Jeffrey Weinstein

Celiac sprue: another autoimmune syndrome associated with hepatitis C

OBJECTIVE:Celiac sprue is being diagnosed with increasing frequency by screening individuals with epidemiologically associated autoimmune syndromes. We sought to test our hypothesis that hepatitis C also may predispose to celiac sprue because it can trigger autoimmune reactions.METHODS:Two hundred fifty-nine consecutively evaluated patients with chronic hepatitis C infection, 59 with autoimmune liver disease, 137 with other hepatic diseases, 356 with various GI syndromes, and 221 normal volunteers underwent serologic screening for celiac sprue. Patients with antigliadin, antiendomysial, and antitissue transglutaminase antibodies in serum underwent duodenoscopy and biopsy.RESULTS:There was a statistically significantly higher prevalence of antigliadin antibody in all groups of patients with liver disease compared with GI controls and normal controls. However, only patients with hepatitis C (n = 3; 1.2%) or autoimmune liver disease (n = 2; 3.4%) had antiendomysial/antitissue transglutaminase antibody in serum. One of 221 normal volunteers (0.4%) was antigliadin, antiendomysial, and antitissue transglutaminase positive; this individual also was found to have hepatitis C (previously undiagnosed). Each of these six individuals had mild intestinal symptoms, duodenal histopathology consistent with celiac sprue, and the celiac-associated HLA-DQ2 allele. Five of the six followed a prescribed gluten-free diet and experienced symptomatic improvement.CONCLUSION:Celiac sprue is epidemiologically associated with chronic hepatitis C infection and with autoimmune liver disease. Because hepatitis C is much more frequently encountered than autoimmune liver disease, hepatitis C appears to be the most common hepatic disease associated with the development of celiac sprue.

The changing clinical presentation of recurrent primary biliary cirrhosis after liver transplantation

Background. Recurrent disease after liver transplant is a significant problem. Recurrent primary biliary cirrhosis (RPBC) is a histologic diagnosis. Clinical data is unreliable in predicting or diagnosing recurrence. RPBC appears to have a changing clinical presentation in recent years. Materials and Methods. The diagnosis of RPBC after liver transplantation was made histologically. Data were obtained from our prospectively maintained liver-transplant database and evaluated statistically. Results. Between 1985 and 1999, 1,835 liver transplants were performed, 169 for PBC. One hundred fifty-six patients were evaluated (one patient received retransplantation, and 13 were excluded). Seventeen (10.9%) experienced recurrence. Median posttransplantation follow-up time was 72.1 months. Median time to recurrence was 49.6 months. Median follow-up time after recurrence was 11.5 months. Neither acute rejection episodes (P =0.34) nor OKT3 use (P =0.36) before diagnosis of recurrence was significant. The combination of cyclosporine, azathioprine, and prednisolone demonstrated recurrence in 6 of 71 (8.4%). Six of 49 (12.2%) patients treated with cyclosporine with or without mycophenolate mofetil and prednisolone experienced recurrence. Six of 36 (16.7%) patients treated with tacrolimus and prednisolone with or without mycophenolate mofetil experienced recurrence. Patients treated with cyclosporine had numerically fewer recurrences than those treated with tacrolimus (P =0.11). Conclusions. Patients with RPBC demonstrated prolonged survival. Clinical factors did not aid in predicting RPBC. The clinical course of RPBC appears to be different than in the earlier years of liver transplantation. Immunosuppression may play a role. The use and type of antimetabolite drugs had no affect on recurrence. RPBC demonstrated a different clinical course with tacrolimus treatment (shorter time to recurrence) and increased incidence when compared with cyclosporine treatment. Controlled randomized studies are necessary to determine differences between tacrolimus and cyclosporine treatment, if any.

Pretransplant MELD score as a predictor of outcome after liver transplantation for chronic hepatitis C

The Model of End‐Stage Liver Disease (MELD) score, an accurate predictor of mortality in patients awaiting liver transplantation (OLTX), did not predict graft or patient survival in the post‐transplant setting. Our aim was to test the model in patients who underwent OLTX for chronic hepatitis C. Two hundred and eighty‐seven adult patients who underwent primary OLTX for chronic hepatitis C between December 1993 and September 1999 were studied from a prospectively maintained database. The group was stratified by MELD scores of less than 15, 15–24, and greater than 24. Patient survival, graft survival, and interval liver biopsy pathology were reviewed. Both patient and graft survival at 3, 6, and 12u2003months were significantly lower in the higher MELD score groups, as was patient survival at 24u2003months (p‐values, 0.01–0.05). The difference in survival between the low, medium, and high MELD score groups increases in time. The survival without bridging fibrosis in the allograft at 1u2003year post‐transplant was significantly lower with higher MELD scores (pu2003=u20030.037). The decrease in survival seen in hepatitis C patients with MELD scores greater than 24 raises questions of transplant suitability for these patients. Therapeutic modalities to decrease post‐transplant graft injury in these patients should be explored.

A multicenter, randomized trial of daily high-dose interferon-alfa 2b for the treatment of chronic hepatitis C : Pretreatment stratification by viral burden and genotype

A multicenter, randomized trial of daily high-dose interferon-alfa 2b for the treatment of chronic hepatitis C: pretreatment stratification by viral burden and genotype

Analysis of kidney function and biopsy results in liver failure patients with renal dysfunction: a new look to combined liver kidney allocation in the post-MELD era.

Background. Renal dysfunction in the context of liver failure negatively impacts orthotopic liver transplantation (OLT) outcomes. Appropriate allocation of combined liver and kidney transplants (CLKT) is crucial with the current organ shortage and lack of standard selection criteria. Methods. We propose a practical workup algorithm for CLKT by using three variables: duration of renal insufficiency and glomerular filtration rate measured by the iodine-125 iothalamate (Glofil) test and renal biopsy findings. The study was divided into two phases. In the first phase, we retrospectively reviewed the clinical and laboratory database of all liver transplant patients (n=196) performed in our institution. In the second phase, we prospectively implemented the algorithm on 20 selected patients with liver failure and renal dysfunction (chronic kidney disease stage 3 and acute kidney injury) worked up for OLT. Results. Based on the workup algorithm, we recommended OLT for 12 patients and CLKT for eight patients. We were able to avoid CLKT for six patients without causing adverse renal outcomes among 11 patients transplanted by using this algorithm. The average 12-month renal outcomes of these transplanted patients seem to be favorable with the mean serum creatinine 1.3 mg/dL in OLT group and 1.1 mg/dL in CLKT group. Conclusion. The workup algorithm, which primarily uses duration of renal failure, glofil measurement, and renal biopsy findings, offers a practical approach to this complicated decision-making process regarding appropriate allocation of organs for CLKT.

Two‐stage total hepatectomy and liver transplantation for acute deterioration of chronic liver disease: A new bridge to transplantation

Two‐stage total hepatectomy and liver transplantation has been reported for acute liver disease such as fulminant hepatic failure, primary graft failure, severe hepatic trauma, and spontaneous hepatic rupture secondary to hemolysis, elevated liver function tests, low platelets syndrome, and preeclampsia. This is the first report of patients with cirrhosis to undergo a 2‐stage total hepatectomy and liver transplantation. From 1984 to 2002, our institution performed 2008 orthotopic liver transplantations. We identified 4 patients with chronic liver disease who underwent a 2‐stage hepatectomy and liver transplantation. This is a retrospective review of these 4 patients and a review of the literature on this procedure. All 4 patients were young men with an age range of 29–31 years and had underlying cirrhosis as well as a previous transjugular intrahepatic portosystemic shunt (TIPS)procedure. Acute decompensation fulfilling Ringes criteria for toxic liver syndrome secondary to an upper gastrointestinal bleed occurred in all patients. The approximate average time between hepatectomy and liver transplantation was 20 hours (range: 8–42 hours). In all cases, the explanted liver showed histological changes of acute hepatic necrosis within the background of cirrhosis. After hepatectomy, vasopressor requirements were well documented in 2 patients. For 1 patient, there was a clear improvement in their hemodynamic status. The mean hospital stay of the 4 patients was 63 days. All patients were discharged from the hospital and are alive and well with adequate liver function at 6 to 37 months follow‐up. Two‐stage total hepatectomy and liver transplantation may be a life‐saving procedure in highly selected cirrhotic patients with acute hepatic decompensation and multiorgan dysfunction. (Liver Transpl 2004;10:564–570.)

Syndromic incidence of ovarian carcinoma after liver transplantation, with special reference to anteceding breast cancer

Ovarian cancer is the gynecologic malignancy with the highest number of deaths in the United States. Previous studies had found a decreased incidence of female gynecological malignancies after liver transplantation. In order to estimate the incidence of ovarian carcinoma after liver transplantation, we evaluated 1708 consecutive liver transplant recipients from 1984 to 2001. Of them, 770 (43%) were female. Routine follow-ups were performed at 1, 2, 5, and 10 years after transplantation. There were two cases of ovarian carcinoma. Both occurred in recipients with a previous history of breast cancer. Based on these data, we conclude that the incidence of ovarian cancer is 1:385 among all female liver transplant recipients, and 1:6.5 among those with a history of pretransplant breast cancer. We recommend that regular check-ups should be undertaken, especially in the population at highest risk.

Pseudohypocalcemia after magnetic resonance imaging with gadolinium in patients with cirrhosis

Hypocalcemia in patients with cirrhosis may be due to a number of causes. We noted a relationship between injection with gadodiamide, a particular gadolinium chelate, during magnetic resonance imaging of the liver and the development of a falsely low serum total calcium level in a patient with cirrhosis. A cross‐reference and retrospective chart review identified 10 additional patients in whom this phenomenon was noted. We describe the temporal relationship and clinical characteristics of these patients. Pseudohypocalcemia following magnetic resonance imaging with gadodiamide contrast should be considered in the differential diagnosis of hypocalcemia in patients with cirrhosis. (Liver Transpl 2004;10:136–140.)

Celiac sprue: Another autoimmune syndrome associated with hepatitis C

Background: Celiac sprue is epidemiologically associated with other autoimmune syndromes, including autoimmune liver disease. We hypothesized that chronic infection with the hepatitis C virus (HCV) also may be associated with celiac sprue because it can trigger autoimmune reactions, both within the liver and extrahepatically. Methods: 259 consecutively evaluated patients with chronic HCV infection underwent serologic screening for celiac sprue. 59 patients with autoimmune liver disease served as positive controls, and 138 with other hepatic diseases, 356 with various GI syndromes, and 221 normal volunteers were screened as negative controls. Patients with serum antigliadin (AGA), antiendomysial (AEA), and antitissue transglutaminase antibody (ATTA) underwent duodenoscopy and biopsy, and HLA-DQ typing. Results: There was a higher prevalence of AGA in all groups of patients with liver disease compared to GI controls and normal controls (see Table). However, only patients with HCV (n=3; 1%) or autoimmune hepatitis (n=2;3%) had AENATTA. One of 221 normal volunteers (0.4%) was AGA,AEA,and ATTA positive; this individual had HCV infection as well (previously undiagnosed). All six AEA! ATTA positive individuals had mild intestinal symptoms, duodenal histopathology consistent with celiac sprue, and the celiac-associated HLADQ2 allele. Five of the six followed a prescribed gluten-free diet and experienced symptomatic improvement. Conclusion: Celiac sprue is epidemiologically associated with chronic HCV infection and with autoimmune liver disease. Because HCV is encountered much more frequently than autoimmune liver disease, HCV appears to be the most common hepatic disease predisposing to celiac sprue.