Cytomegalovirus Duodenitis Causing Persistent Hypoalbuminemia and Ascites After Liver Transplantation.

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.

Endoscopic Ultrasound-guided Liver Biopsy: Missing the Limitations in the Hype.

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.

Post-transplant Non-alcoholic Fatty Liver Disease and Metabolic Syndrome After Living Donor Liver Transplantation in Indians.

Background: Post-transplant non-alcoholic fatty liver disease (NAFLD) is common but is not well described in the living donor liver transplantation (LDLT) setting. Methods: 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. Results: 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. Conclusion: 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.

The Renal Histological Correlates of Refractory Renal Dysfunction After Liver Transplantation.

Background: Kidney dysfunction is common after liver transplantation (LT) and is often attributed to calcineurin inhibitors (CNIs). Very few studies have looked at histological causes. Material and methods: 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). Results: 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. Conclusion: 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.

Liver Stiffness Values in Persons with Normal Histology.

Background and aims: 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. Methods: 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. Results: 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). Conclusions: 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.

Nonalcoholic Fatty Liver Disease in Living Donor Liver Transplant Recipients: A Histology-Based Study.

Background: 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). Material and methods: 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). Results: 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]. Conclusion: 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.

Diagnostic Accuracy and Optimal Cut-off of Controlled Attenuation Parameter for the Detection of Hepatic Steatosis in Indian Population.

Background and aims: 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. Methods: 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. Results: 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%. Conclusions: 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.

Poor Outcomes after Recidivism in Living Donor Liver Transplantation for Alcohol-Related Liver Disease.

BACKGROUND: Recidivism in patients who underwent liver transplantation for alcohol-related liver disease (ALD) is shown to be associated with poor survival in some studies. METHODS: 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. RESULTS: 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. CONCLUSION: Recidivism was associated with significant morbidity and mortality after liver transplantation.

Outcomes of COVID-19 in Patients with Cirrhosis or Liver Transplantation.

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.

Successful Outcome of Bariatric Surgery in Living Donor Liver Transplant Recipients With Multidisciplinary Approach: A Preliminary Experience.

INTRODUCTION: Liver transplant recipients may develop weight gain, metabolic syndrome, and subsequent nonalcoholic steatohepatitis of the transplanted liver which impairs graft function. Bariatric surgery is an effective modality for management of morbid obesity and metabolic syndrome. Our aim is to review the role of bariatric surgery in such high-risk posttransplant patients not responding to medical management and highlight the important considerations. METHODOLOGY: We review the management of two cases with posttransplant metabolic syndrome not responding to medical management and discuss the literature available on bariatric surgery in organ transplant patients. RESULTS: The first patient was a 51-year-old man who underwent living donor liver transplantation 3 years prior, and follow-up ultrasound and fibroscan was suggestive of steatohepatitis of the graft. After liver transplantation, he had gained 30 Kg weight and was on oral hypoglycemic agents with HbA1c of 8%. The second patient was a 65-year-old man, who gained 30 Kg weight with risk of graft impairment 4 years after of combined liver and kidney transplant. Both patients were evaluated thoroughly preoperatively for risk stratification including an upper gastro-intestinal (GI) endoscopy. The immunosuppression was reduced and monitored closely perioperatively. Both patients underwent laparoscopic sleeve gastrectomy (LSG) and were discharged on postoperative day 3. The first patient was evaluated a year after surgery with body mass index (BMI) reduction from 42 to 34 and second at 2 months with BMI reduction from 38 to 33; both patients were free of diabetes and had stable graft functions. CONCLUSION: Bariatric surgery in liver transplant recipients has significant challenges with higher complication rates as patients are on immunosuppression which often impairs wound healing. LSG is safe and effective in such patients which often requires good coordination between the bariatric team and liver transplant team.

Restructuring Living-Donor Liver Transplantation at a High-Volume Center During the COVID-19 Pandemic.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Treatment Armamentarium of COVID-19: Evolving Strategies and Evidence So Far.

The outbreak of SARS-CoV-2 started in Hubei province of China in December 2019 and rapidly spread all over the world. It has infected more than 7 million people worldwide and has pushed half of the world in a state of lockdown. There is an urgent unmet need of interventions both for prevention and treatment of this disease and more than 500 clinical trials are ongoing in this regard. At present, no study with robust methodology have clearly demonstrated benefits of hydroxychloroquine for treatment, preexposure prophylaxis in healthcare workers or post exposure prophylaxis in COrona VIrus Disease-2019. Remdesivir has been shown to have modest benefits in moderate to severe disease, if administered early. Given the rapid pace of clinical information and discoveries, it is important for clinicians to be up to date with the latest, evidence-based treatment options available for this novel disease. Keeping up with this current pace of information, we review the clinical studies of different therapeutic options available to treat SARS-CoV-2.