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 acute liver failure due to sickle cell intrahepatic cholestasis

BACKGROUND: Sickle cell intrahepatic cholestasis is a potentially catastrophic complication of sickle cell anemia Once acute liver failure develops, transplantation is the only option. We describe a patient with sickle cell intrahepatic cholestasis who underwent liver transplantation. METHODS: Data were obtained from the chart. Serial hemoglobin S levels were monitored, and measures were taken to maintain hemoglobin S <20% to prevent sickle cell crisis. RESULTS: Although the allograft functioned well initially, the patient developed veno-occlusive disease and required repeat transplantation at 5 months after transplant. Histologic examination of the explant revealed occlusion of the terminal hepatic venules due to fibrosis and packed red cells. Repeat transplant was complicated by thrombosis of the intrahepatic portion of the hepatic artery, and sepsis. The patient died of sepsis after a third transplant. CONCLUSION: Liver transplantation for sickle cell disease involving the liver may carry a high risk of graft loss due to vascular problems. Repeat transplantation may not be feasible if disease recurs.     

IgG4-related intrahepatic sclerosing cholangitis resulting in sepsis caused by secondary suppurative inflammation: report of a case

We report a case of pre-disseminated intravascular coagulation caused by secondary suppurative inflammation in a patient with immunoglobulin (Ig) G4-related sclerosing cholangitis. The patient was a 78-year-old man in whom a localized stenosis of the intrahepatic bile duct was found without any other bile duct stricture or symptoms. He underwent surgical resection 6 months later for acute severe cholangitis and sepsis caused by bile duct obstruction. The resected specimen contained an abscess and nodulary mass in the liver. Immunohistochemical analysis revealed IgG4-positive plasma cell infiltration, whereby we diagnosed IgG4-related sclerosing cholangitis. As IgG4-related sclerosing cholangitis limited to within the intrahepatic portion is extremely rare, we present this case with a review of the literature.     

Characteristics of jaundice and cholestasis in a Finnish population.

A prospective study of a Finnish population of about 250,000 patients with jaundice or unjaundiced cholestasis was carried out. During a two-and-a-half year period altogether 343 patients entered the study. The male/female ratio was 46%/54%. The mean age was 64.9 years (range 19-92). Extrahepatic obstructive diseases constituted two-thirds of the cases both in the jaundiced and unjaundiced cholestatic patient groups. The leading extrahepatic diseases causing jaundice were gallstone disease (61%) and pancreatic carcinoma (19%). Among the nonobstructive intrahepatic diseases causing jaundice, the most frequent diseases were alcoholic liver disease (32%) and viral hepatitis (21%). In patients with unjaundiced cholestasis, the spectrum of diseases resembled that of the jaundiced patients, gallstone disease and pancreatic carcinoma being the largest disease groups. In conclusion, extrahepatic obstructive processes seem to be the major aetiology of jaundice and unjaundiced cholestasis in our study population.     

Ketorolac-induced irreversible renal failure in sickle cell disease: a case report

 Nonsteroidal anti-inflammatory drugs are often used in the management of those with acute pain secondary to sickle cell disease due to potent analgesic effects along with a lack of addictive potential, respiratory depression, and central nervous system effects, as may occur with narcotics. Caution should be observed in the use of nonsteroidal anti-inflammatory drugs in patients with compromised renal function. We present a case of a 17-year-old sickle cell disease patient with an acute painful episode and normal renal function indices who subsequently developed irreversible renal failure and a perirenal hematoma following the administration of ketorolac, despite adequate hydration. Due to its inhibitory effect on prostaglandin-mediated vasodilation, we advise caution in the use of ketorolac for the pain management of sickle cell painful episodes. We recommend following the administration guidelines for ketorolac for renal-compromised patients in those with painful episodes of sickle cell disease, and if used in this patient population, renal function must be very closely monitored. Received: 24 March 1998 / Revised: 5 June 1998 / Accepted: 10 June 1998     

Diagnosis of primary sclerosing cholangitis

Primary sclerosing cholangitis is a progressive chronic hepatobiliary disorder of unknown aetiology for which no effective medical therapy currently exists. This syndrome occurs most commonly in young men and is frequently associated with ulcerative colitis. Primary sclerosing cholangitis should be considered in the differential diagnosis of all patients presenting with chronic cholestasis. The diagnosis is based on a combination of the clinical features and cholestatic biochemical profile accompanied by typical cholangiographic abnormalities and is supported by liver histology findings. The major diagnostic criterion is the finding at cholangiography of irregularly distributed multifocal strictures within both the intrahepatic and extrahepatic bile ducts. The most characteristic histological feature of primary sclerosing cholangitis is periductal concentric obliterative fibrosis of small interlobular bile ducts with or without proliferation of bile ducts in portal tracts, but liver biopsy findings alone are infrequently diagnostic. Nevertheless, liver histology remains important to exclude other causes of chronic cholestasis and in staging the disease. Received for publication on March 29, 1999; accepted on April 30, 1999     

Liver transplantation in a patient with S(beta)o-thalassemia

BACKGROUND: Patients presenting sickle cell disease may develop different types of hepatic complications. Intrahepatic cholestasis is a potentially fatal complication of the disease, and sometimes the only possible solution is transplantation. Postoperative transfusion management has not yet been well established. In this report, we describe the transfusional program of a patient presenting sickle cell disease and intrahepatic cholestasis who underwent liver transplantation 2 years ago. METHODS: Data were obtained from the chart and the blood bank records. RESULTS: The liver transplantation was performed successfully. Despite mild allograft dysfunction 3 months after surgery, secondary to intrahepatic sickling, the patient has been doing well with the transfusional management adopted (sickle-cell hemoglobin <20%). CONCLUSION: Sickle cell disease should not be a criterion for exclusion from liver transplantation. Regular transfusion with monitoring of sickle-cell hemoglobin is a very important measure to minimize the risk of intrahepatic sickling and possible rejection.     

Primary sclerosing cholangitis.

Primary sclerosing cholangitis is a condition of unknown cause. It is recognized by liver dysfunction and its characteristic radiologic appearance, which is related to portal tract inflammation, bile duct proliferation, and periductal fibroses involving small intrahepatic and large extrahepatic ducts. The disease lasts about 10 years from the time of diagnosis. Primary sclerosing cholangitis is recognized by abnormal results on routine liver function tests or by the development of clinical jaundice. An autoimmune cause has been suggested because of its strong association with inflammatory bowel disease, certain antigens, AIDS, and immunoregulatory abnormalities. Results of medical management of sclerosing cholangitis have been disappointing. Immunosuppressive drugs, copper chelating agents, and antibiotics have failed to alter progression of the disease. Colectomy in patients with inflammatory bowel disease also has no influence. The judicious use of dilations of strictures, bypass procedures, or resection can palliate jaundice in patients with primary sclerosing cholangitis, but liver transplantation is the definitive treatment. Because palliative operations increase the hazards of liver transplantation, percutaneous dilations and stentings are preferred initially. Cirrhosis and portal hypertension are indications for transplantation. In the future, transplantation may be indicated earlier in the course of the disease.     

Liver transplantation for a renal transplantation recipient with secondary sclerosing cholangitis by choledochoduodenal fistula

Choledochoduodenal fistula (CDF) complicated by peptic diseases or following surgical or endoscopic approaches of the common bile duct is not uncommon. However, it usually occurs without significant symptoms and can be well controlled with conservative treatment in normal immunized patients. Here we report a case involving a 58-year-old male patient with diabetic nephropathy, who received a choledocholithotomy for choledocholithiasis in November 2007 and renal transplantation in March 2008. The patient had recurring cholangitis during the 5 months following his renal transplantation. Cholangiography and liver biopsy revealed sclerosing cholangitis. The patient underwent liver transplantation (LT) in May 2009 because radiological and endoscopic procedures failed to control his jaundice. A proximal CDF was found during the LT procedures. We considered that the patient's advanced secondary sclerosing cholangitis was induced by this fistula. At the 16 months' follow-up, the patient was surviving well and the graft remained intact. To our knowledge, this is the first report of a renal transplantation recipient receiving LT because of uncontrolled cholangitis caused by a CDF.     

Severe acute pancreatitis as the presenting symptom of primary sclerosing cholangitis: treatment by endoscopic insertion of a biliary stent

Primary sclerosing cholangitis is a chronic, fibrosing, inflammatory condition of unknown origin of extra and intrahepatic bile ducts. Recurrent cholangitis and jaundice are the most frequent clinical manifestation in symptomatic patients. We report a patient with primary sclerosing cholangitis presented with recurrent attacks of acute pancreatitis. Such a combination was not reported till now in the literature. The acute pancreatitis was probably due to reflux of bile and sludge into the pancreatic duct due to stricture of the distal part of a common bile and pancreatic ducts. Endoscopic insertion of a biliary stent managed to prevent jaundice and recurrent pancreatitis.     

Renal transplantation in sickle cell disease

A 49 year old West Indian man with sickle cell disease and chronic renal failure was maintained on hemodialysis for 10 months before receiving a cadaveric renal transplant. Nine months post-transplant his renal function is good. His main problem has been high HbS levels needing repeated exchange transfusions. We conclude that hemodialysis and transplantation may be use successfully performed in patients with sickle cell disease with end-stage renal failure.     

Can exchange transfusions treat postoperative intrahepatic colestasis in patients with sickle cell anemia?

BACKGROUND: Although the most common cause of liver failure (LF) in hematologic patients is viral hepatitis, several episodes of sickle cell intrahepatic cholestasis (IHC) have been reported as rare but potentially causative of fulminant LF. Reviewing the literature, we have presented a single case of intrahepatic cholestasis after major liver resection, which was effectively treated by exchange transfusion. METHODS: Serial hemoglobin S, D levels and liver enzymes were monitored postoperatively. RESULTS: Although the patient's intra- and postoperative courses were uneventful, an increased serum bilirubin was identified to be due to intrahepatic sinusoid congestion and subsequent cholestasis. Exchange transfusion was required to maintain HbS below 20% and reverse bilirubin levels to normal values. CONCLUSION: Sickle cell anemia is a rare cause of cholestasis after major hepatic surgery. To our knowledge, this case is the only documented incidence of IHC following major hepatectomy that was effectively treated with exchange transfusion.     

Liver transplantation as rescue treatment in a patient with primary AL kappa amyloidosis

Although involvement of the liver is common in systemic amyloidosis, clinical manifestations of hepatic dysfunction and liver biochemical abnormalities are often absent or only mild. Here we report on a patient with primary amyloidosis and rapid development of liver failure, who was successfully treated by liver transplantation. The patient is a 61-year-old Swedish man who was admitted to the local hospital for spontaneous rupture of the spleen. Before admission, he had suffered from diffuse upper abdominal discomfort, diminished appetite, and had lost 15 kg in 6 months. Shortly after splenectomy, he developed cholestatic liver failure with moderate hepatomegaly, jaundice, ascites and hyponatremia. Over a period of 3 weeks his liver failure progressed, renal function deteriorated rapidly, and he developed encephalopathy. Liver transplantation was performed on the 35th day after splenic rupture. Histological examination revealed extensive deposits of amyloid in the spleen and liver. ¶N-terminal amino acid sequence analysis of the amyloid protein, purified from the patient's native liver, revealed an AL protein of kappa ¶I-type origin. The postoperative course was uncomplicated, apart from one episode of sepsis and one course of treatment for acute rejection. He was discharged from hospital with normal liver function and good kidney function. One year after surgery, he was in good condition, with normal liver function. However, a liver biopsy taken at the same time showed de novo amyloid deposits in the grafted liver. We conclude that liver transplantation may be indicated as a life-saving procedure in rapidly progressing hepatic amyloidosis with cholestatic jaundice, although the underlying disease has not changed.     

Portal vein aneurysm as late complication of liver transplantation: a case report

OBJECTIVE: A case of intrahepatic portal vein aneurysm in the late postoperative period after liver transplantation, as well its complications, is reported. CASE REPORT: A 59-year-old man underwent orthotopic liver transplantation in 1996 for treatment of hepatitis C virus cirrhosis. The patient received a graft from a 10-year-old child. During the follow-up from 1996 to 1998, the patient did not show any alterations. In 1999, during an annual routine exam, a portal vein aneurysm was identified; however, it had no impact on graft function. In November 2002, the patient developed jaundice and serious graft dysfunction requiring hospital admission. Helicoidal CT scan showed an intrahepatic image compatible with a portal vein aneurysm without biliary tract dilatation. During the same hospitalization, he developed upper gastrointestinal bleeding due to variceal rupture as well as kidney and liver failure, and expired on December 31, 2002. The necropsy demonstrated an intrahepatic portal vein aneurysm with portal vein thrombosis and chronic liver disease. The evolution in this case suggests that if there is an intrahepatic portal vein aneurysm after liver transplantation, the patient is likely to experience an eventual recurrence of portal hypertension; retransplant may be an alternative.     

Repeated testicular infarction in a patient with sickle cell disease: a possible mechanism for testicular failure

We report a case of repeated testicular infarction in a 39-year-old man with sickle cell disease. The patient presented with a 2-week history of testicular pain and was found clinically and sonographically to have a testicular mass, suspicious for a testicular tumor. The pathologic examination of the orchiectomy specimen revealed multiple infarcts, showing temporal variation ranging from acute (several days old) to recent (2 to 3 weeks old) to remote. This is the fifth case of segmental testicular infarction reported in patients with sickle cell disease/trait. We propose repeated testicular infarction as a probable mechanism of testicular failure and impaired fertility in patients with sickle cell disease.     

Stauffer''s syndrome variant associated with renal cell carcinoma

Cholestasis, as a paraneoplastic syndrome, has been well described in patients with malignant lymphohyperplastic diseases and renal cell cancer. Non-metastatic nephrogenic hepatic dysfunction syndrome without jaundice has often been described in patients with Stauffer's syndrome. Paraneoplastic cholestatic jaundice is extremely uncommon. We report, a patient who presented with pruritus and cholestatic jaundice and was diagnosed with renal cell carcinoma (RCC) in the right kidney. Liver malfunction and cholestatic icterus was attributed to RCC. Jaundice and liver dysfunction gradually restored to normal after surgical resection of the tumor. Malignancies may cause cholestatic jaundice through well-recognized mechanisms. Paraneoplastic syndromes associated with malignancy, can induce a reversible form of cholestasis through an unclear pathogenetic mechanism.     

Usefulness of transpapillary cytology and biopsy in diagnosing cholangiocarcinoma that mimics primary sclerosing cholangitis

Two patients with a sclerosing type of cholangiocarcinoma are reported. One, a 68-year-old male, presented with jaundice and mild right upper abdominal pain. Endoscopic retrograde cholangiography showed diffuse narrowing and irregularity of the intra- and extrahepatic bile ducts, suggestive of primary sclerosing cholangitis. The other patient was a 72-year-old female who complained of slight right upper abdominal pain, lassitude, and anorexia. Both ultrasonography and computed axial tomography demonstrated slight dilatation of the anterior branch of the right hepatic duct, but no mass. Endoscopic cholangiography revealed stenosis of that duct and diffuse irregularity of the other intrahepatic ducts, also suggestive of primary sclerosing cholangitis. In both patients, however, transpapillary cytology of bile demonstrated malignant cells, and biopsy from within the bile duct showed cholangiocarcinoma. Both transpapillary cytology and biopsy, especially the latter, are useful procedures for the diagnosis of this unique clinical entity.     

Papillomatosis of intra- and extrahepatic biliary tree: Successful treatment with liver transplantation.

Approximately 60 cases of biliary papillomatosis have been reported in the world literature, while only 6 cases have been reported to be treated with liver transplantation. This rare disease, which is characterized by relapsing episodes of obstructive jaundice and cholangitis that lead to secondary cirrhosis and death from sepsis or liver failure, it is also considered premalignant because of its frequent malignant transformation (25-50%). We present a case of a 43-year-old white man with papillomatosis of intra- and extrahepatic biliary tree who sought care for repeated episodes of obstructive jaundice and cholangitis. The diagnosis was suspected after endoscopic retrograde cholangiopancreatography and confirmed by liver and common bile duct biopsies. The patient underwent orthotopic liver transplantation with Roux-en-Y hepatico-jejunostomy to treat end-stage liver cirrhosis. Fifteen months' follow-up revealed a patient with normal graft function and with no clinically or laboratory findings of disease recurrence or cancer development.     

Living-donor liver transplantation for Caroli's disease with intrahepatic adenocarcinoma

A 36-year-old woman who had Caroli's disease with refractory cholangitis and complicated intrahepatic cholangiocarcinoma was successfully treated with living-donor liver transplantation. Preoperative computed tomography and ultrasonography showed a small nodule in the dilated intrahepatic bile duct. In the resected liver specimen, a small papillary tumor was located in the dilated intrahepatic bile duct of the right lobe. The pathological finding revealed a well differentiated papillary adenocarcinoma without invasion to the parenchyma. The patient is currently doing well 2.5 years after transplantation, with no signs of recurrence of the disease. For Caroli's disease, we believe we can achieve good results with liver transplantation, not only for cholangitis but also for the carcinoma when it is localized in the liver and the patient is carefully followed up. Received: December 22, 2000 / Accepted: February 15, 2001     

Hepatitis A virus-related late-onset hepatic failure: a case report

Late-onset hepatic failure, the least of the fulminant hepatic failures, has not occurred in patients with hepatitis A virus-related acute liver failure. We report a rare case of hepatitis A virus-related late-onset hepatic failure treated successfully by an emergent liver transplant. A 58-year-old Japanese woman who presented with fever and general malaise was diagnosed as having jaundice and liver dysfunction by a positive serum test for anti-hepatitis A virus IgM, which ultimately led to a diagnosis of acute hepatitis A virus associated hepatitis. Despite intensive treatment, her general condition was poor, and she developed a hepatic coma 79 days from the onset of the disease. Under a diagnosis of hepatitis A virus-related late onset hepatic failure, she was given a living-donor liver transplant 82 days from the start of the disease. The resected native liver revealed submassive necrosis with marked cholestasis, compatible with late-onset hepatic failure. Today, 5 years after the transplant, she is alive and well with no signs of recurrent hepatitis A virus-hepatitis. This case should alert the physician to the clinical management of a patient with hepatitis A virus-related acute liver failure.