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Background: Spontaneous portosystemic shunts (SPSS) are common in cirrhosis. Their characterization and clinical implications remain unclear., Aims: To devise a system of assessment of these shunts, and assess their clinical implications METHODS: We retrospectively studied patients with cirrhosis who underwent imaging in a liver transplant program. A novel index was computed to assess total SPSS -the diameter of a circle having an area equivalent to the sum of the areas of all the existing shunts. This 'SPSS equivalent diameter' was compared with the clinical variables., Results: Among 127 patients, 70% (CI 95% 62-77) had SPSS, and 57% (CI 95% 62-77) had multiple SPSS. The risk for SPSS was related to the severity of cirrhosis (Child-Pugh B/C vs. A: OR 2.4 CI 95% 1.1-5.4) and alcoholic aetiology (OR 2.9 CI 95% 1.2-7.1). The SPSS equivalent diameter was related to a history of HE, cognitive impairment (EEG/PHES) and ammonia(p<0.05). The diameter of the inferior cava vein >19.5 mm was a predictor of large SPSS (AUC 0.77, CI 95% :0.68-0.87, p ≤ 0.001)., Conclusions: The SPSS equivalent diameter, a comprehensive assessment of portosystemic shunting, was associated with severity of liver disease, hyperammonemia, and cognitive dysfunction. The diameter of the inferior vena cava was a good predictor of SPSS., Competing Interests: Declaration of Competing Interest In the name of all the authors, I undersigned Piero Amodio, declares that no Author has any conflict of interest with the paper., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Liver cirrhosis accounts for over 2 million deaths annually worldwide. A subset of these patients - those with alcoholic hepatitis and decompensated cirrhosis, have abysmal short-term survival. Liver transplant is the only intervention of proven survival benefit; however organ availability is a major limitation. It is thus imperative to assess potential benefit of experimental therapies as a bridge to transplant. Stem cell therapies have shown some promise in patients with end-stage liver disease. Of these, bone-marrow derived hematopoietic stem cells have generated the most interest. Animal as well as human data suggest biological plausibility of stem cell translocation from bone marrow to liver, giving credence to cytokine therapies based on bone marrow stimulation. Granulocyte colony stimulating factor has been the most frequently used cytokine for this purpose. This intervention has shown encouraging results in terms of safety as well as survival benefits in small clinical trials. The evidence, however, is sparse and heterogeneous. In this review we describe the biological plausibility, mechanisms of action, and clinical evidence of the use of cytokine based stem cell therapy in patients with end-stage liver disease., (Copyright © 2020 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Many international guidelines on psoriasis management have emphasized upon the need to identify risk factors for liver fibrosis and that the risk may be increased after a certain total cumulative dose of methotrexate., Methods: Consecutive patients with moderate-to-severe psoriasis were assessed for liver fibrosis using transient elastography and noninvasive scores. Based on the presence of significant liver fibrosis, the Odds ratio associated with various factors was calculated using logistic regression analysis. Receiver operating characteristic curves were calculated to find maximal cutoff values of noninvasive tests to detect fibrosis., Results: In this cross-sectional study, 134 patients completed the study. Significant fibrosis (liver stiffness measurement ≥7, corresponding to F2 fibrosis or higher) was seen in 33 (24.6%) patients. Neither methotrexate exposure nor total cumulative dose of ≥1.5 was associated with significant fibrosis. Female sex (P = 0.024) and the presence of metabolic syndrome (P = 0.034) were the two variables associated with significant liver fibrosis. On logistic regression analysis, the odds ratio for the female gender and metabolic syndrome was estimated to be 2.51 (95% confidence interval - 1.09-5.81) and 2.33 (95% confidence interval - 1.03-5.27), respectively. Aspartate transaminase to platelet ratio index, nonalcoholic fatty liver disease score and the fibrosis-4 index had low sensitivity in comparison to transient elastography., Limitations: These included small sample size, small number of patients with a total cumulative methotrexate dose of >3-4.5 g, and lack of control group consisting of healthy persons. Another is the absence of liver biopsies considered as the gold standard in the diagnosis of liver fibrosis., Conclusions: Metabolic syndrome and female sex are associated with the development of significant liver fibrosis in patients with psoriasis. Methotrexate exposure does not seem to be significantly associated with significant liver fibrosis., Competing Interests: None

Background and Aim: The aim of this study is to evaluate the epidemiology and impact of bacterial infections at admission in patients with acute decompensation (AD) of cirrhosis., Methods: A cohort with AD of cirrhosis (European Association for the Study of the Liver criteria) admitted at a tertiary center was evaluated between 2013 and 2014 for the presence of bacterial infections at admission. Clinical, demographic, and microbiological data were collected prospectively till death, transplant, or 90 days., Results: Of 179 patients with AD, 102 (56.9%) had bacterial infections at admission. The commonest infections were spontaneous bacterial peritonitis (SBP) (n = 65; 63.7%), spontaneous bacteremia (n = 10; 9.8%), pneumonia (n = 9; 8.8%), urinary tract infection (n = 8; 7.8%), spontaneous bacterial empyema (n = 4; 3.9%), and cellulitis (n = 2; 1.9%). The commonest source was community acquired (n = 85; 83.3%). Serum albumin and sodium levels were lower in infected as compared with non-infected cohort (P = 0.015; for both). Escherichia coli was the commonest organism isolated from SBP (n = 14; 21.5%), urinary tract infection (n = 5; 45.5%), and bacteremia (n = 3; 20%). There was a trend toward higher 28-day mortality in infected cohort as compared with non-infected cohort (48 [52.7%] vs 28 [32%]; P = 0.152). Multidrug-resistant organisms (MDROs) were isolated in 63% of all culture-positive infections. The presence of MDRO was an independent predictor of 28-day mortality., Conclusions: Infections are the leading reason for the occurrence of AD; SBP is the most common infection, and E. coli is the commonest microorganism based on this single-center study of Indian patients with AD of cirrhosis. There is a high prevalence of MDROs among culture-positive infections that independently predict 28-day mortality in AD of cirrhosis., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background & Aims: The prevalence of anti-hepatitis C virus antibody in Punjab, India is 3.6%, with 728,000 people estimated to have viremic chronic hepatitis C (CHC). The Mukh-Mantri Punjab Hepatitis C Relief Fund, launched on 18th June 2016, provides no-cost generic direct-acting antivirals (DAAs) with sofosbuvir + ledipasvir ± ribavirin or sofosbuvir + daclatasvir ± ribavirin with the goal of eliminating CHC from Punjab. We assessed the safety and efficacy of decentralized treatment of CHC in a public health care setting., Methods: Primary care providers from 3 university and 22 district hospitals were trained to provide algorithm-based DAA treatment and supervised by telehealth clinics conducted fortnightly. The diagnosis of cirrhosis was based on clinical and radiological evidence, including aspartate aminotransferase-to-platelet ratio index (APRI ≥2.0) and FIB-4 score (>3.25), or on liver stiffness measurement ≥12.5 kPa on Fibroscan®., Results: We enrolled 48,088 individuals with CHC (63.8% male; mean age 42.1 years; 80.5% rural; 14.8% compensated cirrhosis; 69.9% genotype [GT] 3) between 18th June 2016 to 31st July 2018. While 36,250 (75.4%) patients completed treatment, 5,497 (11.4%) had treatment interruptions and 6,341 (13.2%) patients are currently ongoing treatment. Sustained virological response at 12 weeks after treatment completion (SVR12) was achieved in 91.6% of patients per protocol, 67.6% in intention-to-treat (ITT) analysis, where all interruptions were treated as failures, and 91.2% in a modified ITT analysis where all patients with successful SVR12 in the interruptions arm were included as cured. SVR12 rates in patients with and without cirrhosis and GT3 versus non-GT3 were comparable. The SVR12 rate was 84.4% in patients who had treatment interruptions., Conclusion: Decentralized care of patients with CHC using generic all-oral DAA regimens is safe and effective regardless of genotype or presence of cirrhosis. ClinicalTrials.gov number: NCT01110447., Lay Summary: We assessed the safety and efficacy of public health care using no-cost all-oral generic direct-acting antiviral drugs against hepatitis C in the state of Punjab, India. The goal is elimination of chronic hepatitis C (CHC) by 2030 and involves primary care providers at 25 sites in the state. We enrolled 48,088 individuals (63.8% male; mean age 42.1 years; 80.5% rural; 14.8% compensated cirrhotic; 69.9% genotype 3) between 18th June 2016 to 31st July 2018. Cure was achieved in 91.6% of patients, demonstrating that decentralized care of CHC with generic all-oral regimens is safe and effective., (Copyright © 2019. Published by Elsevier B.V.)

Background and Aims: The patients with end stage renal disease (ESRD) are at greater risk of acquiring chronic hepatitis B or C and subsequently development of liver disease. The aim of the study was to assess liver fibrosis by transient elastography (TE) and look for factors associated with change in liver stiffness measurement (LSM) with one session of hemodialysis (HD)., Methods: Consecutive ESRD patients on maintenance hemodialysis (MHD) with suspected liver disease were enrolled. They underwent LSM by TE before and after one session of HD. Bioelectric impedance analysis was done to evaluate the volume status at the time of TE., Results: Sixty-eight patients with mean age of 40 ± 14 years were included. There was a significant reduction in LSM after HD (18.5 [95% CI 14.8-23.1] vs. 11.2 [95% CI 8.8-13.7] kPa, p < 0.001), with a mean LSM reduction of 7.2 [95% CI 5.25-9.19] kPa. On stratification in two groups by net ultrafiltration during HD (> or < 2.5 liters [L]), change in LSM was substantially higher in patients when total fluid removed was > 2.5 L (8.6 [95% CI 5.7-11.5] vs. 5.1 [95% CI 2.9-7.5], p = 0.05). In 18 patients who underwent liver biopsy, LSM after HD performed better at detecting significant fibrosis, with area under receiver operating characteristics curve 0.71 [95% CI 0.46-0.97], versus 0.64 [95% CI 0.38-0.90], respectively. An LSM value of 12.2 kPa after HD was 71% sensitive and 74% specific for detection of significant fibrosis (≥ F2), while values less than 9 kPa ruled out significant fibrosis with a sensitivity and specificity of 37 and 100%, respectively., Conclusion: LSM by TE decreases significantly after HD in patients with ESRD on long-term MHD. Hence, TE should be done after HD for accurate assessment of liver fibrosis.