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The prevalence of NAFLD increases in obese diabetics. Accurate diagnosis of NAFLD requires invasive liver biopsies, which is costly, and time consuming and labor intensive. Currently, there is a lack of non-invasive diagnostic methods to identify those with NASH, in obese Indians. To develop an accurate non-invasive scoring system using clinical and biochemical parameters to predict the risk of developing non-alcoholic steatohepatitis (NASH). Clinical and biochemical parameters were recorded pre-operatively from 290 patients who were posted for bariatric/metabolic surgery, between September 2017 and October 2018 and compared with the result of intra-operative liver biopsy NAFLD activity scores (NAS). The mean weight and BMI of the patients were 120.3 ± 24.6 and 45.5 ± 7.8 respectively. In the final histopathological examination, 196/290 (67.6%) had simple steatosis, 92/290 (31.7%) had NASH, and 2/290 (0.007%) had cirrhosis. Binary logistic regression analysis of multiple independent predictors yielded five independent factors that were statistically significant (HbA1c, AST, ALT, liver span on USG, and serum triglycerides). These were used to create a scoring system, with a range of scores from 0 to 6, with maximum predictability at a score of 6. Patients with scores of ≧ 3 were at high risk of NASH diagnosis. The sensitivity of this scoring system was 85.87% and diagnostic accuracy was 75.35%. Our study not only confirms the significant association of NAFLD with obesity but also outlines a simple non-invasive scoring system to identify obese individuals at high risk for NASH.

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the “APASL ACLF Research Consortium (AARC)” was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the ‘Golden Therapeutic Window’, extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here., Article Highlights Updated on the basis of AARC data of >3300 cases enrolled into AARC registry prospectivelyACLF is distinct form Acute Decompensation of cirrhosisNewer sections on DILI-ACLF, AIH-ACLF, PVT/HVOTO–ACLFReversibility of Chronic Liver Disease in ACLFPortal and systemic hemodynamics and their relevance in ACLFAcute Portal Hypertension and Variceal progression in ACLFAARC score as a guide for treatment strategies in ACLFACLF in Children-first consensus on pediatric ACLF

Prophylaxis with hepatitis B immunoglobulin (HBIG) and nucleoside analogs can prevent hepatitis B virus (HBV) recurrence after liver transplant (LT).To determine the efficacy and cost of maintaining immunoprophylaxis with HBIG and hyperimmune plasma (HIP) for 6 months after LT.The study included 22 HBV related LT recipients who were on entecavir and either HBIG or HIP for 6 months. Post transplant HBIG or HIP dose and cost incurred towards prophylaxis were noted. The cost of 200 IU of HBIG at the time of study was Rs 8250/- (US Dollars 135) and that of 2000 IU of HIP was Rs 8000/- (USD 130.7). The loading and maintenance costs at end of 6 months were compared between the two groups. Response to HBIG and HIP was assessed by checking for HBsAg reactivity, anti HBs titer response and HBV DNA viral load.Median and range, Kruskal Wallis (KW) sign rank Sum Test and Correlation Coefficient (r2) was used for analysis.Thirteen recipients received HBIG and 9 recipients HIP. The anti HBs response to HIP was significantly high compared to HBIG (KW Sign rank Sum test P 0.05); titers remained high until the study period. Between 8 and 30 days, the titer achieved by both HBIG and HIP was similar (KW Sign rank Sum test not significant). Despite low anti HBs titer of100 IU/L, none of the recipients on HBIG had HBsAg reactivity while 3 on HIP had transient HBsAg positivity. The total cost with HBIG was 13.9 times the cost of HIP.HIP immunoprophylaxis in combination with entecavir achieves a high anti HBs titer at a significant low cost during anhepatic and loading phase. HBV reactivation rates with HBIG and HIP is low despite low anti HBs titer.

Tuberculosis (TB) is a serious disease for liver transplant recipients (LTRs). Data on post–liver transplant TB from high-burden countries are scant. The aims of this study were to describe the prevalence of TB in LTRs from a high-prevalence area and to analyze the risk factors for the development of post–liver transplant TB. We performed a retrospective review of our database and a case-control study of identified cases with TB and age-matched LTRs without TB. The overall prevalence of TB in LTRs was comparable to the prevalence of TB in LTRs from low-prevalence countries (5/214 or 2.3%). A low rate of interferon-γ release assay (IGRA) testing before liver transplantation was observed (68/214 or 31%). Most patients were screened clinically and with chest radiography alone before transplantation. TB developed variably after transplantation [median = 72 days, interquartile range (IQR) = 534 days]. The presentation was mostly extrapulmonary and/or disseminated (4/5 or 80%). When cases with posttransplant TB were compared with matched healthy LTRs, the presence of unexplained granulomas in explants (2/5 or 40%, P = 0.01) was the only factor associated with the development of TB. When all explants showing granulomas were reviewed, TB (52.9%) remained the most common cause; however, in almost half (47.1%), other attributable causes were found. Patients were treated with a standard daily regimen for a median of 12 months (IQR = 7.5 months). Posttransplant TB was associated with a high mortality rate (2/5 or 40%). In conclusion, we observed a low prevalence of TB in LTRs from a high-prevalence region. The presence of granulomas suggestive of TB in liver explants warrants isoniazid prophylaxis in the absence of disease. Post–liver transplant TB is associated with a high mortality rate. The roles of routine IGRA testing and isoniazid prophylaxis in a high-prevalence setting urgently need to be studied. Liver Transpl 20:960-966, 2014. © 2014 AASLD.

Tacrolimus is an important immunosuppressant administered to patients following liver transplantation (LT), with a recommended trough concentration of 8 to 11 ng/mL to prevent allograft rejection. We retrospectively examined our data to identify the tacrolimus trough concentration that combined efficacy with minimal adverse effects.The case records of LT recipients, who were nondiabetic, nonhypertensive, and with normal renal parameters prior to LT were retrospectively examined for acute cellular rejection (ACR) episodes and three major adverse effects of tacrolimus, i.e. neurotoxicity, nephrotoxicity, and new onset diabetes mellitus (NODM).Thirty-two LT recipients fulfilled the criteria for the study. The mean (±SD) tacrolimus level for the 290 troughs (after 10 days) was 8.5 ± 3.8 ng/mL. At 10 days, 1 month, 3 months, and 6 months, the trough values were 7.3 ± 2.9, 9.7 ± 3.4, 7.9 ± 3.3, and 7.6 ± 2.6 ng/mL, respectively. The mean time taken for stabilization of the blood pressure and biochemical parameters was 7 ± 2 days. Overall, a trough window with the least adverse effect was 7 to 7.9 ng/mL. Neurotoxicity was least in the trough range 5 to8 ng/mL. Symptoms included headache in four, tremors in three, seizure in one, confusion and psychosis in two, and combination in three. Nephrotoxicity was least in trough 8 to11 ng/mL. One patient progressed to chronic kidney disease at 6 months. NODM was present in 11 % to 18 % across the various trough range, including the extremes (mean trough level, 8.4 ± 4.4 ng/dL). At 6 months, five recipients were on treatment for NODM. Three recipients developed ACR, two within the first month and one at 7 weeks. The trough levels were 8.5, 9, 15.2 ng/mL, respectively. All recovered with three pulse doses of methylprednisolone.Tacrolimus concentration of 5 to8 ng/mL was associated with least overall toxicity, neurotoxicity, and ACR.

Liver transplantation for end-stage liver disease is increasingly being undertaken in India.(1) Routine tuberculin skin testing (TST) for latent Mycobacterium tuberculosis infection (LTBI) and isoniazid prophylaxis in TST-positive liver-transplant recipients (LTRs) is recommended(2,3) but seldom implemented worldwide.(4-7) The role of TST-testing and isoniazid prophylaxis in LTRs remains further undefined in high prevalence areas, including India. We describe the burden of LTBI in LTRs; the epidemiological aspects of M. tuberculosis infection in high prevalence areas; identifiable risk factors for M. tuberculosis infection; the limitations of current diagnostic techniques for LTBI in LTRs and the efficacy and toxicity of isoniazid prophylaxis in TST-positive LTRs and suggest directions for future investigations in this area.

Deceased donor (DDLT) and living donor (LDLT) liver transplant (LT) is in vogue in several centers in India. Most centers are resorting to LDLT as a preferred surgery due to shortage of deceased donor liver. The risk of infection and its effect on survival in both groups of recipients from the Indian subcontinent are not known. The study was conducted to compare the bacterial infection rates among LDLT and DDLT recipients and their impact on survival at a tertiary referral center.Retrospective data on 67 LT recipients were reviewed. Data on pre-, per-, and postoperative bacterial infection rates and the common isolates were obtained.Thirty-five patients had LDLT and 32 had DDLT. The prevalence of pre-operative bacterial infection and the isolates was similar in both groups. The perioperative bacterial infection rates were significantly higher in DDLT recipients (P0.01) (relative risk: 1.44 95% confidence interval 1.04-1.9). In both LDLT and DDLT, the common source was urinary tract followed by bloodstream infection. The common bacterial isolates in either transplant were Klebsiella followed by Escherichia coli, Pseudomonas spp. and nonfermenting gram-negative bacteria. Six patients (four LDLT; two DDLT) were treated for tuberculosis. Among the risk factors, cold ischemic time, and duration of stay in the intensive care unit was significantly higher for DDLT (p0.01). The death rates were not significantly different in the two groups. However, the odds for death were significantly high at 26.8 (p0.05) for postoperative bacterial infection and 1.8 (p0.001) for past alcohol.Liver transplant recipients are at high-risk for bacterial infection irrespective of type of transplant, more so in DDLT.