Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of native portal vein thrombosis (PVT) in liver transplant recipients has been reported to range from 2.1 to 13.8%. We have identified an inordinately high incidence of PVT in a consecutive series of U.S. veterans receiving liver transplants. Between October 1989 and February 1994, 88 consecutive U.S. veterans received 99 orthotopic liver transplants under primary Tacrolimus (Prograf, formerly FK506) based immunosuppression. A number of clinical features were examined in an effort to identify risk factors for PVT and outcome was compared to patients without PVT. Native PVT was present in 23/88 (26%) patients. All of these patients were male U.S. veterans with a mean age of 47 years. When compared to the 65 patients without PVT, we found no significant difference with respect to underlying liver disease, age, Childs-Pugh score (mean = 12), UNOS status as defined prior to April 1995 (95% UNOS 3 or 4), previous abdominal surgery, or liver volume. Median blood loss for patients with PVT (21 units of packed red blood cells) was greater than for those without PVT (14 units, P = 0.04). Portal thrombectomy was performed in 11 patients, 11 patients required mesoportal jump grafts, and 1 patient had an interposition graft. Standard veno-venous bypass was used in 10 patients with single bypass utilized for the remainder. Actuarial patient survival for all patients at 1, 2, and 4 years was 88, 85, and 79%, respectively. There was no significant difference in patients with or without PVT. Patients with PVT had poorer graft survival than patients without PVT (86% vs 65%, 1 year; 81% vs 65%, 2 years; 81% vs 61%, 4 years; P = 0.03); however, this was not related to technical problems with the portal venous inflow. PVT occurred in 26% of U.S. veterans undergoing liver transplantation. These patients had significantly higher operative blood loss and poorer graft survival. The high incidence of postnecrotic cirrhosis in a predominantly male group of patients with advanced disease, as is evident by the high mean Childs-Pugh score and UNOS status, perhaps accounts for our observations.
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PMID:A high incidence of native portal vein thrombosis in veterans undergoing liver transplantation. 859 64

We report the case of a 41-year old patient who underwent orthotopic liver transplantation because of decompensated liver cirrhosis due to chronic HCV-infection. Severe acute allograft rejection was insufficiently controlled by cyclosporine A, steroids and a 6-day regimen of OKT 3 monoclonal antibody therapy. As a consequence immunosuppressive therapy was switched to FK 506 in a dose of 3 mg bid. The FK 506 concentration in whole blood consistently ranged between 5.1 and 7.8 ng/ml. Seven weeks after the onset of FK 506 therapy the patient developed severe diabetes mellitus with fasting blood glucose levels up to 640 mmol/l. The C-peptide was elevated reflecting a higher than normal insulin secretion. Intravenous insulin therapy with application of up to 85 units regular insulin per day was initiated. Because of the severe diabetes immunosuppression was changed back to cyclosporine A. After six weeks the patient did no longer require insulin and showed an entirely normal glucose tolerance test, C-peptide and Hb A1-level. This case shows that the diabetogenic side effect of FK 506 is more pronounced than that of cyclosporine A. We propose to change immunosuppressive therapy to cyclosporine A in cases of FK 506 induced severe diabetes mellitus, since long-term prognosis of many transplant recipients may depend on side effects of the immunosuppressive agents.
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PMID:Complete reversal of FK 506 induced diabetes in a liver transplant recipient by change of immunosuppression to cyclosporine A. 865 88

We report two cases of Kaposi's sarcoma (KS) after orthotopic liver transplantation for cirrhosis of the liver related to hepatitis C virus. Both cases were Saudi-born Arabs who were negative for human immunodeficiency virus; one patient was receiving FK506 plus prednisolone, and the other patient was receiving FK506. One patient died of fulminant multicentric KS. The other patient, with lesions confined to the lower limbs, is still alive. These are the first case reports of KS in liver transplant recipients in the Kingdom of Saudi Arabia and, to our knowledge, these are the first case reports of KS in liver transplant recipients on FK506. All previous reports were related to either cyclosporine or conventional immunosuppressive therapy, i.e., azathioprine plus prednisolone.
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PMID:Kaposi's sarcoma in liver transplant recipients on FK506: two case reports. 917 20

The optimal immunosuppressive regimen in patients transplanted for hepatitis C (HCV) is still under discussion. High immunosuppression may promote viral replication and recurrent graft hepatitis. But acute and chronic rejection frequently seen in conjunction with HCV recurrence may require some rescue therapy. One hundred and thirty-seven patients transplanted for HCV cirrhosis, who were HCV-RNA positive prior to transplantation, were analyzed. Seventy-nine patients received CSA-based immunosuppression and 58 patients FK506-based immunosuppression. One-month patient survival was 100% in both groups. Three month and 1-year survival rates and the cumulative 1-5-year patient survival was similar in CsA-treated [67/79 (84.8%)] and FK506-treated patients [50/58 (86.2%)]. Retransplantations for HCV recurrence were performed in 5.1% of CsA-treated patients and 6.9% of FK506-treated patients; it was successful in 50% and 75% of patients, respectively. Conversion from CsA to FK506 and vice versa was high with 25 out of 79 patients (31.6%) converting in the CsA group and 8 out of 58 patients (13.8%) converting in the FK506 group. Conversion to FK506 was performed due to acute and chronic rejection and to CsA because of toxicity and HCV recurrence. In both groups, 25% of converted patients died. Five patients of the CsA group and 9 of the FK506 group received OKT3; more than one-third of each group died. Five patients in the CsA group and 6 in the FK506 group received mycophenolate mofetil (MMF) for HCV recurrence or acute and chronic rejection in conjunction with HCV recurrence. All patients of this critical group are alive with good graft function. In conclusion, survival rates of HCV patients were similar to those seen for other indications. Conversion from CsA to FK506 and vice versa was high and reflects a critical group concerning patient survival. OKT3 treatment should be avoided. A promising therapeutic option for critical patients experiencing acute or chronic rejection in conjunction with HCV recurrence may be treatment with MMF.
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PMID:Searching for the optimal management of hepatitis C patients after liver transplantation. 966 81

To determine the frequency, risk factors, and consequences of recurrent autoimmune hepatitis after liver transplantation, 41 patients with type 1 disease were monitored after surgery in accordance with a surveillance protocol. Tacrolimus or cyclosporine plus prednisone were administered to each patient, and liver biopsy examinations were performed at least annually according to protocol. Corticosteroid therapy was ultimately discontinued in only 2 patients. Recurrent disease was defined as the presence of lymphoplasmacytic infiltrates in liver tissue in the absence of other causes of allograft dysfunction. Autoimmune hepatitis recurred in 7 patients (17%), and the mean time to recurrence was 4.6 +/- 1 years. Recurrence was asymptomatic in 4 of 7 patients and detected only by surveillance liver biopsy assessment in 2 patients. Histological changes were mild, and there was no progression to cirrhosis during 4.9 +/- 0.9 years of observation. Five-year patient (86% v. 82%; P =.9) and graft (86% v. 67%; P =.5) survival rates were not statistically different between patients with and without recurrent disease. HLA-DR3 or HLA-DR4 occurred more commonly in patients with than without recurrence (100% v. 40%; P =.008) and healthy subjects (100% v. 49%; P =.01). Recurrent disease was unrelated to donor HLA status. In conclusion, recurrence after transplantation for type 1 autoimmune hepatitis is common. Its mild manifestations and favorable prognosis may reflect early detection by a surveillance protocol and/or continuous corticosteroid treatment. HLA-DR3- or HLA-DR4-positive recipients are at risk for recurrence regardless of donor HLA status.
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PMID:Recurrent autoimmune hepatitis after orthotopic liver transplantation. 1130 89

Tacrolimus has proven to be a potent immunosuppressive agent in liver transplantation (LT). Its introduction has led to significantly less frequent and severe acute rejection. Little is known about the rate of chronic rejection (CR) in primary LT using tacrolimus therapy. The aim of the present study is to examine the long-term incidence of CR, risk factors, prognostic factors, and outcome after CR. The present study evaluated the development of CR in 1,048 consecutive adult primary liver allograft recipients initiated and mostly maintained on tacrolimus-based immunosuppressive therapy. They were evaluated with a mean follow-up of 77.3 +/- 14.7 months (range, 50.7 to 100.1 months). To assess the impact of primary diagnosis on the rate and outcome of CR, the population was divided into 3 groups. Group I included patients with hepatitis C virus (HCV)- or hepatitis B virus (HBV)-induced cirrhosis (n = 312); group II included patients diagnosed with primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), or autoimmune hepatitis (AIH; n = 217); and group III included patients with all other diagnoses (n = 519). Overall, 32 of 1,048 patients (3.1%) developed CR. This represented 13 (4.1%), 12 (5.5%), and 7 patients (1.3%) in groups I, II, and III, respectively. The relative risk for developing CR was 3.2 times greater for group I and 4.3 times greater for group II compared with group III. This difference was statistically significant (P =.004). The incidence of acute rejection and total number of acute rejection episodes were significantly greater in patients who developed CR compared with those who did not (P <.0001). Similarly, the mean donor age for CR was significantly older than for patients without CR (43.0 v 36.2 years; P =.02). Thirteen of the 32 patients (40.6%) who developed CR retained their original grafts for a mean period of 54 +/- 25 months after diagnosis. Seven patients (21.9%) underwent re-LT, and 12 patients (38.3%) died. Serum bilirubin levels and the presence of arteriopathy, arterial loss, and duct loss on liver biopsy at the time of diagnosis of CR were significantly greater among the 3 groups of patients. In addition, patient and graft survival for group I were significantly worse compared with groups II and III. We conclude that CR occurred rarely among patients maintained long term on tacrolimus-based immunosuppressive therapy. When steroid use is controlled, the incidence of acute rejection, mean donor age, HBV- and/or HCV-induced cirrhosis, or a diagnosis of PBC, PSC, or AIH were found to be predictors of CR. Greater values for serum bilirubin level, duct loss, arteriopathy, arteriolar loss, and presence of HCV or HBV were found to be poor prognostic factors for the 3 groups; greater total serum bilirubin value (P =.05) was the only factor found to be significant between patients who had graft loss versus those who recovered.
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PMID:Does tacrolimus offer virtual freedom from chronic rejection after primary liver transplantation? Risk and prognostic factors in 1,048 liver transplantations with a mean follow-up of 6 years. 1146 Feb 30

Liver transplantation (OLT) for end-stage chronic hepatitis-B-virus (HBV) infection is frequently complicated by HBV recurrence. In the present study we investigated whether human leucocyte antigen (HLA)-matching influences the outcome after OLT. In a retrospective analysis we reviewed 84 recipients of liver transplants for end-stage HBV-cirrhosis and complete HLA-typing for outcome after OLT. Follow-up ranges from 1 to 110 months (median = 55.6 months). Immunosuppression consisted of Cyclosporin A (CsA)-based quadruple induction therapy or Tacrolimus-based induction protocols. Immunoprophylaxis with hepatitis B immunoglobulin was started at OLT and continued long-term. Actuarial 1- and 5-yr graft survival figures were 90.5 and 80.4%, respectively. Hepatitis-B recurrence was responsible for 15 of 20 (75%) graft failures. We observed a significantly improved graft survival in patients with more HLA-A, -B compatibilities (p = 0.02), whereas the degree of HLA-DR compatibilities did not influence the outcome. The occurrence of HBV-reinfection was significantly lower in HLA-A, -B matched grafts (p < 0.05). Additionally, graft survival was prolonged in patients with HBV-reinfection and 1 or 2 HLA-B compatibilities when compared with patients with HBV-reinfection and a complete HLA-B mismatch (p = 0.02). In conclusion, this retrospective analysis shows that more HLA-A, -B compatibilities seems to be associated with an improved graft survival in patients after OLT for end-stage HBV infection.
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PMID:Impact of HLA-compatibilities in patients undergoing liver transplantation for HBV-cirrhosis. 1196 82

Recurrent hepatitis C virus (HCV) infection is an important cause of fibrosis and cirrhosis after liver transplantation (LT), with histological recurrence developing in at least 50% of patients within the first year. The aim of this study is to assess the safety and efficacy of interferon alfa-2b plus ribavirin in treating histological recurrent HCV after LT. Since 1998, patients with HCV with significant histological recurrence (fibrosis >/= 3 and/or histological activity index >/= 5) or progressive cholestatic disease after LT were treated with interferon alfa-2b (3 million units subcutaneously three times weekly) plus ribavirin (800 to 1,000 mg/d) for 12 months. Immunosuppression was tapered to cyclosporine/FK506 monotherapy. HCV RNA was assessed at entry, week 24, end of treatment, and 6 months after therapy. The primary end point was loss of HCV RNA 6 months after therapy, whereas the secondary end point was histological response. Fifty-four patients met criteria for treatment and have completed follow-up. Patients were mainly men (71% men; mean age, 51 +/- 5 years) with genotype 1 infection (88%) and high viral load (mean HCV RNA, 38 +/- 9 mEq/mL). Dose modification was required in 72% of patients because of cytopenia or side effects. Intent-to-treat analysis showed that serum HCV RNA was undetectable in 19 patients (35%) week 24, 21 patients (38%) week 48, and 16 patients (30%) at the 6-month follow-up. Paired liver biopsy results (before and within 6 months after treatment) were available for 35 patients. Patients who achieved viral eradication had no significant progression of fibrosis after 1 year of therapy. In summary, combination therapy is a reasonable antiviral option for recurrent HCV infection for established post-LT hepatitis and appears to prevent histological progression of disease if viral eradication is successful.
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PMID:Combination of interferon alfa-2b and ribavirin in liver transplant recipients with histological recurrent hepatitis C. 1242 12

With increasing long-term survival rates after orthotopic liver transplantation (OLT), metabolic alterations complicating the clinical course, such as diabetes mellitus (DM), become increasingly important. Liver cirrhosis is associated with severe alterations in glucose metabolism. However, it is currently unclear whether these changes are reversed by successful OLT. We therefore characterized glucose metabolism in patients with liver cirrhosis and normal fasting glucose levels before OLT (cir), in the clinically stable long-term course after OLT (OLT), and control subjects (con) using oral glucose tolerance tests (cir = 100, OLT = 62, con = 32), euglycemic-hyperinsulinemic clamps (cir = 10, OLT = 27, con = 14), and positron emission tomography (PET) scan analysis with 18F-fluorodeoxyglucose (FDG) as a tracer (cir = 7, OLT = 7, con = 5). Fasting insulin and C-peptide levels were significantly elevated in patients with liver cirrhosis compared with both control subjects (P <.001) and patients after OLT (P <.001). After OLT, insulin was normalized, whereas C-peptide remained elevated (P < 0.01). In the patients with liver cirrhosis, 27% had a normal glucose tolerance, 38% had an impaired glucose tolerance (IGT), and 35% were diabetic. After OLT, 34% had a normal glucose tolerance, 29% an IGT, and 37% were diabetic. Comparison of the same patients before and after OLT demonstrated that IGT or diabetes before OLT was the major risk factor for these conditions after OLT, which was independent of either immunosuppression (cyclosporine vs FK506) or low-dose prednisolone. Total glucose uptake was reduced in patients with liver cirrhosis to less than half the values in control subjects (21.2 +/- 2.8 vs 43.7 +/- 2.4 micromol/kg/minute, respectively, P <.001), whereas patients after OLT showed intermediate values (35.7 +/- 1.4 micromol/kg/minute, P < 0.05 vs con, P < 0.01 vs cir). This difference was caused by a reduction in nonoxidative glucose metabolism in patients with liver cirrhosis compared with control subjects (7.4 +/- 1.9 vs 28.7 +/- 1.8 micromol/kg/minute, respectively, P <.01) and patients after OLT (20.1 +/- 1.4 micromol/kg/minute, P < 0.05 vs con and OLT). In the PET study, skeletal muscle glucose uptake was significantly reduced in patients with liver cirrhosis compared with control subjects (3.5 +/- 0.4 vs 11.8 +/- 2.5 micromol/100g/minute, respectively, P <.05). After OLT, muscle glucose uptake improved compared with patients with liver cirrhosis (5.9 +/- 1.0 micromol/100g/minute, P <.05) but remained significantly lower than in control subjects (P <.05). In conclusion, these results demonstrate that preexisting IGT or diabetes are the major risk factors for IGT and diabetes after OLT. This finding was independent of the immunosuppressive medication. The peripheral insulin resistance in cirrhosis is characterized by a decrease in nonoxidative glucose disposal that is improved, but not normalized, after OLT.
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PMID:Alterations in glucose metabolism associated with liver cirrhosis persist in the clinically stable long-term course after liver transplantation. 1539 Mar 30

Acute renal failure (ARF) is a frequent medical complication after liver transplantation (LT). We analyzed cadaveric related liver transplant recipients who had developed ARF early in the postoperative course. Between January 1982 and August 2003, a total of 67 patients underwent cadaveric related LT. Their mean age was 28.64 years at LT. The 67 recipients had the following indications: biliary atresia (n = 17), Wilson's disease (n = 15), hepatitis B-related liver cirrhosis (n = 14), hepatitis C-related liver cirrhosis (n = 4), primary biliary cirrhosis (n = 4), hepatitis B-related liver cirrhosis with hepatoma (n = 3), hepatitis C-related liver cirrhosis with hepatoma (n = 2), Budd-Chiari syndrome (n = 2), neonatal hepatitis (n = 1), choledochus cyst (n = 1), autoimmune cirrhosis (n = 1), neuroendocrine tumor (n = 1), and hemangioendothelioma (n = 1). Forty-nine patients received cyclosporine (CsA), azathioprine, and steroids and 18, a combination with tacrolimus (FK506). Eight (11.94%) patients developed ARF at a mean time of 17.25 days after LT. The mean peak serum creatinine was 2.24 mg%. Four of these patients had a diagnosis of hepatitis B-related liver cirrhosis; two, hepatitis C-related liver cirrhosis; one, primary biliary cirrhosis; and one, hepatitis B-related liver cirrhosis with hepatoma. The ARF etiology was multifactorial for the majority of patients. Eight ARF patients had a history of liver cirrhosis, which may be a risk factor for intraoperative ARF. ARF treatment included fluid replacement, decreased or altered immunosuppressive agents, avoiding exposure to nephrotoxic drugs, and adjusting antibiotic dosages. The majority of patients returned to normal renal function at 1 to 3 weeks after the diagnosis of ARF. No patient required dialysis and/or experienced a mortality. We conclude that the incidence of ARF is relatively low and with good outcomes. ARF etiology was multifactorial for the majority of patients, but eight patients had a history of liver cirrhosis, which may be a risk factor for intraoperative ARF. We suggest that in the early postoperative period of LT cases diagnosis and treatment of ARF are important.
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PMID:Acute renal failure after cadaveric related liver transplantation. 1556 Dec 39


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