Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Experience with sirolimus (SRL)-based immunosuppression following orthotopic liver transplantation (OLT) is rapidly accumulating. In combination with calcineurin inhibitors (CNIs), SRL may reduce the incidence of acute rejection and lower overall required drug levels. This study sought to quantify long-term outcome following OLT in patients with cirrhosis and concomitant hepatocellular carcinoma (HCC) who were treated with an SRL-based regimen as a primary therapy. From January 2000 to June 2007, 97 patients underwent OLT for end-stage liver disease and HCC at the University of Colorado Health Sciences Center. Of those, 45 patients received SRL, in addition to CNIs, as a component of their primary immunosuppression regimen post-OLT. Conversely, 52 patients received the standard immunosuppression regimen including CNIs, mycophenolate mofetil, and corticosteroids. The 2 treatment groups were compared with respect to the following variables: age, gender, tumor stage by explant, grade, size, presence of vascular invasion, focality, Child's class, baseline creatinine, and warm and cold ischemic times. The 2 groups were comparable by all factors save for cold ischemic time, which was significantly longer in the CNI-treated group. Overall survival at 1 and 5 years post-OLT for patients treated with SRL was 95.5% and 78.8%, respectively. Conversely, survival in patients treated with CNIs exclusively at the same time intervals was 83% and 62%. Although there was no difference in the incidence of major complications, the SRL group experienced a modest improvement in renal function. Cumulatively, these data suggest a potential survival benefit with SRL-based therapy in patients undergoing OLT for end-stage liver disease and concomitant malignancy.
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PMID:Sirolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma. 1832 56

De novo autoimmune hepatitis has been described in both pediatric and adult liver transplantation (LT) recipients. Studies of small numbers of patients have proposed it to be an alloimmune hepatitis or form of chronic rejection. We have recently noted an increasing number of patients with post-LT recurrent hepatitis C virus (HCV) developing this, with an apparent negative impact on outcome and survival. We term this entity posttransplant plasma cell hepatitis (PCH). A search of our institution's pathology database was performed with the terms "plasma cell(s)," "lymphoplasmacytic infiltrate," and "liver allograft." A histological scoring system was devised to more reliably diagnose PCH in the setting of recurrent HCV. Thirty-eight patients were identified, and their clinical data were analyzed. Sixty percent had a negative outcome as defined by the development of cirrhosis, need for retransplantation, or death. Eighty-two percent had recent lowering of immunosuppression or subtherapeutic calcineurin inhibitor levels; 58% developed PCH within 2 years post-LT. Histologic resolution of PCH was associated with good outcome (P < 0.001). Patients not receiving treatment had a negative outcome (P = 0.007) as did patients receiving corticosteroids as therapy (P = 0.02). Persistence (P = 0.007) or recurrence of PCH was associated with negative outcome. In conclusion, PCH is a histologic variant of rejection. On liver biopsy, PCH can at times be difficult to diagnose, and the use of a standardized scoring system is recommended to differentiate it from other forms of allograft dysfunction. Treatment by optimization of immunosuppression without the use of corticosteroids appears effective. The development of PCH in the setting of recurrent HCV is a negative prognostic factor for patient outcome and allograft failure.
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PMID:Posttransplant plasma cell hepatitis (de novo autoimmune hepatitis) is a variant of rejection and may lead to a negative outcome in patients with hepatitis C virus. 1850 66

It is well recognized that acute and/or chronic renal failure is a frequent complication after orthotopic liver transplantation (OLT). The multifactorial nature of the etiology of early as well as late renal failure in patients affected by HBV-related cirrhosis is not adequately appreciated by the transplant community, since renal dysfunction has mainly attributed to calcineurin inhibitor toxicity, alone or in combination with potentially nephrotoxic drugs. In the meanwhile the potential nephrotoxicity of some intravenous immunoglobulin (IVIg) preparations that more than other could affect the renal function was completely unattended. The use of polyvalent immunoglobulins has been associated in the past with several unresolved issues, including potential nephrotoxicity. Pathologic examination of the kidneys generally reveals changes typical of the osmotic nephrosis. The hypothesis of osmotic nephrosis is further supported by the fact that in most cases, acute renal failure has been associated, in the past, with the sucrose-containing IVIg products. In patients who underwent OLT for hepatitis B virus(HBV)-related liver disease the use of anti HBV immunoglobulins (HBIg) to avoid HBV-recurrence is highly effective and has really changed the outcome of this transplantation procedure. Nevertheless, the inappropriate use of HBIg could increase the risk of renal dysfunction, particularly in combination with nephrotoxic drugs.
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PMID:Nephrotoxicity of intravenous immunoglobulin in the setting of liver transplantation or HBV-related cirrhosis: an undervalued topic. 1861 75

Recurrent infection with HCV after liver transplantation is almost universal and is associated with substantial morbidity, mortality and graft loss. In contrast to immunocompetent individuals, HCV infection in immunosuppressed transplant recipients usually has an accelerated course. Acute hepatitis develops in approximately 75% of HCV recipients in the first six months following orthotopic liver transplantation (OLT). By the fifth postoperative year, over 80% of HCV-infected liver transplant recipients will develop histologic evidence of chronic allograft injury secondary to hepatitis C, with up to 30% developing cirrhosis. While the choice of calcineurin inhibitor has not been clearly shown to affect histologic recurrence of hepatitis C or the frequency of rejection in HCV-infected recipients, cumulative exposure to corticosteroids is associated with increased mortality, higher levels of HCV viremia and more severe histologic recurrence. Unfortunately, treatment of chronic HCV in liver transplant recipients is suboptimal. Combination therapy with interferon (pegylated and nonpegylated forms) plus ribavirin appears to provide maximum benefits. Drug therapy is usually administered for recurrent disease. No prophylactic therapy is available. Preemptive regimens offer no distinctive advantages over treatments initiated for recurrent disease. Overall, treatment is poorly tolerated, with frequent need for dose reductions, especially for cytopenias, and drug discontinuation in up to 50% of patients. Optimizing drug doses is important in maximizing sustained virologic response rates. The achieved SVR is between 33% and 42% in randomized studies treating patients with histologic recurrence and 0% to 33% when used in a preemptive protocol. The potential factors that influence this low SVR rate are: 1) high percentage of patients with genotype 1 virus; 2) high viral load at the start of treatment; 3) high percentage of prior non-responders to therapy; 4) side effects that often make the use of standard doses and duration of treatment difficult; 5) the use or not of growth factors; and 6) the effect of immunosuppression. In post-transplant patients with recurrent HCV disease, combination Peg alfa-2b or alfa-2a in standard dose and ribavirin (800-1200 mg either ab initio or as an increasing dose) regimen for 48 weeks was significantly better than no therapy, but not than any other therapy.
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PMID:[Treatment of recurrent hepatitis C infection after liver transplantation]. 2019 7

The progression of fibrosis due to hepatitis C virus (HCV) recurrence after liver transplantation (OLT) is faster than in the pretransplant setting, leading to histologically documented cirrhosis within 5 years in 25% to 30% of cases. Whether it is associated with biliary complications or previous alcohol abuse, recurrent HCV is the main cause of graft failure and death after OLT. The most important donor risk factor for HCV recurrence is advanced donor age. The disease's course is even more aggressive if it is associated with anti-HCV positivity or graft steatosis. The type of calcineurin inhibitor does not seem to influence HCV recurrence. Avoiding or slowly tapering steroids has been associated with less disease recurrence, while steroid pulses to treat acute rejection episodes have been associated with a worse progression of fibrosis. Antiviral therapy (AT) is not always recommended in OLT patients, but is of some benefit. Fibrosis has been shown to ameliorate in sustained virological responders to AT and to progress significantly more in nonresponders. Using long-term maintenance, AT has recently been shown to increase the probability of biochemical and histological responses, regardless of the timing of the HCV recurrence. In conclusion, the donor- recipient match should be assessed to limit HCV recurrences and their severity; AT is recommended to reduce or reverse the progression of fibrosis.
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PMID:Fibrosis progression and the pros and cons of antiviral therapy for hepatitis C virus recurrence after liver transplantation: a review. 2069 49

Combined liver-kidney transplantations (CLKT) and kidney after liver transplantations (KALT) are established treatments for patients with end-stage hepatic and renal disease and the number of transplantations has continuously increased over the past few years. The most frequent indications for CLKT in adults are polycystic kidney disease with severe liver involvement and liver cirrhosis of different origins with concomitant chronic kidney failure due to chronic glomerulonephritis or diabetic nephropathy. In children, CLKT is most frequently required due to primary oxalosis type I. At present the main indication for KALT still is calcineurin inhibitor-induced chronic nephrotoxicity, emphasizing the need for a nephron-sparing long-term immunosuppression in liver transplant recipients. Compared to KALT, the indications for CLKT are not as well defined and the decision must therefore be made on a case-by-case basis by a multidisciplinary team of experienced clinicians to avoid unnecessary transplantations of both organs in patients with reversible kidney failure, given the scarcity of organs for transplantation worldwide. In hepatorenal syndrome CLKT should only be considered if the GFR is lower than 20 ml/min for more than three months or if the patient has been on renal replacement treatment for more than one month. In CLKT, there appears to be a certain immunological protection for the kidney transplant by the liver transplant.
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PMID:[Combined liver-kidney and kidney after liver transplantation: indications and experiences from a nephrological perspective at a single center]. 2092 39

Living donor liver transplantation (LDLT) has become one of the chief methods of saving patients with end-stage liver disease due to liver cirrhosis. Accumulation of knowledge about indication and perioperative managements improve outcome of this treatment. In this study, we elucidate the risk factors of LDLT, which still exist today. Sixty-one patients received LDLT in our institute between 2003 and 2009 were included in this study. Recipient age and sex, donor age and sex, etiology, preoperative model of end-stage liver disease (MELD) score, hepatocellular carcinoma (HCC), graft versus recipient weight ratio (GRWR), cold and warm ischemic time, operation time, blood loss, ABO compatibility, rejection, cytomegalovirus (CMV) infection, biliary stricture, and calcineurin inhibitor (FK506 or cyclosporin A) were the factors investigated. p < 0.05 was considered as statistically significant in the proportional hazard model. In univariate analysis, the recipients' age (p = 0.024) and rejection episode (p = 0.046) were selected as significant risk factors. In multivariate analysis including the factors that showed p < 0.2 (recipient age, GRWR, ABO compatibility, rejection episode) in univariate analysis, recipient age (p = 0.008, HR: 1.40; 95% CI: 1.09-1.80) and rejection episodes (p = 0.002, HR: 13.33; 95% CI: 2.53-71.43) were still selected as significant independent risk factors after LDLT. Recipient age was shown to be 1.40 times risk per 1 year older and the rejection episode was shown to be 13.33 times risk in the recent era with comprehensive indication and preoperative management for LDLT. Indication must be cautious for elderly patients, and prevention of rejection is crucial for the improvement of results for LDLT.
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PMID:Risk factors of recipient receiving living donor liver transplantation in the comprehensive era of indication and perioperative managements. 2094 66

Sickle cell disease (SCD) frequently affects the liver; if acute liver failure (ALF) develops, the only potentially effective therapeutic option is liver transplantation (LT). Only 12 patients for whom LT was performed for SCD-related ALF have been described so far. We report a retrospective series of 6 adult patients with SCD (3 men and 3 women, median age = 40.1 years) who underwent emergency LT. The indication for LT was ALF complicating cirrhosis in 5 patients (hepatitis C/iron overload-induced cirrhosis in 3 and iron overload-induced cirrhosis in 2); one patient had autoimmune hepatitis. The median follow-up was 52.7 months (0.5-123 months). The 1-, 3-, 5-, and 10-year survival rates were 83.3%, 66.7%, 44.4%, and 44.4%, respectively. One patient died of hepatocellular failure precipitated by hyperacute allograft rejection on post-LT day 10. Soon after LT, 2 patients developed seizures; in 1 case, the seizures were a complication of early calcineurin inhibitor-induced leukoencephalopathy. Four long-term survivors benefited from specific management of SCD; specifically, the hemoglobin S fraction was maintained below 30% and the total hemoglobin level was maintained between 8 and 10 g/dL. Two patients had mild vaso-occlusive crises. Three patients experienced a recurrence of hepatitis C virus (HCV) infection; 2 of these patients experienced reversible neurological complications while they were receiving antiviral treatment. Carefully selected patients with SCD may benefit from emergency LT. However, such patients seem to be particularly susceptible to neurological complications after LT. In contrast, severe SCD-related crises do not seem to recur if specific management is provided. Outcomes may be improved if the neurological complications can be minimized; for example, the administration of a calcineurin inhibitor can be delayed, and the management of HCV infection recurrence can be improved.
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PMID:Transplantation for liver failure in patients with sickle cell disease: challenging but feasible. 2144 21

Liver transplantation is considered to be the most efficient therapeutic option for patients with liver cirrhosis and early stage hepatocellular carcinoma (HCC) in terms of overall survival and recurrence rate. The application of restrictive selection criteria based on tumor size and number of nodules is advised to obtain optimal results. Nevertheless, tumor recurrence occurs in 3.5% to 21% of recipients, despite careful pretransplant staging and patient selection. Post transplant recurrence of hepatocarcinoma clearly has a major negative impact on prognosis. Intuitively, an immunosupressed state is undesirable in cancer patients. Inversely, modulation or minimization of immunosuppressive therapy could influence tumor progression and reduce the negative impact of recurrence on posttransplant survival. Experimental evidence shows that mammalian target of rapamycin (mTOR) inhibitors have antiangiogenic and antiproliferative effects. Thus, their application has been proposed as antineoplastic agents for immunosuppressive protocols in liver transplant recipients with HCC and may reduce the rate or the impact of tumor recurrence. Clinical data about efficacy and safety of mTOR-based immunosuppressant protocols in liver transplant recipients with HCC show promising results, namely low recurrence and higher survival rates compared with standard calcineurin inhibitor-based immunosuppressive protocols, even among patients with extended morphological criteria. The safety profile is regarded generally as adequate.
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PMID:Strategies of immunosuppression for liver transplant recipients with hepatocellular carcinoma. 2148 80

Liver transplantation for patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) remains challenging. The advent of highly active antiretroviral therapy (HAART) for HIV has reduced mortality from opportunistic infection related to acquired immunodeficiency syndrome dramatically, while about 50% of patients die of end-stage liver cirrhosis resulting from HCV. In Japan, liver cirrhosis frequently develops after HCV-HIV coinfection resulting from previously transfused infected blood products for hemophilia. The problems of liver transplantation for those patients arise from the need to control calcineurin inhibitor with HAART drugs, the difficulty of using interferon after liver transplantation with HAART, and the need to control intraoperative coagulopathy associated with hemophilia. We review published reports of liver transplantation for these patients in the updated world literature.
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PMID:Liver transplantation for patients with human immunodeficiency virus and hepatitis C virus coinfection with special reference to hemophiliac recipients in Japan. 2192 53


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