Liver transplantation for hepatocellular carcinoma in India: Are we ready for 2040?

BACKGROUND: Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been widely researched and is well established worldwide. The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience. The variations among the criteria are staggering, and the short- and long-term out comes are controversial. AIM: To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future. METHODS: We conducted a survey of major centers in India that performed LT in December 2022. A total of 23 responses were received. The centers were classified as high- and low-volume, and the current trend of care for patients und ergoing LT for HCC was noted. RESULTS: Of the 23 centers, 35% were high volume center (> 500 Liver transplants) while 52% were high-volume centers that performed more than 50 transplants/year. Approximately 39% of centers had performed > 50 LT for HCC while the percent distribution for HCC in LT patients was 5%-15% in approximately 73% of the patients. Barring a few, most centers were divided equally between University of California, San Francisco (UCSF) and center-specific criteria when choosing patients with HCC for LT, and most (65%) did not have separate transplant criteria for deceased donor LT and living donor LT (LDLT). Most centers (56%) preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC lesion. Positron-emission tomography-computed tomography (CT) was the modality of choice for metastatic workup in the majority of centers (74%). Downstaging was the preferred option for over 90% of the centers and included transarterial chemoembolization, transarterial radioembolization, stereotactic body radiotherapy and atezolizumab/bevacizumab with varied indications. The alpha-fetoprotein (AFP) cut-off was used by 74% of centers to decide on transplantation as well as to downstage tumors, even if they met the criteria. The criteria for successful downstaging varied, but most centers conformed to the UCSF or their center-specific criteria for LT, along with the AFP cutoff values. The wait time for LT from down staging was at least 4-6 wk in all centers. Contrast-enhanced CT was the preferred imaging modality for post-LT surveillance in 52% of the centers. Approximately 65% of the centers preferred to start everolimus between 1 and 3 months post-LT. CONCLUSION: The current predicted 5-year survival rate of HCC patients in India is less than 15%. The aim of transplantation is to achieve at least a 60% 5-year disease free survival rate, which will provide relief to the prediction of an HCC surge over the next 20 years. The current worldwide criteria (Milan/UCSF) may have a higher 5-year survival (> 70%); however, the majority of patients still do not fit these criteria and are dependent on other suboptimal modes of treatment, with much lower survival rates. To make predictions for 2040, we must prepare to arm ourselves with less stringent selection criteria to widen the pool of patients who may undergo transplantation and have a chance of a better outcome. With more advanced technology and better donor outcomes, LDLT will provide a cutting edge in the fight against liver cancer over the next two decades.

Liver Transplantation for Acute Liver Failure Due to Yellow Phosphorus Poisoning - A Comprehensive Review.

Yellow phosphorus or metal phosphide (YP-MP) rodenticide poisoning has been a known cause of acute liver failure (ALF) in many countries of Asia and North and South America over the last decade. It is a highly toxic compound and is a well-known cause of intentional or accidental poisoning in both adults and children. In lower doses, it causes gastrointestinal symptoms and mild hepatic injury, and patients may spontaneously recover. In higher doses, hepatic necrosis and fatty infiltration may cause significant injury and may even lead to ALF, characterized by hepatic encephalopathy, coagulopathy, and lactic acidosis. Cardiotoxicity, rhabdomyolysis, and neutropenia are other well-documented complications. If untreated, it may lead to multi-organ dysfunction and death. Plasmapheresis and continuous renal replacement therapy (CRRT) have been used with limited success in patients who do not recover spontaneously. However, patients who develop ALF often need liver transplantation (LT). Liver transplantation has been successfully performed in ALF due to YP-MP poisoning in several countries, with good results in both adult and pediatric patients. Separate criteria for LT are important to ensure early and rapid listing of critical patients on the waiting list. The success rates of LT for ALF due to YP-MP rodenticide poisoning are very promising, provided there are no contra-indications to transplant. Plasma exchange, CRRT, or cytosorb can be used as a bridge to transplant in selected patients. In the long term, only with an increase in public awareness and sale restrictions can we prevent the intentional and accidental poisoning caused by this easily available, highly toxic compound.

Subcutaneous Fat Obesity in a High Body Mass Index Donor Is Not a Contraindication to Living Donor Hepatectomy.

Background: Living donor liver transplantation (LDLT) has revolutionized the field of transplantation without compromising donor safety. Donor safety is of paramount concern to the transplant team. BMI >35 kg/m2 is mostly considered a contraindication to liver donation. Here, we present a successful right donor hepatectomy from a donor with a BMI of 36.5 kg/m2. Case Summary. A 39-year-old wife donated her right lobe of liver to her 43-year-old husband with nonalcoholic steatohepatitis-related chronic liver disease (CLD). His indications were refractory ascites, hepatic encephalopathy, acute kidney injury, recurrent elbow and urine infections leading to cachexia. She was initially rejected due to a high BMI but failed to lose weight over the next 2 months, and the need for a transplant in her husband was imminent. With no other potential living donors, we decided to proceed with donor evaluation as she had no other comorbidity. We were surprised to find normal liver function tests and a good liver attenuation index (LAI) of +16 on a computed tomography (CT) scan. Magnetic resonance (MR) imaging revealed a fat fraction of 3%. Volumetry confirmed a remnant of 37.9% and a potential graft-to-recipient weight ratio of 1.23. V/S ratio on CT scan (visceral fat area/subcutaneous fat area at L4-level) was <0.4 confirming subcutaneous fat obesity. Both surgeries were uneventful and both donor and recipient recovered well except recipient re-exploration on postoperative day (POD)-1 due to surgical bleeding. The donor was discharged on POD-6 and recipient was discharged on POD-15. At 3 weeks of follow-up, the donor's wound is clean and well-healed, and she is already back to doing her daily life activities without any pain with normal laboratory parameters. Conclusion: Subcutaneous fat obesity should not be considered as a contraindication to liver donation even with a BMI >35 kg/m2. A small percentage of healthy individuals will not have visceral fat obesity and may not have steatotic livers. The CT scan and MR fat fraction estimation can confirm the findings. Biopsy may be avoided if MR fat estimation is <10% in obese donors. Intraoperative visualization in these donors remains the gold standard to decide the need for biopsy. Living donor hepatectomy may be safely performed in a select group of high BMI patients (>35 kg/m2) with pure subcutaneous fat obesity in the absence of other suitable living donors.

Deceased Donor Liver Transplantation in India in the COVID-19 Era: Current Scenario and Future Perspectives.

Coronavirus disease 2019 (COVID-19) has been recently declared a global pandemic. As of June 5, 2020, over 75,000 cases have been reported with nearly 2500 deaths in India alone. COVID-19 has severely impacted deceased donor liver transplant (DDLT) programs throughout the world. Acceptance of deceased liver donors has decreased worldwide because of the unknown risks associated with COVID-19 transmission or postoperative infection in the immediate post-transplant period, along with the risks to the health care workers in a multidisciplinary setting. In India, DDLT has come to a standstill in the setting of a national lockdown. Many national guidelines have emerged on how to safely perform transplant as well on immunosuppressive regimens and care of patients posttransplant. Here, we take a look at the current situation and summarize the different guidelines and future perspectives of DDLT in India in the COVID-19 era.

A Worldwide Survey of Live Liver Donor Selection Policies at 24 Centers With a Combined Experience of 19 009 Adult Living Donor Liver Transplants.

BACKGROUND: Although surgical technique in living donor liver transplantation (LDLT) has evolved with a focus on donor safety and recipient challenges, the donor selection criteria remain considerably disparate. METHODS: A questionnaire on donor selection was sent to 41 centers worldwide. 24 centers with a combined experience of 19 009 LDLTs responded. RESULTS: Centers were categorized into predominantly LDLT (18) or deceased donor liver transplantation (6), and high- (10) or low-volume (14) centers. At most centers, the minimum acceptable graft-to-recipient weight ratio was 0.7 or less (67%), and remnant was 30% (75%). The median upper limit of donor age was 60 years and body mass index of 33 kg/m. At 63% centers, age influenced the upper limit of body mass index inversely. Majority preferred aspartate transaminase and alanine transaminase less than 50 IU/mL. Most accepted donors with nondebilitating mild mental or physical disability and rejected donors with treated coronary artery disease, cerebrovascular accident and nonbrain, nonskin primary malignancies. Opinions were divided about previous psychiatric illness, substance abuse and abdominal surgery. Most performed selective liver biopsy, commonly for steatosis, raised transaminases and 1 or more features of metabolic syndrome. On biopsy, all considered macrovesicular and 50% considered microvesicular steatosis important. Nearly all (92%) rejected donors for early fibrosis, and minority for nonspecific granuloma or mild inflammation. Most anatomical anomalies except portal vein type D/E were acceptable at high-volume centers. There was no standard policy for preoperative or peroperative cholangiogram. CONCLUSIONS: This first large live liver donor survey provides insight into donor selection practices that may aid standardization between centers, with potential expansion of the donor pool without compromising safety.

Graft-versus-host disease of the central nervous system after liver transplantation: A rare complication.

Graft-versus-host disease (GVHD) of the central nervous system (CNS) following solid organ transplantation is a rare but serious complication and has been previously reported after bone marrow transplantation. GVHD after liver transplantation is a rare entity with a high mortality rate. We report the case of a patient who developed GVHD and subsequently had seizures and altered mental status after deceased donor liver transplantation. The diagnosis of GVHD of the CNS was established by short tandem repeat loci analysis of the cerebrospinal fluid using the polymerase chain reaction technique and gene mapping software. To our knowledge, this is the first reported case of CNS-GVHD following liver transplantation. He eventually died of sepsis and multiorgan failure, in keeping with the overall poor prognosis of CNS-GVHD.

Extensive Adhesions in Living Donor Liver Transplantation: A Retrospective Analysis.

BACKGROUND: Adhesions are abnormal fibrous bands of scar tissue between internal organs and tissues. With respect to recipient hepatectomy in living donor liver transplantation (LDLT), we defined extensive adhesions as adhesions in at least two separate locations that required more than 5 % of the total surgical time to lyse. We aimed to identify the etiology and consequences of this preventable burden. METHODS: A simple retrospective case-control study of all cases with extensive adhesions from August 2011 to September 2014 matched by age, sex, and diagnosis at surgery. RESULTS: A total of 380 cases were studied. Thirty-eight and five patients had extensive adhesions from surgical and non-surgical causes, respectively. The incidence and complications in pediatric patients were far less than in adults. In the adult group, the mean operative time was increased by 75 min (12.3 %) and blood loss by 2.5 L.The incidence of bowel perforation and biliary infections were increased in adults, while there was no significant difference in the rate of ascitic or wound infections. The 1-year survival was slightly less (92 %) than the control group (100 %). CONCLUSIONS: The most common cause of extensive adhesions at LDLT was prior liver resection. Extensive adhesions caused increased morbidity by increased blood loss, transfusion requirements, and increased cold ischemia time. There is also a higher risk of bowel perforation during enterolysis. The use of commercially available barrier techniques is advisable in adults at high risk of developing adhesions with a possibility of liver transplantation, such as liver resection for HCC.

The role of peri-operative use of alpha-blocker in preventing lower urinary tract symptoms in high risk patients of urinary retention undergoing inguinal hernia repair in males above 50 years.

Prevalence of lower urinary tract symptoms (LUTS) and groin hernia increase with rising age. Straining in itself is an important aetiology of inguinal hernia. Posthernioplasty retention of urine is one of the most significant complications. The aims of this study are to know the prevalence of signifi- cant LUTS in men > 50 years (n = 200) undergoing inguinal hernia surgery, to identify the high-risk patients for posthernioplasty urinary retention and to assess the role of peri-operative use of alpha- blocker in reducing the incidence of postoperative urinary retention in these patients. This study was performed at RKMSP Hospital, Kolkata from August 2005 to January 2008. All findings were docu- mented. Prevalence of significant LUTS above 50 years undergoing inguinal hernioplasty was found to be 48% (96 out of 200). Out of 96 patients who had International Prostate Symptoms Score>7, 48 patients had maximal urine flow (Qmax) < 10 ml/second and postvoid residual urine > 100 ml, 48 patients belonged to high risk group for postoperative retention of urine. Incidence of postoperative retention of urine among high risk group among tamsulosin users was only 3(12.5%) out of 24 patients and among tamsulosin non-users was 10(41.6%) out of another 24 patients. Therefore, we concluded that among male patients > 50 years of age (undergoing groin hernia surgery) prevalence of significant LUTS increases per decade. We also concluded that tamsulosin is important for alleviation of LUTS and is quite effective for prevention of postoperative retention of urine and helpful for early discharge of patients.