Impact of Diabetes, Drug-Induced Liver Injury, and Sepsis on Outcomes in Metabolic Dysfunction Associated Fatty Liver Disease-Related Acute-on-Chronic Liver Failure.

INTRODUCTION: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute-on-chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied. METHODS: Patients with MAFLD-ACLF were recruited from the Asian Pacific Association for the Study of the Liver-ACLF Research Consortium (AARC registry). The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease as MAFLD (or previous nomenclature such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, or non-alcoholic steatohepatitis-cirrhosis). Patients with coexisting other etiologies of chronic liver disease (such as alcohol, hepatitis B virus, hepatitis C virus, etc.) were excluded. Data were randomly split into derivation (n = 258) and validation (n = 111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered. RESULTS: The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27% and hypertension in 29%. The dominant precipitants included viral hepatitis (hepatitis A virus and hepatitis E virus, 32%), drug-induced injury (drug-induced liver injury, 29%), and sepsis (23%). Model for End-Stage Liver Disease-Sodium (MELD-Na) and AARC scores on admission averaged 32 ± 6 and 10.4 ± 1.9. At 90 days, 51% survived. Nonviral precipitant, diabetes, bilirubin, international normalized ratio, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for nonviral precipitant), and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts. DISCUSSION: Almost half of patients with MAFLD-ACLF die within 90 days. Diabetes and nonviral precipitants such as drug-induced liver injury and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for patients with MAFLD-ACLF.

Long-term outcome of hepatitis delta in different regions world-wide: Results of the Hepatitis Delta International Network.

BACKGROUND AND AIMS: Chronic hepatitis delta represents a major global health burden. Clinical features of hepatitis D virus (HDV) infection vary largely between different regions worldwide. Treatment approaches are dependent on the approval status of distinct drugs and financial resources. METHODS: The Hepatitis Delta International Network (HDIN) registry involves researchers from all continents (Wranke, Liver International 2018). We here report long-term follow-up data of 648 hepatitis D patients recruited by 14 centres in 11 countries. Liver-related clinical endpoints were defined as hepatic decompensation (ascites, encephalopathy and variceal bleeding), liver transplantation, hepatocellular carcinoma or liver-related death. RESULTS: Patient data were available from all continents but Africa: 22% from Eastern Mediterranean, 32% from Eastern Europe and Central Asia, 13% from Central and Southern Europe, 14% from South Asia (mainly Pakistan) and 19% from South America (mainly Brazil). The mean follow-up was 6.4 (.6-28) years. During follow-up, 195 patients (32%) developed a liver-related clinical event after 3.5 (±3.3) years. Liver cirrhosis at baseline and a detectable HDV RNA test during follow-up were associated with a worse clinical outcome in multivariate regression analysis while patients receiving interferon alfa-based therapies developed clinical endpoints less frequently. Patients from South Asia developed endpoints earlier and had the highest mortality. CONCLUSIONS: The HDIN registry confirms the severity of hepatitis D and provides further evidence for HDV viraemia as a main risk factor for disease progression. Hepatitis D seems to take a particularly severe course in patients born in Pakistan. There is an urgent need to extend access to antiviral therapies and to provide appropriate education about HDV infection.

Mesenteric panniculitis associated with non-alcoholic fatty liver disease: A case series.

Mesenter ic p anniculitis (MP) is a b enign infla mmatory condi tion of the abdomin al mesentery, whi ch presents with a wid e variety of symptoms. I t is diagnosed non - invasively through com puted to mography (CT ) scan, whereas biopsy is still co nside red th e gold standa rd. Steroids are the first line of treatment. Here, we report four cases who presented with abdominal pain. These patients were overweight and the CT scan findings were suggestive of mese nte ric panniculitis. Three cases had concomitant non- alcoholic steatohep atitis w ith el evated alanine transaminase levels, dyslipidaemia, and insulin resistance. FibroSca n showed moderate to severe steatosis. PNPLA3 rs738409 genotype was homozygous positive (GG) in one patient, whereas two patients were heterozygous positive (CG ). This a ssociat io n has not been well-described so far and w arrants f ur ther inve s tigation. There may be some common predisposing factors.

Saccharomyces cerevisiae for abdominal pain and discomfort in irritable bowel syndrome patients.

Background: Irritable Bowel Syndrome (IBS) leads to significant impairment of health-related quality of life, for the alleviation of which, the efficacy of available therapies is modest. Limited data is available on the role of Saccharomyces cerevisiae in treating patients with IBS. Methods: Thirty patients with IBS as per Rome-IV criteria, visiting our outpatient department from March 2021 to October 2021, were given capsule Saccharomyces cerevisiae 500 mg twice daily for four weeks. Evaluation for abdominal pain symptoms was done every week and the patient's compliance was assessed. IBS Quality of Life (QOL) questionnaires were filled at baseline and after four weeks of treatment. The QOL and pain scales were adjusted to 0-100 for statistical analysis. Results: Seventeen patients (56.7%) were males. The age range was 21-72 years (mean ± SD: 39. 63 ± 14.32), out of which 18(60%) patients were 20-40 years old. Body Mass Index (BMI) ranged from 18-33 (25.33 ± 4.09), and 17 (56.67%) were overweight or obese. Sixteen patients had constipation predominant (53.3%), nine had diarrhea-predominant (30%), and five had mixed-type (16.7%) IBS. There was an improvement in the pain score from 63.81 at week 0 (W0) to 20.48 at the end of week 4 (W4) (p<0.001). An improvement was noted in all the eight categories of IBS QOL questionnaire, i.e., dysphoria (p<0.001), interference with activity (p<0.001), body image (p<0.001), health worry (p<0.001), food avoidance (p<0.001), social reaction (p<0.001), sexual function (p<0.001) and relationships (p<0.001). There was an overall improvement in QOL score from a mean of 24.68 at baseline to 58.09 at the end of the study duration (p<0.001). The improvement in the pain score showed a positive correlation with the improvement in quality of life (p<0.001). Conclusion: Treatment with Saccharomyces cerevisiae improved the pain and quality of life in patients with IBS and it appears to be a promising option for alleviating symptoms in these patients.

Water stress effects on stay green and chlorophyll fluorescence with focus on yield characteristics of diverse bread wheats.

MAIN CONCLUSION: The study provided an insight toward better understanding of stay-green mechanisms for drought tolerance improvement and identified that synthetic-derived wheats proved as a promising germplasm for improved tolerance against water stress. Stay-green (SG) trait is considered to be related with the ability of wheat plants to maintain photosynthesis and CO2 assimilation. The present study explored the interaction of water stress with SG expression through physio-biochemical, agronomic and phenotypic responses among diverse wheat germplasm comprising of 200 synthetic hexaploids, 12 synthetic derivatives, 97 landraces and 16 conventional bread wheat varieties, for 2 years. The study established that variation of SG trait existed in the studied wheat germplasm and there was positive association between SG trait and tolerance to water stress. The relationship of SG trait with chlorophyll content (r = 0.97), ETR (r = 0.28), GNS (r = 0.44), BMP (r = 0.34) and GYP (r = 0.44) was particularly promising under water stress environment. Regarding chlorophyll fluorescence, the positive correlation of фPSII (r = 0.21), qP (r = 0.27) and ETR (r = 0.44) with grain yield per plant was noted. The improved ΦPSII and Fv/Fm of PSII photochemistry resulted in the high photosynthesis activity in SG wheat genotypes. Regarding relative water content and photochemical quenching coefficient, synthetic-derived wheats were better by maintaining 20.9, 9.8 and 16.1% more RWC and exhibiting 30.2, 13.5 and 17.9% more qP when compared with landraces, varieties and synthetic hexaploids, respectively, under water stress environment. Synthetic derived wheats also exhibited relatively more SG character with good yield and were more tolerant to water stress in terms of grain yield, grain weight per plant, better photosynthetic performance through chlorophyll fluorescence measurement, high leaf chlorophyll and proline content, and hence, may be used as novel sources for breeding drought tolerant materials. The study will further facilitate research on wheat leaf senescence and will add to better understanding of SG mechanisms for drought tolerance improvement.

Point of Care Testing for SARS-COV-2 Antibodies before doing Endoscopy.

Objectives: COVID-19 has taken the world by storm, creating much disparity among both healthcare and non-healthcare centres regarding the provision of services. The purpose of our study was to see the prevalence of the SARS-COV-2 exposure in the asymptomatic patients undergoing the endoscopic procedure, already triaged based on history and examination. Methods: Total 207 patients were enrolled during a time period of five months during October 2020 to April 2021 at Dr. Ziauddin Hospital Clifton campus, Karachi. In this prospective observational study patients undergoing endoscopic procedures were included after taking informed consent. The patients who already tested positive for COVID-19 by PCR were excluded. Patients were tested for Covid serology by immunochromatographic rapid serology test (ICT). Standard Operating Procedures for dealing with endoscopy patients during the COVID era were followed in all patients irrespective of antibody status. Result: Total number of patients included was 207; males were 121 (58.5%). The mean age was 48.5 ± 17.55 (range 13 to 92). Forty eight patients (23.2%) were positive for either antibody suggesting exposure to the COVID-19 virus. Out of these combined IgM and IgG positivity was seen in 24 (11.5%), IgM mono antibody positivity was seen in 7 (3.38%) and 17 (8.21%) of the study population tested positive for IgG only. 15 out of 46 (32.6%) patients with chronic liver disease in the cohort were seropositive for COVID antibodies. Conclusion: About one-fourth of the patients undergoing the endoscopic procedure were tested positive for COVID antibodies of which a significant percentage had chronic liver disease. It stresses the need of observing standard precautions to prevent the spread of infection during these procedures, especially in the vulnerable population.

Patients visiting gastroenterology clinics avoid giving honest history for COVID-19 related symptoms in the pre-clinic triage.

OBJECTIVE: To assess the discrepancy in terms of history related to coronavirus disease-2019 and symptoms given in the pre-clinic triage and to the doctor attending the patient in a gastroenterology clinic. METHODS: The observational study was conducted from September 2020 to January 2021 at the Gastroenterology outpatient department of Dr Ziauddin Hospital's Clifton unit in Karachi, and comprised all patients visiting the facility regardless of age and gender. Data was collected using a questionnaire that was first filled up by the receptionist outside the clinic and was then administered again once the patient entered the clinic. Discrepancy on the answers was then checked and associations were determined with clinical assessment. Data was analysed using SPSS 20. RESULTS: Of the 300 patients, 184(61.3%) were males and 116(38.6%) were females. The overall mean age was 55 ± 16.98 (range: 18-92 years). Discrepancy between pre-clinic and in-clinic self-reported data was significant for fever, cough, fatigue, headache, body ache, diarrhoea, sore throat, loss of sense of smell/taste, shortness of breath, and contact with someone positive for coronavirus disease-2019 was significant (p<0.05). CONCLUSIONS: Patients were found to be afraid of getting barred from seeing a consultant, had fear of hospital-based isolation or were in denial regarding the pandemic.

Impact of metabolic risk factors on the severity and outcome of patients with alcohol-associated acute-on-chronic liver failure.

BACKGROUND: Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. The present study evaluated this effect in patients with alcohol-associated acute-on-chronic liver failure (ACLF). METHODOLOGY: One thousand two hundred and sixteen prospectively enrolled patients with ACLF (males 98%, mean age 42.5 ± 9.4 years, mean CTP, MELD and AARC scores of 12 ± 1.4, 29.7 ± 7 and 9.8 ± 2 respectively) from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) database were analysed retrospectively. Patients with or without metabolic risk factors were compared for severity (CTP, MELD, AARC scores) and day 30 and 90 mortality. Information on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension and dyslipidaemia were available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively. RESULTS: Overall, 392 (32%) patients died at day 30 and 528 (43%) at day 90. Overweight/obesity, T2DM, hypertension and dyslipidaemia were present in 154 (15%), 142 (14%), 66 (7%) and 141 (15%) patients, respectively, with no risk factors in 809 (67%) patients. Patients with overweight/obesity had higher MELD scores (30.6 ± 7.1 vs 29.2 ± 6.9, P = .007) and those with dyslipidaemia had higher AARC scores (10.4 ± 1.2 vs 9.8 ± 2, P = .014). Overweight/obesity was associated with increased day 30 mortality (HR 1.54, 95% CI 1.06-2.24, P = .023). None of other metabolic risk factors, alone or in combination, had any impact on disease severity or mortality. On multivariate analysis, overweight or obesity was significantly associated with 30-day mortality (aHR 1.91, 95% CI 1.41-2.59, P < .001), independent of age, CTP, MELD and AARC scores. CONCLUSION: Overweight/obesity and dyslipidaemia increase the severity of alcohol-associated ACLF, and the former also increases the short-term mortality in these patients.

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

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

RLP, a bacteriophage of the family Podoviridae, rescues mice from bacteremia caused by multi-drug-resistant Pseudomonas aeruginosa.

Antimicrobial resistance is a serious threat to public health around the globe. According to the World Health Organization, there will be a return to the pre-penicillin era by 2050 if no new antimicrobials are discovered. It is therefore necessary to find new antimicrobials and alternatives. Pseudomonas aeruginosa exhibits resistance against many antibiotics and causes a variety of infections in immunocompromised individuals and especially in those with burn wounds and lung infections. Bacteriophage RLP against P. aeruginosa strain PA-1 was isolated from the Ravi River near Lahore. It showed marked stability at different pH values and temperatures, with the maximum storage stability at 4 °C. It demonstrated the ability to inhibit bacterial growth for up to 20 h, replicated in 25 min, and produced 154 virions per infected cell. RLP showed a broad host range, infecting 50% (19/38) of the multiple-drug-resistant (MDR) P. aeruginosa strains that were tested. The 43-kbp-long genome of RLP is a double-stranded DNA molecule that encodes 56 proteins in total: 34 with known functions, and 22 with no homolog in the gene databases. A cascade system of lytic machinery is also present in the form of four genes (R/z, R/z1, holin and endolysin). Therapeutic studies of RLP in bacteremic mice infected with P. aeruginosa strain PA-1 demonstrated a 92% survival rate in the treated group compared with 7.4% in the untreated group, and this result was statistically significant. Based on its physiological and genetic properties, ability to cause a reduction in bacterial growth in vitro and its in vivo therapeutic efficacy, RLP could be a good candidate for use in phage therapy.

High yield expression, characterization, and biological activity of IFNα2-Tα1 fusion protein.

The use of interferon α-2 in combination with thymosin α-1 shows higher anti-cancer effect in comparison when both are used individually because of their synergistic effects. In this study we produced an important human interferon α-2-thymosin α-1 (IFNα2-Tα1) fusion protein with probable pharmaceutical properties coupled to its high-level expression, characterization, and study of its biological activity. The IFNα2-Tα1 fusion gene was constructed by over-lap extension PCR and expressed in Escherichia coli expression system. The expression of IFNα2-Tα1 fusion protein was optimized to higher level and its maximum expression was obtained in modified terrific broth medium when lactose was used as inducer. The fusion protein was refolded into its native biologically active form with maximum yield of 83.14% followed by purification with ∼98% purity and 69% final yield. A band of purified IFNα2-Tα1 fusion protein equal to ∼23 kDa was observed on 12 % SDS-PAGE gel. The integrity of IFNα2-Tα1 fusion protein was confirmed by western blot analysis and secondary structure was assessed by CD spectroscopy. When IFNα2-Tα1 fusion protein was subjected to its biological activity analysis it was observed that it exhibits both IFNα2 & Tα1 activities as well as significantly higher anticancer activity as compared to IFNα-2 alone.

Non-alcoholic fatty liver disease: A real threat in Pakistan.

The rise in obesity, along with its association with unhealthy lifestyles and poor health awareness, has lead to an increasing prevalence of non-alcoholic fatty liver disease (NAFLD). Only a few studies have addressed the changing trends in obesity and have tried to estimate the frequency of NAFLD in Pakistan. Fatty liver is seen in about 15% of the general population. Insulin resistance, diabetes, dyslipidaemia, high body mass index (BMI) and waist circumference, and increasing age are associated with NAFLD. In patients without insulin resistance, dyslipidaemia is usually present. Lean NAFLD is not common. In facilities where elastography in unavailable, NAFLD fibrosis score may be used to predict NAFLD in such patients. There is a need to conduct population-based studies to understand the risks and to design initiatives to increase public awareness regarding this disease. NAFLD screening is advisable in overweight individuals, diabetic patients, and persons at high cardiovascular disease risk.

Addition of bismuth to standard triple therapy for Helicobacter pylori eradication: a randomised controlled trial.

OBJECTIVE: To compare the effect of addition of bismuth to the standard triple therapy for eradication of Helicobacter pylori (H. pylori) in a randomised controlled trial. METHODS: The study was performed from June 2018-May 2019, in the two outpatient departments located at two different campuses of Ziauddin university hospitals (ZUH) Karachi. Ethical approval was obtained from the Ethics Review Committee of ZUH. It was designed as a randomized control trial in a parallel fashion. Arm A received triple therapy including amoxicillin, clarithromycin, and omeprazole for two weeks and Arm B received quadruple therapy adding colloidal bismuth subcitrate to the triple therapy. A stool antigen test was done six weeks post treatment to confirm H. pylori eradication. RESULTS: A total of 196 participants were included, out of which 102(52%) were males and 94 (48%) were females. Among the patients receiving quadruple therapy, 92/98(93.8%) had negative posttreatment stool antigen results, while among triple therapy recipients 83/98 (84.6%) had negative stool antigen results, according to intention-to-treat analysis (p value=0.038; odds ratio 2.77, 95% CI 1.03-7.47). However, p-value changed to 0.082 (odds ratio 2.40, 95% CI 0.87-6.60) in per-protocol analysis as stool antigen results were not available in two patients in the triple therapy arm. No difference in the side-effect profiles of either arm was noted. CONCLUSIONS: Eradication rates of H. pylori may be modestly improved by addition of bismuth to the standard triple therapy. CLINICAL TRIAL NUMBER: 03968302 (clinicaltrials.gov).

Treating chronic hepatitis delta: The need for surrogate markers of treatment efficacy.

Chronic hepatitis delta represents the most severe form of chronic viral hepatitis. The current treatment of hepatitis delta virus (HDV) infection consists of the use of interferons and is largely unsatisfactory. Several new compounds are currently in development for the treatment of HDV infection. However, surrogate markers that can be used to develop clinical endpoints in HDV infection are not well defined. In the current manuscript, we aimed to evaluate the existing data on treatment of HDV infection and to suggest treatment goals (possible "trial endpoints") that could be used across different clinical trials.

Drug-Induced Acute-on-Chronic Liver Failure in Asian Patients.

OBJECTIVES: Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF. METHODS: We identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation. RESULTS: Of the 3,132 patients with ACLF, drugs were implicated as a cause in 329 (10.5%, mean age 47 years, 65% men) and other nondrug causes in 2,803 (89.5%) (group B). Complementary and alternative medications (71.7%) were the commonest insult, followed by combination antituberculosis therapy drugs (27.3%). Alcoholic liver disease (28.6%), cryptogenic liver disease (25.5%), and non-alcoholic steatohepatitis (NASH) (16.7%) were common causes of underlying liver diseases. Patients with drug-induced ACLF had jaundice (100%), ascites (88%), encephalopathy (46.5%), high Model for End-Stage Liver Disease (MELD) (30.2), and Child-Turcotte-Pugh score (12.1). The overall 90-day mortality was higher in drug-induced (46.5%) than in non-drug-induced ACLF (38.8%) (P = 0.007). The Cox regression model identified arterial lactate (P < 0.001) and total bilirubin (P = 0.008) as predictors of mortality. DISCUSSION: Drugs are important identifiable causes of ACLF in Asia-Pacific countries, predominantly from complementary and alternative medications, followed by antituberculosis drugs. Encephalopathy, bilirubin, blood urea, lactate, and international normalized ratio (INR) predict mortality in drug-induced ACLF.

Clinical and virological heterogeneity of hepatitis delta in different regions world-wide: The Hepatitis Delta International Network (HDIN).

BACKGROUND & AIMS: Chronic hepatitis D (delta) is a major global health burden. Clinical and virological characteristics of patients with hepatitis D virus (HDV) infection and treatment approaches in different regions world-wide are poorly defined. METHODS: The Hepatitis Delta International Network (HDIN) registry was established in 2011 with centres in Europe, Asia, North- and South America. Here, we report on clinical/ virological characteristics of the first 1576 patients with ongoing or past HDV infection included in the database until October 2016 and performed a retrospective outcome analysis. The primary aim was to investigate if the region of origin was associated with HDV replication and clinical outcome. RESULTS: The majority of patients was male (n = 979, 62%) and the mean age was 36.7 years (range 1-79, with 9% of patients younger than 20 years). Most patients were HBeAg-negative (77%) and HDV-RNA positive (85%). Cirrhosis was reported in 48.7% of cases which included 13% of patients with previous or ongoing liver decompensation. Hepatocellular carcinoma (HCC) developed in 30 patients (2.5%) and 44 (3.6%) underwent liver transplantation. Regions of origin were independently associated with clinical endpoints and detectability of HDV RNA. Antiviral therapy was administered to 356 patients with different treatment uptakes in different regions. Of these, 264 patients were treated with interferon-a and 92 were treated with HBV-Nucs only. CONCLUSIONS: The HDIN registry confirms the severity of hepatitis delta but also highlights the heterogeneity of patient characteristics and clinical outcomes in different regions. There is an urgent need for novel treatment options for HDV infection.

Development of predisposition, injury, response, organ failure model for predicting acute kidney injury in acute on chronic liver failure.

BACKGROUND AND AIM: There is limited data on predictors of acute kidney injury in acute on chronic liver failure. We developed a PIRO model (Predisposition, Injury, Response, Organ failure) for predicting acute kidney injury in a multicentric cohort of acute on chronic liver failure patients. PATIENTS AND METHODS: Data of 2360 patients from APASL-ACLF Research Consortium (AARC) was analysed. Multivariate logistic regression model (PIRO score) was developed from a derivation cohort (n=1363) which was validated in another prospective multicentric cohort of acute on chronic liver failure patients (n=997). RESULTS: Factors significant for P component were serum creatinine[(≥2 mg/dL)OR 4.52, 95% CI (3.67-5.30)], bilirubin [(<12 mg/dL,OR 1) vs (12-30 mg/dL,OR 1.45, 95% 1.1-2.63) vs (≥30 mg/dL,OR 2.6, 95% CI 1.3-5.2)], serum potassium [(<3 mmol/LOR-1) vs (3-4.9 mmol/L,OR 2.7, 95% CI 1.05-1.97) vs (≥5 mmol/L,OR 4.34, 95% CI 1.67-11.3)] and blood urea (OR 3.73, 95% CI 2.5-5.5); for I component nephrotoxic medications (OR-9.86, 95% CI 3.2-30.8); for R component,Systemic Inflammatory Response Syndrome,(OR-2.14, 95% CI 1.4-3.3); for O component, Circulatory failure (OR-3.5, 95% CI 2.2-5.5). The PIRO score predicted acute kidney injury with C-index of 0.95 and 0.96 in the derivation and validation cohort. The increasing PIRO score was also associated with mortality (P<.001) in both the derivation and validation cohorts. CONCLUSIONS: The PIRO model identifies and stratifies acute on chronic liver failure patients at risk of developing acute kidney injury. It reliably predicts mortality in these patients, underscoring the prognostic significance of acute kidney injury in patients with acute on chronic liver failure.

Systemic inflammatory response syndrome in acute-on-chronic liver failure: Relevance of 'golden window': A prospective study.

BACKGROUND AND AIM: Systemic inflammatory response syndrome (SIRS) is an early marker of sepsis and ongoing inflammation and has been reported in large proportion of acute-on-chronic liver failure (ACLF) patients. Whether sepsis is the cause or the result of liver failure is unclear and is vital to know. To address this, the study investigated the course and outcome of ACLF patients without SIRS/sepsis. METHODS: Consecutive ACLF patients were monitored for the development of SIRS/sepsis and associated complications and followed till 90 days, liver transplant or death. RESULTS: Of 561 patients, 201 (35.8%) had no SIRS and 360 (64.2%) had SIRS with or without infection. New onset SIRS and sepsis developed in 74.6% and 8% respectively in a median of 7 (range 4-15) days, at a rate of 11% per day. The cumulative incidence of new SIRS was 29%, 92.8%, and 100% by days 4, 7, and 15. Liver failure, that is, bilirubin > 12 mg/dL (odds ratio [OR] = 2.5 [95% confidence interval {CI} = 1.05-6.19], P = 0.04) at days 0 and 4, and renal failure at day 4 (OR = 6.74 [95%CI = 1.50-13.29], P = 0.01), independently predicted new onset SIRS. Absence of SIRS in the first week was associated with reduced incidence of organ failure (20% vs 39.4%, P = 0.003), as was the 28-day (17.6% vs 36%, P = 0.02) and 90-day (27.5% vs 51%,P = 0.002) mortality. The 90-day mortality was 61.6% in the total cohort and that for those having no SIRS and SIRS at presentation were 42.8% and 65%, respectively (P < 0.001). CONCLUSION: Liver failure predicts the development of SIRS. New onset SIRS in the first week is an important determinant of early sepsis, organ failure, and survival. Prompt interventions in this 'golden window' before development of sepsis may improve the outcome of ACLF.