index (LFI). Sociodemographic assessment, anthropometry, nutritional assessment, hormone profile, and dual-energy X-ray absorptiometry scan were done in all patients. RESULTS: 116 patients, predominantly males (100 (86.2%) with mean age of 50.16 years (95% CI, 48.43–51.89) were included. Malnutrition was more common in Frail group as compared to Not frail group. Subjective global assessment (SGA) class-B patients were significantly more in Frail group (37 (74%) vs 3 (4.5%), P = 0.001). The prevalence of lower parathyroid hormone (PTH) (14 (28%) vs 2 (3%)), testosterone (33 (66%) vs 15 (22.7%)), vitamin D3 (44 (88%) vs 39 (59.1%)), and cortisol (37 (74%) vs 37 (56.1) levels was higher in Frail group (P < 0.05). The number of patients diagnosed with osteodystrophy (34 (68%) vs 21 (31.8%), P = 0.001) was significantly higher in Frail group. The marker of osteoclastic activity, β-cross laps, was significantly elevated in the Frail group both in males (736 (655–818) vs 380 (329–432), P = 0.001) and (females 619 (479–758) vs 313 (83–543), P = 0.02). Bone mineral density (BMD) at lumbar spine (LS) and neck of femur (NF) had significant correlation with LFI (ρ = 0.60, P = 0.001 for LS and ρ = 0.59, P = 0.001 for NF), serum testosterone (ρ = 0.58, P = 0.001 for LS and ρ = 0.53, P = 0.001 for NF), β-cross laps (ρ = 0.38, P = 0.001for LS and ρ = 0.35, P = 0.000 for NF), vitamin D3 (ρ = 0.23, P = 0.04 for LS and ρ = 0.25, P = 0.01 for NF), PTH (ρ = 0.52, P = 0.001 for LS and ρ = 0.48. P = 0.001 for NF), and cortisol (ρ = 0.50, P = 0.001 for LS and ρ = 0.45, P = 0.001 for NF) levels. CONCLUSION: This is the first study that highlights the high prevalence of hormonal changes and hepatic osteodystrophy in frail patients with cirrhosis and opens a new dimension for research and target of therapy in this field.

Acute-on-chronic liver failure (ACLF) is a rapidly progressive illness with high short-term mortality. Timely liver transplant (LT) may improve survival. We evaluated various indices for assessment of the severity of liver failure and their application for eligibility and timing of living donor LT (LDLT). Altogether 1021 patients were analyzed for the severity and organ failure at admission to determine transplant eligibility and 28 day survival with or without transplant. The ACLF cohort [mean age 44 ± 12.2 years, males 81%) was of sick patients; 55% willing for LT at admission, though 63% of them were ineligible due to sepsis or organ failure. On day 4, recovery in sepsis and/or organ failure led to an improvement in transplant eligibility from 37% at baseline to 63.7%. Delay in LT up to 7 days led to a higher incidence of multiorgan failure (p

We evaluated the dynamics of hepatic encephalopathy (HE) and ammonia estimation in acute-on-chronic liver failure (ACLF) patients due to a paucity of evidence. ACLF patients recruited from the APASL-ACLF Research Consortium (AARC) were followed up till 30 days, death or transplantation, whichever earlier. Clinical details, including dynamic grades of HE and laboratory data, including ammonia levels, were serially noted. Of the 3009 ACLF patients, 1315 (43.7%) had HE at presentation; grades I–II in 981 (74.6%) and grades III–IV in 334 (25.4%) patients. The independent predictors of HE at baseline were higher age, systemic inflammatory response, elevated ammonia levels, serum protein, sepsis and MELD score (p

Multiple predictive models of mortality exist for acute-on-chronic liver failure (ACLF) patients that often create confusion during decision-making. We studied the natural history and evaluated the performance of prognostic models in ACLF patients.Prospectively collected data of ACLF patients from APASL-ACLF Research Consortium (AARC) was analyzed for 30-day outcomes. The models evaluated at days 0, 4, and 7 of presentation for 30-day mortality were: AARC (model and score), CLIF-C (ACLF score, and OF score), NACSELD-ACLF (model and binary), SOFA, APACHE-II, MELD, MELD-Lactate, and CTP. Evaluation parameters were discrimination (c-indices), calibration [accuracy, sensitivity, specificity, and positive/negative predictive values (PPV/NPV)], Akaike/Bayesian Information Criteria (AIC/BIC), Nagelkerke-RThirty-day survival of the cohort (n = 2864) was 64.9% and was lowest for final-AARC-grade-III (32.8%) ACLF. Performance parameters of all models were best at day 7 than at day 4 or day 0 (p 0.05 for C-indices of all models except NACSELD-ACLF). On comparison, day-7 AARC model had the numerically highest c-index 0.872, best accuracy 84.0%, PPV 87.8%, RAPASL-ACLF is often a progressive disease, and models assessed up to day 7 of presentation reliably predict 30-day mortality. Day-7 AARC model is a statistically robust tool for classifying risk of death and accurately predicting 30-day outcomes with relatively lower prediction errors. Day-7 AARC score 12 may be used as a futility criterion in APASL-ACLF patients.

Rhino-orbital-cerebral mucor mycosis (ROCM) is a relatively rare opportunistic infection caused by the Mucorales species. While ROCM suggests involvement of the paranasal sinuses, orbit and brain ROM (rhino-orbital-Mucormycosis) stands for the fungal invasion in sinuses and orbit sans cerebral involvement. In India with the outbreak of the second COVID wave and the delta variant of the virus, there has been a steep increase in this opportunistic fulminant fungal infection, named COVID-associated Mucor mycosis (CAM). The most critical question in orbital management is when to go ahead with an exenteration. Our study aims to design a pertinent minimal invasive surgical protocol for surgeons to manage such cases based on our surgical experience and mitigate the need for exenteration and save the eyes wherever possible.The study is a retrospective analysis of patients of ROM with and without brain involvement, who underwent minimal surgical management between March 2021 to March 2022 along with their follow-up.There were 184 eyes of 148 patients diagnosed with CAM. The mean age was 51.7 years with a male predominance of 103 (70%). All patients developed ROM following the COVID-19 infection and the duration between diagnosis of COVID-19 and ROM was 36 ± 23 days. 18 cases (12%) were bilateral. 76 eyes (41%) had no vision at the presentation. Imaging revealed paranasal sinus involvement (100%), orbital apex involvement (61%), cavernous sinus involvement (53%), and central nervous system (CNS) involvement (47%). All the patients (100%) were treated with systemic Liposomal amphotericin-B and sinus debridement. Endoscopic debridement of the orbital disease was performed in 45 (30.4%) cases, 15(8.1%) eyes underwent exenteration and were later rehabilitated with a customized ocular prosthesis, 103 (56%) eyes underwent transcutaneous retrobulbar amphotericin-B. At a mean follow-up of 13.1 months; the complete resolution was seen in 25 (17%) cases, the residual stable lesion was seen in 77(52%) of the cases and new lesions were developed in 13(9%) of the cases. Mortality was seen in 33 (22%) patients and all of them had CNS involvement.Systemic and protocol-based management can save the life and salvage the eyes.

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, P0.001) 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 (MELD27; 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 (MELD27, hepatic encephalopathy in ≥F3) would reduce ICU stay and improve outcomes.

Background and purposes Minimal hepatic encephalopathy (MHE) has no recognizable clinical symptoms, but patients have cognitive and psychomotor deficits. Hyperammonemia along with neuroinflammation lead to microstructural changes in cerebral parenchyma. Changes at conventional imaging are detected usually at the overt clinical stage, but microstructural alterations by advanced magnetic resonance imaging techniques can be detected at an early stage. Materials and methods Whole brain diffusion kurtosis imaging (DKI) data acquired at 3T was analyzed to investigate microstructural parenchymal changes in 15 patients with MHE and compared with 15 age- and sex-matched controls. DKI parametric maps, namely kurtosis fractional anisotropy (kFA), mean kurtosis (MK), axial kurtosis (AK) and radial kurtosis (RK), were evaluated at 64 white matter (WM) and gray matter (GM) regions of interest (ROIs) in the whole brain and correlated with the psychometric hepatic encephalopathy score (PHES). Results The MHE group showed a decrease in kFA and AK across the whole brain, whereas MK and RK decreased in WM ROIs but increased in several cortical and deep GM ROIs. These alterations were consistent with brain regions involved in cognitive function. Significant moderate to strong correlations (–0.52 to –0.66; 0.56) between RK, MK and kFA kurtosis metrics and PHES were observed. Conclusion DKI parameters show extensive microstructural brain abnormalities in MHE with minor correlation between the severity of tissue damage and psychometric scores.

Background: Modulation of gut dysbiosis with Fecal Microbiota Transplantation (FMT) is a novel modality and has shown promising results in decompensated cirrhosis (DC). We explored the impact of FMT on prognostic scores, complications, ammonia levels, inflammatory markers [(Interleukin -1 (IL-1) and 6 (IL-6)], and 180-day mortality in DC.Methods: Consecutive patients with DC (MELD12-21) were assigned to either FMT (FMT group) delivered as 30gm freshly prepared stool (from a related stool donor) homogenized in 100 ml of normal saline through a nasojejunal tube or standard of care therapy (SOC group). Outcomes were assessed on days 7, 28, 90, and 180.Results: Eighteen patients each with comparable baseline characteristics (88.8% males; mean age, 46.12±6.23 vs. 47.0±4.54; mean CTP, 9.5±0.71 vs. 9.6±0.80; mean MELD, 16.1±1.71 vs. 1.62±1.81) were allocated to FMT or SOC. Although significant differences were noted in the CTP score on day 7 (P=0.02) and day 90 (P=0.01), MELD and MELD-Na scores were similar at all time points. A non-significant reduction in ammonia levels was seen on day 7 and day 28 (P=0.21 and P=0.17; respectively). IL-1 (P=0.01) and IL 6 (P=0.005) levels reduced significantly on day 28. New-onset variceal bleed (P=0.70), breakthrough hepatic encephalopathy events (P=0.61) and 180-day survival (HR, 2.02; 95% CI, 0.37-11.05; P=0.41). were similar. Although transient gastrointestinal side-effects were common (56.2%), no serious adverse events were noted.Conclusion: Single session FMT in DC is safe and leads to selective improvement of CTP scores and systemic inflammatory markers but offers no survival benefit. (ClinicalTrials.gov number, NCT04842539)

Background: Severe alcoholic hepatitis (SAH) presenting as acute-on-chronic liver failure (ACLF) carries a high short-term mortality. Alteration of gut microbiota is a crucial component implicated in its pathogenesis, whose modulation has been suggested as a potential therapeutic tool. We evaluated the safety of fecal microbiota transplantation (FMT) and its efficacy in improving short-term survival and clinical severity scores in patients with SAH-ACLF.Methods: Thirty-three patients [13 in the FMT arm;20 in the standard of care arm (SOC] with SAH-ACLF were included in this open-label study. A single FMT session was administered as a freshly prepared stool suspension from pre-identified healthy family member stool donors through a nasojejunal tube. Patients were followed up on days seven, twenty-eight, and ninety. Results: Survival at twenty-eight and ninety days was significantly better in the FMT arm (100% versus 60%, P=0.01; 53.84% versus 25%, P=0.02). Hepatic encephalopathy resolved in 100% versus 57.14% (FMT versus SOC, P=0.11) patients, while ascites resolved in 100% versus 40% survivors (P=0.04). Major adverse event rates, including spontaneous bacterial peritonitis and gastrointestinal bleeding, were similar in both groups (P=0.77; P=0.70). Median IL1beta decreased by21.39% (IQR -73.67-7.63) in the FMT group, whereas it increased in the SOC by 27.44% (IQR -0.88-128.11) (P=0.01). Percentage changes in bilirubin and ALT between baseline and day seven emerged as predictors of ninety-day mortality.Conclusion: FMT is safe, improves short-term and medium-term survival, and leads to improvement in clinical severity scores in patients with SAH-ACLF.

Background Most of the reported risk score models for coronavirus disease 2019 (COVID-19) mortality are based on the levels of inflammatory markers, comorbidities or various treatment modalities, and there is a paucity of risk score models based on clinical symptoms and comorbidities. Methods To address this need, age, clinical symptoms and comorbidities were used to develop a COVID-19 scoring system (CSS) for early prediction of mortality in severe COVID-19 patients. The CSS was developed with scores ranging from 0 to 9. A higher score indicates higher risk with good discrimination quality presented by Mann Whitney U test and area under receiver operating characteristic curve (AUROC). Results Patient age of ≥60 y, cough, breathlessness, diabetes and any other comorbidity (with or without diabetes) are significant and independent risk factors for non-survival among COVID-19 patients. The CSS showed good sensitivity and specificity (i.e. 74.1% and 78.5% at CSS≥5, respectively), with an overall diagnostic accuracy of 82.8%, which was close to the diagnostic accuracy detected in the validation cohort (81.9%). In the validation cohort, high (8–9), medium (5–7) and low (0–4) CSS groups had 54.80%, 28.60% and 6.5% observed mortality, respectively, which was very close to the predicted mortality (62.40%, 27.60% and 5.2%, respectively, by scoring cohort). Conclusions The CSS shows a positive relationship between a higher score and proportion of mortality and, as its validation showed, it is useful for the prediction of risk of mortality in COVID-19 patients at an early stage, so that referral for triage and admission can be predetermined even before admission to hospital.

ObjectiveDespite treatment availability, chronic hepatitis C virus (HCV) public health burden is rising in India due to lack of timely diagnosis. Therefore, we aim to assess incremental cost per quality-adjusted life year (QALY) for one-time universal screening followed by treatment of people infected with HCV as compared with a no screening policy in Punjab, India.Study designDecision tree integrated with Markov model was developed to simulate disease progression. A societal perspective and a 3% annual discount rate were considered to assess incremental cost per QALY gained. In addition, budgetary impact was also assessed with a payer’s perspective and time horizon of 5 years.Study settingScreening services were assumed to be delivered as a facility-based intervention where active screening for HCV cases would be performed at 22 district hospitals in the state of Punjab, which will act as integrated testing as well as treatment sites for HCV.InterventionTwo intervention scenarios were compared with no universal screening and treatment (routine care). Scenario I—screening with ELISA followed by confirmatory HCV-RNA quantification and treatment. Scenario II—screening with rapid diagnostic test (RDT) kit followed by confirmatory HCV-RNA quantification and treatment.Primary and secondary outcome measuresLifetime costs; life years and QALY gained; and incremental cost-effectiveness ratio for each of the above-mentioned intervention scenario as compared with the routine care.ResultsScreening with ELISA and RDT, respectively, results in a gain of 0.028 (0.008 to 0.06) and 0.027 (0.008 to 0.061) QALY per person with costs decreased by −1810 Indian rupees (−3376 to –867) and −1812 Indian rupees (−3468 to −850) when compared with no screening. One-time universal screening of all those ≥18 years at a base coverage of 30%, with ELISA and RDT, would cost 8.5 and 8.3 times more, respectively, when compared with screening the age group of the cohort 40–45 years old.ConclusionOne-time universal screening followed by HCV treatment is a dominant strategy as compared with no screening. However, budget impact of screening of all ≥18-year-old people seems unsustainable. Thus, in view of findings from both cost-effectiveness and budget impact, we recommend beginning with screening the age cohort with RDT around mean age of disease presentation, that is, 40–45 years, instead of all ≥18-year-old people.

Malnutrition and sarcopenia are common in patients with chronic liver disease and are associated with increased risk of decompensation, infections, wait-list mortality and poorer outcomes after liver transplantation. Assessment of nutritional status and management of malnutrition are therefore essential to improve outcomes in patients with chronic liver disease. This consensus statement of the Indian National Association for Study of the Liver provides a comprehensive review of nutrition in chronic liver disease and gives recommendations for nutritional screening and treatment in specific clinical scenarios of malnutrition in cirrhosis in adults as well as children with chronic liver disease and metabolic disorders.

Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection has caused a pandemic Coronavirus Disease-19 (COVID-19) that began in Wuhan city, China, in December 2019. Till 14th April 19,39,801 people have been affected by this virus 1,20,897 of whom died. Though respiratory symptoms are the typical manifestation of this disease, gastrointestinal (GI) symptoms such as anorexia, nausea, vomiting, loss of taste sensation, diarrhea, abdominal pain, and discomfort have been reported. The pooled prevalence of GI symptom is 17.6% (95% confidence interval [CI], 12.3%–24.5%), as indicated in a meta-analysis. A few studies suggested that the presence of GI symptoms is associated with poorer prognosis. The virus is excreted in feces during the acute disease, and even after the nasopharyngeal swab has become negative for viral ribonucleic acid (RNA). Fecal viral excretion may have clinical significance due to possible feco-oral transmission of the infection. 10.5% to 53% of patients with COVID-19, particularly those with severe disease, have been shown to have an elevation of hepatic enzymes through biochemical and clinical jaundice, are uncommon. Knowledge about this disease in general and GI involvement, in particular, is currently evolving.

Background Acute liver failure caused by the ingestion of yellow phosphorus–containing rodenticide has been increasing in incidence over the last decade and is a common indication for emergency liver transplantation in Southern and Western India and other countries. Clear guidelines for its management are necessary, given its unpredictable course, potential for rapid deterioration and variation in clinical practice. Methods A modified Delphi approach was used for developing consensus guidelines under the aegis of the Liver Transplantation Society of India. A detailed review of the published literature was performed. Recommendations for three areas of clinical practice, assessment and initial management, intensive care unit (ICU) management and liver transplantation, were developed. Results The expert panel consisted of 16 clinicians, 3 nonclinical specialists and 5 senior advisory members from 11 centres. Thirty-one recommendations with regard to criteria for hospital admission and discharge, role of medical therapies, ICU management, evidence for extracorporeal therapies such as renal replacement therapy and therapeutic plasma exchange, early predictors of need for liver transplantation and perioperative care were developed based on published evidence and combined clinical experience. Conclusion Development of these guidelines should help standardise care for patients with yellow phosphorus poisoning and identify areas for collaborative research.

The Liver Transplant Society of India (LTSI) has come up with guidelines for transplant centres across the country to deal with liver transplantation during this evolving pandemic of COVID-19 infection. The guidelines are applicable to both deceased donor as well as living donor liver transplants. In view of the rapidly changing situation of COVID-19 infection in India and worldwide, these guidelines will need to be updated according to the emerging data.

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the “APASL ACLF Research Consortium (AARC)” was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the ‘Golden Therapeutic Window’, extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here., Article Highlights Updated on the basis of AARC data of >3300 cases enrolled into AARC registry prospectivelyACLF is distinct form Acute Decompensation of cirrhosisNewer sections on DILI-ACLF, AIH-ACLF, PVT/HVOTO–ACLFReversibility of Chronic Liver Disease in ACLFPortal and systemic hemodynamics and their relevance in ACLFAcute Portal Hypertension and Variceal progression in ACLFAARC score as a guide for treatment strategies in ACLFACLF in Children-first consensus on pediatric ACLF

Background and Aims Patients with cirrhosis and acute-on-chronic liver failure (ACLF) may have bleeding complications and need for invasive procedures. Point-of-care (POC) coagulation tests like thromboelastography (TEG) and Sonoclot may be better for guiding patient management than the standard coagulation tests (SCTs), like prothrombin time, platelet count and international normalized ratio. Methods We prospectively compared and validated the POC tests and SCTs in 70 persons with ACLF and 72 persons with decompensated cirrhosis who had clinical bleeding and checked for episodes of re-bleeding and transfusion requirements. We assessed pre-procedure requirement of blood components when correction was done based on an SCT or POC strategy. Results Episodes of bleeding were seen in 45% and 28% of ACLF and cirrhosis patient, respectively (p=0.036), with the major site of bleeding being gastrointestinal (31% and 16%, respectively). Platelet counts correlated with TEG-maximum amplitude in cirrhosis (p=0.045) and prothrombin time correlated positively with TEG-reaction (R) time (p=0.032), TEG-Clot kinetics (K) time (p=0.042), Son-activated clotting time (p=0.038) and negatively with clot rate (p=0.043) in ACLF, making these correctable target variables in POC transfusion algorithms. Of 223 procedures, transfusion of fresh frozen plasma and platelet concentrate was reduced by 25% (p=0.035) and 20.8% (p=0.045) by using a POC strategy in 76 patients. Correction of deranged Son-activated clotting time and TEG-reaction time was noted in 68% and 72% after 24 h of fresh frozen plasma transfusion in ACLF and 85% and 80% in cirrhosis, respectively. Conclusions Our study clinically validates that POC tests can better detect coagulation defects and transfusion thresholds in ACLF and cirrhosis, whereas use of conventional tests appear to be less suitable in patients with clinical bleeding. Trial Registration NCT04332484.

Introduction We prospectively studied the frequency, spectrum, and predictors of gastrointestinal (GI) symptoms among patients with coronavirus disease-19 (COVID-19) and the relationship between GI symptoms and the severity and outcome. Methods Consecutive patients with COVID-19, diagnosed in a university hospital referral laboratory in northern India, were evaluated for clinical manifestations including GI symptoms, their predictors, and the relationship between the presence of these symptoms, disease severity, and outcome on univariate and multivariate analyses. Results Of 16,317 subjects tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in their oropharyngeal and nasopharyngeal swabs during April-May 2020, 252 (1.5%) were positive. Of them, 208 (82.5%) were asymptomatic; of the 44 symptomatic patients, 18 (40.9%) had non-GI symptoms, 15 (34.1%) had a combination of GI and non-GI symptoms, and 11 (25.0%) had GI symptoms only. Thirty-three had mild-to-moderate disease, 8 severe, and 5 critical. Five patients (1.98%) died. On multivariate analysis, the factors associated with the presence of GI symptoms included the absence of contact history and presence of non-GI symptoms and comorbid illnesses. Patients with GI synptoms more often had severe, critical illness and fatal outcome than those without GI symptoms. Discussion Eighty-two percent of patients with COVID-19 were asymptomatic, and 10.3% had GI symptoms; severe and fatal disease occurred only in 5% and 2%, respectively. The presence of GI symptoms was associated with a severe illness and fatal outcome on multivariate analysis. Independent predictors of GI symptoms included the absence of contact history, presence of non-GI symptoms, and comorbid illnesses.(Equation is included in full-text article.).

INTRODUCTION Treatment of patients with chronic hepatitis C (CHC) is difficult in the setting of end stage renal disease (ESRD). The present study aimed to analyze the treatment outcome in patients with CHC and ESRD, being evaluated for kidney transplantation. METHODS Data of 65 patients of ESRD with CHC (males: 53, mean age: 39.2 +/- 14.4 years) was analysed retrospectively. Patients were treated with either pegylated or conventional interferon (IFN) without ribavirin. Treatment response was assessed for rapid virological response (RVR), early virological response (EVR), end of treatment response (ETR) and sustained virological response (SVR). RESULTS All patients were receiving hemodialysis (duration 1-60 months). Sixteen patients (25%) (genotype 1: 11, genotype 3: 4, genotype 2: 1) agreed for treatment (13 pegylated IFN and 3 conventional IFN). RVR was achieved in 7 patients (44%) and out of 11 patients (69%) who achieved EVR, ETR was achieved in 7 (44%) patients. Seven patients (44%) dropped out during treatment (2 because of side effects). SVR could be demonstrated in one of 7 patients who achieved ETR (6 patients were lost to follow up after ETR). CONCLUSIONS In our experience, dropouts before, during and after treatment are a major problem in patients with CHC and ESRD. Of those who complete treatment, around half of them are able to achieve the end of treatment response.

Sustained virological response (SVR) rates in patients with hepatitis C are heterogeneous and are influenced by a wide range of host and viral factors.To evaluate the efficacy of combination therapy with pegylated interferon alfa (PEG-IFN-α) and ribavirin (RBV), and document the SVR rates taking into consideration various predictive factors in patients with chronic hepatitis C (CHC) genotype 3.Ninety-seven treatment-naive patients with CHC genotype 3 (mean age 41.46±11.51 years, M:F ratio 79:18), who received a combination of PEG-IFN (α-2a or α-2b) and RBV were retrospectively analyzed (2006-2008) for the early virological response (EVR) at 12 weeks, end of treatment response (ETR), and SVR at 6 months.Eighty-four (86.6%) patients achieved EVR and 81 (83.5%) achieved ETR, while SVR was achieved in 65 (67.0%) patients. Of the 84 patients who achieved EVR, 77 (91.7%) achieved ETR and 61 (72.6%) achieved SVR at 6 months. Age and body mass index (BMI) were found to be important predictors (*P0.05) of SVR. CHC patients with a history of alcohol intake showed decreased SVR (52%) (*P=0.035) as compared to nonalcoholics (80%). Cirrhotic versus noncirrhotic patients showed no difference in SVR (54.5% vs. 70.7%) (P=0.157). Serum alanine aminotransferase (ALT) (P=0.169) and hepatitis C virus (HCV) RNA levels (P=0.42) also did not have an influence on the SVR.Combination therapy with PEG-IFN-α and RBV demonstrated good tolerability in CHC genotype 3 infection. Age, BMI, and alcohol consumption play an important role in determining treatment outcome.

Patients with cirrhosis are more prone to develop metabolic bone disease. Scanty literature data are available on osteodystrophy in patients from India with noncholestatic liver diseases. Patients diagnosed with cirrhosis were prospectively evaluated for bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry at the femoral neck, lumbar spine, and left forearm (distal radius). Correlation of BMD with age, sex, etiology of cirrhosis, Child’s class, serum bilirubin, alkaline phosphatase (ALP), albumin, calcium, phosphate, 25-hydroxyvitamin D (25(OH)D), and parathyroid hormone (PTH) was studied. The study group comprised 115 cirrhotic patients (107 males and 8 females). Etiology of cirrhosis was alcohol in 67 (58.2%) and viral in 48 (41.7%). Hepatitis B was diagnosed in 29 (25.2%) and hepatitis C in 19 (16.5%). Mean age was 49 (± 5.5) years. Prevalence of osteodystrophy was significantly higher in males than in females; 97.1% and 75% respectively (P = .038). Both alcoholic and viral groups had similar baseline characteristics except albumin levels. Child’s class was B in 72 patients and C in 43. Low BMD was present in 97% of patients with alcoholic cirrhosis and 93.7% with viral cirrhosis (P > .05). Low BMD was present at the femoral neck in 80.8% of patients, lumbar spine in 77.3%, and forearm in 59.9%. PTH correlated negatively with BMD. Osteodystrophy is common in alcoholic and viral cirrhosis patients.

Although clinician's skills and experience play a major role in designing and fabrication of the optimum prosthodontic restorations, the selection of denture resins is equally important, especially when the patient has been using the prostheses since long. Eighteen cases who were not satisfied with their conventional acrylic dentures were selected. They were provided flexible dentures along with a questionnaire to precisely evaluate the advantages of new material. Prosthodontic planning & observations regarding this material are discussed on various parameters.

Autoimmune hepatitis (AIH) is a chronic disease of unknown cause, characterized by progressive hepatocellular inflammation and necrosis, frequently leading to cirrhosis. AIH usually affects young women and may influence fertility and pregnancy in them. Nearly 200 pregnancies have been reported so far in the world literature in women with AIH, and no definite guidelines have been established. We hereby report our experience of four pregnancies in women with definite diagnosis of AIH.We studied the maternal and perinatal outcome of four women with AIH. The medical history was recorded in detail. The pregnancies were allowed to continue with careful fetal and maternal surveillance. Antenatal complications, disease course during pregnancy, intrapartum maternal fetal events, mode of delivery, and perinatal outcome were noted.All four patients had preterm labor: three had vaginal delivery and cesarean was done in one due to breech presentation with preterm rupture of membranes. All the infants were live born with birth weight appropriate for gestational age and were born with good Apgar scores and no congenital malformation. The incidence of post partum hemorrhage was 25% and so was the maternal mortality.Successful pregnancy outcome in patients with well-controlled AIH seems to be a realistic expectation with careful monitoring jointly by the Obstetricians and Hepatologists, especially in the post partum period. Steroids seem to be the safe alternative as immunosuppressant therapy although azathioprine has also been seen to be generally safe for mother or baby.

Summary Background Portal vein thrombosis (PVT) is an important cause of portal hypertension. It may occur as such with or without associated cirrhosis and hepatocellular carcinoma. Information on its management is scanty. Aim To provide an update on the modern management of portal vein thrombosis. Information on portal vein thrombosis in patients with and without cirrhosis and hepatocellular carcinoma is also updated. Methods A pubmed search was performed to identify the literature using search items portal vein thrombosis-aetiology and treatment and portal vein thrombosis in cirrhosis and hepatocellular carcinoma. Results Portal vein thrombosis occurs because of local inflammatory conditions in the abdomen and prothrombotic factors. Acute portal vein thrombosis is usually symptomatic when associated with cirrhosis and/or superior mesenteric vein thrombosis. Anticoagulation should be given for 3–6 months if detected early. If prothrombotic factors are identified, anticoagulation should be given lifelong. Chronic portal vein thrombosis usually presents with well tolerated upper gastrointestinal bleed. It is diagnosed by imaging, which demonstrates a portal cavernoma in place of a portal vein. Anticoagulation does not have a definite role, but bleeds can be treated with endotherapy or shunt surgery. Rarely liver transplantation may be considered. Conclusion Role of anticoagulation in chronic portal vein thrombosis needs to be further studied.

Hepatitis C virus (HCV) infection has been associated with insulin resistance or diabetes mellitus, but data are controversial on the role of different HCV genotypes in causing insulin resistance. We have designed a study aimed at determining insulin resistance in patients with chronic hepatitis C with predominant genotype 3. Insulin resistance was measured using a homeostasis model of assessment for insulin resistance in 85 non-diabetic, non-cirrhotic patients with chronic hepatitis C (genotype 3 = 54). The results were compared with 38 biopsy-proven patients with non-alcoholic fatty liver disease and 25 age- and body mass index-matched healthy volunteers. Patients with chronic hepatitis C had a higher fasting insulin and homeostasis model of assessment for insulin resistance values than healthy volunteers (P = 0.0001). A large number of patients with chronic hepatitis C showed evidence of insulin resistance than healthy controls [53 (62.3%) vs. 4 (16%), respectively] (P < 0.0001). Of the various risk factors studied for insulin resistance in patients with chronic hepatitis C, higher waist (P = 0.010) and higher serum triglycerides (P = 0.002) were found to correlate with HOMA-insulin resistance. There was no difference in insulin resistance amongst patients with genotype 1 or 3, respectively. Based on these results, we conclude that insulin resistance is common among non-diabetic, non-cirrhotic patients with chronic hepatitis C. A majority of these patients had genotype 3, but there was no difference in insulin resistance between genotype 1 and genotype 3 patients.

Portal hypertension usually occurs in patients with fulminant hepatic failure (FHF). There is, however, no information on portal venous hemodynamics in patients with FHF. Therefore, we studied the portal venous hemodynamics in patients with FHF using duplex Doppler ultrasonography. We measured the portal vein diameter, flow velocity, and volume flow with duplex Doppler ultrasonography in 29 patients with FHF and 15 patients with uncomplicated acute viral hepatitis. No significant difference was observed in the portal vein parameters in the two groups. Nineteen patients with FHF survived. No difference in portal flow velocity and flow rate was observed between survivors and nonsurvivors. A significantly lower portal flow velocity was observed in nine patients of FHF with ascites compared with those without ascites (12.29 ± 2.81 vs 16.26 ± 4.87 cm/sec; P < 0.01). Portal hemodynamics do not significantly change in fulminant hepatic failure; therefore, it has no prognostic significance.

The objective was to determine whether plasma-derived hepatitis B vaccine is immunogenic in preterm appropriate for gestation babies when administered at birth and to compare the immunogenicity between 5 micrograms and 10 micrograms doses of the vaccine in these babies. Fifty preterm neonates (31-36 weeks gestation) were randomized to receive 5 micrograms or 10 micrograms doses of plasma-derived hepatitis B vaccine at birth, with subsequent doses 1 and 6 months later. Serum specimens were obtained a month after each dose of the vaccine and were tested for antibody to hepatitis B surface antigen (anti-HBs). Thirty six babies (gestation 31-36 weeks), 18 from each group competed the study. While 89.2% of the babies seroconverted, 82.1% achieved seroprotective titres of anti-HBS (10 mIU/ml). There was no difference between weight, gestational age, age of administration of vaccine and age of estimation of anti-HBs between 5 micrograms and 10 micrograms groups. The difference in the seroprotective rates were not statistically different between the groups (5 micrograms 78.5%; 10 micrograms--85.7%). Although immune response to plasma derived hepatitis B vaccine in preterm babies is suboptimal when the first dose is administered at birth, the full course achieves adequate seroprotective levels.

A case with hypokalemic periodic paralysis associated with tropical sprue is described, since no such association has been previously reported.

Colorectal varices and congestive rectopathy or colopathy have been erratically reported in patients with portal hypertension. The clinical importance of these entities has not been described. We assessed the changes in the venous system of the rectum by endoscopy and rectal endosonography (EUS). We also assessed the role of factors such as etiology of portal hypertension, grade of esophageal varices, sclerotherapy, and liver disease severity on the occurrence of these vascular changes.We studied changes in the venous system of the rectum using endoscopy and EUS in 60 patients with portal hypertension (cirrhotic 41, noncirrhotic 19). Ten patients with irritable bowel syndrome and 6 patients with hemorrhoids served as controls. Rectal varices were classified as tortuous, nodular, and tumorous. Corresponding appearances on rectal EUS were classified as single or discrete multiple, multiple, and innumerable submucosal veins, respectively. Evidence of congestive rectopathy was also recorded.Prevalence of rectal varices was 43.3% on endoscopy (73% tortuous, 19% nodular, and 8% tumorous) and 75% on EUS (p0.0005). The latter showed corresponding appearances of submucosal veins in 25 of 26 patients and detected submucosal veins not identified at endoscopy in 19 other patients. Congestive rectopathy was found in 38.3% of patients. Multiple small dilated vessels in the submucosa were seen in 23.3% patients on rectal EUS. The development of these vascular changes was significantly influenced by sclerotherapy, but not by higher grade of esophageal varices, the etiology of portal hypertension, or severity of liver disease.Changes in the rectal venous system are common, with rectal EUS being superior to endoscopy in detecting early, as well as florid, changes.

In experimental animals, sphincterotomy facilitates passage of solids from the gallbladder and inhibits gallstone formation apparently by improvement in gallbladder emptying. In humans, however, gallbladder emptying has not been studied following endoscopic sphincterotomy (ES) in patients with gallstones. We therefore prospectively studied resting and cerulin-stimulated gallbladder volumes by real time ultrasonography in 15 patients of choledocholithiasis with gallbladder in situ (eight with and seven without gallbladder calculi) before and after (after bile duct clearance) ES. ES significantly lowered resting gallbladder volume (21.2 +/- 10.6 vs 11.1 +/- 5.0; P < 0.0001) and cerulin-stimulated residual gallbladder volume (10.8 +/- 5.6 vs 4.4 +/- 2.1; P < 0.0001). ES also significantly increased the gallbladder ejection fraction (47.3 +/- 12.1% vs 58.8 +/- 11.1%; P < 0.0001). The rate constant for gallbladder emptying after cerulin infusion also increased significantly after ES (-0.022/min vs -0.031/ min; P < 0.0001). Significant improvement in gallbladder motility was observed in both groups of patients with and without gallbladder calculi. ES significantly improves gallbladder motility in humans.

BACKGROUND--Endoscopic sclerotherapy (EST) is an established method for controlling and preventing bleeding from oesophageal varices. However, oesophageal varices sclerose easily and require less sessions of EST in some patients while few fail to respond. This study therefore looked at changes in the vascular anatomy of the lower oesophagus and upper stomach that accompany successful sclerotherapy of oesophageal varices. METHODS--Endoscopic ultrasonography was performed in 50 patients with cirrhotic portal hypertension before (control, 20 patients) and after successful obliteration of varices with endoscopic sclerotherapy in a group of responders (EST-R, 20 patients) and in a group of non-responders (EST-NR, 10 patients). RESULTS--The median number and size of submucosal veins at the gastrooesophageal junction and in the lower oesophagus were significantly less in the EST-R group compared with control and EST-NR groups (p values between < 0.00001 and < 0.000001). Concomitantly, the number and size of paraoesophageal collaterals were significantly less in the EST-R group compared with the other two groups (p values between 0.02 and 0.00007). Perforating veins were identified in 14 (70%) patients in the control group, nine (90%) in the EST-NR group and in none in the EST-R group (p < 0.001 for both controls v EST-R and EST-R v EST-NR, and p = NS, control v EST-NR). CONCLUSION--Oesophageal variceal sclerosis is associated with significant reduction in the number and size of paraoesophageal collaterals and disappearance of perforating veins in the lower oesophagus.

Prolonged esophageal pH monitoring is the most accurate method for detecting abnormal gastroesophageal reflux (GER) in patients with gastroesophageal reflux disease (GERD). However, some investigators have found that short-duration postprandial pH monitoring in the upright position is also useful, while others have failed to find such results. Therefore, we have compared a 6-hr period of pH monitoring (3-hr postprandial period after daytime meal and 3-hr supine period) with a total 24-hr period in detecting abnormal gastroesophageal reflux. Sixty-five patients (44 men, mean age 41.3 years) with GERD and 16 healthy volunteers (11 men, mean age 34.3 years) underwent 24-hr pH monitoring according to a standard protocol. Various reflux parameters during 24-hr pH monitoring were compared with reflux parameters during the 6-hr period. Abnormal GER was detected in 56 patients presenting with typical symptoms of GERD (sensitivity 86.2%). These patients could be further divided into upright (N = 18), supine (N = 15), and combined (N = 23) refluxers, depending on the posture in which abnormal reflux occurred. Esophageal pH monitoring during the 3-hr postprandial upright period showed abnormal reflux in only 35 patients (sensitivity 53.8%; P0.00005, compared with the 24-hr pH monitoring period). Abnormal GER was identified in 13 of 18 upright, 19 of 23 combined, and only one of 15 supine refluxers, as well as in two of nine patients with normal 24-hr pH-metry. However, inclusion of the 3-hr supine monitoring period in the 3-hr postprandial upright period improved detection of abnormal GER to 78.5% (51 patients; P = NS compared with 24-hr pH monitoring period). This was related mainly to improved detection of abnormal GER in supine refluxers (11 of 15; 73.3%). Esophageal acid exposure time correlated significantly with severity of esophagitis only during the total and supine periods of both the 24- and 6-hr periods and not during the upright period. Esophageal acid clearance correlated significantly with increasing grades of esophagitis for the supine and total periods only. We conclude that 3-hr postprandial pH monitoring, as has been conventionally practiced, is not appropriate in the detection of abnormal GER; inclusion of a supine period in the short-duration pH monitoring schedule increases the detection of pathological reflux. We therefore recommend that a supine period should be included in short-duration pH monitoring schedules. We also found that supine reflex was the most important factor in the development of esophagitis.