Familial amyloidotic polyneuropathy is an inherited form of amyloidosis associated with a mutant form of a protein called transthyretin. The Methionine-30 variant is the most frequent mutation observed. This disorder is caused by deposition of this protein as amyloid in several organs, such as the heart, kidneys, and peripheral nervous system. The disease is always progressive and fatal, and patients die 7 to 10 years after the onset of symptoms. Liver transplantation is at present the only choice for these patients because it provides improvement of symptoms and/or stops progression of the disease in most patients. We report the case of a patient who showed clear progression of cardiomyopathy and neuropathy after liver transplantation.
Bromfenac, a nonnarcotic analgesic nonsteroidal anti-inflammatory drug, was associated with reversible, minor elevations in serum aminotransferase levels during clinical trials. The aim of this study is to describe the clinical, laboratory, and histological features of 4 patients with severe bromfenac hepatotoxicity identified at 3 tertiary care centers participating in the US Acute Liver Failure Study Group. Bromfenac was administered for chronic musculoskeletal disorders to 4 women in therapeutic doses of 25 to 100 mg/d for a minimum of 90 days. All patients reported a prodrome of malaise and fatigue and presented with severe, symptomatic hepatocellular injury with associated hypoprothrombinemia. None of the subjects had underlying liver or kidney disease, and there was no evidence of a hypersensitivity reaction. Other identifiable causes of acute liver failure were uniformly excluded. Despite supportive measures, all the subjects developed progressive liver failure over 5 to 37 days, leading to emergency liver transplantation in 3 patients and death in 1 patient while awaiting transplantation. Extensive confluent parenchymal necrosis that appeared to begin in the central zones and was accompanied by a predominantly lymphocytic infiltrate was noted in all the livers examined. Nodular regeneration was seen in the 2 patients with a more protracted clinical course. Administration of therapeutic doses of bromfenac for greater than 90 days was associated with the development of acute liver failure leading to liver transplantation or death in 4 adult women. The poor outcomes observed in this series, coupled with the inability to identify individuals at risk for severe, idiosyncratic bromfenac hepatotoxicity, preclude further use of bromfenac in the medical community.
The aim of this study was to compare the long-term effect of tacrolimus and cyclosporine therapies on serum cholesterol levels in liver transplant recipients. We retrospectively studied 127 consecutive adult liver transplant recipients who survived for at least 1 year after transplantation. Basal immunosuppression consisted of cyclosporine plus prednisone in 100 patients and tacrolimus plus prednisone in 27 patients. Hypercholesterolemia was defined as a fasting serum cholesterol level greater than 220 mg/dL. Mean follow-up was 39 months. No statistical significance was found between cyclosporine- and tacrolimus-treated patients regarding age, sex, diagnosis, and previous cholesterol levels; both groups were similar. Significantly more tacrolimus-treated patients were steroid free in the first and second year of follow-up (tacrolimus, 37% and 63%; cyclosporine, 13% and 32%, respectively; P <.01). In the third year of follow-up, this difference was not significant (77% v 56%). The overall incidence of hypercholesterolemia was 34.6% (44 patients). At the end of the study, hypercholesterolemia was found in 24 of 51 and 14 of 70 patients with and without steroids, respectively (P <.002). Also, mean cholesterol levels were 224 +/- 70 and 191 +/- 48 mg/dL before and after steroid withdrawal, respectively, P <.001. Hypercholesterolemia was found in 43.7% of the patients during cyclosporine plus prednisone therapy compared with 46.1% of the patients during tacrolimus plus prednisone therapy (P <.9). Greater mean cholesterol levels were found in the cyclosporine group, particularly in the second and third years of follow-up (P <.01). Hypercholesterolemia was found in 22% of the patients during cyclosporine monotherapy compared with 15% during tacrolimus monotherapy (P <.5). No differences were found in mean cholesterol levels during follow-up when both monotherapy groups were compared. In conclusion, a lower incidence of hypercholesterolemia was achieved in tacrolimus-treated patients, mainly when steroids were still part of the immunosuppressive treatment.
Tacrolimus is an effective immunosuppressant in the rescue of liver allograft patients in whom conventional immunosuppression failed. Efficacy and safety were examined in a multicenter trial of liver transplant recipients converted to tacrolimus because of rejection despite cyclosporine (CyA) therapy or intolerance to CyA. Six hundred seventy-seven patients were enrolled onto the study; 475 patients for rejection, 197 patients for intolerance, and 5 patients treated compassionately. The mean daily dose of tacrolimus was less in the intolerance (Int) patients throughout the study: 0.22 versus 0.17 mg/kg at 1 week and 0.14 versus 0.11 mg/kg at 24 months in rejection (Rej) and Int patients, respectively. Mean blood levels paralleled dosing in both groups, but were greater in the Rej patients (10.7 v 8.3 ng/mL at 18 months). Kaplan-Meier estimates of patient and graft survival were similar in the two groups. Patient survival rates were 80.1% and 81.5%, and graft survival rates were 72.7% and 73.9% at 24 months in the Rej and Int patients, respectively. Most adverse events occurred with a similar incidence in the two groups. Those with a 4% or greater incidence were fever, viral hepatitis, and pneumonia. The incidence of sepsis, gastrointestinal hemorrhage, kidney failure, and convulsion was greater in the Int group. The incidence of abnormal liver function test results, hyperglycemia, headache, and abnormal kidney function was greater in the Rej group. Mean liver function test results decreased with time postrescue in both groups. Mean serum creatinine level increased from baseline to 18 months postrescue in both groups (1.44 to 1.51 mg/dL for Int patients, 1.14 to 1.48 mg/dL for Rej patients). We conclude tacrolimus is safe and effective rescue in liver transplant recipients with rejection or CyA intolerance.
Orthotopic liver transplantation (OLT) has become a frequently used treatment for end-stage liver disease and acute liver failure, and liver function is markedly improved after transplantation. However, no studies have investigated the development in physical capacity after OLT. On this basis, the aim of the present study is to study the influence of OLT on physical fitness during the first postoperative year. Twenty-three men with a mean age of 45.1 years (range, 24 to 62 years) and 15 women with a mean age of 44.6 years (range, 21 to 62 years) were included in the study. Preoperative maximal oxygen uptake (Vo 2max) during graded ergometer bicycling, isokinetic knee extension/flexion moments, and functional performance (i.e., 6-minute walking distance and standardized transfers and squats) was measured. Preoperative fitness and strength was 40% to 50% less than expected in the age-matched general population. Post-OLT, all patients underwent a supervised exercise program for 8 to 24 weeks. Follow-up data showed a significant increase in all tested physical performance parameters after OLT. Six months post-OLT, Vo 2max had increased 43%; knee strength, 60% to 100%; and functional performance, 22% to 27%. One year postsurgery, general health was improved and perceived as excellent or good in all patients. All patients were independent in activities of daily living, and the level of physical activity increased after OLT. No further improvement in either physical performance parameters or self-assessed parameters was seen beyond 6 months after OLT. In conclusion, these findings indicate that OLT combined with a supervised post-OLT exercise program improves physical fitness, muscle strength, and functional performance in individuals with chronic liver disease.
The present study was performed to clarify the recovery of hepatocellular uptake and the biliary secretion of bile acids during the first 14 days after orthotopic liver transplantation (OLT) and to determine the fraction of bile flow appearing outside through the T tube and entering the duodenum. Therefore, we determined primary and secondary bile acids in bile samples obtained from the T tube at day 5 after OLT, while the T tube was permanently open, and at days 10 and 14 after OLT, i.e., 4 and 9 days after closure of the T tube, respectively, thus restoring enterohepatic bile acid circulation. In addition, we performed hepatobiliary scintigraphy using technetium 99m-labeled [2,4,6 trimethyl-3-bromo]imino-diacetic acid (technetium 99m-BRIDA) in 12 patients between days 4 and 17 after OLT. Chromatographic analyses of biliary bile acids showed no secondary bile acids during the first 5 days after OLT, as opposed to 10 and 14 days after OLT when enterohepatic circulation was restored. Eleven patients with an uncomplicated postoperative course after OLT showed a significantly reduced hepatic uptake and biliary secretion of 99mTc-BRIDA during the first days after OLT with progressive recovery. One patient with an acute allograft rejection episode showed almost no uptake and only minimal secretion. The bile fraction appearing outside through the inserted T tube represented 94.6% +/- 6.2% of the injected 99mTc-BRIDA. We conclude that OLT results in markedly impaired hepatocellular uptake and biliary secretion of organic anions. Simultaneously, bile acid synthesis is significantly reduced, which, in addition, diminishes bile secretion of the graft. We show that T tube bile is a valid tool for bile physiological studies in patients in whom transplantation was successfully performed.
Disseminated infection with Bartonella spp with granulomatous hepatitis was diagnosed in a liver transplant recipient presenting with fever of unknown origin. Pathological findings on liver biopsy were atypical, with scant granulomas seen only after a second biopsy. The patient responded promptly to antibiotic therapy. Infections caused by Bartonella spp should be considered in transplant recipients with fever of unknown origin.
We compared the capacity of University of Wisconsin (UW) and of sodium-lactobionate-sucrose (SLS) hypothermic preservation solutions to maintain the integrity of the hepatic cytochrome P-450-dependent mono-oxygenase system. Isolated rat hepatocytes were stored for 0, 10, 24, and 48 hours in UW or SLS solution and were subsequently cultured shortly at 37 degrees C. Cell viability declined slightly but significantly in a time-dependent manner during cold preservation in either UW or SLS solution, and warm culture exacerbated this effect. Total cytochrome P-450 declined gradually after cold preservation and warm culture to reach values of 70% and 52% of unstored controls in cells preserved for 24 and 48 hours in cold UW solution, respectively. Storage in cold SLS solution yielded a similar decrease to 79% and 59% of unstored controls for the equivalent preservation times. Cytochrome P-450 activity was assessed by the metabolism of theophylline after various cold preservation times in UW or SLS solutions. Production of the major metabolite 1,3-dimethyluric acid was not significantly affected by extended cold preservation periods in either UW or SLS solutions. Similarly, the amount of residual theophylline remained stable in all groups, suggesting that alternative metabolic routes were not modified. These studies show that cold preservation in SLS solution is as effective as that in UW solution in terms of cell viability, cytochrome P-450 content, and activity toward theophylline. In addition, the significant reduction in cytochrome P-450 in conjunction with unaffected theophylline disposition suggests that certain cytochrome P-450 isoforms are specifically damaged by cold preservation and rewarming.
Budd-Chiari syndrome is characterized by hepatic venous outflow obstruction. Although myeloproliferative disorders are usually responsible for this severe thrombotic disorder, deficiency or dysfunction of the natural anticoagulants can be involved. Resistance to activated protein C caused by factor V Leiden mutation has been recently identified as a major cause of thrombophilia. We report 6 patients with Budd-Chiari syndrome associated with factor V Leiden mutation combined with another acquired thrombophilic state (myeloproliferative disorder and lupus anticoagulant in 3 cases) and without another thrombophilic disorder in the other 3 cases. We conclude that factor V Leiden mutation should be evaluated in any case of hepatic vein occlusion because the prevalence of this mutation in the general population is high.
The CD40-CD40L (CD154) interaction plays a pivotal role in the effector mechanisms of allograft rejection. Blockade of the CD40/CD40L costimulatory pathway prevents the development of chronic allograft rejection in several animal transplant models. The relevance of in situ CD40 and CD40L expression in human liver allografts was assessed by immunohistochemistry during ductopenic chronic rejection (CR). In CR allograft specimens (n = 8), marked CD40L expression was detected on Kupffer cells (KCs) and sinusoidal macrophages with a unique centrilobular distribution (P <.001). The CD40L+ KCs and macrophages were shown to be CD68+ after immunohistochemical analysis of serial sections with anti-CD68 monoclonal antibody. Moderate staining of vascular and sinusoidal endothelial cells and mononuclear infiltrates was observed in some CR cases. These findings were in contrast to the absence of CD40L expression in controls (n = 11) consisting of stable liver allograft and normal liver tissue specimens. Only occasional CD40 expression in some cases of CR and controls was observed. In CR, CD40L (CD154) expression is manifested on KCs and macrophages. The present novel data show another important cellular source of CD40L expression and suggest a potential role of KCs/macrophages and CD40/CD40L costimulatory interactions in the pathogenesis of chronic rejection ductopenic liver allograft.
A retrospective review of 100 liver transplantations in 98 children was performed to determine the incidence of infection caused by Candida organism in these patients and to identify risk factors that may predispose to serious fungal infection. Thirty-one infections caused by Candida organisms developed during the initial 28 days posttransplantation: 19 were definite invasive infections (one deep site or one positive blood culture), 2 were probable invasive infections (three superficial sites), and 10 were urinary tract infections. Eleven of 19 patients had fungemia or a disseminated infection (two noncontiguous deep organs involved and/or positive blood cultures) and 8 of 19 had peritoneal candidiasis. Infection caused by Candida organisms was a contributing factor to mortality in 7 of 21 patients (case fatality rate of 33%) with invasive infection. Risk factors that were predictive for invasive infection by univariate analysis included the following: pretransplantation antibiotic therapy, length of transplant operation, transfusion requirement, number of days in the intensive care unit, number of days intubated, number of concurrent bacterial infections, number of antibiotics administered, number of laparotomies performed posttransplantation, retransplantation, hepatic artery thrombosis, bile leaks, and renal and respiratory failure. By logistic regression analysis, bile leak, hepatic artery thrombosis, preoperative steroid use, transfusion requirement, and the number of days intubated were identified as independent risk factors for invasive infection caused by Candida organisms. The use of prophylactic antifungal agents in high-risk patients may be important in reducing the serious morbidity and mortality associated with sepsis caused by Candida organisms in pediatric liver transplant recipients.
Corticosteroid withdrawal after orthotopic liver transplantation (OLT) represents an attractive therapeutic option for ameliorating post-OLT metabolic complications, although several reports suggest patients who undergo transplantation for autoimmune hepatitis (AIH) may have a greater incidence of acute and chronic rejection when withdrawn from corticosteroid therapy. The aim of this study is to evaluate the success of corticosteroid withdrawal in patients with AIH after OLT. Twenty-six patients underwent successful OLT for AIH. In 21 of these patients, stable maintenance immunosuppression consisted of cyclosporine (CSA) and prednisone (n = 20) or tacrolimus (TAC) and prednisone (n = 1). In this group, a trial of prednisone withdrawal was initiated when patients were 6 months or more post-OLT, with normal liver function, and receiving an average prednisone dosage of 10 mg/d. Five additional patients treated with either TAC (n = 4) or CSA (n = 1) plus mycophenolate mofetil underwent a 14-day taper of prednisone. Overall, 17 of 25 patients (68%) were successfully withdrawn from corticosteroids, with a mean follow-up of 22 months (range, 1 to 34 months). Of the remaining 8 patients, 5 patients received a lower dosage of prednisone or required prednisone to control inflammatory bowel disease. Only 3 patients remained dependent on prednisone to maintain stable liver allograft function. Withdrawal from 10 to 5 mg of prednisone (n = 21) resulted in four episodes of steroid-responsive and two episodes of steroid-resistant rejection in 3 patients, and 18 of 21 patients (86%) were rejection free. Withdrawal from 5 to 0 mg prednisone (n = 17) resulted in eight episodes of steroid-responsive and no episodes of steroid-resistant rejection in 4 patients; 13 of 17 patients (76%) were rejection free. Of the 5 patients in the 14-day prednisone-taper group, 3 patients had steroid-responsive rejection and 1 patient required OKT3. Seventeen of 21 patients (81%) with AIH were successfully withdrawn from corticosteroids. It is notable that corticosteroid withdrawal was associated with a reduction in serum cholesterol levels, decreased use of antihypertensive agents, and reduced need for insulin or oral hypoglycemic agents. We propose corticosteroid withdrawal should be attempted in patients with underlying AIH who undergo OLT because most will benefit without significantly jeopardizing the liver allograft.
Immunoprophylaxis using intravenous (IV) hepatitis B immune globulin (HBIG) decreases the recurrence of hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT). However, IV HBIG is expensive, has significant side effects, and is inconvenient to administer. An alternative approach for prophylaxis using intramuscular (IM) HBIG and oral lamivudine was prospectively evaluated in this study. Ten consecutive patients with cirrhosis with HBV infection who underwent OLT were included in this study. Nine of 10 patients received lamivudine, 150 mg/d, for an average duration of 8.6 months before OLT. Two of 10 patients with detectable HBV DNA at the time of OLT received 10,000 U (45 mL) of IV HBIG daily for 7 consecutive days, followed by 5 mL of IM HBIG weekly for the next 3 weeks, then every 3 weeks. The other 8 patients were HBV DNA negative at OLT and received one dose of IV HBIG (45 mL) during surgery, followed by 5 mL of IM HBIG weekly for 4 weeks, then every 3 weeks. All patients received lamivudine, 150 mg/d, after OLT. During a mean follow-up of 15.6 months, 9 of 10 patients achieved a protective hepatitis B surface antibody (HBsAb) titer greater than 200 IU/L and had no evidence of HBV recurrence. One patient failed to develop an adequate HBsAb titer and developed histological and virological evidence of recurrence. One patient died unrelated to HBV recurrence. Our preliminary data suggest that this combination prophylaxis with IM HBIG and lamivudine is effective and potentially cost saving.
The aim of this study is to determine the origin, clinical outcome, allograft histological characteristics, and virological outcome of de novo hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT). We studied 136 hepatitis B surface antigen (HBsAg)-negative liver transplant recipients. HBV DNA was detected by dot-blot hybridization and polymerase chain reaction (PCR). The S gene was sequenced. Hepatitis C virus (HCV) RNA was assessed by PCR. The long-term clinical and histological outcome was determined. Six of 136 HBsAg-negative patients (4.4%) became HBsAg positive after transplantation. The source of HBV infection was reactivation of latent HBV infection in 2 patients and was not identified in 4 patients. Two donors had isolated core antibody. Two of these 6 patients developed acute liver failure related to hepatitis B. The 4 other patients had severe chronic hepatitis related to hepatitis B. All patients had high-level HBV replication. No significant mutations in the S gene were found. These data suggest that de novo hepatitis B infection is not a mild disease and might represent a significant cause of graft dysfunction. This is the first report of fulminant hepatitis caused by de novo hepatitis B infection after OLT.
The clinical presentation and causes of hepatic artery pseudoaneurysm vary widely in the postoperative liver transplant recipient, although infection is the most common cause. Although uncommon, hepatic artery complications continue to be an important source of morbidity in liver transplant recipients. Thrombosis, stenosis, and pseudoaneurysm formation are the most common posttransplantation arterial complications. Pseudoaneurysms are most commonly mycotic in origin. Prompt recognition of hepatic artery pseudoaneurysms with aggressive intervention (both surgical and angiographic) may decrease the morbidity associated with this rare clinical entity. The records of 263 consecutive patients who underwent orthotopic liver transplantation between 1991 and 1996 were reviewed retrospectively and assessed for hepatic artery complications. Two patients (0.7%) developed hepatic artery pseudoaneurysm, neither associated with infection. Both patients required operative repair and are doing well without vascular complications at a mean follow-up of 22.5 months. The clinical presentation and causes of hepatic artery pseudoaneurysm vary widely in the postoperative liver transplant recipient. Prompt recognition of hepatic artery pseudoaneurysms with aggressive intervention (both surgical and angiographic) may decrease the morbidity associated with this rare clinical entity.
Liver Transplantation and SurgeryVolume 5, Issue 4 p. 339-340 ProceedingsFree Access Transesophageal echocardiography and orthotopic liver transplantation: General concepts Andre De Wolf, Corresponding Author Andre De Wolf Department of Anesthesiology, Northwestern University Medical School, Chicago, ILAddress reprint requests to Andre De Wolf, MD, Associate Professor of Anesthesiology, Department of Anesthesiology, Northwestern University Medical School, Passavant Pavilion, Suite 360, 303 East Superior St, Chicago, IL 60611-3053Search for more papers by this author Andre De Wolf, Corresponding Author Andre De Wolf Department of Anesthesiology, Northwestern University Medical School, Chicago, ILAddress reprint requests to Andre De Wolf, MD, Associate Professor of Anesthesiology, Department of Anesthesiology, Northwestern University Medical School, Passavant Pavilion, Suite 360, 303 East Superior St, Chicago, IL 60611-3053Search for more papers by this author First published: 30 December 2003 https://doi.org/10.1002/lt.500050408Citations: 27AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume5, Issue4July 1999Pages 339-340 ReferencesRelatedInformation
Wilson's disease is a hereditary defect in copper excretion leading to the accumulation of copper in the tissues, with subsequent tissue damage. The most serious sequela is that of progressive central nervous system involvement. The use of orthotopic liver transplantation (OLT) has been controversial for those patients with neurological symptoms attributed to Wilson's disease. The aim of this study is to determine the effectiveness of OLT for patients with Wilson's disease, including those with neurological involvement attributed to copper accumulation in the central nervous system. OLT was performed in 45 patients (19 men [42.2%], 26 women [57.8%]) with Wilson's disease between 1971 and 1993 who were followed up for at least 4 years. The age at diagnosis of Wilson's disease ranged from 3 to 41 years (mean, 17.7 +/- 7.4 years). The age at OLT ranged from 8 to 52 years (mean, 22.3 +/- 9.4 years). Nineteen patients (42.2%) were aged younger than 18 years at OLT. The indications for OLT included chronic hepatic failure in 15 patients (33.3%) and fulminant (FHF) or subfulminant hepatic failure in 30 patients (66. 6%). All but 1 of the 19 pediatric patients (94.7%) were in the latter group. Twenty-five patients (55.5%) were receiving D-penicillamine, 9 patients for more than 1 year; none of the patients treated long term presented as FHF. Thirty-three patients (73.3%) survived more than 5 years after OLT. Fourteen patients (31%) died during the posttransplantation period; 7 of the 14 patients (50%) were aged younger than 18 years. Twelve patients died during the first 3 months after OLT of complications of disease and surgery, 10 of whom underwent transplantation for FHF. The other 2 patients died 6 and 9 years after transplantation of infectious problems. Eleven patients (24.4%) required retransplantation because of a primary nonfunctioning graft (n = 6), chronic rejection (n = 4), and hepatic artery thrombosis (n = 1). Seventeen patients (37.7%) presented with neurological abnormalities; 14 patients with Wilsonian neurological manifestations and 3 patients with components of increased intracranial pressure. Ten of the 13 surviving patients with hepatic insufficiency and neurological abnormalities at OLT showed significant neurological improvement. Our experience shows OLT is a life-saving procedure in patients with end-stage Wilson's disease and is associated with excellent long-term survival. The neurological manifestation of the disease can improve significantly after OLT. Earlier transplantation in patients with an unsatisfactory response to medical treatment may prevent irreversible neurological deterioration and less satisfactory improvement after OLT.
Hepatic artery thrombosis remains one of the most serious complications after orthotopic liver transplantation. Sepsis, biliary leakage and strictures, and retransplantation are often the result of this devastating complication. Because retransplantation or reoperation is sometimes not possible or advisable, other means of reestablishing hepatic artery continuity are desirable. We describe a liver transplant recipient who developed a dissection of an iliac artery conduit after retransplantation that was treated with fibrinolytic therapy followed by successful placement of an endovascular stent.
The occurrence of hepatocellular carcinoma (HCC) in renal transplant recipients has typically been associated with hepatitis B or C infection. We encountered two cases of HCC in renal transplant recipients with negative hepatitis B and C markers and no underlying liver pathology, in whom immunosuppression therapy consisted of prednisone and azathioprine (AZA). Patient no. 1 is a 66-year-old man with diabetes who underwent cadaveric renal transplantation 13 years before presentation. An ultrasound obtained for evaluation of a prolonged prothrombin time and decreased serum albumin level showed a suspicious nodular lesion in the left lobe of the liver. A computed tomographic (CT) scan confirmed a 4- x 5- x 5-cm mass that, on biopsy, was determined to be well-differentiated HCC. There was no evidence of metastasis, and the results of random biopsies of the surrounding parenchyma were normal. The patient underwent a left lateral segmentectomy, did well, and an initial alpha-fetoprotein (AFP) level of 85995 ng/mL decreased to 9 ng/mL. Approximately 20 months postoperatively, however, a surveillance CT scan showed three hypervascular lesions in the right lobe of the liver and the AFP level increased to 28,370 ng/mL. Subsequent percutaneous alcohol injections yielded good results, and the patient is alive and well 13 months later. Patient no. 2 is a 57-year-old man who underwent cadaveric renal transplantation 24 years earlier. A CT scan of the abdomen obtained for evaluation of lower abdominal pain showed a 4- x 4- x 6.5-cm mass in the right lobe of the liver that, on biopsy, was found to be poorly differentiated HCC. Multiple biopsies of adjacent liver parenchyma showed no evidence of cirrhosis, AFP level was normal, and imaging studies showed no evidence of tumor spread. The patient underwent a right hepatic lobectomy and is doing well without evidence of recurrence 27 months postoperatively. Our two patients had no evidence of viral hepatitis, cirrhosis, or metabolic liver disease, yet both developed HCC. The use of AZA may have had a role in the development of HCC. In renal transplant recipients on long-term immunosuppression therapy, particularly AZA, it is prudent to maintain a high index of suspicion for HCC when liver enzyme level or function abnormalities are encountered.
Two patients with previous distal splenorenal shunts (DSRSs) performed 6 years earlier underwent liver transplantation (LT). A preoperative selective mesenteric artery angiogram showed collateral veins draining mesenteric venous flow into the shunt. Intraoperative flow measurements were performed to assess the steal of portal venous flow by the shunt and determine the need for shunt occlusion. Portal vein, hepatic artery, and shunt flows were measured by ultrasound transit-time flow probes in the native liver and after graft implantation with and without temporary shunt occlusion. Hemodynamic studies showed that long-standing DSRSs are high-flow shunts that steal portal flow. After graft implantation, DSRS flows remained high. Occlusion of the shunts produced an increase in portal vein flow at an amount similar to those of splenorenal shunt. Thus, the flow measurements showed persistent steal by the shunts after graft implantation and, therefore, the DSRSs were occluded but splenectomy was not performed. We conclude that the decision to occlude a DSRS should be based on the demonstration of steal of portal flow by the shunt and reversibility once the shunt is occluded. Splenectomy is not required when the DSRS is occluded.
