Initial Poor Function and Primary Nonfunction in Deceased-Donor Orthotopic Liver Transplantation Maintaining Short Cold Ischemic Time.

BACKGROUND: Nations with emerging deceased-donor liver transplantation programs, such as India, face problems associated with poor donor maintenance. Cold ischemic time (CIT) is typically maintained short by matching donor organ recovery and recipient hepatectomy to achieve maximum favorable outcome. We analyzed different extended criteria donor factors including donor acidosis, which may act as a surrogate marker of poor donor maintenance, to quantify the risk of primary nonfunction (PNF) or initial poor function (IPF). METHODS: A single-center retrospective outcome analysis of prospectively collected data of patients undergoing deceased-donor liver transplantation over 2 years to determine the impact of different extended criteria donor factors on IPF and PNF. RESULTS: From March 2013 to February 2015, a total of 84 patients underwent deceased-donor liver transplantation. None developed PNF. Thirteen (15.5%) patients developed IPF. Graft macrosteatosis and donor acidosis were only related to IPF ( P = .002 and P = .032, respectively). Cold ischemic time was maintained short (81 cases ≤8 hours, maximum 11 hours) in all cases. CONCLUSION: Poor donor maintenance as evidenced by donor acidosis and graft macrosteatosis had significant impact in developing IPF when CIT is kept short. Similar study with larger sample size is required to establish extended criteria cutoff values.

A Review of Machine Perfusion Strategies in Liver Transplantation.

The acceptance of liver transplantation as the standard of care for end-stage liver diseases has led to a critical shortage of donor allografts. To expand the donor organ pool, many countries have liberalized the donor criteria including extended criteria donors and donation after circulatory death. These marginal livers are at a higher risk of injury when they are preserved using the standard static cold storage (SCS) preservation techniques. In recent years, research has focused on optimizing organ preservation techniques to protect these marginal livers. Machine perfusion (MP) of the expanded donor liver has witnessed considerable advancements in the last decade. Research has showed MP strategies to confer significant advantages over the SCS techniques, such as longer preservation times, viability assessment and the potential to recondition high risk allografts prior to implantation. In this review article, we address the topic of MP in liver allograft preservation, with emphasis on current trends in clinical application. We discuss the relevant clinical trials related to the techniques of hypothermic MP, normothermic MP, hypothermic oxygenated MP, and controlled oxygenated rewarming. We also discuss the potential applications of ex vivo therapeutics which may be relevant in the future to further optimize the allograft prior to transplantation.

Archimedes Absorbable Internal Biliary Stent in Liver Transplants to Prevent Bile Leak.

BACKGROUND: Biliary complications, especially bile leaks, are an important cause of early postoperative morbidity and, rarely, mortality after liver transplant. The risk is higher in living donor liver transplant (LDLT) compared to deceased donor liver transplant (DDLT). Attempts to reduce bile leaks have included refinements in the biliary anastomosis technique and use of various external and internal stents, with inconsistent benefits. Recent availability and successful use of the absorbable Archimedes stent has prompted its intrabiliary placement across the anastomosis. METHODS: In this retrospective study, we analyzed the data of 20 adult patients who underwent a liver transplant with duct-to-duct biliary anastomosis using the Archimedes stent. Both DDLT and LDLT were performed using cava-preserving hepatectomy followed by standard implantation methods. Duct-to-duct biliary anastomosis was performed in all cases using interrupted sutures with extracorporeal knots over an absorbable intrabiliary stent. In addition to standard postoperative care, patients were monitored for bile leak. RESULTS: Nine DDLTs had a single anastomosis over a 10-Fr stent. Out of 11 LDLT patients, 7 had a single anastomosis and 4 patients had 2 anastomoses, all over a 6-Fr stent. Two patients died, 1 as a result of graft primary nonfunction and another because of multidrug-resistant pneumonia. One patient had ascending cholangitis owing to stent migration in the duodenum. This episode was treated with endoscopic stent removal and appropriate antibiotics, with good recovery. None of the other patients had bile leaks, biloma, or stent-related complications. CONCLUSIONS: Archimedes internal absorbable biliary stents can be safely used in both living and deceased donor liver transplants to prevent bile leaks.

Acute liver failure secondary to yellow phosphorus rodenticide poisoning: Outcomes at a center with dedicated liver intensive care and transplant unit.

Accidental or suicidal poisoning with yellow phosphorus or metal phosphides (YPMP) such as aluminum (AlP) zinc phosphide (Zn3P2) commonly cause acute liver failure (ALF) and cardiotoxicity. These are used as household, agricultural and industrial rodenticides and in production of ammunitions, firecrackers and fertilizers. In absence of a clinically available laboratory test for diagnosis or toxin measurement or an antidote, managing their poisoning is challenging even at a tertiary care center with a dedicated liver intensive care unit (LICU) and liver transplant facility. PATIENTS AND METHODS: Patients with YPMP related ALF were monitored using standardized clinical, hemodynamic, biochemical, metabolic, neurological, electrocardiography (ECG) and SOFA score and managed using uniform intensive care, treatment and transplant protocols in LICU. Socio-demographic characteristics, clinical and biochemical parameters and scores were summarized and compared between 3 groups i.e. spontaneous survivors, transplanted patients and non-survivors. Predictors of spontaneous survival and the need for liver transplant are also evaluated. RESULTS: Nineteen patients with YPMP related ALF were about 32 years old (63.2% females) and presented to us at a median of 3 (0 - 10) days after poisoning. YPMP related cardiotoxicity was rapidly progressive and fatal whereas liver transplant was therapeutic for ALF. Spontaneous survivors had lower dose ingestion (<17.5 grams), absence of cardiotoxicity, < grade 3 HE, lactate < 5.8, SOFA score < 14.5, and increase in SOFA score by < 5.5. Patients with renal failure need for CVVHDF and KCC positivity on account of PT-INR > 6.5 had higher mortality risk. Patients undergoing liver transplant and with spontaneous recovery required longer ICU and hospital stay. At median follow-up of 3.4 (2.6 - 5.5) years, all spontaneous survivors and transplanted patients are well with normal liver function. CONCLUSIONS: Early transfer to a specialized center, pre-emptive close monitoring, and intensive care and organ support with ventilation, CVVHDF, plasmapheresis and others may maximize their chances of spontaneous recovery, allow accurate prognostication and a timely liver transplant.

Live donor liver transplantation for acute liver failure: A single center experience.

INTRODUCTION: Acute liver failure (ALF) is an indication for emergency liver transplantation (LT). Although centers performing only deceased donor liver transplants (DDLT) have shown improved outcomes in this situation, they still have relatively long waiting lists. An alternative would be living donor liver transplantation (LDLT), which has shown equivalent outcomes in the elective situation but there is limited evidence of its results in ALF. AIM: The purpose of this study was to assess the outcomes in patients with ALF undergoing emergency LDLT in our center in Delhi, India. METHODS: We prospectively collected data on 479 patients who underwent LT in our hospital between January 2009 and December 2015 to evaluate the outcomes of those with ALF. The ALF patients were listed for transplantation after they met the Kings' College criteria and rapid evaluation was done following a protocol consisting of three phases. Patients with grade III/IV encephalopathy were put on mechanical ventilation. Data regarding their postoperative course, morbidity, and mortality were analyzed. RESULTS: Thirty-six (7.5%) out of the 479 patients underwent emergency LT for ALF. Their mean age was 27.5 years (range 4-59 years) and the male to female ratio of 2:3. Preoperative intubation was required in 15 of 25 patients who had encephalopathy. Wilson's disease was the most common cause of ALF in children while in adults, it was acute viral hepatitis. The time interval between listing and transplantation was a mean of 36 ± 12.4 h. The mean graft to recipient weight ratio (GRWR) was 1.06 ± 0.3. The recipients were extubated postoperatively after a mean period of 2.6 days and their mean ICU stay was 6.3 days. Postoperative infection was the most common complication and required upgradation of antifungal and antibiotic treatments. Neurological complications occurred in five patients. Thirty-one of 36 (86.1%) patients survived and progressive cerebral edema and sepsis were the most common causes of mortality. Patients who died had higher model for end-stage liver disease scores, longer cold ischemia time (CIT), and higher grades of encephalopathy (though 80% patients with encephalopathy survived). There was no donor mortality. At long-term follow up of a median of 56 months, 29 (80.5%) of 36 patients were still alive. CONCLUSIONS: In our experience, LDLT is an alternative procedure to DDLT in patients with ALF and is associated with good outcomes even in patients with high grades of encephalopathy.

Acute Mesenteric Ischaemia-An Indian Perspective.

In Western countries, acute mesenteric ischaemia is commonly due to arterial occlusion and occurs in patients who are usually in their seventh decade. A venous cause for intestinal gangrene has been reported in only about 10 %. We examined whether this was so in India and compared the clinical features of patients with mesenteric arterial and venous ischaemia and relate these to their ultimate prognosis. We studied retrospectively, the records of all patients admitted or referred to the department with a diagnosis of acute mesenteric ischaemia between January 1997 and October 2012, noting their demographic details and mode of presentation, the results of preoperative imaging and blood investigations, the extent of bowel ischaemia, and the length of bowel that was resected at operation and their outcome. There were 117 patients, 85 males and 32 females whose median age was 53 years. Mesenteric venous thrombosis was seen in 56 patients (48 %) and mesenteric arterial occlusion in 61 (52 %). Forty six patients died (39 %); 15 with venous occlusion (27 %) and 31 with arterial occlusion (51 %). Compared to patients with arterial occlusion, the patients with venous obstruction were younger, had a longer duration of symptoms, were less frequently hypotensive at presentation, had higher platelet counts, had a shorter length of bowel resected, had fewer colonic resections and had a lower mortality. Other predictors of mortality on multivariate analysis were a longer duration of symptoms, lower serum albumin and higher creatinine levels at presentation and a shorter length of residual bowel. In India, acute mesenteric ischaemia in tertiary care centres is due to venous thrombosis in almost half of the patients who are at least a decade younger than those in the West. Significant predictors of mortality include low serum albumin and raised creatinine levels, a shorter residual bowel length and an arterial cause for mesenteric ischaemia.

Living donor intestinal transplant using a standardized technique: first report from India.

AIM: We describe the first living donor intestinal transplant (LDIT) in India and discuss the indications and problems of this complex procedure. METHODS: A 43-year-old male patient required massive bowel resection for gangrene due to thrombosis of the superior mesenteric artery. He was maintained on parenteral nutrition but developed cholestasis and well as repeated catheter related infections with progressive loss of venous access due to thrombosis of central veins. A LDIT was performed using 200 cm of small intestine from the patient's son. The graft was based on the continuation of the superior mesenteric vessels beyond the ileocolic branch. The artery was anastomosed directly to the aorta and the vein to the venacava. RESULTS: The graft functioned well and he was weaned off parenteral nutrition. However, he later developed complications (wound dehiscence and enterocutaneous fistula) and developed sepsis. He succumbed to sepsis with a functioning graft 6 weeks after the transplant. The donor recovered uneventfully and was discharged on the 4th postoperative day. CONCLUSIONS: LDIT can be life saving in patients with intestinal failure and failure of parenteral nutrition. There is a need to introduce this modality in India. In a setting of scarcity of deceased donor organs the living donor option has advantages.