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Recidivism in patients who underwent liver transplantation for alcohol-related liver disease (ALD) is shown to be associated with poor survival in some studies. Living donor liver transplantation (LDLT) recipients for ALD with at least 2 years of follow-up and history of significant alcohol relapse were included. The recipients underwent LDLT from June 2010 to December 2016, and data were analyzed until June 2019. The cohort had a median follow-up of 54 (33–78 IQR) months. Recidivism (significant alcohol intake) was defined as >21 units per week. A total of 27 of 463 (5.8%) LDLT recipients (all men), aged 43.5 ± 9.6 years, had significant alcohol intake. A liver biopsy was performed on demand in 14 patients (in the presence of raised levels of liver enzymes or jaundice). The histological diagnoses in these patients were as follows: alcoholic hepatitis in 7 (50%), alcoholic hepatitis and acute cellular rejection or chronic rejection in 4 (28.5%), cirrhosis in 2 (14.2%), and acute cellular rejection and cirrhosis in 1 (7.1%) patient. Four of 5 patients with a biopsy diagnosis of acute or chronic rejection were noncompliant with immunosuppression. Six of these patients died. The mortality after 1 year of transplant was significantly more in patients with recidivism. Recidivism was associated with significant morbidity and mortality after liver transplantation. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is associated with a significant morbidity and mortality in patients with cirrhosis. There is a significantly higher morbidity and mortality due to COVID-19 in patients with decompensated cirrhosis as compared to compensated cirrhosis, and in patients with cirrhosis as compared to noncirrhotic chronic liver disease. The fear of COVID-19 before or after liver transplantation has lead to a significant reduction in liver transplantation numbers, and patients with decompensated cirrhosis remain at risk of wait list mortality. The studies in liver transplantation recipients show that risk of mortality due to COVID-19 is generally driven by higher age and comorbidities. The current review discusses available literature regarding outcomes of COVID-19 in patients with cirrhosis and outcomes in liver transplant recipients. [ABSTRACT FROM AUTHOR]

Liver transplantation (LT) is the only cure for patients with end-stage liver disease, which offers good long-term survival. The long-term issues after LT affecting survival are cardiovascular disease, chronic kidney disease, de novo malignancies, recurrence of original disease and immunological causes. Alcoholic-related liver disease (ALD) is one of the most common indications for LT worldwide including India. LT for ALD is associated with several unique challenges as compared with other etiologies. Long-term survival after LT in patients with ALD is affected by recidivism. Various studies have shown different predictors of relapse; the main predictors of relapse are pretransplant abstinence, psychiatric comorbidities, and lack of social support. Although several risk scores have been proposed, these scores are not validated. Studies with active involvement of psychiatrist have shown lower relapse rates. The relapse prevention strategy for reducing likelihood and severity of relapse after initial cessation of alcohol uses a combination of pharmacotherapy and cognitive behavioral approach (identifying and addressing high-risk situations for relapse). [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. In addition to the liver-related morbidity and mortality, NAFLD is now also associated with various extrahepatic diseases. Pathogenesis of NAFLD is multifactorial with limited pharmacotherapy options for the treatment of patients with NAFLD. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that are involved in the transcriptional regulation of lipid metabolism, glucose homeostasis, energy balance, inflammation, and atherosclerosis. PPAR agonists are attractive options for treatment of NAFLD as they can act at multiple targets involved in the pathogenesis of NAFLD. We reviewed the available literature on the pathophysiological role of PPARs and use of PPAR agonists in the treatment of NAFLD. Original studies and review articles available on PubMed regarding the role of PPARs in the pathogenesis and utility of PPAR agonists in the treatment of NAFLD were included in this review article. ClinicalTrials.gov and Clinical Trials Registry-India sites were searched for ongoing studies on saroglitazar. The available literature suggests that PPARs play an important role in the pathogenesis of NAFLD. Use of PPAR gamma agonists is associated with histological improvement in NAFLD. Dual PPAR agonists with no or minimal PPAR gamma activity are being explored in the treatment of NAFLD. Because of the pathophysiological role of PPARs in NAFLD, PPAR agonists are attractive options for the treatment of patients with NAFLD. Dual PPAR agonists without significant gamma activity appear promising for the treatment of NAFLD. [ABSTRACT FROM AUTHOR]

Post-transplant nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) is common and can be recurrent or de novo. The available data suggest that progression of fibrosis is accelerated in these patients compared to NASH in general population. The long-term data suggest more risk of metabolic syndrome and associated metabolic comorbidities and cardiovascular disease in these patients. The current review focuses on prevalence and prevention/treatment of post-transplant NAFLD or NASH. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Patients with NAFLD are at a higher risk of developing cardiovascular disease (CVD). In fact, CVD-related mortality is more common in patients with NAFLD in comparison to liver-related mortality. This association is related to the common metabolic risk factors such as obesity, dyslipidemia, diabetes, and hypertension shared by both NAFLD and CVD, and also there is independent association of NAFLD with CVD because of risk factors such as insulin resistance, systemic inflammation, and atherogenic dyslipidemia. While there is abundant literature on association of NAFLD with CVD, there is sparse literature regarding the screening for CVD in patients with NAFLD. In the current review article, we discuss as to which patients with NAFLD to screen and how to screen for CVD. [ABSTRACT FROM AUTHOR]

Background Acute-on chronic liver failure (ACLF) is defined as acute insult on previous liver disease that causes sudden worsening of liver functions. Methods ACLF is characterized by high incidence of organ failure and prognosis is remarkably worse than patients with cirrhosis. Incidence of organ failures is very high despite best medical care and timely liver transplant before development of multi organ failure is associated with good survival rates. Results At present, there are no reliable score or ways to correctly identify patients who are going to recover from patients who will need transplantation. Organ failures are important part of prognosis and to define need or futility of early liver transplantation. Conclusion Asian Pacific Association for the Study of the Liver (APASL) published their recommendations regarding ACLF in 2014. Several important studies regarding course/nature of disease and transplantation for ACLF became available after 2014 APASL recommendations and still there are some unanswered areas. The current review discusses various issues regarding liver transplantation in patients with ACLF. [ABSTRACT FROM AUTHOR]

Background Liver steatosis is the leading cause of donor rejection in living donor liver transplantation. Rapid weight loss is difficult to achieve in a short period of time, moreover it has been thought to worsen liver histology. Methods Donors who had significant steatosis based on liver biopsy were recommended 1200 Kcal/day and a minimum of 60 min/day moderate cardio training. Two patients were advised statins for dyslipidemia. None of the donors had metabolic syndrome. A second ultrasound guided liver biopsy was done at 28 ± 10 days. Donors with nonalcoholic steatohepatitis/fibrosis or >30% steatosis were not included. Results From July 2010 to January 2015, 16 donors were advised aggressive life style modification after initial biopsy; 15 (10 males, age 27.5 ± 6.5 years, baseline body mass index 28.4 ± 2.1 Kg/M 2 ) successfully reduced weight and 14 underwent donation after favorable second biopsy. Mean weight loss was 7 ± 4.3 kg (8.4 ± 4.6%). Second liver biopsy was done at 28 ± 10 days, there was decrease in steatosis in all but one including normalization of liver biopsy in 7 donors. Three donors had mild inflammation on first biopsy and they had improvement in second biopsy. All the donors and their recipients had an uneventful post-operative course. Conclusion Steatosis can be reversed in a short duration by aggressive life style modifications in highly motivated liver donors. [ABSTRACT FROM AUTHOR]

Background and Aim Liver biopsy-based studies have shown that serum levels of aminotransferases are lower than conventional cut-off of 40 IU/mL in persons with normal histology. There is no such study in Indian population based on liver histology. This study aims to estimate normal values of serum aminotransferases in healthy Indian population with normal liver histology. Methods This retrospective study includes all liver donors who underwent liver donation at our centre and had a preoperative liver biopsy done for various reasons. All the donors had negative viral markers. Nonalcoholic fatty liver ( NAFL) was defined as > 5% hepatocytes having steatosis and no changes of steatohepatitis. Results The study included 331 donors (147 males) with the ages of 35.7 ± 10.2 years. NAFL was present in 167 donors (50.4%). In comparison with male donors with normal histology ( n = 67), donors with NAFL ( n = 80) had significantly higher age, body mass index, aspartate aminotransferase ( AST), alanine aminotransferase ( ALT), alkaline phosphatase, gamma-glutamyl transpeptidase, total cholesterol, low-density lipoprotein, and fasting blood sugar. In comparison with female donors with normal histology, donors with NAFL had significantly higher body mass index, ALT, and triglycerides; however, there was no significant difference regarding other parameters. Of the AST and ALT in normal histology donors, 95th percentile were 33.8 IU/L and 38.6 IU/L for males and 31 IU/L and 35.2 IU/L for females. Twenty-five donors had lean NAFL (body mass index < 23 kg/m2). Conclusion Serum aminotransferase values in healthy Asian Indian population with normal histology are provided. Histological NAFL is present in half of apparently normal donors, and it has different clinical and biochemical associations in males and females. [ABSTRACT FROM AUTHOR]

Background Various vasoconstrictors have shown promising results in the management of type 1 hepatorenal syndrome ( HRS). However, there are very few studies on vasopressors in the management of type 2 HRS. Terlipressin has been used commonly; however, it is costly and not available in some countries. In this study, we evaluated the safety and efficacy of terlipressin and noradrenaline in the treatment of type 2 HRS. Methods Forty-six patients with type 2 HRS were managed with terlipressin (group A, N = 23) or noradrenaline (Group B, N = 23) with albumin in a randomized controlled trial at a tertiary centre. Results HRS reversal could be achieved in 17(73.9%) patients in group A as well as in group B ( P = 1.0). Univariate analysis showed that the baseline model of end-stage liver disease score, urine output, urinary sodium, serum creatinine and mean arterial pressure were associated with response. However, in multivariate analysis only baseline serum creatinine, urine output and urinary sodium were associated with the response. Eight patients in group A and 9 in group B died within 90 days of follow-up ( P > 0.05). Noradrenaline was less expensive than terlipressin ( P < 0.05). No major adverse effects were seen. Conclusions The results of this randomized study suggest that terlipressin and noradrenaline are safe and effective in the treatment of type 2 HRS and baseline serum creatinine, urine output and urinary sodium are predictive of response. Noradrenaline is less expensive than terlipressin in the treatment of type 2 HRS (ClinicalTrials.gov, Number NCT01637454). [ABSTRACT FROM AUTHOR]

Objective The aim of the study was to assess the performance of various prognostic scores including the acute physiology and chronic health evaluation ( APACHE II), sequential organ failure assessment ( SOFA), Child- Turcotte- Pugh ( CTP) and model for end-stage liver disease ( MELD) scores in predicting short-term mortality in patients with acute-on-chronic liver failure ( ACLF). Methods Altogether 100 consecutive patients with ACLF were evaluated prospectively. The diagnosis of ACLF was based on the Asian- Pacific Association for the Study of the Liver criteria except for the inclusion of non-hepatic insults as acute events. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for predicting short-term mortality was calculated for APACHE II, SOFA, CTP and MELD in all patients and Maddrey's discriminant function ( DF) and Glasgow alcoholic hepatitis scores ( GAHS) for patients with alcoholic hepatitis only. Results Most patients had alcohol-related cirrhosis and alcoholic hepatitis as acute insults for ACLF. A total of 53 patients either died or left hospital in very sick status and were confirmed to have died the same day after leaving hospital. Overall, the area under the receiver operating characteristic curve of APACHE II was higher than those of MELD, SOFA and CTP scores for predicting short-term mortality. Even for patients with alcoholic hepatitis, APACHE II performed better than DF and GAHS. Conclusions Short-term mortality is high in patients with ACLF. APACHE II scoring system is superior to other prognostic scores in predicting its short-term mortality. [ABSTRACT FROM AUTHOR]

Renal dysfunction is very common among patients with chronic liver disease, and concomitant liver disease can occur among patients with chronic kidney disease. The spectrum of clinical presentation and underlying etiology is wide when concomitant kidney and liver disease occur in the same patient. Management of these patients with dual onslaught is challenging and requires a team approach of hepatologists and nephrologists. No recent guidelines exist on algorithmic approach toward diagnosis and management of these challenging patients. The Indian National Association for Study of Liver (INASL) in association with Indian Society of Nephrology (ISN) endeavored to develop joint guidelines on diagnosis and management of patients who have simultaneous liver and kidney disease. For generating these guidelines, an INASL-ISN Taskforce was constituted, which had members from both the societies. The taskforce first identified contentious issues on various aspects of simultaneous liver and kidney diseases, which were allotted to individual members of the taskforce who reviewed them in detail. A round-table meeting of the Taskforce was held on 20–21 October 2018 at New Delhi to discuss, debate, and finalize the consensus statements. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong and weak) thus reflects the quality (grade) of underlying evidence (I, II, III). We present here the INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease. [ABSTRACT FROM AUTHOR]