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Kidney dysfunction is common after liver transplantation (LT) and is often attributed to calcineurin inhibitors (CNIs). Very few studies have looked at histological causes. The study is a retrospective analysis of histological findings and diagnosis in all patients who underwent a kidney biopsy after LT from 2010 to 2020. Data are shown as mean ± standard deviation or medians (25–75 interquartile range). The study cohort consisted of 26 patients (25 males, 1 female), aged 55 ± 7 years at the time of the kidney biopsy. Kidney biopsies were done at 27.5 (6.7–60.7) months after LT. At the time of the kidney biopsy, the median serum creatinine was 2.10 (1.50–2.86) mg/dl and proteinuria was 3.8 (1.8–5.9) gm/day. Twenty-four (92%) patients were on CNIs. The diagnoses on kidney biopsies were diabetic nephropathy (n = 7), focal segmental glomerulosclerosis (n = 4), CNI nephrotoxicity (n = 3), IgA nephropathy (n = 4), chronic glomerulonephritis (n = 3), hypertensive nephropathy (n = 1), membranous glomerulonephritis (n = 1), acute on chronic interstitial nephritis (n = 1), and C1q nephropathy (n = 1), and the sample was inadequate in one patient. A total of sixteen patients had progression of kidney disease. The kidney function remained stable/improved in 6 (23%) patients, follow-up data were not available for 4 patients. Fourteen (53.8%) patients (including one with CNI nephrotoxicity) required hemodialysis at 13.5 (5.7–29) months after the kidney biopsy. Although the kidney biopsy diagnosed the cause of unexplained renal insufficiency in LT recipients, the majority of patients progressed to end-stage renal disease despite treatment modifications. The use of CNIs was an uncommon cause of renal impairment. [ABSTRACT FROM AUTHOR]

Most studies to date have focused on liver stiffness measurement (LSM) in patients with different chronic liver diseases, and normal LSM is defined based on normal liver function tests or the absence of fibrosis. Very few studies have defined LSM based on completely normal liver biopsies. The current study was done to define the distribution of LSM values in individuals with normal liver biopsies. All prospective liver donors presenting to Medanta, the Medicity hospital between September 2020 and September 2021 fulfilling the eligibility criteria were included in this study. A total of 63 donors (36 females and 27 males) were included in the study, 37 (58.7%) donors had normal liver biopsies, and 26 (41.2%) donors showed the presence of non-alcoholic fatty liver disease. LSM values in the normal liver histology group were 5.01 ± 1.99 kPa by the M probe and 5.34 ± 2.25 kPa by the XL probe. Even though the correlation was weak (r = 0.29, P = 0.03), M probe LSM correlated positively with body mass index. There was a good correlation between the LSM measured by the M probe and the XL probe (r = 0.73, P = <0.001). LSM value in the biopsy-proven normal liver histology group was 5.01 ± 1.99 by the M probe and 5.34 ± 2.25 by the XL probe. [Display omitted] [ABSTRACT FROM AUTHOR]

Recurrent or de novo nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are common after liver transplantation (LT) and may be associated with rapid progression to fibrosis; however, there is limited data in this regard after living donor liver transplantation (LDLT). This is a retrospective study at a high volume LDLT center of all liver biopsies performed in patients with post-transplant NAFLD diagnosed on ultrasound of the abdomen. Liver biopsy was indicated for raised transaminases and/or high liver stiffness on TE. The association between these prebiopsy parameters and inflammation and fibrosis on histology was analyzed. Data are shown as mean ± standard deviation or median (25–75 interquartile range). The study cohort consisted of 31 males and 3 females, aged 43 ± 10 years. The LT to liver biopsy interval was 44 (28–68) months. The prebiopsy AST and ALT were 71 (38–119) and 66 (50–156), respectively. The histology suggested no nonalcoholic steatohepatitis (NASH) in 7 (20%), borderline NASH in 15 (44%), and NASH in 12 (35%) patients. A total of 15 patients (44%) had stage 1 or stage 2 fibrosis. The proportion of patients having fibrosis was significantly higher in patients with NASH (83%) compared to patients with borderline NASH (33%) or no NASH (none had fibrosis, P = 0.001). Among 18 patients who underwent TE (on FibroScan), liver stiffness was significantly higher in patients with fibrosis [18.1 (9.7–22.5)] than in those without fibrosis [9.7 (4.0–12.7); P = 0.043]. Over a third of the LDLT recipients with post-transplant NAFLD developed NASH, and nearly half, borderline NASH 3–5 years after transplant. Most with established NASH also had fibrosis on histology. Prevention of risk factors and early diagnosis is warranted in these patients. [ABSTRACT FROM AUTHOR]

Ultrasound of the liver is not good to pick up mild steatosis. Controlled attenuation parameter (CAP) evaluated in transient elastography (FibroScan) is widely available in India. However, data regarding the diagnostic accuracy and optimal cut-off values of CAP for diagnosing hepatic steatosis are scarce in Indian population. MRI-PDFF is an accurate technique for quantifying hepatic steatosis. Thus, this study examined the diagnostic accuracy and optimal cut-off values of CAP for diagnosing steatosis with MRI-PDFF as reference standard. A total of 137 adults underwent CAP and MRI-PDFF measurements prospectively. A subset of participants (n = 23) underwent liver biopsy as part of liver transplantation evaluation. The optimal cut-off values, area under the receiver operating characteristic (AUROC) curves, sensitivity, and specificity for CAP in detecting MRI-PDFF ≥5% and ≥10% were assessed. The mean age and body mass index (BMI) were 44.2 ±10.4 years and 28.3 ±3.9 kg/m2, respectively. The mean hepatic steatosis was 13.0 ±7.7% by MRI-PDFF and 303 ±54 dB/m by CAP. The AUROC of CAP for detecting hepatic steatosis (MRI-PDFF ≥5%) was 0.93 (95% CI, 0.88–0.98) at the cut-off of 262 dB/m, and of MRI-PDFF ≥10% was 0.89 (95% CI, 0.84–0.94) at the cut-off of 295 dB/m. The CAP of 262 dB/m had 90% sensitivity and 91% specificity for detecting MRI-PDFF ≥5%, while the CAP of 295 dB/m had 86% sensitivity and 77% specificity for detecting MRI-PDFF ≥10%. The optimal cut-off of CAP for the presence of liver steatosis (MRI-PDFF ≥5%) was 262 dB/m in Indian individuals. This CAP cut-off was associated with good sensitivity and specificity to pick up mild steatosis. [ABSTRACT FROM AUTHOR]

Hepatitis B and C are common causes of end-stage liver disease and etiologies of liver transplantation. It is important to prevent recurrence in cases of hepatitis B. Nucleos(t)ide analogs are the mainstay of HBV treatment before (in patients with decompensated cirrhosis) and after liver transplantation. After the introduction of direct-acting antivirals, the treatment of HCV has become considerably easy. In patients with advanced HCV-related cirrhosis, it is better to do transplantation first and treat them after liver transplantation. The sustained virological response rates have improved from 8 to 50% in the interferon era to 90% in the direct-acting antivirals era. In the current review, we discuss the treatment of HBV and HCV before and after liver transplantation. [ABSTRACT FROM AUTHOR]

Post-transplant non-alcoholic fatty liver disease (NAFLD) is common but is not well described in the living donor liver transplantation (LDLT) setting. The study was conducted at a large volume LDLT center in north India. Adult (age >18 years at the time of transplant) liver transplantation (LT) recipients were included. Patients with any history of alcohol use were excluded. The study was conducted prospectively from July 2022 to April 2023, and all patients with a minimum of 1-year follow-up after transplant attending outpatient services were included. NAFLD was diagnosed by ultrasound showing steatosis in the absence of other etiologies. The study cohort included 103 males and 14 females, aged 48 ± 10 years at the time of LT and 53 ± 10 years at the time of inclusion in the study. The median follow-up from LT was 62 (32–97 months). A total of 39 (33%) patients suffered from post-LT NAFLD. NAFLD was recurrent in 9/23 (39%, in patients with NASH or cryptogenic cirrhosis as etiology of LT) and de novo in 30/94 (31%). Pre and post-LT higher body mass index, presence of diabetes and higher serum triglycerides values were associated with the development of post-LT NAFLD. Post-transplant metabolic syndrome was present in 58/95 (61%) LDLT recipients using HbA1c 5.7 to 6.4 as a marker of prediabetes. Post-LT NAFLD was present in one-third of the patients and metabolic syndrome in the majority of the patients at a median follow-up of 62 months after LDLT. [ABSTRACT FROM AUTHOR]

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]

Generally diagnosis of non-alcoholic fatty disease is made on imaging, however, mild steatosis is difficult to diagnose on imaging. Liver biopsy is the procedure of choice but is not carried out as it is an invasive procedure. We describe our experience of 157 liver biopsies in living liver donors with normal body mass index (BMI) <23 kg/M2 (lean). The study was conducted at a tertiary care center in north India. Data of lean living donors who underwent a liver biopsy before donation were analyzed. Data are presented as percentage, mean, or median (25–75 interquartile range). Of 718 donors who had a liver biopsy before donation, 157 (21.8%) donors were lean (BMI < 23 kg/M2). Seventy-eight percent of lean donors had no or only one metabolic risk factor. Fifty-three (33.7%) of lean donors had nonalcoholic fatty liver (NAFL) in liver biopsy. When donors with NAFL were compared to donors with normal histology, donors with NAFL had significantly higher aspartate transaminase (26.6 ± 7.5 versus 23.7 ± 5.4, p = 0.007), alanine transaminase (33.4 ± 11.7 versus 27.8 ± 10.7, p = 0.003), and gamma glutamyl transpeptidase [25 (16–40.5) versus 18 (14–23), p = 0.003]. Only triglycerides (TGs) were statistically different among metabolic factors in lean NAFL and normal histology groups, 97 (70–161) versus 86 (62.5–114.7), p = 0.043. A total of 30% donors in the lean NAFL group had TGs >150 mg/dl as compared with 12.5% in the normal histology group, p = 0.009. Other metabolic risk factors were not statistically different. One third of lean donors had NAFL. Among all metabolic risk factors, only higher TGs levels showed a significant association with NAFL. [ABSTRACT FROM AUTHOR]

Recipients of liver transplantation (LT) remain at higher risk (adjusted for other risk factors) of de novo malignancies (DNMs). The higher risk can be attributed to the effect of immunosuppression and patient-related risk factors (age, tobacco, alcohol, etiology of liver disease). DNMs are an important cause of late mortality in liver transplant recipients. The pattern (type) of posttransplant malignancies reflects pattern in local population. The common types include skin cancers, solid organ malignancies, and post-transplant lymphoproliferative disorders. Counseling of patients about risk factors and surveillance protocols may help in the prevention and diagnosis at early stage. We also discuss the results of LT in patients with a history of extrahepatic malignancy in the pretransplant period. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) pandemic has led to deferral of elective transplants and proactive pretransplant testing of the donor/recipient. The impact of these on living-donor liver transplantation (LDLT) activity and outcome is not known. We performed LDLT only for sick patients or patients with advanced hepatocellular carcinoma in this period, with special COVID protocols. Patients undergoing LDLT counseling, evaluation, and transplant in the period March to June 2020 (group A) under COVID-19 restrictions and special protocols were included. LDLT activity and outcomes among these patients were compared with those in the same period in 2019 (group B). In the period March 15–June 10, we performed 39 and 23 (59%) LDLTs in 2019 and 2020, respectively. The adult patients with cirrhosis in group A (n = 20) had a significantly higher MELD score, 19.8 ± 7.0 versus 16.1 ± 5.6 in group B (n = 36), p = 0.034. Early recipient mortality was similar in 2019 (2/39) and 2020 (2/23). One of 23 post-transplant recipients, 3/71 recipients and donors during evaluation, and 8/125 healthcare workers (HCWs) developed COVID-19, all of whom recovered uneventfully. LDLT activity substantially reduced during the COVID era. The incidence and outcome of COVID-19 among the waiting or transplanted patients and HCWs were similar to those of the general population. The outcome after LDLT in the COVID era was similar to that in non-COVID times. These data suggest that LDLT may be extended to more stable patients with strict protocols. [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]

The survival of liver transplantation (LT) recipients has been improved remarkably in short-term. The major causes of mortality in long-term include nonimmunological causes such as cardiovascular, de novo malignancy, chronic kidney disease, and recurrence of primary disease. Rejection-related mortality is rare in the long-term after LT. We discuss nonrejection causes of long-term morbidity/mortality, risk factors, and management strategies in LT recipients. In addition, we discuss osteoporosis, contraception, and pregnancy in LT recipients. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound-guided liver biopsy is increasingly being performed at several centers. It is also being promoted at endoscopy conferences. The currently available literature does not support the routine use of endoscopic ultrasound-guided liver biopsy as results are either inferior or comparable to percutaneous liver biopsy. We discuss the technical limitations of endoscopic ultrasound-guided liver biopsy when compared to percutaneous liver biopsy and the comparative studies in the current review. The routine use of endoscopic ultrasound-guided liver biopsy should be discouraged as it may get less tissue, the complication rate is similar and it is more costly. [ABSTRACT FROM AUTHOR]

Mucormycosis is a rare but emerging fungal infection complicating solid organ transplantation. It is associated with a high mortality rate. We describe an unusual case of hepatic mucormycosis in a living donor liver transplant recipient presenting as delayed graft dysfunction, which was successfully treated with combination of liposomal amphotericin B and oral posaconazole therapy, without surgical resection. The patient had clinical improvement with normalization of liver function tests. [ABSTRACT FROM AUTHOR]

Primary sclerosing cholangitis (PSC) is a progressive cholestatic disorder with liver transplantation (LT) being the only definitive treatment in end-stage disease. Recurrence of PSC after LT is a significant concern which can lead to graft loss. The aim of this study is to find out the disease recurrence and long-term outcome after living donor liver transplantation (LDLT) in PSC. We conducted a retrospective review of all patients undergoing LDLT for PSC at our centre. Of 2268 adult LTs from August 2004 to July 2018, 32 (1.4%) patients underwent LDLT for PSC including 6 with PSC and autoimmune hepatitis overlap. The data were reviewed to look for PSC recurrence, complications, and overall survival. All patients received tacrolimus-based immunosuppression. Data are shown as number, percentage, median, and interquartile range (IQR). The mean age of 32 LDLT recipients was 44 ± 12 years (males 22, females 10). At the time of transplantation, the mean child's score was 9 ± 1.6 and model for end-stage liver disease score was 18.9 ± 6.4. Ulcerative colitis was seen in 7 patients and none had cholangiocarcinoma. Majority of patients (n = 29) received right lobe graft and all but 3 underwent hepaticojejunostomy for biliary reconstruction. PSC recurrence was seen in 6 (20%) patients during a median follow-up of 59 (29–101) months, after exclusion of 2 patients with early mortality. A total of five patients died during follow-up, and one of these deaths was due to PSC recurrence. There were 2 perioperative deaths due to sepsis and 3 deaths on follow-up (sepsis in 2 and PSC recurrence in 1). LDLT can be performed in PSC with good overall long-term outcomes. [ABSTRACT FROM AUTHOR]

There are few data on genetic relation of the donor and outcomes in living donor liver transplantation (LDLT) recipients. We compared outcomes of LDLT between recipients of genetically related and unrelated donors in a large single-center series. The study included 1372 adult, ABO-compatible, primary LDLT recipients, who received a graft from either a first-degree relative (parent, sibling, son, or daughter; n = 756) or unrelated donor (spouse or relative of the spouse; n = 616). The mean age of the recipients with a related donor was 50.2 ± 10.8 years compared with 47.3 ± 9.3 years for recipients with unrelated donors (P = 0.000). Chronic rejection was significantly more common in the genetically unrelated donor group than in the genetically related donor group (28 [4.5%] versus 9 [1.1%]; P = 0.000) at a mean follow-up of 37 months (15–95 months). There were no significant differences in other outcomes between the 2 groups. The 12-month and 36-month survival between the unrelated and related groups was 87.6% versus 90%, and 86.3% versus 89.7% respectively (P = 0.115). The multivariate analysis revealed genetically unrelated donors (odds ratio [OR]: 3.88, 95% confidence interval [CI]: 1.80–8.34, P = 0.001) and history of acute cellular rejection (OR: 3.39, 95% CI: 1.68–6.81, P = 0.001) as predictors of chronic rejection. Although chronic rejection was found to be more common in genetically unrelated donors, the patient survival after LDLT was similar. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) is a catastrophic illness, which is associated with high mortality in absence of liver transplantation. ALF is associated with multisystem involvement including acute kidney injury (AKI). AKI worsens the already poor prognosis of ALF. There is limited literature on impact of AKI on outcomes of liver transplantation (LT). The use of continuous renal replacement therapy (CRRT) may have a role in transplant-free survival or bridging to LT. Although results suggest a somewhat lower survival in patients with ALF and AKI, LT is a life-saving option and should not be deferred in absence of other contraindications. In the current review, we discuss impact of AKI on transplant-free survival, possible role of CRRT, and role of LT in patients with ALF associated with AKI. [ABSTRACT FROM AUTHOR]

Metastatic pancreatic leiomyosarcoma is a rare entity. EUS FNA supplemented with cell block and IHC can accurately diagnose metastatic deposits in pancreas and guide patient management. Spindle cell lesions of pancreas are reviewed. [ABSTRACT FROM AUTHOR]

Performance status may adversely affect living donor liver transplantation (LDLT) outcomes. We present our data regarding performance status and posttransplantation survival in a large LDLT cohort. Patients with ABO incompatibility, of pediatric age, with acute liver failure, with hepatocellular carcinoma, and/or who had incomplete data were excluded. Two hundred sixty adults who had decompensated cirrhosis and underwent LDLT from January 2016 to March 2018 were included. Performance status was assessed by Karnofsky Performance Score (KPS). The data are depicted as number, mean (SD), or median (25–75 interquartile range [IQR]). The cohort included 232 males and 28 females, aged 48.3 ± 9.8 years. Etiology of liver disease was hepatitis B in 33, hepatitis C in 19, alcohol related in 120, nonalcoholic steatohepatitis/cryptogenic in 68, and other etiologies in 20 patients. The mean Child's score was 9.6 ± 1.7, Model for End-Stage Liver Disease (MELD) score was 18.0 ± 5.8, and donor age was 33.4 ± 9.9 years. Forty-one recipients died at median follow-up of 11 months. The KPS was 100 in 6 (no deaths), 90 in 53 (2 deaths), 80 in 93 (12 deaths), 70 in 69 (14 deaths), 60 in 26 (8 deaths), and 50 in 13 (5 deaths) (P = 0.003). The area under the receiver operating characteristic curve of KPS to predict mortality was 0.698 (P = 0.000, 95% confidence interval [CI] = 0.616–0.780), and the best sensitivity (63%) and specificity (67%) were achieved at KPS ≤70. The survivors and nonsurvivors had a significant difference with respect to KPS (77.6 ± 10.9 versus 69.5 ± 10.9, P 0.000), age of the patient (47.8 ± 9.4 versus 51.1 ± 11.7; P = 0.047), postoperative infections (53.8% versus 85.3%, P = 0.001), and need of packed red cells transfusion. Multivariate analysis (Cox proportional-hazard) showed KPS (hazard ratio [HR] = 0.96, 95% CI = 0.93–0.99, P = 0.007), postoperative infections (HR = 2.3, 95% CI = 1.04–5.1, P = 0.038), and recipient age (HR = 1.03, 95% CI = 1.002–1.07, P = 0.039) as predictors of mortality. Pretransplant performance status is one of the predictors of mortality after LDLT. [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]

Hepatic encephalopathy due to portosystemic shunts is a well-defined entity in patients with cirrhosis. Rarely, liver transplant recipients develop hepatic encephalopathy owing to persistence or surgically created portosystemic shunts. We present a case of post-transplant recurrent hepatic encephalopathy due to a surgically created portocaval shunt. The patient was managed by a covered metal stent placement in the inferior vena cava, thus causing functional closure of the shunt. [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]

Introduction: There are limited data on outcomes of living donor liver transplantation (LDLT) for patients with severe alcoholic hepatitis.Methods: The study included LDLT recipients for severe alcoholic hepatitis (n = 39) who did not improve with medical treatment and compared their outcomes with patients who underwent LDLT for alcoholic liver disease (n = 461). The diagnosis of severe alcoholic hepatitis was based on both clinical and explants data. No patients had psychiatric contraindications for liver transplant and all had good family support. The data are shown as number, mean (SD), or median (25-75 interquartile range).Results: All transplant recipients were males, aged 42 ± 8 years. The patients with alcoholic hepatitis were abstinent for a duration of 4 ± 1.8 months at the time of LDLT. All patients underwent LDLT with a graft to recipient weight ratio of 0.95 ± 0.17. The post-transplant ICU and hospital stay were 5.4 ± 1.3 and 17.6 ± 8.4 days, respectively. When patients with alcoholic hepatitis (n = 39) were compared to patients who underwent LDLT for alcoholic liver disease without alcoholic hepatitis (n = 461), patients with alcoholic hepatitis were significantly younger (43.2 ± 8.5 vs. 48.2 ± 9.1 years, p = 0.001) and had higher Child's (10.9 ± 1.5 vs. 9.8 ± 1.8) and MELD scores (22.1 ± 4.5 vs. 18.4 ± 5.9, p = 0.000). Post-operative infections were also significantly more common in the alcoholic hepatitis group (71.7% vs. 51.6%, p = 0.018). Fungal infections developed in 23% of alcoholic hepatitis patients as compared to 14% in the rest of the alcoholic patients (p = 0.247). Six recipients (15.7%) died at a median follow-up of 28 (6-37) months due to infections, and five (12.8%) patients had relapse of alcohol drinking. Survival was not different between the two groups.Conclusion: Living donor liver transplantation can be successfully performed with good survival for patients with severe alcoholic hepatitis. [ABSTRACT FROM AUTHOR]

While Autoimmune Hepatitis (AIH) may recur in patients after liver transplant, an AIH like presentation (positive auto antibodies, raised immunoglobulin G, raised transaminases and histology showing plasma cell rich infiltrate) may also occur in liver transplant recipients who had transplant for some other disease, called De novo Autoimmune Hepatitis (DAIH). A timely diagnosis and treatment can prevent further graft dysfunction. We report 4 cases of DAIH after living donor liver transplantation. [ABSTRACT FROM AUTHOR]

Introduction Although liver transplantation is a definitive cure for Wilson's disease (WD), there is limited data about results of living donor liver transplantation (LDLT) in adults. Material and methods 18 adults underwent LDLT for WD. The presentations before LDLT were decompensated cirrhosis ( n = 16), acute on chronic liver failure ( n = 1) and acute liver failure ( n = 1). The donors were parents ( n = 2), siblings ( n = 3), cousin ( n = 1), daughter ( n = 1), nephew ( n = 1), spouse or relatives of spouse ( n = 9) and from swap transplantation ( n = 1). All genetically related donors were negative for screening of WD. Results The study cohort comprised of 15 males and 3 females, aged 32 ± 10 years. Severity of liver disease (excluding acute liver failure patient) was as follows; Child's score 10 ± 2, model for end-stage liver disease (MELD) score 18 ± 6. The graft to recipient weight ratio was 1 ± 0.2. The ICU and hospital stay were 5.5 ± 0.9 and 15 ± 5 days. Two patients died in first month after liver transplantation, rest of patients are doing well at median 15 (8–38 months). Two patients had acute cellular rejection that responded to steroids, one had hepatic artery thrombosis and 2 had biliary strictures. Three patients had neurological symptoms; 2 of these patients had partial recovery while one had complete recovery. There was no significant difference between LDLT from genetically related or unrelated donors. Conclusion LDLT for WD in adults is associated with good outcomes. [ABSTRACT FROM AUTHOR]

Introduction Results of Sofosbuvir based regimens for hepatitis C (HCV) recurrence after liver transplantation are available from well-designed clinical trials. Most of the data is from deceased donor liver transplant (DDLT) setting, and data on “real world” experience for HCV recurrence after living donor liver transplantation (LDLT) is limited. Material and methods Consecutive 78 patients who completed Sofosbuvir based HCV treatment after liver transplantation were included. Following Sofosbuvir based regimens were used; Sofosbuvir + Ribavirin ( n = 58), Sofosbuvir + Ledipasvir ± Ribavirin ( n = 5), Sofosbuvir + Daclatasvir ± Ribavirin ( n = 15). Treatment was given for 12 weeks (triple therapy) or 24 weeks (dual therapy). Results A total of 74/78 (94.8%) patients achieved end of treatment response (ETR) while 4 did not achieve ETR. A total of 68/76 (89.4%) patients achieved sustained virological response at 12 weeks (SVR12). while 2 are waiting for 12 weeks follow up after ETR. Twelve patients had history of failed previous treatment with Peginterferon and Ribavirin after LDLT, all these patients achieved ETR and 11/12 had SVR12. There was no statistical difference in response rates between genotype 1 or 3. Eighteen patients (16 on Ribavirin) had hemoglobin < 8 g/dl; two patients complained fatigue in absence of anemia. Conclusion Sofosbuvir based regimens are safe and highly effective in treatment of HCV recurrence after LDLT. [ABSTRACT FROM AUTHOR]

While antibody mediated hyper-acute vasculitic rejection is rare in liver transplant recipients, acute and chronic rejection have clinical significance. The liver allograft behaves differently to other solid organ transplants as acute rejection generally does not impair graft survival and chronic rejection (CR) is uncommon. The incidence of acute and chronic rejection has declined in current era due to improved immunosuppressive regimens. Acute rejection generally improves with steroid boluses and steroid resistant rejection is uncommon. CR may improve with escalation of immunosuppression or may result in irreversible loss of graft function leading to retransplantation or death. The current review discusses diagnosis and management of acute and chronic liver allograft rejection. [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]

Intraductal ultrasonography (IDUS) utilizes probe catheter and operates at a higher frequency (12-30 MHz). It can be passed down the biopsy channel of a side-view endoscope during endoscopic retrograde cholangiopancreatography, and it provides real-time, high-quality imaging of pancreatobiliary ducts and the surrounding structures. IDUS has been used in defining choledocholithiasis, evaluating biliary as well as pancreatic strictures or thickening, and local staging of tumor. We shall discuss the utility of IDUS in the current review. [ABSTRACT FROM AUTHOR]

Background Metabolic risk factors should be important in addition to imaging for prediction of steatosis in prospective liver donors. Materials and methods The study group included all prospective liver donors who had a liver biopsy during workup. Risk factors of metabolic syndrome were analyzed, and body mass index ( BMI) ≥25 kg/m2 was used in place of waist circumference. Three BMI cutoffs (25, 28, and 30 kg/m2) and two CT-measured liver attenuation index ( LAI) cutoffs (<5 and ≤10) were used for steatosis assessment of ≥5%, ≥10%, and ≥20%. Results Of the 573 prospective donors (307 females), 282 (49.2%) donors had nonalcoholic fatty liver ( NAFL). When donors with NAFL were compared with donors having normal histology, multivariate analysis showed BMI, ALT, triglycerides, and LAI as significant predictors of NAFL. BMI ≥25 kg/m2 and LAI <10 were better cutoffs. The presence of ≥2 metabolic risk factors had better sensitivity than CT- LAI for the presence of NAFL and ≥20% steatosis (58% and 54% vs 47% and 22%, respectively, for CT- LAI ≤10). The presence of LAI >10 and <2 metabolic risk factors predicted <10% steatosis with 96% specificity and 92% positive predictive value. Conclusion The presence of ≥2 metabolic risk factors improves sensitivity of CT- LAI for prediction of donor steatosis. [ABSTRACT FROM AUTHOR]

Background: Etiology of acute pancreatitis (AP) remains idiopathic in 30% of patients. Endoscopic ultrasound (EUS) has been shown to increase the diagnostic yield in patients with idiopathic AP (IAP). Aim: The aim of this study was to evaluate the role of EUS in achieving etiological diagnosis in patients with IAP. Materials and Methods: Consecutive 192 patients with IAP were evaluated prospectively with EUS over a period of 2 years. Patients who had no etiological diagnosis for AP after detailed history, clinical examination, laboratory investigations, and magnetic resonance cholangiopancreatography were included in the study. Results: The mean age of patients was 34.6 ± 12 and male:female ratio was 2.1:1. Of these, 135 patients had gallbladder intact (Group A) and 57 patients had undergone cholecystectomy (Group B). In Group A, EUS identified a possible cause in 79 (58.5%) patients; microlithiasis (n = 48), chronic pancreatitis (CP) (n = 23), common bile duct (CBD) and gallbladder stone (n = 3), pancreatic divisum (n = 3), small pancreatic tumor (n = 1), and anomalous pancreaticobiliary junction (n = 1). In Group B, EUS yielded diagnosis in 28 (49.1%) patients; CP (n = 22), ascariasis (n = 3), CBD stone (n = 2), and pancreatic divisum (n = 1). Overall EUS helped in achieving etiological diagnosis in 107 (55.1%) of patients with IAP. The presence of intact gallbladder showed a tendency for increased diagnostic yield (P = 0.06). Conclusion: EUS is a useful modality to establish the diagnosis in IAP and this technique should be incorporated in the evaluation of IAP. [ABSTRACT FROM AUTHOR]

Background: There is very limited literature on results of fine needle aspiration (FNA) of small (defined as ≤1 cm at long and short axis) lymph nodes, particularly in the setting of pyrexia of unknown origin (PUO). Methods: The study was conducted from July 2014 to December 2015 at a tertiary care center. A total of 34 endoscopic ultrasound (EUS)-guided FNAs in 33 patients were done for lymph nodes =1 cm at long and short axis and these were included in the analysis. Results: The study cohort comprised 33 patients; 23 males and 10 females, mean age of 58 ± 12 years. Indication of FNA was to look for malignancy (n = 15), PUO (n = 16), unexplained weight loss (n = 1), and presence of lymphadenopathy in prospective liver donor (n = 1). The FNA was taken from mediastinal nodes (n = 20, 14 subcarinal) and abdominal (n = 14, 8 at porta). The mean size of lymph nodes was 87 ± 11 mm at large axis and 68 ± 17 mm at short axis. A total of 3 (8.8%) FNAs were nondiagnostic (inadequate material). The cytopathologic diagnosis was malignancy in 8 (23.5%), granulomatous change in 8 (23.5%), and reactive lymphadenopathy in 15 (44.1%). Thus, EUS-guided FNA of these small nodes changed the management decisions in 44% of cases (one patient had tubercular lymphadenopathy at two sites). The 22-gauge EUS FNA needle was used in majority of patients (n = 26). There was no significant difference between pathologic (malignant and granulomatous) and reactive lymph nodes regarding size at long or short axis, ratio of long and short axis, hypoechogenicity, and sharply defined borders. Conclusion: EUS-guided FNA of small lymph nodes showed pathological enlargement in 44% of cases. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease (ALD) is a common indication for liver transplantation. It is a much debated indication for deceased donor liver transplantation due to organ shortage and potential of alcohol relapse after liver transplantation. A six-month abstinence before liver transplantation is required at most centers to decrease chances of alcohol relapse after liver transplantation. However, this rule is not relevant for patients with severe alcoholic hepatitis or severely decompensated patients who are unlikely to survive till 6 months. Long-term care of these patients after liver transplantation includes assessment of relapse, smoking, and surveillance of de novo malignancies. Current review discusses role of abstinence, factors affecting alcohol relapse, liver transplantation for alcoholic hepatitis, role of living donor liver transplantation, and long-term care of ALD patients who undergo liver transplantation. [ABSTRACT FROM AUTHOR]

Drug induced liver injury (DILI) is uncommon and severe forms are associated with significant morbidity and mortality. Female sex hormones (estrogens and progestogens) related DILI generally occur with estrogen component. Progesterone component related DILI are infrequently reported. Norethisterone is commonly used drug in gynecologic practice to prevent excess per vaginal bleeding. We report 3 cases of Norethisterone related DILI manifesting as significant rise of transaminases. All of these patients took Norethisterone for prolonged periods and improved completely after withdrawal of drug. [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]

Objective There are limited data about sarcopenic obesity in liver transplant recipients. Methods Living donor liver transplant recipients with at least 12 months of follow-up were included. Metabolic syndrome ( MS) was defined as ≥3 ATP III criteria. Body composition was assessed by bioelectrical impedance. Immunosuppression protocol included short-term steroids, mycophenolate and calcineurin inhibitors (mainly tacrolimus). Data are shown as percentage, mean ± SD, or median (25-75 IQR). Results The study comprised 82 patients (males 69), aged 50.5 ± 10.65 yr, and follow-up 24 (12-38.5) months. Etiology for cirrhosis was alcohol 29%, hepatitis C 22%, hepatitis B 17%, cryptogenic 24%, and others 7%. Post-transplant sarcopenic obesity was present in 72 (88%), and MS was present in 43 (52%) of recipients with no significant difference among etiologies. There were significant differences between pre- and post-transplant body mass index, triglycerides, high-density lipoprotein, low-density lipoprotein (p = 0.000 for all), prevalence of hypertension (18% vs. 39%), and diabetes (20% vs. 56%). Patients with sarcopenic obesity had significantly higher body mass index, waist circumference, and MS (57% vs. 20%, p = 0.041) when compared to patients without sarcopenic obesity. Conclusion Despite resuming routine activities, the majority of liver transplant recipients develop sarcopenic obesity and MS. The importance and role of appropriate nutrition and exercise after transplantation merits further investigation. [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]

With advancements in immunosuppressive strategies and availability of better immunosuppressive agents, survival rate following liver transplantation has improved significantly in the recent times. Besides improvements in surgical techniques, the most important factor that has contributed to this better outcome is the progress made in the field of immunosuppression. Over the last several years, the trend has changed to tailored immunosuppression with the aim of achieving optimal graft function while avoiding its undesirable side effects. Induction agents are no longer used routinely and the aim is to provide minimal immunosuppression in the maintenance phase. The present review discusses the various types of immunosuppressive agents, their mechanism of action, clinical utility, advantages and disadvantages, and their side effects in short and long-term. It also discusses about tailoring immunosuppression in presence of various situations such as renal dysfunction, metabolic syndrome, hepatitis C recurrence, cytomegalovirus infections and so on. The issue of chronic kidney disease and the available renal sparing immunosuppressive strategies has been particularly stressed upon. Finally, it discusses about the practical aspects of various immunosuppression regimens including drug monitoring. [Copyright &y& Elsevier]

Living donor liver transplantation (LDLT) needs "Mercedes Benz" or "J-shaped" incision, causing short and long-term complications. An upper midline incision (UMI) is less invasive alternative but technically challenging. Reporting UMI for recipients in LDLT vs. conventional J-shaped incision. Retrospective analysis, July 2021 to December 2022. Peri-operative details and post-transplant outcomes of 115 consecutive adult LDLT recipients transplanted with UMI compared with 140 recipients with J-shaped incision. Cohorts had similar preoperative and intraoperative variables. The UMI group had significant shorter time to ambulation (3 ± 1.6 vs. 3.6 ± 1.3 days, p = 0.001), ICU stay (3.8 ± 1.3 vs. 4.4 ± 1.5 days, p = 0.001), but a similar hospital stay (15.6±7.6 vs. 16.1±10.9 days, p = 0.677), lower incidence of pleural effusion (11.3% vs. 27.1% p = 0.002), and post-operative ileus (1.7% vs. 9.3% p = 0.011). The rates of graft dysfunction (4.3% vs. 8.5% p = 0.412), biliary complications (6.1% vs. 12.1% p = 0.099), 90-day mortality (7.8% vs. 12.1% p = 0.598) were similar. UMI-LDLT afforded benefits such as reduced pleuropulmonary complications, better early post-operative recovery and reduction in scar-related complaints in the medium-term. This is a safe, non-inferior and reproducible technique for LDLT. [ABSTRACT FROM AUTHOR]

Mammalian target of rapamycin inhibitors (mTORis) are immunosuppression agents that are commonly used in solid organ transplantation. Available mTORis include sirolimus and everolimus. Interstitial lung disease (ILD) is an uncommon side effect of mTORis in liver transplantation. A high index of suspicion is needed, and timely intervention can reverse the disease. We present a case of sirolimus-induced ILD that improved after discontinuation of sirolimus. [ABSTRACT FROM AUTHOR]

Statins are commonly used drugs in patients with liver and cardiac disease. Statin-induced severe myopathy is a very uncommon presentation and rhabdomyolysis may occur in extreme cases which leads to renal failure. Patients with comorbidities like diabetes, hypothyroidism, and liver disease have higher chances of development of statin-induced myopathy. We describe a case of Child's C cirrhosis wherein the patient had acute onset significant muscle weakness and improved on statin discontinuation. [ABSTRACT FROM AUTHOR]