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)

Liver histology is important for prognosis and treatment strategy in patients with hepatitis C. We report a 10-year experience of transjugular liver biopsy (TJLB) in patients with haemophilia and other congenital bleeding disorders (CBD) in terms of safety, efficiency and therapeutic consequences. TJLB was proposed to patients who were regularly followed for CBD, and were hepatitis C virus (HCV) positive by polymerase chain reaction. Patients with inhibitors or who were human immunodeficiency virus (HIV) positive with CD4 cells <0.2 x 10(9)/l or with evidence of liver failure were excluded. TJLB was performed during a short hospitalization with factor replacement. Between 1992 and 2002, 88 TJLB were performed in 69 of 151 adult HCV patients (39% HIV positive). CBD was haemophilia A in 68% and haemophilia B in 24%. Few mild adverse events were recorded. Histology was assessable in 78 of 88 procedures (89%). Twenty-nine (37%) cases demonstrated minimal change (METAVIR A </= 1 and F </= 1). Extended fibrosis or cirrhosis was recorded in 23 procedures (26%), all in patients whose infection period was longer than 20 years. No relationship between liver histology, HIV status or HCV genotype was found. TJLB appears to be safe and useful in HCV patients with CBD. One-third of patients had minimal histological changes and could avoid systematic anti-HCV treatment.
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PMID:Interest of transjugular liver biopsy in adult patients with haemophilia or other congenital bleeding disorders infected with hepatitis C virus. 1518 Aug 67

Hepatitis C is a major cause of morbidity and mortality in haemophiliacs who received clotting factor concentrates before the availability of virus-inactivated factors in the mid-1980s. Early studies gave conflicting indications as to the severity of hepatitis C (originally termed non-A non-B hepatitis), as mild, slowly progressive hepatitis was documented in several infants and young adults with haemophilia who were examined with repeat liver biopsies, whereas more progressive hepatitis and cirrhosis was documented in others. One major point of dispute was whether these discrepancies could in part be accounted for by epidemiological differences among studies, as hepatitis C acquired early in life may initially run a benign course and later worsen owing to spontaneous recrudescence of hepatitis or interference with such comorbidity factors as alcohol abuse or infection with the human immunodeficiency virus (HIV). In the mid 1990s, the latter infection overshadowed hepatitis C as a cause of death in this patient population. Because hepatocellular carcinoma is emerging as an important complication in haemophiliacs with long-standing hepatitis C virus (HCV) infection who survived HIV infection, and because of recent advances in treating HIV, morbidity and mortality associated with chronic hepatitis C have regained emphasis amongst haemophiliacs. The development of newer interferon-based therapies provides an opportunity for modifying the natural history of HCV infection in a substantial number of haemophilic patients.
Haemophilia 2004 Oct
PMID:Hepatitis C in haemophilia: lights and shadows. 1547

Prior to the introduction of virally inactivated clotting factor concentrates, the majority of individuals with congenital bleeding disorders became infected with the hepatitis C virus. Although liver biopsy is valuable in prognosis and guiding antiviral therapy, there is a reluctance to perform biopsies in this population because of the risk of hemorrhage. The purpose of this study was to evaluate the safety of transjugular liver biopsy, and the usefulness of evaluating liver histology in this patient population. Liver histopathology was assessed by the METAVIR index and compared with corrected sinusoidal pressures, platelet counts, and abdominal ultrasonography. Liver biopsy was performed at seven Canadian centers in 65 patients with hemophilia or von Willebrand's disease. Biopsies were done on an outpatient basis, followed by a 4-hr observation period in hospital. Normal hemostasis was maintained during the peribiopsy period, with follow-up doses of factor concentrate self administered by the patient at home. One patient (1.4%) had significant bleeding leading to readmission and red cell transfusion. Liver histology showed 14 patients (22%) had cirrhosis. Ten patients had elevated corrected sinusoidal pressures; 7 of these (70%) had cirrhosis on biopsy, and the other 3 (30%) likely had cirrhosis although histology showed stage 3 fibrosis. This series represents the largest reported experience of transjugular biopsy in individuals with congenital bleeding disorders. We conclude that this procedure can be safely performed on an outpatient basis. The diagnosis of cirrhosis and/or portal hypertension was made in a substantial proportion of individuals (26%), all of whom had asymptomatic liver disease.
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PMID:A Canadian multicenter retrospective study evaluating transjugular liver biopsy in patients with congenital bleeding disorders and hepatitis C: is it safe and useful? 1568 11

We report the first case of unrelated living liver transplantation for hepatitis C related hepatocellular carcinoma (HCC) in a Chinese patient with haemophilia A. The development of cirrhosis and HCC was insidious in this patient, who has previously failed interferon treatment despite low viral load and genotype 6a. With factor VIII and novoseven support, there were no operative complications and there was no need for blood transfusion. Postoperative pegulated interferon treatment resulted in viral clearance with no increased cellular rejection. The use of living donors represent a potential life saving therapeutic options for hepatitis C virus related complications in haemophiliac, especially in countries of organ shortage. Careful patient and donor choice, meticulous surgical expertise and proper counselling, however, are prudent requirements.
Haemophilia 2005 Jul
PMID:Living donor liver transplantation for hepatitis C related hepatocellular carcinoma in a haemophilia A patient. 1601 95

Coinfection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is common as a result of shared routes of transmission, especially in high-risk groups such as injection drug users and persons with hemophilia. HIV is known to influence the natural history of HBV, hastening progression to end-stage liver disease and cirrhosis. Antiretroviral therapy for HIV, and associated immune reconstitution, may result in immune-mediated liver damage as HBV-infected hepatocytes are targeted. This can lead to liver enzyme elevations that may be misattributed to drug-related toxicity. Thus, it is important that HIV-infected patients be tested for HBV and that clinicians be aware of the possibility of atypical serologic markers of HBV in HIV-infected patients. In managing coinfected patients, control of HIV is the priority. In patients with controlled HIV who are candidates for HBV therapy, the goals are the same as in the HBV-monoinfected population: hepatitis B e antigen seroconversion, liver enzyme normalization, and HBV DNA suppression. Treatment options include interferon-based regimens, lamivudine, adefovir, tenofovir, and entecavir. All of these agents have been shown to be relatively effective in HBV-monoinfected patients. However, few randomized, controlled HBV treatment trials have been conducted in coinfected subjects, and thus additional studies are warranted.
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PMID:Management of HBV/HIV-coinfected Patients. 1610 81

Liver transplantation may induce immune tolerance to factor VIII inhibitors but de novo development of inhibitors after transplantation may cause intractable haemorrhage. We report a patient with mild haemophilia A and high-titre FVIII inhibitors who received an orthotopic liver transplantation for complications of hepatitis C virus cirrhosis. Recombinant activated FVII was used in addition to routine haemostatic agents. Conventional immunosuppression was supplemented with antithymocyte globulin and cyclophosphamide. FVIII inhibitors disappeared from the circulation with liver transplantation but they were found to have bound to the graft endothelium, which became activated and induced catastrophic microangiopathy. A subsequent anamnestic response resulted in FVIII inhibitor titres of 1000 Bethesda Units. Uncontrollable haemorrhage persisted until the recipient's death. In patients with high-titre FVIII inhibitors resilient desensitization is required before liver transplantation.
Haemophilia 2005 Nov
PMID:Catastrophic microangiopathy induced by high-titre factor VIII inhibitors after liver transplantation for haemophilia A with cirrhosis. 1623 13

Treatment of patients with bleeding disorders (especially those with hemophilia) with blood products has been associated with infections with blood-borne viruses. Of these, hepatitis B and C viruses (HBV and HCV, respectively) and the human immunodeficiency virus (HIV) have created major health problems. Although virus-inactivation procedures have virtually eliminated these viruses from newer factor concentrates since 1985, the risk remains in developing countries where there is no ready access to these concentrates. Although a few of these countries have established their own fractionation facilities and in others the respective governments make concentrates available, the large majority of countries still face the problems of blood-borne infections. HCV will invariably lead to liver damage and many hemophiliacs who were exposed to the HCV virus will succumb to cirrhosis. Only approximately 10% of hemophilic patients infected with HCV will clear the infection naturally. Coinfection with HIV shortens the life expectancy. The HIV epidemic in hemophiliacs began in the mid-1980s. Patients in developed countries were especially affected because they were predominantly treated with factor concentrates that were manufactured from thousands of blood donors. Hemophiliacs in developing countries have considerably less HIV infection, although it does exist and depends largely on the source of the plasma fractions. Progress has been made not only in the purification of factor concentrates, but also in the understanding of the HIV virus and in the development of antiretroviral treatment modalities. However, there are still several challenges in delivering antiretroviral treatment that must be addressed before the full impact of these transmitted infections is known.
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PMID:Transfusion-transmitted infection in hemophilia in developing countries. 1627 61

Prior to the introduction of viral inactivation techniques in the mid-1980s, the vast majority of patients with hemophilia who received plasma-derived clotting factor concentrates were exposed to and infected with the hepatitis C virus (HCV), a lipid-enveloped bloodborne pathogen. Hemophilia patients may also have been co-infected with the human immunodeficiency virus (HIV) after receiving contaminated blood products. HCV mono-infection has a very slow progression, but patients with hemophilia who are co-infected with HCV and HIV can exhibit a comparatively rapid progression of liver disease. Potential complications of chronic HCV infection are subsequent cirrhosis with hepatic failure and the ultimate onset of hepatocellular carcinoma. The treatment of either of these may involve orthotopic liver transplantation. Liver biopsy and morphologic evaluation of tissue remain the current "gold standard" by which the severity of HCV-induced liver disease can be reliably assessed. Although there has been a reluctance to perform invasive percutaneous liver biopsies in patients with hemophilia, available evidence suggests that they appear to be safe and they certainly provide greater specificity and sensitivity than radiographic techniques such as computerized tomography or magnetic resonance imaging. Treatment of HCV-infected patients is targeted towards preventing the progression of early cirrhosis and end-stage liver disease. The current standard of care for individuals with hemophilia has generally been considered to be the combination of standard interferon-alpha (IFN-alpha) with ribavirin for at least 6 months. Data concerning the use of PEGylated IFN, substituting for standard IFN-alpha, are now emerging, although relatively little of this information relates specifically to hemophilia patients with liver disease. Nevertheless, the favorable data from large non-hemophilia-related HCV disease with early cirrhosis have been extrapolated to the hemophilia scenario, and there has been no evidence in the limited number of hemophiliacs treated in this way to refute this conclusion.
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PMID:Update on liver disease in hemophilia patients. 1642 78

Patients with cirrhosis and impaired coagulation often pose major therapeutic problems during bleeding episodes or invasive procedures. Recombinant activated factor VII (rFVIIa), which has been licensed for the treatment of haemophilia patients with factor VIII or IX inhibitors, has been occasionally used in cirrhotic patients. We present five patients with cirrhosis and coagulopathy who received 1-4 recombinant activated factor VII infusions either prophylactically in order to safely undergo an invasive procedure or therapeutically in order to control a severe bleeding episode which did not respond to standard supportive care. In particular, recombinant activated factor VII infusions were given in two patients before a percutaneous liver biopsy, in one patient before teeth extraction and in two patients with haemoperitoneum after an invasive procedure. Infusions of recombinant activated factor VII achieved rapid correction of prothrombin time in all cases allowing the safe performance of invasive procedures or resulting in efficient control of the bleeding episode. In conclusion, recombinant activated factor VII seems to be a rather promising agent for the prevention or treatment of complications of haemostasis impairment in cirrhotic patients. However, its exact role in this setting needs to be evaluated within well-designed, controlled clinical trials.
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PMID:Prophylactic and therapeutic use of recombinant activated factor VII in patients with cirrhosis and coagulation impairment. 1678 69

Both HCV and HIV are common in haemophiliacs previously treated with non-viral-inactivated clotting factor concentrates. Because of increased bleeding risks, little data are available on the safety of percutaneous outpatient liver biopsy (LBx) and impact of HIV coinfection in this population. This study aims at reporting our experience with percutaneous LBx in a cohort of haemophiliacs infected with HCV and describe the spectrum of disease and impact of HIV coinfection. A retrospective review of consecutive patients with haemophilia and HCV who underwent percutaneous LBx was performed. All patients were positive for HCV RNA by commercial assay and received factor concentrate prior to biopsy. A total of 29 male patients (mean age 36, 24 haemophilia A, five haemophilia B, and 44% coinfected with HIV) underwent successful outpatient percutaneous LBx without bleeding complication. Histologic activity index was 6.44 with advanced fibrosis (bridging fibrosis/cirrhosis) in 31%. When patients were stratified by HIV positive (n = 13) vs. HIV negative (n = 16), coinfected patients had higher fibrosis scores and higher proportion advanced fibrosis (54% vs. 12%; P = 0.0167) with no differences in age, demographic or other laboratory parameters. Multivariate logistic regression found that HIV positivity was independently associated with advanced fibrosis (OR = 3.7; 95% CI: 1.17-11.8; P = 0.026). Outpatient percutaneous LBx can be safely performed in patients with haemophilia. Despite similar age, HIV coinfection was an independent predictor of advanced fibrosis. These data support the hypothesis that HIV accelerates fibrosis progression in those coinfected with HCV and highlights the importance of liver histology in this population.
Haemophilia 2007 Mar
PMID:Percutaneous liver biopsy in adult haemophiliacs with hepatitis C virus: safety of outpatient procedure and impact of human immunodeficiency virus coinfection on the spectrum of liver disease. 1728 69


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