Impact of Diabetes, Drug-Induced Liver Injury, and Sepsis on Outcomes in MAFLD-Related Acute-on-Chronic Liver Failure.

BACKGROUND: 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 AARC registry. The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease (CLD) as MAFLD (or previous nomenclature such as NAFLD, NASH, or NASH-cirrhosis). Patients with coexisting other etiologies of CLD (such as alcohol, HBV, HCV, etc.) were excluded. Data was 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 (HAV and HEV, 32%), drug-induced injury (DILI, 29%) and sepsis (23%). MELD-Na and AARC scores upon admission averaged 32±6 and 10.4±1.9. At 90 days, 51% survived. Non-viral precipitant, diabetes, bilirubin, INR, 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 non-viral precipitant) and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts. CONCLUSION: Almost half of MAFLD-ACLF patients die within 90 days. Diabetes and non-viral precipitants such as DILI and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for MAFLD-ACLF patients.

Diet and feeding behavior of a group of high-altitude rhesus macaques: high adaptation to food shortages and seasonal fluctuations.

Diet and feeding behavior data are crucial to a deep understanding of the behavioral response and adaptation of primates to a high-altitude environment. From August 2019 to June 2021, we collected data on the feeding behavior of a high-altitude rhesus macaque Macaca mulatta group from Yajiang County, Western Sichuan Plateau, which has an altitude of over 3,500 m. The results showed that feeding (33.0 ± 1.8%) and moving (28.3 ± 2.6%) were the dominant behavior of rhesus macaques. Macaques ate 193 food items, comprising 11 food categories from 90 species. Our study found that plant roots (30.9 ± 30.1%) and young leaves (28.0 ± 33.1%) were the main foods eaten by macaques. The preferred foods of rhesus macaques were young leaves, fruits, and seeds, and the consumption of these items was positively correlated with its food availability. When the availability of preferred foods was low, macaques took plant roots, barks, and fallen leaves as fallback foods. In particular, roots were a dominant food item in winter, and this way of feeding became a key survival strategy. Our results suggest that, facing the relative scarcity and strong seasonal fluctuations of food resources in high-altitude habitat, macaques adopt active foraging strategies, relying on a variety of food species and adjusting flexibly their food choices based on food availability, which may help to maximize the energy efficiency of high-altitude macaques.

Acute variceal bleeding portends poor outcomes in patients with acute-on-chronic liver failure: a propensity score matched study from the APASL ACLF Research Consortium (AARC).

BACKGROUND AND AIMS: Limited data exist regarding outcomes of acute variceal bleeding (AVB) in patients with acute-on-chronic liver failure (ACLF), especially in those with hepatic failure. We evaluated the outcomes of AVB in patients with ACLF in a multinational cohort of APASL ACLF Research Consortium (AARC). METHODS: Prospectively maintained data from AARC database on patients with ACLF who developed AVB (ACLF-AVB) was analysed. This data included demographic profile, severity of liver disease, and rebleeding and mortality in 6 weeks. These outcomes were compared with a propensity score matched (PSM) cohort of ACLF matched for severity of liver disease (MELD, AARC score) without AVB (ACLF without AVB). RESULTS: Of the 4434 ACLF patients, the outcomes in ACLF-AVB (n = 72) [mean age-46 ± 10.4 years, 93% males, 66% with alcoholic liver disease, 65% with alcoholic hepatitis, AARC score: 10.1 ± 2.2, MELD score: 34 (IQR: 27-40)] were compared with a PSM cohort selected in a ratio of 1:2 (n = 143) [mean age-44.9 ± 12.5 years, 82.5% males, 48% alcoholic liver disease, 55.7% alcoholic hepatitis, AARC score: 9.4 ± 1.5, MELD score: 32 (IQR: 24-40)] of ACLF-without AVB. Despite PSM, ACLF patients with AVB had a higher baseline HVPG than without AVB (25.00 [IQR: 23.00-28.00] vs. 17.00 [15.00-21.75] mmHg; p = 0.045). The 6-week mortality in ACLF patients with or without AVB was 70.8% and 53.8%, respectively (p = 0.025). The 6-week rebleeding rate was 23% in ACLF-AVB. Presence of ascites [hazard ratio (HR) 2.2 (95% CI 1.03-9.8), p = 0.026], AVB [HR 1.9 (95% CI 1.2-2.5, p = 0.03)], and MELD score [HR 1.7 (95% CI 1.1-2.1), p = 0.001] independently predicted mortality in the overall ACLF cohort. CONCLUSION: Development of AVB confers poor outcomes in patients with ACLF with a high 6-week mortality. Elevated HVPG at baseline represents a potential risk factor for future AVB in ACLF.

Prevalence and new genotypes of Enterocytozoon bieneusi in wild rhesus macaque (Macaca mulatta) in China: A zoonotic concern.

Enterocytozoon bieneusi is a zoonotic pathogen with a wide range of animal host. There are only few reports of E. bieneusi infection in wild Chinese rhesus macaques. Here, we determined the prevalence of E. bieneusi in nine wild rhesus macaque populations and assessed their zoonotic potential by performed genotype of ITS gene. A total of 324 fecal samples of rhesus macaque were collected in nine geographical populations from five Chinese provinces (Sichuan, Chongqing, Qinghai, Tibet and Hainan). 38 samples (11.7%) were found to be infected with E. bieneusi, and 11 genotypes were identified including three known genotypes (D, EbpC and SCC-2) and eight novel genotypes named Mul6∼13. Genotype D (63.2%) was the most prevalent, being observed in seven populations except XZ-2 and QH, and other genotypes were identified only in a single area. According to the phylogenetic analysis, Mul6∼9, Mul11∼13 and zoonotic genotype D were clustered into Group 1, indicating that these genotypes may be potentially zoonotic. Among nine populations, population SC-3 had the highest infection rate (26.3%), and the lowest was the wild QH population without infection, but the difference of infection rate among the nine populations is not significant. It is concluded that, rhesus macaque populations are generally infected E. bieneusi in many areas of China, and there may be a risk of cross infection with E. bieneusi in some areas found having zoonotic genotypes, and these areas should be paid more attention to prevent.

'First week' is the crucial period for deciding living donor liver transplantation in patients with acute-on-chronic liver failure.

BACKGROUND AND AIMS: 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). METHODS: 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. RESULTS: 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 < 0.01) contributing to 23% of the first week and 55% of all-cause 28-day mortality. In a matched cohort analysis, the actuarial survival with LT (n = 41) and conditional survival in the absence of transplant (n = 191) were comparable, when the condition, i.e., transplant was adjusted. The comparison curve showed differentiation in survival beyond 7 days (p < 0.01). CONCLUSIONS: ACLF is a rapidly progressive disease and risk stratification within the first week of hospitalization is needed. 'Emergent LT' should be defined in the first week in the ACLF patients; the transplant window for improving survival in a live donor setting.

Comparative accuracy of prognostic models for short-term mortality in acute-on-chronic liver failure patients: CAP-ACLF.

BACKGROUND: 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. METHODS: 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-R2, relative prediction errors, and odds ratios. RESULTS: Thirty-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%, R2 0.609 and lower prediction errors by 10-50%. Day-7 NACSELD-ACLF-binary was the simple model (minimum AIC/BIC 12/17) with the highest odds (8.859) and sensitivity (100%) but with a lower PPV (70%) for mortality. Patients with day-7 AARC score > 12 had the lowest 30-day survival (5.7%). CONCLUSIONS: APASL-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.

Emerging Super-specialty of Neurology: Intraoperative Neurophysiological Monitoring (IONM) and Experience in Various Neurosurgeries at a Tertiary Care Hospital in Doha, Qatar.

Introduction Intraoperative neurophysiological monitoring (IONM) helps in better patient outcomes by minimizing risks related to the functional status of the nervous system during surgical procedures. An IONM alert to the surgical team during the surgery can help them identify the cause and take immediate corrective action. IONM confers possible benefits, including improved surgical morbidity and mortality, better patient care, minimal neurological deficits, reduced hospital stay, medical costs, and litigation risk. In addition, a highly skilled IONM team will make a better patient outcome. Methods We retrospectively reviewed 62 consecutive patients who underwent intracranial and spinal neurosurgical procedures. Multimodality IONM was utilized, including somatosensory evoked potentials, transcranial electrical motor evoked potential, spontaneous and triggered electromyography, electroencephalography, electrocorticography, cortical sensory mapping, and direct electrical cortical stimulation. Of a total of 62 patients, two patients revealed neurotonic EMG discharges during IONM, and most patients woke up without any new neurological deficit. Results Sixty-two patients were included, ranging from age 5 to 77 years (mean 43.5 years), with 54.8% men and 45.2% female. Multimodality IONM was used in all patients. Two EMG alerts were recorded during IONM, during a brain tumor resection, and right acetabular hip surgery with postoperative right foot drop. Conclusion Multimodality IONM is the gold standard of care for any surgical services and is used as real-time monitoring of functional integrity of neural structures at risk. If utilized by trained and expert teams, numerous surgeries may benefit from multimodality intraoperative neurophysiologic monitoring.

The impacts of combined social and economic empowerment training on intimate partner violence, depression, gender norms and livelihoods among women: an individually randomised controlled trial and qualitative study in Afghanistan.

Introduction: We assessed whether the Women for Women International (WfWI) economic and social empowerment programme could reduce women's experiences of intimate partner violence (IPV) and depression in Afghanistan. Methods: We conducted a two-arm individually randomised controlled trial in six urban and peri-urban communities. Communities were selected by WfWI for being conflict affected and showing signs of economic vulnerability (eg, little or no education, living in extreme poverty). Individual eligibility were female, aged 18-49, able to consent to participate and one woman per household. At 22 months, three primary outcomes were assessed: past year physical IPV experience; past year severe IPV experience; depressive symptoms. There was no blinding to arms. We conducted an intention-to-treat analysis, controlling for age. We also conducted qualitative interviews at endline, analysed using thematic analysis. Results: 1461 women (n=933 married) were recruited and randomised. Retention at endline was n=1210 (82%). Primary outcomes were in the hypothesised direction, but showed no significant impacts: physical IPV (adjusted OR (aOR) 0.88 (0.62 to 1.23)), severe IPV (aOR 0.75 (0.50 to 1.11)) and depressive symptoms (ß -0.35 (-1.19 to 0.48)). Women reported reduced food insecurity (ß -0.48 (-0.85 to -0.12)), higher earnings (ß 3.79 (0.96 to 6.61)) and savings (ß 11.79 (9.95 to 13.64)). Women reported less gender-inequitable attitudes (ß -0.89 (-1.15 to -0.62)), more household decision-making (ß 0.35 (-0.04 to 0.74)) and increased mobility (aOR 1.78 (1.27 to 2.50)). Twenty-eight in-depth interviews were conducted. Conclusion: The intervention did not impact IPV or depression. The intervention did improve livelihoods, create more gender-equitable relationships and increase women's mobility. Translating these gains into IPV and depression reduction is critical. Trial registration number: NCT03236948, registered 2 August 2017.

An individually randomized controlled trial to determine the effectiveness of the Women for Women International Programme in reducing intimate partner violence and strengthening livelihoods amongst women in Afghanistan: trial design, methods and baseline findings.

BACKGROUND: Intimate Partner Violence (IPV) is the most common form of violence in conflict and post-conflict settings, but there are few evaluations of interventions to prevent IPV in such settings. METHODS: The Women for Women International (WfWI) intervention is a year-long combined economic and social empowerment intervention for marginalized women survivors of conflict. Primarily, it seeks to support women to achieve four key outcomes: women earn and save money; women improve their health and well-being; women influence decisions in their homes and communities; women connect to networks for support. The organization recognizes Violence Against Women and Girls (VAWG) as a significant barrier to women's empowerment and expects to see reduction in VAWG, and specifically IPV, as part of building women's social and economic empowerment. This program is being quantitatively evaluated through an individually randomized control trial amongst women in Afghanistan, with a 24-month follow up. A comparison of baseline characteristics of participants is also included as well as a discussion of implementation of the baseline research. DISCUSSION: There is a high demand amongst Afghan women for such interventions, and this posed challenges in completing the randomization and baseline. In addition, the complex security situation in Afghanistan also posed challenges. However, despite these issues, recruitment was successfully achieved and the arms were balanced on socio-demographic measures. The evaluation will contribute to the limited evidence base on interventions to prevent IPV in conflict-affected settings. TRIAL REGISTRATION: NCT03236948 . Registered 28 July 2017, retrospectively registered.

Association of COL4A1 (rs605143, rs565470) and CD14 (rs2569190) genes polymorphism with coronary artery disease.

Coronary artery disease (CAD) is the leading cause of death worldwide and it is basically caused by atherosclerosis. The atherosclerotic process includes complex events and each one involves a specific biological pathway and different genes. According to World Health Organization report, Cardiovascular diseases will be the largest cause of death and disability by 2020, with an estimated 2.6 million Indians predicted to die due to CAD predominantly with myocardial infarction. Genetic factors are estimated to contribute 30-60% of the CAD risk. The aim of this study is to investigate the association of COL4A1 and CD14 genes polymorphism with CAD. This study included 345 subjects, 185 CAD cases and 160 healthy controls. Single-nucleotide polymorphisms were evaluated by polymerase chain reaction and restriction fragment length polymorphism. Alleles and genotype frequencies between cases and controls were compared using χ2 and Student's t tests. Odds ratios and 95% confidence intervals were calculated by logistic regression to assess the relative association between disease and genotypes. In this study, CD14 (rs2569190), CC (P = 0.008) genotypes, and C allele (P = 0.007) were found to be a positive risk factor, while TT genotype (P = 0.045) and T allele (P = 0.007) as negative risk factor for CAD. Significant differences were not observed in COL4A1 (rs605143 and rs565470) gene polymorphism with CAD. It seems that CD14 gene polymorphism might be associated with the risk of CAD, whereas COL4A1 gene polymorphism was not found to confer any risk of CAD.

Understanding how Afghan women utilise a gender transformative and economic empowerment intervention: A qualitative study.

The processes through which women's economic empowerment interventions are envisaged to improve women's health are strongly embedded in notions of building women's agency and autonomy. Yet despite the ubiquity of such interventions, there remains incredibly little qualitative work exploring how women actually utilise interventions to reshape their lives and wellbeing. Drawing on 9 focus groups discussions among 52 women who participated in the Women for Women International intervention in Afghanistan, an economic strengthening and social empowerment intervention, we explore processes of change. Data showed women learnt new skills around numeracy and animal husbandry; they perceived themselves to have become more respected within the household setting; they invested cash they received for intervention attendance in businesses, primarily their husband's or family's, and saved cash. Women did not, however, report their relationships to have been radically restructured. Rather women described incremental changes in their relationships within their household and used what they gained from the intervention to secure and sustain this. This conceptualisation of agency and empowerment reflects approaches to understanding agency, which move away from 'action-oriented' understandings, to ones that recognise 'distributed agency' as pathways to change through interventions.

Left atrial ball valve thrombus in restrictive cardiomyopathy and normal mitral valve: Loose cannon in heart.

Left atrial ball valve thrombus is an unusual condition, especially in patients with normal mitral valve. In the present case, we describe a 61-year-old female with restrictive cardiomyopathy who presented with a large left atrial ball valve thrombus, which subsequently embolized to right carotid artery and was treated with intravenous thrombolysis. This case provides useful insight into the genesis of such thrombi and highlights management dilemmas of a rare clinical problem.

Prevalence and risk factors of asymptomatic hepatitis C virus infection in bangladesh.

OBJECTIVES: There are paucity of information about prevalence and risk factor of hepatitis C virus (HCV) in Bangladesh. METHODS: Blood was collected from 1018 randomly selected subjects from a semi-urban area of Bangladesh. Anti-HCVs were checked in the blood twice using a third-generation commercial kit. The data of the questionnaires were analyzed to find possible risk factors. RESULTS: Nine of the 1018 subjects (88%) were tested positive for anti-HCV. The HCV-positive subjects were >28 years old. Major risk factors for HCV infection were treatment by unqualified and traditional practitioners, history of mass-vaccination against smallpox, hair cutting and shaving by barbers, and body piercing. However, known risk factors such as blood transfusion, surgery, invasive therapy, and intravenous drug use were not detected in any HCV-infected subjects. CONCLUSION: Control of HCV infection in Bangladesh may be difficult because the risk factors are related to normal tradition and culture of Bangladeshi people.

Combination therapy with antiviral drugs and hepatitis B vaccine in incidentally-detected and asymptomatic chronic hepatitis virus B carriers at Bangladesh.

Abstract Asymptomatic chronic hepatitis B virus (HBV) carriers are at risk of developing complications of liver disease, but these patients are not recommended for treatment with antiviral drugs. In fact, antiviral drugs are ineffective in these patients in the immune tolerance phase, when they have inadequate levels of host immunity. We postulated that combination therapy of an immune modulator and antiviral drugs may have potential to help these patients. Twenty-five patients with incidentally-detected asymptomatic chronic HBV were immunized with hepatitis B vaccine (10 microg of hepatitis B surface antigen) intramuscularly five times (at 0, 1, 2, 6, and 12 mo) to induce HBV-specific immunity. The patients were also treated with lamivudine (100 mg) daily for 12 mo. The combination therapy was safe for all patients with asymptomatic chronic HBV, and no increases in alanine aminotransferase or liver damage were detected in any patient. Although all of the patients were expressing HBV DNA in their serum before treatment, HBV DNA became undetectable in 16 of 25 patients, and was reduced in 9 of 25 patients at the end of the combination therapy. Combination therapy with the antiviral agent lamivudine and an immune modulator (hepatitis B vaccine) represents a potential therapeutic option for the control of HBV without liver damage in asymptomatic chronic HBV carriers.

HEV infection as an aetiologic factor for acute hepatitis: experience from a tertiary hospital in Bangladesh.

Acute hepatitis is seen sporadically round the year in Bangladesh. The incidence of acute viral hepatitis E increases after floods as this allows sewerage contamination of piped and groundwater. The aim of this retrospective study was to assess the burden of hepatitis E virus (HEV infection) in Bangladesh. Patients attending the Hepatology Unit III of the Bangabandhu Sheikh Mujib Medical University, during June 2004-December 2006, were included in the study. All viral markers were tested by enzyme-linked immunosorbent assay. The study population was divided in four groups. Group 1 included 144 patients with acute viral hepatitis. The inclusion criteria were: nausea and/or vomiting, loss of appetite, serum bilirubin >200 micromol/L, raised serum transaminases, and prothrombin time >3 seconds prolonged beyond control value. In Group 2, there were 31 pregnant women with acute viral hepatitis. All the patients had prodrome, icterus, raised serum bilirubin and raised serum transaminase levels. Group 3 included 23 patients presenting with fulminant hepatic failure. In Group 4, 69 patients with cirrhosis of liver were included. They presented with features of decompensation for the first time. The inclusion criteria were: patients with established cirrhosis with jaundice and/or ascites and/or hepatic encephalopathy. In Group 1, 58.33% of the 144 patients had acute viral hepatitis E. In Group 2, 45.16% of the pregnant women also had acute viral hepatitis E. HEV was responsible for 56.52% cases of fulminant hepatic failure in Group 3. In 21.7% cases in Group 4, decompensation of cirrhosis was due to HEV. Acute viral hepatitis E in the third trimester of pregnancy and HEV-induced fulminant hepatic failure were associated with 80% of mortality despite the best possible care. In this clinical context, acute viral hepatitis E is the leading cause of wide spectrum of liver disease ranging from severe acute viral hepatitis, fulminant hepatic failure, to decompensation of liver in cirrhotics in Bangladesh. Sewerage contamination of piped water following floods may contribute to the higher incidence of HEV infection.

Hepatitis B virus genotypes: an overview.

BACKGROUND: Hepatitis B virus (HBV) infection is a major cause of mortality and morbidity globally. The quest continues to identify viral factors that influence disease progression and severity as well as responses to treatment of HBV infection. Based on variations in HBV, the virus has been divided into a number of genotypes. DATA SOURCES: Review of published literature on HBV genotypes. RESULTS: HBV genotypes are likely to be important in determining the severity and progression of HBV-induced liver disease as well as responses to different anti-viral agents. CONCLUSION: Although HBV genotyping is not yet recommended for routine use in treating HBV infection, available data suggest that, as in hepatitis C virus infection, HBV genotyping is also likely to become a routine investigation for HBV treatment, perhaps in the not too distant future.