Liver transplantation in sickle cell anemia: a case of acute sickle cell intrahepatic cholestasis and a case of sclerosing cholangitis

Very few cases of liver transplantation in patients with sickle cell disease have been reported in peer-reviewed literature. We reviewed the medical records of two patients with sickle cell disease that received liver transplantation at our institution. The first patient was a 27-year-old female who presented with encephalopathy and cholestatic jaundice with a Hemoglobin S (HbS) level of 69.6%. She was diagnosed with acute sickle cell intrahepatic cholestasis. The second patient was a 26-year-old female with sclerosing cholangitis who presented with encephalopathy, bleeding, and cholestatic jaundice. Her HbS level was normal. Both patients underwent liver transplantation successfully but died in the postoperative period from multiorgan failure. We report a rare case of liver transplantation for acute sickle cell intrahepatic cholestasis and a novel case of transplantation in a patient with sickle cell disease and sclerosing cholangitis. Liver transplantation did not lead to a successful outcome in either case.     

Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient

Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.     

Liver transplantation in children with progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis (PFIC) is caused by mutations of the bile salt export pump or the multidrug resistance P-glycoprotein, resulting in chronic hepatic failure. Partial external diversion of bile or ileal bypass is effective in some cases and, in others, liver transplantation (OLT) is necessary. Forty-two children were included in this study. Twenty-six children suffered from PFIC type 2 and 16 from PFIC type 3. Symptoms included pruritus, cholestasis, liver cirrhosis, and growth retardation. Seventeen patients received external biliary diversion. Ten had to undergo OLT in the following course. As of this report, three of the remaining patients were on the wait list for OLT. Twenty-three children received a liver graft primarily with excellent outcome. Our data show that OLT is the option of choice in symptomatic PFIC and whenever liver cirrhosis is present. We suggest a very restrictive recommendation of external biliary diversion. However, gene therapy may be a future option for children with PFIC.     

Bridging a patient with acute liver failure to liver transplantation by the AMC-bioartificial liver

Recently a phase I clinical trial has been started in Italy to bridge patients with acute liver failure (ALF) to orthotopic liver transplantation (OLT) by the AMC-bioartificial liver (AMC-BAL). The AMC-BAL is charged with 10 x 10(9) viable primary porcine hepatocytes isolated from a specified pathogen-free (SPF) pig. Here we report a patient with ALF due to acute HBV infection. This patient was treated for 35 h by two AMC-BAL treatments and was bridged to OLT. There was improvement of biochemical and clinical parameters during the treatment. No severe adverse events were observed during treatment and follow-up of 15 months after hospital discharge. Possible porcine endogenous retrovirus (PERV) activity could not be detected in the patient's blood or blood cells up to 12 months after treatment.     

Combined liver and kidney transplantation in a patient with sickle cell disease

Sickle cell intrahepatic cholestasis is a potentially fatal end-organ complication of sickle cell anemia. Renal involvement in sickle cell anemia is common, and in some cases, can present as acute renal failure. Although renal transplants have been performed in patients with sickle cell anemia since the late 1960s and a number of liver transplants have been recently performed for these complications, there has not been experience with dual organ transplantation for sickle cell anemia-related complications. We describe the case of a patient with sickle cell anemia who underwent successful combined liver and kidney transplantation after the development of acute sickle cell intrahepatic cholestasis and renal failure requiring continuous venovenous hemodialysis. The patient underwent a successful combined liver and kidney transplant with limited perioperative complications and preserved allograft function. At 22 months posttransplant, the patient expired as a result of an acute pulmonary embolus in the setting of bilateral hip fractures. Autopsy revealed no evidence of liver or kidney allograft rejection and evidence of chronic sickle cell nephropathy in the native kidney. Combined liver and kidney transplantation is a viable therapeutic option in patients with severe end-organ effects of sickle cell anemia.     

Liver transplantation in a patient with hemophilia A and end stage liver failure

We report the case of a 50 year-old man factor VIII deficient haemophiliac and hepatitis C cirrhosis. The patient underwent orthotopic liver transplantation because of episodes of variceal bleeding and encephalopathy. He received factor VIII replacement therapy perioperatively. Factor VIII returned to normal within 24 hours postoperatively and factor VIII replacement was stopped. Liver transplantation can be considered as definitive therapy for haemophilia.     

Orthotopic liver transplantation in a patient with acute liver failure resulting from aortic dissection

We report a case of acute liver ischemia resulting in liver failure that occurred due to celiac trunk occlusion by an aortic dissection. A 53-year-old patient presented with clinical signs of acute abdomen. He underwent an urgent laparotomy, which revealed a splenic infarction and thrombosis of the celiac artery all the way to the porta hepatis. Imaging showed that an acute thoracoabdominal aortic dissection was present, resulting in compression of the celiac trunk. The aorta was repaired with an intervascular graft; however, an acute insufficiency of the liver ensued, and the patient was urgently transplanted. To the best of our knowledge, this is the first report of vascular compromise of the liver due to acute aortic dissection that would require liver transplantation.     

Auxiliary partial orthotopic liver transplantation in acute liver failure due to hepatitis B

Auxiliary partial orthotopic liver transplantation is an alternative therapeutic modality in acute liver failure, wherein the capacity of native liver to regenerate is preserved. A case of acute liver failure due to hepatitis B in an 18-year-old male patient treated with an auxiliary left lateral segment graft is described. There was no recurrence of hepatitis B in the auxiliary graft and the patient cleared the virus after 9 months whilst receiving lamivudine. Immunosuppression was withdrawn at 14 months, and the auxiliary graft atrophied secondary to hepatic arterial conduit thrombosis, possibly precipitated by immunosuppression withdrawal. The native liver regenerated completely, and the patient is well and off immunosuppressive and antiviral therapy 3 years after transplantation. Auxiliary partial orthotopic liver transplantation is an attractive treatment option in acute liver failure due to hepatitis B infection and allows a life free of long-term immunosuppression.     

Liver transplantation for acute liver failure: trying to define when transplantation is futile

BACKGROUND: Recently, the model of end-stage liver disease (MELD) index has been used to select patients with acute liver failure (ALF) or transplantation. By the time the indication for orthotopic liver transplantation (OLT) is defined, the patient's clinical status may worsen. OBJECTIVE: In this study, MELD was used to define patients beyond OLT. METHODS: Among adult patients ALF was responsible for 17 OLT. Their medical records were reviewed to calculate the MELD score just before the OLT. MELD of the deceased patients after OLT (group 1, n=8), was compared with the MELD score of living recipients (group 2, n=9). Creatinine level, need for dialysis, use of vasoactive amines, and mechanical ventilation before OLT were also analyzed in these groups. A significant difference was defined when P<.05. RESULTS: The mean MELD score+/-SD was 51.86+/-12.3 for group 1, and 38.47+/-7.1 for group 2 (P=.02). There was no difference between the creatinine values for patients in the 2 groups (P=.20). Also, the use of vasoactive amines or the need of dialysis before OLT were not different (P=.12 and P=.25, respectively). Group 1 was more frequently under mechanical ventilation, and showed a 4.29 relative risk for death after OLT. CONCLUSION: MELD score could be useful to define the prognosis of OLT among patients with ALF.     

Dearterialization of the liver causes intrahepatic cholestasis due to reduced bile transporter expression

BACKGROUND: Bile duct injury after hepatic artery thrombosis (HAT) in liver transplantation is believed to be caused by ischemia predominantly. We aimed to define the involvement of bile secretory dysfunction in the pathogenesis of liver injury after HAT. METHODS: In a murine model, the main hepatic artery, the extrahepatic peribiliary plexus, or both arterial connections to the liver were interrupted (n=5 for each group). After 1, 14, or 28 days, hepatobiliary function was assessed by analysis of bile transporter expression, serum bile acids and bilirubin, and hepatic ATP content. In addition, cellular injury was assessed by light microscopy and biochemical markers. RESULTS: There were no signs of hepatobiliary dysfunction or injury in sham-operated animals or in mice with interruption of the hepatic artery or the extrahepatic peribiliary plexus alone. However, as early as 24 hr after complete dearterialization, bile transporter expression was significantly reduced and intrahepatic cholestasis started to progress the following weeks. Histologic studies at 28 days after complete dearterialization showed severe hepatobiliary injury. CONCLUSIONS: This study indicates that arterial blood supply is critical for normal bile secretion. Bile duct injury after complete arterial deprivation is preceded by a loss of bile secretory function and subsequent intrahepatic cholestasis.     

Liver transplantation for acute liver failure: the Hungarian experience

Acute liver failure (ALF) counts for 9%-11% of activity in leading liver transplant programs. We have summarized the Hungarian Liver Transplant Program experience for ALF among 412 consecutive orthotopic liver transplantations (OLTs). All OLTs were performed without an extended international donor background. The proportion of ALF among the indications for OLT was lower (5.8% vs 9%) and early mortality higher than the European Liver Transplant Registry (1 year cumulative patients survival is 70% in ELTR vs 60% in the HU LT Program). The waiting time for a donor was longer than expected in the Eurotransplant community. Regarding postoperative complications, there was a higher incidence of initial poor function, bacterial infection, sepsis, and multiorgan failure. We conclude that ALF can be managed with reasonable results but requires an extended donor pool with an integrated international network to improve postoperative morbidity and mortality.     

Liver failure in transplanted liver due to Amanita falloides

Two patients underwent liver transplantation due to Amanita falloides poisoning. In one of them the clinical symptoms, signs, and laboratory findings related to liver failure were similar to the findings before the transplantation. The patient died and the pathological examination of the liver was similar to the patient's earlier explanted liver.     

Successful orthotopic liver transplantation in a patient with a positive SARS-CoV2 test and acute liver failure secondary to acetaminophen overdose

SARS-CoV2, first described in December 2019, was declared a pandemic by the World Health Organization in March 2020. Various surgical and medical societies promptly published guidelines, based on expert opinion, on managing patients with COVID-19, with a consensus to postpone elective surgeries and procedures. We describe the case of an orthotopic liver transplantation (OLT) in a young female who presented with acute liver failure secondary to acetaminophen toxicity to manage abdominal pain and in the setting of a positive SARS-CoV2 test. Despite a positive test, she had no respiratory symptoms at time of presentation. The positive test was thought to be residual viral load. The patient had a very favorable outcome, likely related to multiple factors including her young age, lack of respiratory COVID-19 manifestations and plasma exchange peri-operatively. We recommend a full work-up for OLT in COVID-19 patients with uncomplicated disease according to standard of care, with careful interpretation of COVID-19 testing in patients presenting with conditions requiring urgent or emergent surgery as well as repeat testing even a few days after initial testing, as this could alter management.     

Living donor liver transplantation as a means of rescuing post-embolization hepatic failure in a patient with idiopathic intrahepatic arteriovenous malformation in the liver

Interventional radiology used to be a first-line treatment for cardiac failure caused by idiopathic hepatic arteriovenous malformation (AVM). Here, we report a 64-year-old male patient treated by living donor liver transplantation (LDLT) following failed hepatic artery embolization for idiopathic hepatic AVM. Hepatic artery reconstruction in LDLT was very difficult in this case due to the adverse effects of the pre-transplant intervention. In the treatment of widespread AVM in the liver, arterial embolization should be avoided and primary liver transplantation should be considered.     

Living related liver transplantation in 13 cases of progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis (PFIC) is a heterogenous group of disorders with various etiologies. Recent molecular and genetic studies have categorized the spectrum of types. Liver transplantation is a curative modality of treatment in this disease. We report our experience with 13 patients with PFIC who underwent living related liver transplantation. The follow-up periods ranged from 12 to 50 months. Two children died at 1 and 2 years posttransplantation, leading to a decrease in survival rate from 100% in the first year to 84.6%.