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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]

A 44-year-old male had persistent hypoalbuminemia and ascites after liver transplantation. Imaging of the liver and gastrointestinal system was normal. Urine examination was negative for proteinuria. A diagnosis of protein-losing enteropathy was suspected, and a duodenal biopsy was done. Duodenal biopsy was positive for cytomegalovirus (CMV). The patient improved with CMV treatment. [Display omitted] [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]

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]

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]

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]

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]

Highlights from the article: Poor Performance Status Is an Independent Predictor of Mortality after Living Donor Liver Transplantation We present our data regarding performance status and post transplantation survival in a large LDLT cohort. B Conclusions: b Pre-transplant performance status independently predicts post LDLT mortality.

Bleeding from post-banding esophageal ulcers is uncommon. It is associated with significant morbidity and mortality. The bleeding from post-banding ulcers is difficult to manage and may be refractory to endotherapy and pharmacological treatment; transjugular intrahepatic portosystemic shunt can be used in such cases. We present a case of refractory post-banding ulcer bleed in a liver transplant recipient, which was managed by placement of removable esophageal metal stent. [ABSTRACT FROM AUTHOR]

Liver transplantation (LT) recipients such as all organ transplant recipients, have a risk of developing de novo malignancies owing to prolonged immunosuppression. However, there is limited data on this after living donor liver transplantation (LDLT), wherein immunosuppression levels are less than in deceased donor transplantation. We aim to describe experience of de novo malignancies from a predominantly LDLT center. A total of 2100 adults (age >18 years) who underwent LT between January 2006 and December 2017 were retrospectively analyzed from a prospectively collected database. The data were analyzed up to June 2019. Data are shown as number, percentage, mean ± standard deviation, and median (interquartile range). Of 2100 patients who underwent LDLT, 21 (1%) patients developed de novo malignancy after transplantation. The de novo malignancy cohort comprised 20 males and 1 female, aged 50 ± 8.8 years. The distribution of de novo malignancies was as follows: 7 oropharyngeal (carcinoma of buccal and oral mucosa), 4 lung, 2 squamous cell carcinoma of skin, 2 lymphoma, 1 each of brain, colonic, gastric; ovary, pancreatic, and prostate. These malignancies were diagnosed at a median follow-up of 42 months (32–73) after LT. Over a median follow-up of 38 months (10–56) after the diagnosis of de novo malignancy, 6 patients (28.5%) died. Patients with de novo malignancy had a higher follow-up after LDLT, 94.3 ± 32.9 versus 62.5 ± 41.8 months, P = 0.000. Patients with alcohol as etiology for LT had higher trend of de novo malignancies (33.3% versus 26.4%), P = 0.46. The incidence of de novo malignancy was 1% at a median follow-up of 42 (32–73) months. De novo malignancies following LDLT, although uncommon, are associated with significant mortality. A careful screening protocol should be followed after transplantation for early detection of de novo malignancies. [ABSTRACT FROM AUTHOR]

Drug induced liver injury (DILI) is a cause of significant morbidity; timely diagnosis is important and requires a high index of suspicion. Terbinafine induced liver injury is rare. We report a case of Terbinafine induced hepatitis-cholestatic injury. The patient had a prolonged recovery phase lasting 3 months after discontinuation of drug. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection is the most common viral infection in liver transplant recipients, affecting post-transplant patients and graft survival. Recent advances in diagnosis and management of CMV have led to marked reduction in incidence, severity, and its associated morbidity and mortality. CMV DNA assay is the most commonly used laboratory parameter to diagnose and monitor CMV infection. Current evidence suggests that both pre-emptive and universal prophylaxis approaches are equally justified in liver transplant recipients. Intravenous ganciclovir and oral valganciclovir are the most commonly used drugs for treatment of CMV disease. Most of the centre use valganciclovir prophylaxis for prevention of CMV disease in liver trasplant recipient. The aim of this article is to review the current standard of care for diagnosis and management of CMV disease in liver transplant recipients. [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]

Highlights from the article: B Background and Aims: b Liver recipients like all organ transplant recipients, have a risk of developing denovo malignancies due to prolonged immunosuppression. B Results: b Of 1639 patients who underwent LDLT, 20 (1.22%) developed de novo malignancy after transplantation, among which 19 were males and 1 female. Of 20 de novo malignancies, 6 had oropharyngeal malignancy (carcinoma of oral and buccal mucosa), 4 lung cancer, 2 squamous cell carcinoma of skin, 2 lymphoma and 1 each had hepatoblastoma, bone tumor, carcinoma stomach; carcinoma ovary, pancreatic cancer and prostate cancer.

Highlights from the article: Good Long Term Outcome With Low Recurrence Rate in Patients With Primary Sclerosing Cholangitis Undergoing Living Donor Liver Transplantation B Background and Aims: b Primary sclerosing cholangitis (PSC) is a progressive cholestatic disorder with liver transplantation being the only definitive treatment in end stage disease. The aim of this study is to find out the disease recurrence and long term outcome following living donor liver transplantation (LDLT) in PSC.