Manav Wadhawan

Post-transplant biliary complications: An analysis from a predominantly living donor liver transplant center

Biliary anastomosis is the Achilles heel of liver transplant. The reported incidence of biliary complications is 5–15% after deceased donor liver transplantation, and 20–34% after right‐lobe live donor liver transplantation (LDLT). We report our experience from an LDLT program.

Cytomegalovirus infection: its incidence and management in cytomegalovirus-seropositive living related liver transplant recipients: a single-center experience.

It is believed that antiviral prophylaxis decreases the incidence of cytomegalovirus (CMV) reactivation and disease. There are few data regarding weekly assays for CMV DNA after transplantation and the subsequent management of CMV. Here we report a cohort of living related liver transplantation (LRLT) patients who were treated for invasive CMV disease or for CMV infections if they were receiving steroids for rejection. Patients who underwent liver transplantation at our center between September 2006 and August 2010 and were recipient‐positive/donor‐positive (R+/D+) were prospectively included. Patients were tested for CMV DNA 3 weeks after transplantation. CMV DNA–positive patients underwent weekly DNA monitoring until there were 2 consecutive negative reports. Those who developed CMV disease or had rising DNA titers while they were on treatment for rejection were treated. A Cox regression analysis was performed for factors predicting survival. Two hundred sixty‐six of the 306 R+/D+ patients were CMV DNA–negative 3 weeks after transplantation, and 40 had detectable DNA. One of the DNA‐negative patients developed CMV disease after treatment for rejection with methylprednisolone. Thirty patients had <500 copies/mL, and 10 had ≥500 copies/mL. Two of the 30 patients with DNA levels < 500 copies/mL developed CMV disease. Six of the 10 patients with DNA levels ≥500 copies/mL developed disease. CMV disease occurred in 9 of the 306 patients (2.9%). One patient received treatment for a rise in DNA titers while he was receiving steroids. There was a significant correlation between steroid administration for acute cellular rejection (ACR) and CMV reactivation (P = 0.003) and disease (P = 0.002). A multivariate analysis showed that CMV reactivation/disease did not predict survival. There was no difference in survival between CMV DNA–positive patients and CMV DNA–negative patients (P = 0.68). In conclusion, CMV reactivation is common after LRLT (13%), but the disease is rare (2.9%) without prophylaxis in CMV immunoglobulin G–positive recipients. The administration of steroids for ACR strongly correlates with CMV reactivation and disease. CMV reactivation and disease did not affect survival in our patient cohort. Liver Transpl, 2012.

Consensus Statement of HCV Task Force of the Indian National Association for Study of the Liver (INASL). Part II: INASL Recommendations for Management of HCV in India.

The estimated prevalence of hepatitis C virus (HCV) infection in India is between 0.5 and 1.5% with hotspots showing much higher prevalence in some areas of northeast India, in some tribal populations and in certain parts of Punjab. Genotype 3 is the most prevalent type of infection. Recent years have seen development of a large number of new molecules that are revolutionizing the treatment of hepatitis C. Some of the new directly acting agents (DAAs) like sofosbuvir have been called game-changers because they offer the prospect of interferon-free regimens for the treatment of HCV infection. These new drugs have not yet been approved in India and their cost and availability is uncertain at present. Till these drugs become available at an affordable cost, the treatment that was standard of care for the whole world before these newer drugs were approved should continue to be recommended. For India, cheaper options, which are as effective as the standard-of-care (SOC) in carefully selected patients, are also explored to bring treatment within reach of poorer patients. It may be prudent to withhold treatment at present for selected patients with genotype 1 or 4 infection and low levels of fibrosis (F1 or F2), and for patients who are non-responders to initial therapy, interferon intolerant, those with decompensated liver disease, and patients in special populations such as stable patients after liver and kidney transplantation, HIV co-infected patients and those with cirrhosis of liver.

Living Related Liver Transplantation for Biliary Atresia in the Last 5 years: Experience from the First Liver Transplant Program in India

ObjectiveTo study the clinical, biochemical profile and outcome of patients with biliary atresia (BA) who underwent living related liver transplantation (LRLT) at authors’ institute in the last 5xa0y (2008–2013).MethodsCase records of the 20 patients diagnosed with biliary atresia who had undergone living related liver transplantation at authors’ centre in the last 5xa0y were analysed.ResultsEighteen patients with BA with a failed Kasai procedure and 2 without a prior Kasais portoenterostomy received a liver transplant. At a median follow up of 2 y and 6 mo, both the patient and graft survival rates were 90xa0%. The median age of the recipients at the time of LRLT was 8 mo and 12 (60xa0%) of the transplanted children were less than or equal to 1 y of age. The male–female ratio was 1.8:1. The median weight was 7.3xa0kg (5.8–48xa0kg); two thirds were less than 10xa0kg. The median pre-transplant total serum bilirubin (TSB) and international normalized ratio (INR) were 12.98 (0.5–48.3) mg/dl and 1.3 (1.0–3.9) respectively. All patients received a living related graft and there was no donor mortality. The median duration of postoperative ventilation was 14xa0h. The post-operative complications were infection (30xa0%), vascular complications (20xa0%) and acute rejection (20xa0%). The median duration of postoperative hospital stay was 21 d (17–42). Two patients died of combined hepatic and portal vein thrombosis in the early postoperative period. Late rejection was encountered in 1 patient and another developed chronic kidney disease necessitating a renal transplant. There were no late vascular occlusions or development of post transplant lymphoproliferative disease.ConclusionsThus, LRLT for BA with or without a prior portoenterostomy, is a feasible and successful treatment modality with good outcomes attained despite the challenges of age and size. This treatment modality is now well established in India.

Experience of 100 solid organ transplants over a five-yr period from the first successful pediatric multi-organ transplant program in India

To analyze the clinical profile and outcome of pediatric patients who had undergone a liver and/or RT at our center over a five yr period, case records of all the patients who had undergone a liver or RT were analyzed retrospectively. One hundred solid organ transplants were performed at our center between January 2007 and January 2012. These included 50 liver, 44 renal, one sequential liver and renal, and two CLKT. BA was the most common indication for an LT (38%). At a median follow‐up of two yr three months, the patient survival was 88%. The most common indication for an RT was chronic glomerulonephritis (54.5%). At a median follow‐up of three yr, the survival was 91%. The CLKT were performed for hyperoxaluria. Two yr post LT, a sequential RT was performed for ESRD resulting from transplant associated microangiopathy. All patients received a living related graft. The common post‐operative complications were infections, vascular complications, and graft dysfunction. Survival rates for liver and RT at our center are comparable to those in the established centers in the West.

Comparative accuracy of CT, dual-echo MRI and MR spectroscopy for preoperative liver fat quantification in living related liver donors

Background: It is of significant importance to assess the extent of hepatic steatosis in living donor liver transplant (LDLT) surgery to ensure optimum graft regeneration as well as donor safety. Aim: To establish the accuracy of non-invasive imaging methods including computed tomography (CT), dual-echo in- and opposed-phase magnetic resonance imaging (MRI), and MR spectroscopy (MRS) for quantification of liver fat content (FC) in prospective LDLT donors with histopathology as reference standard. Settings and Design: This retrospective study was conducted at our institution on LDLT donors being assessed for biliary and vascular anatomy depiction by Magnetic Resonance Cholangiopancreatography (MRCP) and CT scan, respectively, between July 2013 and October 2014. Materials and Methods: Liver FC was measured in 73 donors by dual-echoT1 MRI and MRS. Of these, CT liver attenuation index (LAI) values were available in 62 patients. Statistical Analysis: CT and MRI FC were correlated with histopathological reference standard using Spearman correlation coefficient. Sensitivity, specificity, positive predictive value, negative predicative value, and positive and negative likelihood ratios with 95% confidence intervals were obtained. Results: CT LAI, dual-echo MRI, and MRS correlated well with the histopathology results (r = 0.713, 0.871, and 0.882, respectively). An accuracy of 95% and 96% was obtained for dual-echo MRI and MRS in FC estimation with their sensitivity being 97% and 94%, respectively. False-positive rate, positive predictive value (PPV), and negative predicative value (NPV) were 0.08, 0.92, and 0.97, respectively, for dual-echo MRI and 0.03, 0.97, and 0.95, respectively, for MRS. CT LAI method of fat estimation has a sensitivity, specificity, PPV, and NPV of 73%, 77.7%, 70.4%, and 80%, respectively. Conclusion: Dual-echo MRI, MRS, and CT LAI are accurate measures to quantify the degree of hepatic steatosis in LDLT donors, thus reducing the need for invasive liver biopsy and its associated complications. Dual-echo MRI and MRS results correlate better with histological results in the study, as compared to CT LAI method for fat quantification.

Posttransplant Complex Inferior Venacava Balloon Dilatation After Hepatic Vein Stenting

Orthotopic and living related liver transplantation is an established mode of treatment of end-stage liver disease. One of the major causes of postoperative complications is vascular anastomotic stenosis. One such set of such complications relates to hepatic vein, inferior vena cava (IVC), or portal vein stenosis, with a reported incidence of 1–3%. The incidence of vascular complications is reported to be higher in living donor versus cadaveric liver transplants. We encountered a patient with hepatic venous outflow tract obstruction, where the hepatic vein had been previously stented, but the patient continued to have symptoms due to additional IVC obstruction. The patient required double-balloon dilatation of the IVC simultaneously from the internal jugular vein and IVC.

Reply: Donor vaccination: Is it necessary to prevent HBV recurrence after living donor liver transplantation?

We appreciate the interest generated by the concept of adoptive immunity. The ultimate proof of the engraftment of donor lymphocytes would come from bone marrow studies, which we did not perform in this trial. However, the fact that engraftment does occur is quite evident from the fact that 19 of 75 patients developed significant antibody titers. Fourteen of these 17 patients had spontaneous antibody production, whereas the other 5 patients had antibody production as a response to vaccination more than 6 months after transplantation. There are other facts that underline the durability of engraftment. All the patients who developed significant antibody titers maintained titers greater than 10 mIU/mL over a median follow-up period of 17 months (range 5 6-70 months). Moreover, even the patients who did not form significant antibody titers did clear hepatitis B surface antigen, and they maintained a seronegative status throughout the follow-up. Sixty-six of the 75 patients in our cohort cleared hepatitis B surface antigen without significant recurrence over a long period of time (the actuarial probability of clearance was 92% at 2 years). This high seroclearance rate has not been documented in nontransplant patients with chronic hepatitis B. As for the other queries from Jiang et al., first, we did not systematically study the donor antibody response during the study period. However, this is being done in a follow-up trial. Second, most of the recipients received blood and blood products; we agree that this may have been contributory. Third, double-dose vaccination is very safe. None of the donors had any adverse events due to vaccination. Fourth, the low HBV DNA count before transplantation was deliberate. We actually postponed many elective transplants so that we could administer oral antivirals for at least 4 to 6 weeks to bring down DNA counts.