Changing Etiological Spectrum of Hepatocellular Carcinoma in India-A Systematic Review and Meta-analysis.

Background: Recent studies from both India and outside India have shown a change in the etiological profile of hepatocellular carcinoma (HCC). We aimed to analyze the etiological spectrum and changing trends of HCC etiology in India using a systematic review of current literature and meta-analysis. Methods: Electronic databases of PubMed/Medline, Scopus, and Embase were searched from inception to July 2023 for studies reporting the data on the etiology of HCC from India. The pooled proportions with 95% confidence interval were calculated using summative statistics. Results: A total of 60 studies (n = 12,327) were included in the final analysis. The pooled proportions of HCC cases with at least one positive and negative viral marker were 56.0 (49.5-62.6) and 43.1% (36.5-49.8), respectively. The pooled proportion of HCC cases with positive hepatitis B virus (HBV) markers was 41.0 (35.8-46.1), while those with positive markers for hepatitis C virus were 20.3 (17.0-23.6). The pooled proportion of cases with HCC with significant alcohol intake was 19.0% (15.6-22.4), and those related to nonalcoholic fatty liver disease (NAFLD) were 16.9% (12.1-21.7). Around 7.9% (5.8-10.0) of the cases had HCC with multiple etiologies. Subgroup analysis showed a significant variation with the location of the study based on zone. Meta-regression analysis based on publication year (1990-2023) showed a significant reduction in the proportion of cases with HBV and an increase in cases with NAFLD. In contrast, the proportion of cases with hepatitis C virus and alcohol did not change significantly. Conclusion: Viral hepatitis is the most common etiology of HCC in India, predominantly HBV. The proportions of cases with HCC related to NAFLD are increasing, and those related to HBV are declining.

Dynamic Assessment of Modified Quick Sequential Organ Failure Assessment in Acutely Deteriorated Patients with Chronic Liver Disease.

Background/Aims: Quick sequential organ failure assessment (qSOFA) has been suggested to identify those who have poor outcomes in patients with suspected infection. We aimed to evaluate the ability of the modified qSOFA (m-qSOFA) to identify high-risk patients in acutely deteriorated patients with chronic liver disease (CLD), especially acute-on-chronic liver failure (ACLF). Methods: We used the data of both Korean Acute-on-Chronic Liver Failure (KACLiF) and Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) cohorts. qSOFA was modified by replacing the Glasgow Coma Scale with hepatic encephalopathy, and m-qSOFA≥2 was considered high. Results: Patients with high m-qSOFA had a significantly lower 1-month transplant-free survival (TFS) in both cohorts and higher organ failure development in KACLiF than patients with low m-qSOFA (Ps<0.05). Subgroup analysis by ACLF showed that patients with high m-qSOFA had lower TFS than patients with low m-qSOFA. m-qSOFA was an independent prognostic factor (hazard ratios (HR)=2.604, 95% confidence interval (CI) 1.353-5.013, P=0.004 in KACLiF and HR=1.904, 95% CI 1.484-2.442, P<0.001 in AARC). The patients with low m-qSOFA at baseline but high m-qSOFA on the 7th day had a significantly lower 1-month TFS than the patients with high m-qSOFA at baseline but low m-qSOFA on the 7th day (52.6% vs. 89.4%, P<0.001 in KACLiF and 26.9% vs. 61.5%, P<0.001 in AARC). Conclusion: Baseline and dynamic changes in m-qSOFA were useful to identify patients with a high risk of organ failure development and short-term mortality among CLD patients with acute deterioration.

Ammonia is associated with liver-related complications and predicts mortality in acute-on-chronic liver failure patients.

The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients.

Expert consensus on the diagnosis and treatment of end-stage liver disease complicated by infections.

End-stage liver disease (ESLD) is a life-threatening clinical syndrome and when complicated with infection the mortality is markedly increased. In patients with ESLD, bacterial or fungal infection can induce or aggravate the occurrence or progression of liver decompensation. Consequently, infections are among the most common complications of disease deterioration. There is an overwhelming need for standardized protocols for early diagnosis and appropriate management for patients with ESLD complicated by infections. Asia Pacific region has the largest number of ESLD patients, due to hepatitis B and the growing population of alcohol and NAFLD. Concomitant infections not only add to organ failure and high mortality but also to financial and healthcare burdens. This consensus document assembled up-to-date knowledge and experience from colleagues across the Asia-Pacific region, providing data on the principles as well as evidence-based current working protocols and practices for the diagnosis and treatment of patients with ESLD complicated by infections.

Post-Liver Transplant Metabolic Syndrome.

Non-alcoholic steatohepatitis (NASH) is the second most frequent cause of liver transplantation following alcoholic liver disease. With longer follow-up and increased survival rates, the occurrence rate of the metabolic syndrome is increasing with time among liver transplant recipients. Reappearances of non-alcoholic fatty liver disease after transplantation, both as recurring cases and new instances, are prevalent; nonetheless, the recurrence of fibrosis is minimal. Recognizing populations at elevated risk and enhancing the management of metabolic-related conditions are crucial for maintaining a healthy transplanted organ, particularly considering the prolonged utilization of immunosuppressive treatments. Furthermore, NASH-related cirrhosis patients who had transplant are at a greater risk of cardiovascular, renal events and increased incidence of cancer, necessitating a unique care strategy. This review discusses post-transplant metabolic syndrome, risk factors, pathogenesis, diagnosis, prevention strategy, recurrent and de novo NAFLD and customized immunosuppression.

Geographic disparities in access to liver transplant for advanced cirrhosis: Time to ring the alarm!

Decompensated cirrhosis and hepatocellular cancer are major risk factors for mortality worldwide. Liver transplantation (LT), both live-donor LT or deceased-donor LT, are lifesaving, but there are several barriers toward equitable access. These barriers are exacerbated in the setting of critical illness or acute-on-chronic liver failure. Rates of LT vary widely worldwide but are lowest in lower-income countries owing to lack of resources, infrastructure, late disease presentation, and limited donor awareness. A recent experience by the Chronic Liver Disease Evolution and Registry for Events and Decompensation consortium defined these barriers toward LT as critical in determining overall survival in hospitalized cirrhosis patients. A major focus should be on appropriate, affordable, and early cirrhosis and hepatocellular cancer care to prevent the need for LT. Live-donor LT is predominant across Asian countries, whereas deceased-donor LT is more common in Western countries; both approaches have unique challenges that add to the access disparities. There are many challenges toward equitable access but uniform definitions of acute-on-chronic liver failure, improving transplant expertise, enhancing availability of resources and encouraging knowledge between centers, and preventing disease progression are critical to reduce LT disparities.

Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation.

Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.

Liver Transplantation in Chronic Liver Disease and Acute on Chronic Liver Failure- Indication, Timing and Practices.

Liver transplantation (LT) is the second most common solid organ transplantation worldwide. LT is considered the best and most definitive therapeutic option for patients with decompensated chronic liver disease (CLD), hepatocellular carcinoma (HCC), acute liver failure (ALF), and acute-on-chronic liver failure (ACLF). The etiology of CLD shows wide geographical variation, with viral hepatitis being the major etiology in the east and alcohol-related liver disease (ALD) in the west. Non-alcoholic fatty liver disease (NAFLD) is on an increasing trend and is expected to be the most common etiology on a global scale. Since the first successful LT, there have been radical changes in the indications for LT. In many circumstances, not just the liver disease itself but factors such as extra-hepatic organ dysfunction or failures necessitate LT. ACLF is a dynamic syndrome that has extremely high short-term mortality. Currently, there is no single approved therapy for ACLF, and LT seems to be the only feasible therapeutic option for selected patients at high risk of mortality. Early identification of ACLF, stratification of patients according to disease severity, aggressive organ support, and etiology-specific treatment approaches have a significant impact on post-transplant outcomes. This review briefly describes the indications, timing, and referral practices for LT in patients with CLD and ACLF.

Psychosocial Assessment and Management-related Issues Among Liver Transplant Recipients.

Background and aim: Liver transplant cases have been rising and becoming the choice of treatment for many patients with end-stage liver diseases. With an increasing number of qualified treatment centers and facilities, the effectiveness of liver transplants has been observed to increase over the years. But the success of liver transplants and the quality of life post-transplant have been observed to be influenced due to psychiatric comorbidities. Method: We searched for literature using terms for 'Psychosocial factors', 'liver transplant', 'psychiatric disorders', 'treatment outcomes', and related terms, 'AUD/SUD' in three databases: PubMed, Embase, and Scopus. Articles published in English and that provided original data analyses were included while commentaries and review articles were excluded. This review article focuses on an association between various psychiatric disorders/ Substance Use Disorder (SUD)/Alcohol Use Disorder (AUD) and liver transplant outcomes which indicated the need for psychiatric treatment and its role in improved overall transplant outcomes and enhanced quality of life. Results: Majority of the studies indicated a negative association between psychiatric disorder, AUD, and SUD with the treatment outcomes post liver transplant. A few studies were found supporting a multidisciplinary approach to handling liver transplant patients for a more effective and improved treatment outcome. Conclusion: The current evidence suggests a need for developing an integrated approach to assessment and management of psychiatric and psychosocial issues related to liver transplant recipients.

e-GLR Score Predicts Early Graft Loss in Adult Live-Donor Liver Transplantation.

Objective: This study aimed to analyze risk factors and develop a predictive model for early allograft loss due to early graft dysfunction (EGD) in adult live-donor liver transplantation (LDLT). Methods: Data of patients who underwent LDLT from 2011 to 2019 were reviewed for EGD, associated factors, and outcomes. A homogeneous group of 387 patients was analyzed: random cohort A (n = 274) for primary analysis and random cohort B (n = 113) for validation. Results: Of 274 recipients, 92 (33.6%) developed EGD. The risk of graft loss within 90 days was 29.3% and 7.1% in those with and without EGD, respectively (P < 0.001). Multivariate logistic regression analysis determined donor age (P = 0.045), estimated (e) graft weight (P = 0.001), and the model for end-stage liver disease (MELD) score (0.001) as independent predictors of early graft loss due to EGD. Regression coefficients of these factors were employed to formulate the risk model: Predicted (P) early graft loss risk (e-GLR) score = 10 × [(donor age × 0.052) + (e-Graft weight × 1.681) + (MELD × 0.145)] - 8.606 (e-Graft weight = 0, if e-Graft weight ≥640 g and e-Graft weight = 1, and if e-Graft weight < 640 g). Internal cross-validation revealed a high predictive value (C-statistic = 0.858). Conclusions: Our novel risk score can efficiently predict early allograft loss following graft dysfunction, which enables donor-recipient matching, evaluation, and prognostication simply and reliably in adult LDLT.

Safety and Efficacy of Transjugular Intrahepatic Portosystemic Shunt for Non-tumoral Cirrhotic Portal Vein Thrombosis Not Responding to Anticoagulation Therapy.

OBJECTIVES: To evaluate the feasibility, safety, and efficacy of add-on transjugular-intrahepatic-portosystemic shunt (TIPS) for portal vein recanalization (PVR) in cirrhotic patients with non-tumoral chronic portal vein thrombosis (PVT) after 6 months of monitored anticoagulation therapy (ACT). METHODS: We conducted a retrospective search of the hospital database for patients who underwent TIPS for persistent PVT despite 6 months of ACT (January 2011 to August 2021). These patients were compared to control group (ACT group; no TIPS but continued on ACT). Post-TIPS periodic assessment was done to look for clinical outcome, PVR (using contrast-enhanced CT scan), and complications. RESULTS: A total of 90 patients were analyzed. Thirty-six patients in TIPS group and 54 patients in ACT group. TIPS was successfully performed in all patients. TIPS group showed complete recanalization of portal vein in 77.8%, partial recanalization in 16.7%, and stable thrombus in 5.5% of the patients. TIPS thrombosis was seen in 3 patients, all underwent successful endovascular thrombolysis. Seven patients developed post-TIPS hepatic encephalopathy and were managed conservatively. In contrast, no patient in ACT group achieved PVR on 12-month follow-up. After propensity score matching, patients in TIPS group showed significantly lower incidence of variceal re-bleeding (22.2% vs. 77.8%, p = 0.03) and refractory ascites (11.1% vs. 51.9%, p < 0.01) with significantly better 12-month survival as compared to ACT group (88.9% vs. 69.4%, p = 0.04). CONCLUSION: TIPS in cirrhotic patients with PVT result in superior recanalization rates, better control of ascites, and variceal re-bleeding resulting in better survival. TIPS may be considered a preferred therapy after anticoagulation failure. CLINICAL IMPACT: TIPS is associated with good technical and clinical success in patients of cirrhosis with PVT and should be considered in patients not responding to ACT.

Global disparities in mortality and liver transplantation in hospitalised patients with cirrhosis: a prospective cohort study for the CLEARED Consortium.

BACKGROUND: Cirrhosis, the end result of liver injury, has high mortality globally. The effect of country-level income on mortality from cirrhosis is unclear. We aimed to assess predictors of death in inpatients with cirrhosis using a global consortium focusing on cirrhosis-related and access-related variables. METHODS: In this prospective observational cohort study, the CLEARED Consortium followed up inpatients with cirrhosis at 90 tertiary care hospitals in 25 countries across six continents. Consecutive patients older than 18 years who were admitted non-electively, without COVID-19 or advanced hepatocellular carcinoma, were enrolled. We ensured equitable participation by limiting enrolment to a maximum of 50 patients per site. Data were collected from patients and their medical records, and included demographic characteristics; country; disease severity (MELD-Na score); cirrhosis cause; medications used; reasons for admission; transplantation listing; cirrhosis-related history in the past 6 months; and clinical course and management while hospitalised and for 30 days post discharge. Primary outcomes were death and receipt of liver transplant during index hospitalisation or within 30 days post discharge. Sites were surveyed regarding availability of and access to diagnostic and treatment services. Outcomes were compared by country income level of participating sites, defined according to World Bank income classifications (high-income countries [HICs], upper-middle-income countries [UMICs], and low-income or lower-middle-income countries [LICs or LMICs]). Multivariable models controlling for demographic variables, disease cause, and disease severity were used to analyse the odds of each outcome associated with variables of interest. FINDINGS: Patients were recruited between Nov 5, 2021, and Aug 31, 2022. Complete inpatient data were obtained for 3884 patients (mean age 55·9 years [SD 13·3]; 2493 (64·2%) men and 1391 (35·8%) women; 1413 [36·4%] from HICs, 1757 [45·2%] from UMICs, and 714 [18·4%] from LICs or LMICs), with 410 lost to follow-up within 30 days after hospital discharge. The number of patients who died while hospitalised was 110 (7·8%) of 1413 in HICs, 182 (10·4%) of 1757 in UMICs, and 158 (22·1%) of 714 in LICs and LMICs (p<0·0001), and within 30 days post discharge these values were 179 (14·4%) of 1244 in HICs, 267 (17·2%) of 1556 in UMICs, and 204 (30·3%) of 674 in LICs and LMICs (p<0·0001). Compared with patients from HICs, increased risk of death during hospitalisation was found for patients from UMICs (adjusted odds ratio [aOR] 2·14 [95% CI 1·61-2·84]) and from LICs or LMICs (2·54 [1·82-3·54]), in addition to increased risk of death within 30 days post discharge (1·95 [1·44-2·65] in UMICs and 1·84 [1·24-2·72] in LICs or LMICs). Receipt of a liver transplant was recorded in 59 (4·2%) of 1413 patients from HICs, 28 (1·6%) of 1757 from UMICs (aOR 0·41 [95% CI 0·24-0·69] vs HICs), and 14 (2·0%) of 714 from LICs and LMICs (0·21 [0·10-0·41] vs HICs) during index hospitalisation (p<0·0001), and in 105 (9·2%) of 1137 patients from HICs, 55 (4·0%) of 1372 from UMICs (0·58 [0·39-0·85] vs HICs), and 16 (3·1%) of 509 from LICs or LMICs (0·21 [0·11-0·40] vs HICs) by 30 days post discharge (p<0·0001). Site survey results showed that access to important medications (rifaximin, albumin, and terlipressin) and interventions (emergency endoscopy, liver transplantation, intensive care, and palliative care) varied geographically. INTERPRETATION: Inpatients with cirrhosis in LICs, LMICs, or UMICs have significantly higher mortality than inpatients in HICs independent of medical risk factors, and this might be due to disparities in access to essential diagnostic and treatment services. These results should encourage researchers and policy makers to consider access to services and medications when evaluating cirrhosis-related outcomes. FUNDING: National Institutes of Health and US Department of Veterans Affairs.

Acute Kidney Injury (AKI) at Admission Predicts Mortality in Patients With Severe Alcoholic Hepatitis (SAH).

Background & aims: Severe alcoholic hepatitis (SAH) is a grave condition, and the presence of acute kidney injury (AKI) further jeopardizes patient survival. However, the impact of AKI on survival in SAH has not been assessed from this region of Asia. Materials and methods: This study was conducted on consecutive alcohol-associated liver disease (ALD) patients hospitalized in Gastroenterology Department, SCB Medical College, Cuttack, India, between October 2016 and December 2018. On diagnosis of SAH (mDF score ≥32), demographic, clinical, and laboratory parameters were recorded, and survival was compared between patients with and without AKI (AKIN criteria). In addition, survival was compared among SAH patients defined by other criteria and prognostic models in the presence and absence of AKI. Results: 309 (70.71%) of ALD patients had SAH, and 201 (65%) of them had AKI. SAH patients with AKI had higher total leucocyte count, total bilirubin, serum creatinine, serum urea, INR, MELD (UNOS), MELD (Na+), CTP score, mDF score, Glasgow score, ABIC score, and increased prevalence of acute on chronic liver failure (ACLF) as per EASL-CLIF Consortium criteria (P < 0.001). Further, they had prolonged hospital stay, and increased death during hospitalization, at 28 days as well as 90 days (P < 0.001). Significant differences in survival were also seen in SAH (as per MELD, ABIC, and GAHS criteria) patients above the marked cut offs in respect to AKI. Conclusions: Over two-thirds of ALD patients had SAH, and about two-thirds had AKI. Patients with SAH and AKI had an increased prevalence of ACLF, longer hospital stay, and increased mortality during hospitalization at 28 days and 90 days. Lay summary: SAH is a critical condition, and the presence of AKI negatively affects their survival. Hence, early identification of SAH and AKI, as well as early initiation of treatment, is crucial for better survival. Our study from the coastal part of eastern India is the first to demonstrate the prevalence of SAH among patients with ALD along with the prevalence of AKI among SAH patients in this region. This knowledge will be helpful in managing these patients from this region of world.

Incidence and predictors of alcohol relapse following living donor liver transplantation for alcohol related liver disease.

BACKGROUND: Alcohol relapse after liver transplantation has a negative impact on outcomes. There is limited data on its burden, the predictors, and impact following live donor liver transplantation (LDLT). METHODS: A single-center observational study was carried out between July 2011 and March 2021 for patients undergoing LDLT for alcohol associated liver disease (ALD). The incidence, predictors of alcohol relapse, and post-transplant outcomes were assessed. RESULTS: Altogether 720 LDLT were performed during the study period, 203 (28.19%) for ALD. The overall relapse rate was 9.85% (n = 20) with a median follow-up of 52 months (range, 12-140 months). Sustained harmful alcohol use was seen in 4 (1.97%). On multivariate analysis, pre-LT relapse (P = .001), duration of abstinence period (P = .007), daily intake of alcohol (P = .001), absence of life partner (P = .021), concurrent tobacco abuse before transplant (P = .001), the donation from second-degree relative (P = .003) and poor compliance with medications (P = .001) were identified as predictors for relapse. Alcohol relapse was associated with the risk of graft rejection (HR 4.54, 95% CI: 1.751-11.80, P = .002). CONCLUSION: Our results show that the overall incidence of relapse and rate of harmful drinking following LDLT is low. Donation from spouse and first degree relative was protective. History of daily intake, prior relapse, shorter pretransplant abstinence duration and lack of family support significantly predicted relapse.

Identifying the early predictors of non-response to steroids in patients with flare of autoimmune hepatitis causing acute-on-chronic liver failure.

BACKGROUND AND AIMS: Early identification of non-response to steroids is critical in patients with autoimmune hepatitis (AIH) causing acute-on-chronic liver failure (ACLF). We assessed if this non-response can be accurately identified within first few days of treatment. METHODS: Patients with AIH-ACLF without baseline infection/hepatic encephalopathy were identified from APASL ACLF research consortium (AARC) database. Diagnosis of AIH-ACLF was based mainly on histology. Those treated with steroids were assessed for non-response (defined as death or liver transplant at 90 days for present study). Laboratory parameters, AARC, and model for end-stage liver disease (MELD) scores were assessed at baseline and day 3 to identify early non-response. Utility of dynamic SURFASA score [- 6.80 + 1.92*(D0-INR) + 1.94*(∆%3-INR) + 1.64*(∆%3-bilirubin)] was also evaluated. The performance of early predictors was compared with changes in MELD score at 2 weeks. RESULTS: Fifty-five out of one hundred and sixty-five patients (age-38.2 ± 15.0 years, 67.2% females) with AIH-ACLF [median MELD 24 (IQR: 22-27); median AARC score 7 (6-9)] given oral prednisolone 40 (20-40) mg per day were analyzed. The 90 day transplant-free survival in this cohort was 45.7% with worse outcomes in those with incident infections (56% vs 28.0%, p = 0.03). The AUROC of pre-therapy AARC score [0.842 (95% CI 0.754-0.93)], MELD [0.837 (95% CI 0.733-0.94)] score and SURFASA score [0.795 (95% CI 0.678-0.911)] were as accurate as ∆MELD at 2 weeks [0.770 (95% CI 0.687-0.845), p = 0.526] and better than ∆MELD at 3 days [0.541 (95% CI 0.395, 0.687), p < 0.001] to predict non-response. Combination of AARC score > 6, MELD score > 24 with SURFASA score ≥ - 1.2, could identify non-responders at day 3 (concomitant- 75% vs either - 42%, p < 0.001). CONCLUSION: Baseline AARC score, MELD score, and the dynamic SURFASA score on day 3 can accurately identify early non-response to steroids in AIH-ACLF.

Comparative genomics reveals the diversity of CRISPR-Cas locus in Azotobacter organisms.

Clustered regularly interspaced short palindromic repeats (CRISPRs) are known to provide adaptive immunity to bacteria against invading bacteriophages. In recent years, CRISPR-based technologies have been used for creating improved plant varieties; however, the indigenous CRISPR-Cas elements of plant growth-promoting bacteria are usually neglected. These indigenous genetic cassettes have evolved over millions of years and have shaped the bacterial genome. Therefore, these genetic loci can be used to study the adaptive capability of the bacteria in the environment. This study aims to bioinformatically analyze the genomes of a common free-living nitrogen-fixing Azotobacter spp. to assess their CRISPR-Cas diversity. Strains of Azotobacter vinelandii and Azotobacter chroococcum were found to harbor a large number of spacers. The phylogeny of different Cas and Cse1 proteins revealed a close evolutionary relationship among A. chroococcum B3, A. chroococcum NCIMB 8003 locus II, and A. vinelandii DJ locus I. The secondary structure of the hairpin loop of the repeat was also analyzed, and a correlation was derived between the structural stability of the hairpin loop and the number of spacers acquired by the CRISPR loci. These findings revealed the diversity and evolution of the CRISPR sequences and Cas proteins in Azotobacter species. Although the adaptive immune system of bacteria against bacteriophage, CRISPR-Cas, has been identified in many bacteria, studies of plant growth-promoting bacteria have been neglected. These indigenous CRISPRs have shaped the genome over millions of years and their study can lead to the understanding of the genome composition of these organisms. Our results strengthen the idea of using A. chroococcum and A. vinelandii as biofertilizer strains as they possess more spacers with highly stable repeat sequences, thereby imparting them higher chance of survival against mobile genetic elements like phages and plasmids.

Hepatic artery-related complications after live donor liver transplantation.

BACKGROUND: Hepatic artery-related complications (HARC) after live donor liver transplantation (LDLT) is associated with high morbidity and mortality rate. METHODS: Prospectively maintained data from July 2011 to September 2020 was analyzed for etiology, detection, management, and outcome of HARC. RESULTS: Six hundred fifty-seven LDLT (adult 572/pediatrics 85) were performed during the study period. Twenty-one (3.2%) patient developed HARC; 16 (2.4%) hepatic artery thrombosis (HAT) and 5 (0.76%) non-thrombotic hepatic artery complication (NTHAC). Ninety percent (19/21) HARC were asymptomatic and detected on protocol Doppler. Median time to detection was day 4 (range - 1 to 35), which included 18 early (within 7 days) vs 3 late incidents. Only one pediatric patient had HAT. Seven patients underwent surgical revascularization, 11 had endovascular intervention and 3 with attenuated flow required only systemic anticoagulation. All NTHAC survived without any sequelae. Revascularization was successful in 81% (13/16) with HAT. Biliary complications were seen in 5 (23.8%); four were managed successfully. Overall mortality was 14.8% (3/21). The 1-year and 5-year survival were similar to those who did not develop HARC (80.9% vs 84.2%, p = 0.27 and 71.4% vs 75.19%, p = 0.36 respectively) but biliary complications were significantly higher (23.8% vs 14.2%, p = 0.03). On multivariate analysis, clockwise technique of arterial reconstruction was associated with decreased risk of HAT (1.7% vs 4.1% (p value - 0.003)). CONCLUSION: Technical refinement, early detection, and revascularization can achieve good outcome in patients with HARC after LDLT.

APASL-ACLF Research Consortium-Artificial Intelligence (AARC-AI) model precisely predicts outcomes in acute-on-chronic liver failure patients.

BACKGROUND AND AIMS: We hypothesized that artificial intelligence (AI) models are more precise than standard models for predicting outcomes in acute-on-chronic liver failure (ACLF). METHODS: We recruited ACLF patients between 2009 and 2020 from APASL-ACLF Research Consortium (AARC). Their clinical data, investigations and organ involvement were serially noted for 90-days and utilized for AI modelling. Data were split randomly into train and validation sets. Multiple AI models, MELD and AARC-Model, were created/optimized on train set. Outcome prediction abilities were evaluated on validation sets through area under the curve (AUC), accuracy, sensitivity, specificity and class precision. RESULTS: Among 2481 ACLF patients, 1501 in train set and 980 in validation set, the extreme gradient boost-cross-validated model (XGB-CV) demonstrated the highest AUC in train (0.999), validation (0.907) and overall sets (0.976) for predicting 30-day outcomes. The AUC and accuracy of the XGB-CV model (%Δ) were 7.0% and 6.9% higher than the standard day-7 AARC model (p < .001) and 12.8% and 10.6% higher than the day 7 MELD for 30-day predictions in validation set (p < .001). The XGB model had the highest AUC for 7- and 90-day predictions as well (p < .001). Day-7 creatinine, international normalized ratio (INR), circulatory failure, leucocyte count and day-4 sepsis were top features determining the 30-day outcomes. A simple decision tree incorporating creatinine, INR and circulatory failure was able to classify patients into high (~90%), intermediate (~60%) and low risk (~20%) of mortality. A web-based AARC-AI model was developed and validated twice with optimal performance for 30-day predictions. CONCLUSIONS: The performance of the AARC-AI model exceeds the standard models for outcome predictions in ACLF. An AI-based decision tree can reliably undertake severity-based stratification of patients for timely interventions.

Intragastric Balloon in Obese Compensated Nonalcoholic Steatohepatitis Cirrhosis Patients Is Safe and Achieves Significant Weight Reduction at 6-Months.

BACKGROUND AND STUDY AIMS: Weight reduction is the mainstay treatment for Nonalcoholic steatohepatitis (NASH). intragastric balloon (IGB) placement has proven benefit in terms of weight reduction. The aim of the present study is to assess the safety and efficacy of IGB placement in compensated NASH cirrhosis. PATIENTS AND METHODS: Nonalcoholic steatohepatitis cirrhosis patients with CTP ≤ 7, BMI of > 30, and who were unable to achieve weight reduction with lifestyle modification in past 3 months were prospectively enrolled. Spatz3™ adjustable gastric balloon was placed endoscopically. Primary objective was to determine efficacy in weight loss at 6 months, with secondary objectives of reduction in hepatic venous pressure gradient (HVPG), liver fat (controlled attenuation parameter, CAP), liver stiffness measurement (LSM) and clinical events as well as the tolerability and adverse events due to IGB placement. RESULTS: Altogether 56 cirrhosis patients, with a baseline BMI of 35.24 ± 3.92 and a CTP score of 6.27 ± 1.28 underwent IGB placement. The absolute weight reduction achieved was 15.88 kg (- 16.46%) and reduction in BMI was - 10.1% at 6 months. The percentage total body weight loss of ≥ 10% was achieved in 31 (55.35%) patients. The reduction in HVPG at 6-months was 11.12% (n = 16, 14.18 ± 2.12 to 12.60 ± 1.67 mmHg). The mean reduction in LSM was 28.6% and in CAP was 10.09%. Three (5.36%) patients required removal of IGB before 6-months due to persisting vomiting. No patient developed new-onset decompensation or any serious adverse event. CONCLUSION: IGB placement is a safe, well tolerated and effective option for reduction in weight and portal pressure in compensated obese cirrhosis patients. TRIAL REGISTRY: Clinicaltrails.gov identifier no: NCT03753438.

In-depth evaluation of nutritive, chemical constituents and anti-glycemic properties of jackfruit (Artocarpus heterophyllus Lam) clonal accessions with flake colour diversity from Eastern Sub-Himalayan plains of India.

The study was designed to elucidate the potential of jackfruit clonal accessions having diverse flake colours from nutritional and medicinal perspectives. Jack fruit accessions with deep yellow flakes were found to contain the highest flavonoids, antioxidant activity, ascorbic acid, and α-glucosidase inhibition whereas, orange-red flakes exhibited the highest ß-carotene, phenol, minerals (iron and zinc) and better inhibition of α-amylase and ß-glucosidase enzymes. Phenolic compounds profiling revealed the presence of higher sinapic acid, ferulic acid and quercetin contents in the orange-red-coloured flakes. Metabolite analysis revealed presence of anti-diabetic compounds (n-Hexadecanoic acid, tridecane, 2-Heptadecenal etc.) in deep yellow and orange-red coloured jack flakes with lower glycemic load. Considering the abundant health benefits as evident from the present study, orange-red and deep yellow-coloured flakes may be recommended for consumption to manage the hyperglycemic condition.