Best Fit DNA-Based Cryptographic Keys: The Genetic Algorithm Approach.

DNA (Deoxyribonucleic Acid) Cryptography has revolutionized information security by combining rigorous biological and mathematical concepts to encode original information in terms of a DNA sequence. Such schemes are crucially dependent on corresponding DNA-based cryptographic keys. However, owing to the redundancy or observable patterns, some of the keys are rendered weak as they are prone to intrusions. This paper proposes a Genetic Algorithm inspired method to strengthen weak keys obtained from Random DNA-based Key Generators instead of completely discarding them. Fitness functions and the application of genetic operators have been chosen and modified to suit DNA cryptography fundamentals in contrast to fitness functions for traditional cryptographic schemes. The crossover and mutation rates are reducing with each new population as more keys are passing fitness tests and need not be strengthened. Moreover, with the increasing size of the initial key population, the key space is getting highly exhaustive and less prone to Brute Force attacks. The paper demonstrates that out of an initial 25 × 25 population of DNA Keys, 14 keys are rendered weak. Complete results and calculations of how each weak key can be strengthened by generating 4 new populations are illustrated. The analysis of the proposed scheme for different initial populations shows that a maximum of 8 new populations has to be generated to strengthen all 500 weak keys of a 500 × 500 initial population.

Combination of granulocyte colony-stimulating factor and erythropoietin improves outcomes of patients with decompensated cirrhosis.

BACKGROUND & AIMS: Patients with decompensated cirrhosis have significantly reduced survival without liver transplantation. Granulocyte colony-stimulating factor (G-CSF) has been shown to increase survival in patients with acute-on-chronic liver failure, and erythropoietin promoted hepatic regeneration in animal studies. We performed a double-blind, randomized, placebo-controlled trial to determine whether co-administration of these growth factors improved outcomes for patients with advanced cirrhosis. METHODS: In a prospective study, consecutive patients with decompensated cirrhosis seen at the Institute of Liver and Biliary Sciences, New Delhi (from May 2011 through June 2012) were randomly assigned to groups given subcutaneous G-CSF (5 µg/kg/d) for 5 days and then every third day (12 total doses), along with subcutaneous darbopoietin α(40 mcg/wk) for 4 weeks (GDP group, n = 29), or only placebos (control group, n = 26). All patients also received standard medical therapy and were followed for 12 months. Histology was performed on liver biopsies. The primary end point was survival at 12 months. RESULTS: Baseline characteristics of patients were comparable; alcohol intake was the most common etiology of cirrhosis. A higher proportion of patients in the GDP group than controls survived until 12 months (68.6% vs 26.9%; P = .003). At 12 months, Child-Turcotte Pugh scores were reduced by 48.6% in the GDP group and 39.1% in the control group, from baseline (P = .001); Model for End Stage Liver Disease scores were reduced by 40.4% and 33%, respectively (P = .03). The need for large-volume paracentesis was significantly reduced in GDP group, compared with controls (P < .05). A lower proportion of patients in the GDP group developed septic shock (6.9%) during follow-up compared with controls (38.5%; P = .005). No major adverse events were observed in either group. CONCLUSIONS: In a single-center randomized trial, a significantly larger proportion of patients with decompensated cirrhosis given a combination of G-CSF and darbopoietin α survived for 12 months more than patients given only placebo. The combination therapy also reduced liver severity scores and sepsis to a greater extent than placebo. Clinicaltrials.gov ID: NCT01384565.

Altered frequencies of dendritic cells and IFN-gamma-secreting T cells with granulocyte colony-stimulating factor (G-CSF) therapy in acute-on- chronic liver failure.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a serious hepatic ailment with impaired immunity and poor treatment options resulting high mortality. Treatment with granulocyte colony-stimulating factor(G-CSF) mobilizes CD34(+) cells in ACLF patients; however its effect on impaired immune responses remains to be elucidated. To analyse the effect of G-CSF in immune modulation in ACLF. METHODS: We have analysed the frequencies of circulating and intrahepatic myeloid (mDCs) and plasmacytoid(pDCs) dendritic cells (DCs) and T cells in ACLF patients treated with G-CSF (Group A; n = 23) and placebo (Group B; n = 24) using flow cytometry. IFN-c production was compared in both groups following stimulation of PBMCs with phorbol myristate acetate (PMA). RESULTS: In Group A, circulating and intrahepatic mDCs, pDCs (P < 0.04, P < 0.02) and T cells(CD3, CD4 and CD8) increased significantly post-G-CSF treatment in comparison to placebo group. Importantly in Group A, IFN-c-producing CD8 T cells were significantly decreased (P > 0.05) along with decreased serum bilirubin and international normalized ratio (INR). Intrahepatic DCs and IFN-clevel were compared in survivor and non-survivor. Non-survivors from both groups, showed decreased DCs, high IFN-c level and no improvement in clinical parameters including s-bilirubin and INR. CONCLUSIONS: G-CSF therapy increased the frequencies of dendritic cells and reduced IFN-c secreting CD8 T cells with improved clinical severity indices. Decreased IFN- c production may contribute to reduced hepatocellular damage in ACLF patients.Our observations support the basis for further use of G-CSF therapy as immune modulator in these patients.

Efficient feature selection based novel clinical decision support system for glaucoma prediction from retinal fundus images.

The process of feature selection (FS) is vital aspect of machine learning (ML) model's performance enhancement where the objective is the selection of the most influential subset of features. This paper suggests the Gravitational search optimization algorithm (GSOA) technique for metaheuristic-based FS. Glaucoma disease is selected as the subject of investigation as this disease is spreading worldwide at a very fast pace; 111 million instances of glaucoma are expected by 2040, up from 64 million in 2015. It causes widespread vision impairment. Optic nerve fibres can be degraded and cannot be replaced later in this disease. As a starting point, the retinal fundus images of glaucoma infected persons and healthy persons are used, and 36 features were retrieved from these images of public benchmark datasets and private dataset. Six ML models are trained for classification on the basis of the GSOA's returned subset of features. The suggested FS technique enhances classification performance with selection of most influential features. The eight statistical performance evaluating parameters along with execution time are calculated. The training and testing have been performed using a split approach (70:30), 5-fold cross validation (CV), as well as 10-fold CV. The suggested approach achieved 95.36 % accuracy. Due to its auspicious performance, doctors might use the suggested method to receive a second opinion, which would also help overburdened skilled medical practitioners and save patients from vision loss.

Granulocyte colony-stimulating factor mobilizes CD34(+) cells and improves survival of patients with acute-on-chronic liver failure.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) develops in patients with chronic liver disease and has high mortality. Mobilization of bone marrow-derived stem cells with granulocyte colony-stimulating factor (G-CSF) could promote hepatic regeneration. METHODS: Consecutive patients with ACLF were randomly assigned to groups given 5 µg/kg G-CSF subcutaneously (12 doses; group A, n = 23) or placebo (group B, n = 24) plus standard medical therapy. We assessed survival until day 60; Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD), and Sequential Organ Failure Assessment (SOFA) scores; and the development of other related complications. RESULTS: After 1 week of treatment, group A had higher median leukocyte and neutrophil counts than group B (P < .001). Sixteen patients in group A (69.6%) and 7 in group B (29%) survived; the actuarial probability of survival at day 60 was 66% versus 26%, respectively (P = .001). Treatment with G-CSF also reduced CTP scores in group A by a median of 33.3% compared with an increase of 7.1% in group B (P = .001), along with MELD (median reduction of 15.3% compared with an increase of 11.7% in group B; P = .008) and SOFA scores (median reduction of 50% compared with an increase of 50% in group B; P = .001). The percentages of patients who developed hepatorenal syndrome, hepatic encephalopathy, or sepsis were lower in group A than in group B (19% vs 71% [P = .0002], 19% vs 66% [P = .001], and 14% vs 41% [P = .04], respectively). After 1 month of treatment, G-CSF increased the number of CD34(+) cells in the liver (by 45% compared with 27.5% in group B; P = .01). CONCLUSIONS: G-CSF therapy more than doubles the percentage of patients with ACLF who survive for 2 months; it also significantly reduces CTP, MELD, and SOFA scores and prevents the development of sepsis, hepatorenal syndrome, and hepatic encephalopathy.

Hepatic and systemic hemodynamic derangements predict early mortality and recovery in patients with acute-on-chronic liver failure.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a clinical entity where there is a potential for reversibility of hepatic dysfunction once the acute hepatic insult resolves. The portal and systemic hemodynamics in ACLF patients to study its relevance in determining the clinical outcomes was studied. METHODS: Clinical, laboratory, portal, and systemic hemodynamic assessments were done at admission and after 3 months. Standard medical care was given to all the patients. RESULTS: Fifty-seven patients with ACLF were enrolled, and they underwent baseline hepatic venous pressure gradient (HVPG) measurement. Twenty-six (46%) patients died during the 3-month follow-up. Presence of high HVPG and hepatic encephalopathy were found to be independent baseline predictors of mortality. Of the 31 surviving patients, 24 consented for a repeat HVPG. The baseline HVPG reduced from 16 (range 12-30) to 13 (range 6-21) mmHg; (P < 0.05). The reduction in HVPG correlated with clinical and biochemical recovery, and reduction in Child-Turcotte-Pugh score score (P < 0.05), while the aortic mean arterial pressure, cardiac index and systemic vascular resistance index improved significantly (< 0.05). Six (25%) patients developed upper gastrointestinal bleed; the median HVPG between bleeders and non-bleeders was not different possibly because of early onset of bleed (median 20 [15-45 days]). CONCLUSIONS: Baseline HVPG is an independent predictor of mortality in ACLF patients. The portal and systemic circulatory anomalies regress substantially by 90 days and correlate with clinical recovery. However, in the initial phase, the raised portal pressure predisposes these patients to high risk of variceal bleeding.

Controlled attenuation parameter for non-invasive assessment of hepatic steatosis: does etiology affect performance?

BACKGROUND: Hepatic steatosis is an important parameter to assess in chronic liver disease patients. The controlled attenuation parameter (CAP) assesses liver steatosis using transient elastography. AIM: To determine the accuracy of CAP for evaluation of hepatic steatosis in chronic hepatitis B virus (CHBV)-infected, chronic hepatitis C virus (CHCV)-infected, and non-alcoholic fatty liver disease (NAFLD) patients and to determine the influence of etiology on the diagnostic accuracy of CAP. METHODS: One hundred forty-six CHBV patients, 108 CHCV-infected patients and 63 patients with NAFLD, who underwent both liver biopsy and successful CAP measurements within the study period, were assessed. Area under the receiver operating characteristics was used to evaluate performance of CAP for diagnosing steatosis compared with biopsy. RESULTS: Multivariate analysis found that CAP correlated with body mass index (odds ratio, 95% confidence interval = 4.09 [1.2-6.8] for CHBV; 4.7 [1.1-8.4] for CHCV, and 16.2 [9.1-24.5] for NAFLD patients respectively) and hepatic steatosis score on biopsy (odds ratio, 95% confidence interval = 30.7 [19.2-42.2] for CHBV; 24.2 [11.5-37.3] for CHCV, and 21.8 [10.1-45.0] for NAFLD patients respectively). Area under the receiver operating characteristics for CAP was 0.683 (0.601-0.757) for steatosis (S) ≥ 6%, 0.793 (0.718-0.856) for S > 33%, and 0.841 (0.771-0.896) for S > 66% respectively for CHBV-infected patients. There was no difference in accuracy of CAP for assessing liver fat among CHBV, CHCV, and NAFLD patients. CONCLUSIONS: CAP is a novel, non-invasive tool that can detect and quantify steatosis accurately among CHBV, CHCV, and NAFLD patients, the accuracy being similar for all the three groups of patients.

Liver stiffness measurements in patients with different stages of nonalcoholic fatty liver disease: diagnostic performance and clinicopathological correlation.

BACKGROUND: The present study evaluated performance characteristics of liver stiffness measurement (LSM) by FibroScan in patients with different stages of nonalcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: A total of 307 subjects (120 NAFLD, 85 NAFLD related cirrhosis, and 102 healthy controls) were studied. RESULTS: In NAFLD patients, LSM had significant correlation with fibrosis (r = 0.68, p < 0.001), and increased progressively with increasing fibrosis (p < 0.001). However, the difference between stage 1 and stage 2 fibrosis was not significant (p = 0.07). The LSM in NAFLD without fibrosis and healthy controls was similar (p = 0.37). The areas under receiver-operating characteristics (AUROC) curve of LSM for stages ≥1, ≥2, ≥3, and 4 were 0.82, 0.85, 0.94, and 0.96, respectively. The best LSM (kPa) cut-offs for fibrosis stages ≥1, ≥2, ≥3 and 4 were 6.1, 7.0, 9.0, and 11.8, respectively. The negative predictive value of LSM for excluding advanced fibrosis was 95%. For advanced fibrosis, the AUROC curve of LSM was 0.94, followed by FIB-4 (0.75), BARD score (0.68), NAFLD fibrosis score (0.66), and aspartate platelet ratio index (0.60). In multivariate analysis, LSM was the only independent predictor of advanced fibrosis (odds ratio 1.47). In patients with NAFLD cirrhosis, LSM correlated significantly with Child-Pugh score (r = 0.40, p < 0.001), serum bilirubin (r = 0.34, p = 0.02), and grades of esophageal varices (r = 0.23, p = 0.04). CONCLUSION: LSM is a useful tool for evaluation of patients with NAFLD, and is the best among other non-invasive predictors of liver fibrosis.

Tenofovir improves the outcome in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure.

UNLABELLED: Spontaneous reactivation of chronic hepatitis B (CHB) is an important cause of acute-on-chronic liver failure (ACLF). Antiviral drugs may help reduce the high morbidity and mortality in such patients, especially in places where liver transplant is not available. The aim was to evaluate the efficacy of tenofovir and to determine the predictors of mortality in patients with spontaneous reactivation of CHB with ACLF. Consecutive patients of ACLF due to spontaneous reactivation of CHB were randomized to receive either tenofovir or placebo. The primary endpoint was survival at 3 months. Of the 90 patients with ACLF of different etiologies, 27 (26%) were due to reactivation of CHB and were enrolled. The median baseline hepatitis B virus (HBV) DNA level was 9 × 10(5) IU/mL. Fourteen patients received tenofovir and 13 placebo. At 3 months the probability of survival was higher in the tenofovir than the placebo group (8/14 [57%] versus 2/13 [15%], respectively; P = 0.03). The cause of death in the 15 patients was progressive liver failure leading to multiorgan failure. Liver transplantation could not be offered due to its nonavailability. In the surviving patients, there was a significant improvement in the Child-Turcotte Pugh (CTP) and model for endstage liver disease (MELD) scores and significant decline in the HBV DNA levels in the tenofovir group, whereas these parameters did not change significantly in the placebo group. More than 2 log reduction in HBV DNA levels at 2 weeks was found to be an independent predictor of survival. CONCLUSION: Tenofovir significantly reduces HBV-DNA levels, improves CTP and MELD scores, and reduces mortality in patients with severe spontaneous reactivation of CHB presenting as ACLF. Reduction in HBV-DNA levels at 2 weeks should be a desirable goal and is a good predictor of survival.

Performance evaluation of various deep learning based models for effective glaucoma evaluation using optical coherence tomography images.

Glaucoma is the dominant reason for irreversible blindness worldwide, and its best remedy is early and timely detection. Optical coherence tomography has come to be the most commonly used imaging modality in detecting glaucomatous damage in recent years. Deep Learning using Optical Coherence Tomography Modality helps in predicting glaucoma more accurately and less tediously. This experimental study aims to perform glaucoma prediction using eight different ImageNet models from Optical Coherence Tomography of Glaucoma. A thorough investigation is performed to evaluate these models' performances on various efficiency metrics, which will help discover the best performing model. Every net is tested on three different optimizers, namely Adam, Root Mean Squared Propagation, and Stochastic Gradient Descent, to find the best relevant results. An attempt has been made to improvise the performance of models using transfer learning and fine-tuning. The work presented in this study was initially trained and tested on a private database that consists of 4220 images (2110 normal optical coherence tomography and 2110 glaucoma optical coherence tomography). Based on the results, the four best-performing models are shortlisted. Later, these models are tested on the well-recognized standard public Mendeley dataset. Experimental results illustrate that VGG16 using the Root Mean Squared Propagation Optimizer attains auspicious performance with 95.68% accuracy. The proposed work concludes that different ImageNet models are a good alternative as a computer-based automatic glaucoma screening system. This fully automated system has a lot of potential to tell the difference between normal Optical Coherence Tomography and glaucomatous Optical Coherence Tomography automatically. The proposed system helps in efficiently detecting this retinal infection in suspected patients for better diagnosis to avoid vision loss and also decreases senior ophthalmologists' (experts) precious time and involvement.

HPi: A Novel Parameter to Predict Graft-related Outcome in Adult Living Donor Liver Transplant.

BACKGROUND: Portal hyperperfusion is frequently associated with early allograft dysfunction (EAD). It is imperative to identify patients who would require portal inflow modulation. We aimed to identify factors associated with hyperperfusion-related graft injury and develop a predictive index for the same. METHODS: Prospectively maintained database was queried to identify 135 adult living donor liver transplant recipients between September 2016 and July 2020. According to the calculated sample size, 96 patients were randomly selected for "test cohort". The remaining 39 patients made the "validation cohort." EAD was defined according to the A2ALL study. "Hyperperfusion index (HPi)," defined as posttransplant portal pressure gradient (ΔPpost)/graft-to-recipient splenic volume ratio (GRSVR), was devised on the basis of laws of flow dynamics and regression analysis. RESULTS: Overall, 40 patients (29.6%) had EAD, six 90-d mortalities (4.4%) were attributable to EAD. In the test cohort, EAD patients (n = 29, 30.2%) had lower GRSVR (1.00 versus 2.22, P < 0.001), higher ΔPpost (14.8 versus 11.9, P = 0.004), and HPi (20.89 versus 8.67, P < 0.001). Multivariate analysis revealed GRSVR, ΔPpost, and HPi as significant factors to predict EAD. Receiver operating characteristic determined cutoff of HPi ≥9.97 could predict EAD with sensitivity of 90% and specificity of 73% (F-score = 0.712). HPi ≥16.25 predicted 90-d mortality with sensitivity of 100% and specificity of 78.9%. Patients with higher HPi had delayed graft-related recovery. Non-EAD patients had a higher 1-y (96% versus 79%) and 2-y (88% versus 79%) survival. The cutoff of HPi was validated well in the validation cohort (F-score = 0.645) (Hosmer-Lemeshow test, P = 0.89). CONCLUSIONS: While predicted GRSVR may help identify at-risk patients preoperatively, intraoperatively calculated HPi is more accurate in identifying patients who would require portal inflow modulation. Achieving an HPi below target cutoff significantly decreases the risk of EAD even in low-GRSVR patients.

Type Va Duplication of the Common Bile Duct With Type IIIa Intrahepatic Bile Duct Anatomy: A Rare Combination of Dual Biliary Ductal Anomaly With Difficulty to Extract Common Bile Duct Stone.

Extrahepatic duplication of the common bile duct (CBD) is an extremely rare anatomic variation seen in the biliary tract. It represents failure of regression of the primitive duplicated biliary ductal system, resulting in five different subtypes of the duplicated CBD as described by Choi et al. To date, only few such cases have been reported in the literature. Associated variation in branching of intrahepatic bile ducts presenting as combined dual ductal anomaly is even rarer phenomena to be seen. We report a case of a 67-year-old man with chronic kidney disease and obstructive jaundice resulting from choledocholithiasis. Evaluation revealed type IIIa branching of intrahepatic bile ducts with type Va duplication of the CBD.

Transient elastographic evaluation in adult subjects without overt liver disease: influence of alanine aminotransferase levels.

BACKGROUND AND AIM: Studies on normal values of liver stiffness (LS) in subjects at "low risk" for liver disease are scant. The aim of the present study was to assess liver stiffness values in the subjects without overt liver disease with normal alanine aminotransferases (ALT) and to determine potential factors, which may influence these values with special reference to newly suggested updated upper limits of normal for ALT. METHODS: Liver stiffness measurements were performed in 445 subjects without overt liver disease (mean age, 41.1±13.6; male, 73.5%) and normal liver enzymes. RESULTS: Mean LS value was 5.10±1.19kPa. LS values were higher in men than in women (5.18±1.67 vs 4.86±1.24kPa, respectively, P=0.008); in subjects with higher body mass index (BMI) category (Normal, overweight and obese subjects; 4.10±0.75, 5.08±0.66, and 6.05±1.28kPa, respectively; P<0.001); in subjects with metabolic syndrome than in those without (5.63±1.37 vs 5.01±1.14kPa, P=0.001); and in subjects with ALT levels more than updated limits of normal compared to subjects with ALT levels less than updated limits of normal (5.68±1.21 vs 4.77±1.05kPa, P<0.001). On multiple linear regression, BMI and ALT was found to be significant predictor of LS. CONCLUSIONS: Liver stiffness values in subjects without overt liver disease with normal ALT are influenced by BMI and ALT levels. Subjects with ALT levels less than updated limits of normal have lower LS values as compared to those with higher levels.

An enhanced deep image model for glaucoma diagnosis using feature-based detection in retinal fundus.

This paper proposes a deep image analysis-based model for glaucoma diagnosis that uses several features to detect the formation of glaucoma in retinal fundus. These features are combined with most extracted parameters like inferior, superior, nasal, and temporal region area, and cup-to-disc ratio that overall forms a deep image analysis. This proposed model is exercised to investigate the various aspects related to the prediction of glaucoma in retinal fundus images that help the ophthalmologist in making better decisions for the human eye. The proposed model is presented with the combination of four machine learning algorithms that provide the classification accuracy of 98.60% while other existing models like support vector machine (SVM), K-nearest neighbors (KNN), and Naïve Bayes provide individually with accuracies of 97.61%, 90.47%, and 95.23% respectively. These results clearly demonstrate that this proposed model offers the best methodology to an early diagnosis of glaucoma in retinal fundus.

Recurrent Hepatic Artery Thrombosis Following Living Donor Liver Transplant as Sequelae of SARS-CoV-2 Infection-a Case Report.

As the second wave of COVID-19 disease is gripping the globe, liver transplant centers are increasingly receiving patients recovered from SARS-CoV-2 infection in recent few weeks. Unexpected complications in these patients are increasingly being recognized. We performed liver transplantation on a 51-year-old gentleman with decompensated liver disease 23 days after recovering from a mild SARS-CoV-2 infection. Surprisingly, despite massive blood loss and a prolonged anhepatic phase, his thromboelastographic (TEG) parameters persistently revealed hypercoagulability. After a brief uneventful early post-operative period, he developed hepatic arterial thrombosis on the 14th post-operative day, and again after 4 days, both of which required surgical intervention. Following discharge, the artery was thrombosed again which was only picked up when he developed a cholangiolar abscess, leading to graft loss necessitating re-transplantation. There is a lot of evidence suggesting that patients with SARS-CoV-2 infection tend to be hypercoagulable. We believe that this hypercoagulability might have played a significant role in the development of hepatic arterial thrombosis and eventual graft loss in this patient. This highlights the importance of revisiting anticoagulation protocols in liver transplant recipients recovered from COVID-19 and base them on TEG rather than routine parameters such as INR and APTT, which are routinely deranged in such patients.

Bone Cancer Detection Using Feature Extraction Based Machine Learning Model.

Bone cancer is considered a serious health problem, and, in many cases, it causes patient death. The X-ray, MRI, or CT-scan image is used by doctors to identify bone cancer. The manual process is time-consuming and required expertise in that field. Therefore, it is necessary to develop an automated system to classify and identify the cancerous bone and the healthy bone. The texture of a cancer bone is different compared to a healthy bone in the affected region. But in the dataset, several images of cancer and healthy bone are having similar morphological characteristics. This makes it difficult to categorize them. To tackle this problem, we first find the best suitable edge detection algorithm after that two feature sets one with hog and another without hog are prepared. To test the efficiency of these feature sets, two machine learning models, support vector machine (SVM) and the Random forest, are utilized. The features set with hog perform considerably better on these models. Also, the SVM model trained with hog feature set provides an F1-score of 0.92 better than Random forest F1-score 0.77.

Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study).

BACKGROUND AND AIMS: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon comorbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis. METHODS: Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19. RESULTS: Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR = 2.1 (1.1-3.7), p = 0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR = 8.1 (1.9-38.8), p = 0.002] predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5 (11.6%)] or acute decompensation [4 (9%)]. Liver related complications increased (p < 0.05) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted high mortality [AUROC 0.94, HR = 19.2 (95 CI 2.3-163.3), p < 0.001, sensitivity 85.7% and specificity 94.4%). In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis patients. CONCLUSIONS: SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored.

Sofosbuvir and Ribavirin for 24 Weeks Is An Effective Treatment Option for Recurrent Hepatitis C Infection After Living Donor Liver Transplantation.

BACKGROUND: Recurrent hepatitis C virus (HCV) has been a serious problem after liver transplantation (LT). We report our experience of 24-week therapy with sofosbuvir (SOF) and ribavirin (RBV) in post-LT recurrent HCV in living donor liver transplantation (LDLT) setting in South Asia. METHODS: Data from all patients treated for post-transplantation HCV recurrence in a single center were analyzed. Treatment regimen was 24 weeks of SOF 400 mg daily and RBV (starting at 800 mg daily, increased as tolerated). Sustained virological response (SVR) was assessed 12 weeks and 24 weeks after completion of treatment. RESULTS: 63 patients (median age 52 [range 30-69] years; 80% males) were treated. Most (76.2%) were treatment experienced and predominant HCV genotype was 3 (77.7%) followed by 1 (20.6%). Median transient elastography (Fibroscan) score was 7 (range 3-11) kPa and none of the patients had cirrhosis. SVR12 was achieved in 60 of 63 patients (95.2%) while SVR24 was noted in 59 (93.7%). SVR12 rates were as good in genotype-3 as in genotype-1. Older age, longer period after transplantation, higher Fibroscan value and higher need for erythropoietin were likely to be associated with relapse. Adverse effects were noted in 34 patients and weakness and fatigue were the commonest side effects. Significant drop in hemoglobin (<8 g/dL) was seen in 6 patients. CONCLUSIONS: SOF + RBV combination therapy for 24 weeks was safe and effective in treatment of for post-LT recurrent HCV in a single LT center and remains relevant due to its low cost and lack of drug interactions.