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.

Assessment of the Performance of Non-invasive Criteria for the Evaluation of Clinically Significant Portal Hypertension in Patients with Compensated Advanced Chronic Liver Disease.

BACKGROUND AND AIMS: Assessment of clinically significant portal hypertension (CSPH) non-invasively using a combination of liver stiffness measurement (LSM) and platelet counts is proposed as an alternative to hepatic venous pressure gradient (HVPG) estimation. Utility of these criteria in compensated advanced chronic liver disease (cACLD) patients of different etiologies including nonalcoholic steatohepatitis (NASH) with BMI  >  30 kg/m2 was studied in a large cohort. METHODS: Consecutive patients of cACLD with available anthropometric and laboratory details, LSM, and HVPG were included in a retrospective analysis. A LSM of ≥ 25 kPa alone and LSM ≤ 15 kPa plus platelets ≥ 150 × 109/L were evaluated as non-invasive rule-in and rule-out criteria for CSPH, respectively. The NASH-ANTICPATE model (composite of BMI, platelets, and LSM) was evaluated in patients with obese NASH. RESULTS: Patients with cACLD (n = 626) (mean age: 50.8 ± 12.4 years, 74.2% males) with alcohol (ALD, 30.3%), NASH (26.4%), hepatitis C (HCV, 16.6%), hepatitis B (HBV,10.2%) etiology were included. The prevalence of CSPH was  >  80% across all etiologies except in HBV (62.5%) and in obese non-NASH (71-72%). The rule-in criteria had a PPV  >  90% for all etiologies except in HBV (80.8%). The rule-out criteria had a negative predictive value (NPV) of 65%, 53%, and 40% in ALD, HCV, and NASH, respectively. The NASH-ANTCIPATE model had specificity of 100% and NPV of 33% to detect CSPH in obese NASH (n = 62). CONCLUSIONS: LSM ≥ 25 kPa predicted CSPH in most etiologies except HBV. A significant proportion of patients have CSPH despite satisfying the rule-out criteria. The NASH-ANTICIPATE model is specific but fails to exclude CSPH in nearly two-third patients with obesity and NASH. There is a need for precise disease-specific non-invasive models for detecting CSPH.

Role of contrast-enhanced ultrasound with Perfluorobutane in lesion detection, guidance for microwave ablation, and response assessment of hepatocellular carcinoma.

PURPOSE: To evaluate role of perfluorobutane in guiding microwave ablation of HCC and to compare treatment response at 3 h of ablation using contrast-enhanced US (CEUS) with Sonazoid with 1-month follow-up contrast-enhanced CT/MRI. METHODS: This was a single center prospective study and consecutive patients planned for microwave ablation of HCC from October to November 2021 were enrolled. Pre-procedure CEUS were performed using Sonazoid in both vascular and Kupffer phase and number of Kupffer defects compared with gray scale US. Precise needle placement of microwave applicator was done in the Kupffer phase. 3 hours post ablation CEUS was repeated to evaluate response assessment using Liver Imaging Reporting and Data System Treatment Response criteria (LR TR). One-month follow-up imaging was done using multiphasic CECT/dynamic CEMRI and comparison was done with post procedure CEUS.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 5 Given name: [Manoj Kumar] Last name [Sharma]. Author 6 Given name: [Shiv Kumar] Last name [Sarin]. Also, kindly confirm the details in the metadata are correct. all the names and affiliations are correct RESULTS: A total of 26 patients (24 males and 2 females, mean age 61.38 ± 9.76 years) having 40 lesions, of mean tumor diameter 21.4 ± 7.7 mm, underwent CEUS and ablation. Most common etiology for cirrhosis was viral hepatitis, followed by non-alcoholic steatohepatitis (NASH). Four (10%) additional lesions (which were seen on pre-procedure imaging) were detected in Kupffer phase over gray scale US. All lesions showed complete response in the immediate post procedure CEUS. Technique efficacy at 1-month was 95% according to the LR TR criteria.Please check the edit made in article title and amend if necessary.The edit is correct and appropriatePlease check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.All the names and their respective affiliations are correct CONCLUSION: CEUS with Sonazoid is an excellent modality for precise needle placement for ablation due to stable nature and excellent lesion visibility of Kupffer phase.

Health and economic burden due to alcohol-associated liver diseases in the Union Territory of Delhi: A Markov probabilistic model approach.

BACKGROUND: Nearly one-fifth of all deaths attributable to alcohol are due to liver diseases. METHODS: The study employs a Markov Probabilistic Modeling approach considering various clinical spectrum of alcohol-associated liver diseases (ALD), to gauge the health and economic burden due to ALD for the national capital territory of Delhi, from March 2017 to February 2018. The health impact was estimated through Disability Adjusted Life Years (DALYs), years of life lost (YLL), and total deaths due to ALD. The economic burden of ALD was assessed assuming the current health-seeking preferences and assuming that all the diseased individuals are cared for in the public health systems. Sensitivity analysis was done by Monte Carlo simulations. RESULTS: Total number of estimated deaths due to ALD in the national capital territory of Delhi for one year period from March 2017 was 8367. The DALYs due to ALD were estimated to be 0.247 million life years; this includes 0.178 million YLL and 0.069 million life years lost due to disability. The total cost of treating ALD was estimated to be 92.94 billion Indian rupees, if patients sought care based on current preferences and 55.52 billion Indian rupees if all diseased individuals were cared for in public health systems. The total excise revenue due to alcohol to the Government is being Indian rupees 43.1 billion in the said year. CONCLUSION: The high burden of ALD in terms of lives lost, DALYs lost, and more than two times higher estimated expense for care than the revenue generation due to alcohol clearly indicates that it would be prudent to initiate social engineering and preventive strategies to lessen the growing burden of ALD in India. The Delhi model for health and economic burden of ALD could help the country develop policies for better health outcomes of these patients.

Pooled nasopharyngeal swab collection in a single vial for the diagnosis of SARS CoV-2 infection: An effective cost saving method.

BACKGROUND: Pool testing is one of the strategy to expedite testing capacities while simultaneously conserving various diagnostic kits, reagents and consumables and time. In the present study, we investigated potential role of combined specimen collection technique for the diagnosis of SARS-CoV-2 virus infection where five nasopharyngeal swabs were collected from different individuals and pooled together in a single viral transport medium (VTM). MATERIAL AND METHODS: This pilot study was conducted on different cohorts of Delhi state. Two nasopharyngeal swabs were collected from each enrolled individual. One swab was put into VTM vial to be further used for individual swab testing (ID). The other swab was put into a fresh VTM for pool swab collection. Each pool comprised five swabs collected from five different patients in one VTM vial. Both IDs and pools were tested in parallel for the detection of SARS-CoV-2 using real time PCR. RESULTS: A total of 46 pools were collected from 230 enrolled individuals.Among 230 ID tested, 60 were found to be positive for both E and RdRp gene. Among 46 pools, 25 pools included all negatives samples and remaining 21 pools included one or more positives. Comparing ID with pool results, overall concordance was seen in 42 pools (91.3%). Four pools showed false positive results as all included samples on ID testing were found to be negative. Considering ID results as reference, swab pool showed 100% sensitivity, 84% specificity, 84% positive predictive value and 100% negative predictive value. CONCLUSION: The pooling of swab strategy could be beneficial only among asymptomatic in low prevalence areas.

Pooled RNA sample reverse transcriptase real time PCR assay for SARS CoV-2 infection: A reliable, faster and economical method.

BACKGROUND: Corona virus disease 2019 (COVID-19) which initially started as a cluster of pneumonia cases in the Wuhan city of China has now become a full-blown pandemic. Timely diagnosis of COVID-19 is the key in containing the pandemic and breaking the chain of transmission. In low- and middle-income countries availability of testing kits has become the major bottleneck in testing. Novel methods like pooling of samples are the need of the hour. OBJECTIVE: We undertook this study to evaluate a novel protocol of pooling of RNA samples/elutes in performance of PCR for SARS CoV-2 virus. STUDY DESIGN: Extracted RNA samples were randomly placed in pools of 8 on a 96 well plate. Both individual RNA (ID) and pooled RNA RT-qPCR for the screening E gene were done in the same plate and the positivity for the E gene was seen. RESULTS: The present study demonstrated that pool testing with RNA samples can easily detect even up to a single positive sample with Ct value as high as 38. The present study also showed that the results of pool testing is not affected by number of positive samples in a pool. CONCLUSION: Pooling of RNA samples can reduce the time and expense, and can help expand diagnostic capabilities, especially during constrained supply of reagents and PCR kits for the diagnosis of SARS-CoV-2 infection.

Asian-Pacific Association for the Study of the Liver (APASL) consensus guidelines on invasive and non-invasive assessment of hepatic fibrosis: a 2016 update.

Hepatic fibrosis is a common pathway leading to liver cirrhosis, which is the end result of any injury to the liver. Accurate assessment of the degree of fibrosis is important clinically, especially when treatments aimed at reversing fibrosis are being evolved. Despite the fact that liver biopsy (LB) has been considered the "gold standard" of assessment of hepatic fibrosis, LB is not favored by patients or physicians owing to its invasiveness, limitations, sampling errors, etc. Therefore, many alternative approaches to assess liver fibrosis are gaining more popularity and have assumed great importance, and many data on such approaches are being generated. The Asian Pacific Association for the Study of the Liver (APASL) set up a working party on liver fibrosis in 2007, with a mandate to develop consensus guidelines on various aspects of liver fibrosis relevant to disease patterns and clinical practice in the Asia-Pacific region. The first consensus guidelines of the APASL recommendations on hepatic fibrosis were published in 2009. Due to advances in the field, we present herein the APASL 2016 updated version on invasive and non-invasive assessment of hepatic fibrosis. The process for the development of these consensus guidelines involved review of all available published literature by a core group of experts who subsequently proposed consensus statements followed by discussion of the contentious issues and unanimous approval of the consensus statements. The Oxford System of the evidence-based approach was adopted for developing the consensus statements using the level of evidence from one (highest) to five (lowest) and grade of recommendation from A (strongest) to D (weakest). The topics covered in the guidelines include invasive methods (LB and hepatic venous pressure gradient measurements), blood tests, conventional radiological methods, elastography techniques and cost-effectiveness of hepatic fibrosis assessment methods, in addition to fibrosis assessment in special and rare situations.

Reviewing the diagnostic criteria for acute-on-chronic liver failure.

INTRODUCTION: For over 20 years, acute-on-chronic liver failure (ACLF) has taken multiple definitions and/or classifications. The definition outlines the acute and chronic insults to include a homogenous patient group with liver failure and an expected outcome in a specific time frame. Early and accurate diagnosis is essential as this inflammation of the liver may tilt the balance of liver destruction and regeneration adversely. Various factors such as superadded systemic sepsis, liver reserve, cause of primary chronic liver disease, state of immune system or the state of gut microbial flora might determine the ultimate prognosis. Areas covered: To date, there has been no universally accepted definition of ACLF. In this review, we discuss the strengths and weaknesses, controversies and basis for early identification and accurate diagnosis of ACLF. PubMed and Google scholar database searches were conducted, search terms included 'acute on chronic liver failure,' 'ACLF,' and 'diagnostic criteria.' Expert commentary: With recent advances in the management of advanced cirrhosis, research will gradually shift towards ACLF in the near future, focusing on the pathogenesis, new treatment options and improving survival. Once we improve understanding of this syndrome, newer definitions will evolve, thereby enabling earlier diagnosis and novel therapeutic avenues.

Prevalence and prognostic significance of hyperkalemia in hospitalized patients with cirrhosis.

BACKGROUND: The prevalence and clinical significance of hyponatremia in cirrhotics have been well studied; however, there are limited data on hyperkalemia in cirrhotics. AIM: We evaluated the prevalence and prognostic significance of hyperkalemia in hospitalized patients with cirrhosis and developed a prognostic model incorporating potassium for prediction of liver-related death in these patients. METHODS: The training derivative cohort of patients was used for development of prognostic scores (Group A, n = 1160), which were validated in a large prospective cohort of cirrhotic patients. (Group B, n = 2681) of cirrhosis. RESULTS: Hyperkalemia was seen in 189 (14.1%) and 336 (12%) in Group A and Group B, respectively. Potassium showed a significant association that was direct with creatinine (P < 0.001) and urea (P < 0.001) and inverse with sodium (P < 0.001). Mortality was also significantly higher in patients with hyperkalemia (P = 0.0015, Hazard Ratio (HR) 1.3, 95% confidence interval 1.11-1.57). Combination of all these parameters into a single value predictor, that is, renal dysfunction index predicted mortality better than the individual components. Combining renal dysfunction index with other known prognostic markers (i.e. serum bilirubin, INR, albumin, hepatic encephalopathy, and ascites) in the "K" model predicted both short-term and long-term mortality with an excellent accuracy (Concordance-index 0.78 and 0.80 in training and validation cohorts, respectively). This was also superior to Model for End-stage Liver Disease, Model for End-stage liver disease sodium (MELDNa), and Child-Turcott-Pugh scores. CONCLUSIONS: Cirrhotics frequently have impaired potassium homeostasis, which has a prognostic significance. Serum potassium correlates directly with serum creatinine and urea and inversely with serum sodium. The model incorporating serum potassium developed from this study ("K"model) can predict death in advanced cirrhotics with an excellent accuracy.

Critical flicker frequency for diagnosis and assessment of recovery from minimal hepatic encephalopathy in patients with cirrhosis.

BACKGROUND: Minimal hepatic encephalopathy (MHE) impairs quality of life and predicts overt hepatic encephalopathy (HE) in cirrhotic patients. Diagnosis of MHE requires cumbersome tests. Lactulose is effective in the treatment of MHE. This study aimed to evaluate the use of critical flicker frequency (CFF) for the diagnosis of MHE in cirrhotic patients after treatment. METHODS: One hundred and ten patients were evaluated by psychometry (number connection tests A, B or figure connection tests A, B), P300 auditory event related potential (P300ERP), venous ammonia, and CFF for MHE. MHE was diagnosed by abnormal psychometry (>2SD age matched controls) and P300ERP. MHE patients were treated with lactulose for one month. Response was defined by normalization (<2SD of matched controls) of both psychometry and P300ERP. RESULTS: Of the 110 patients [Child Turcott Pugh score A:B:C 39:42:29 (age 41.6+/-11.6 years, M:F 82:28)], 75 (68%) had abnormal results of psychometric tests, and 74 (67%) had prolonged P300ERP. Fifteen (20%) patients with abnormal results of psychometric tests had normal P300ERP. Thus sixty (54.5%) patients were diagnosed as having MHE. After treatment for one month, 34 (57%) recovered while 26 (43%) continued to have abnormal resents of psychometric or P300ERP tests. CFF was <39 Hz in 72 (65.4%) patients before treatment and in 20 (33.3%) after treatment. CFF sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for the assessment of recovery of MHE were 65%, 91%, 85%, 77% and 80%, respectively. CONCLUSION: CFF is a simple, relatively reliable, and accurate test without any dependence on age or literacy in the diagnosis and assessment of recovery of patients with MHE.