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 diseases are an important cause of high morbidity and mortality in HIV-infected patients, and liver cirrhosis is the commonest cause of ascites in this population. We describe the case of a 38-year-old HIV-positive male (CDC stage B3, CD4 cell count 199/mm3) with a history of hepatitis C-associated liver cirrhosis. Following pneumonia he developed spontaneous bacterial peritonitis due to Streptococcus constellatus. Clinically noticeable was the gradually worsening course with few symptoms, despite the initially high ascitic fluid leucocyte count of over 11,000/microliter, but a favourable response to betalactam antibiotics.
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PMID:[Spontaneous bacterial peritonitis with Streptococcus constellatus in an HIV positive patient]. 1068 83

The therapeutic goals in chronic hepatitis B are to prevent or decrease cirrhosis and hepatocellular carcinoma in patients with pre-cirrhotic or early cirrhotic disease and to stabilise patients with end-stage cirrhosis. Lamivudine is an oral nucleoside analogue that suppresses hepatitis B virus (HBV) replication, and so may achieve both these treatment objectives. The active 5'-triphosphate metabolite of lamivudine has two modes of viral suppression. First, it mimics deoxycytidine triphosphate and is incorporated into newly synthesised HBV DNA to cause chain termination. Second, it demonstrates competitive inhibition of viral DNA-dependent and RNA-dependent DNA polymerase activity (i.e., reverse transcriptase activity). Lamivudine may, therefore, act at four possible stages during HBV replication: reverse transcription of pre-genomic mRNA into nascent minus-strand DNA; formation of plus strand DNA from nascent minus-strand DNA; completion of double-stranded DNA; and formation of covalently closed circular DNA. In clinical studies, lamivudine therapy reduced serum HBV DNA and this was associated with significant improvements in liver histology and significant and sustained enhancement of the proliferative CD4-mediated response to HBeAg and hepatitis B core antigen (HBcAg), and an increased frequency of HBeAg-specific T cells. HBV DNA concentrations often returned to pre-treatment values when therapy ended prior to the loss of hepatitis B e antigen (HBeAg). Although the emergence of HBV variants with a mutation in the YMDD (tyrosine-methionine-aspartate-aspartate) motif has been observed, such variants show reduced susceptibility to lamivudine due to limited replication competence, and their emergence is not a signal to cease lamivudine therapy. In conclusion, viral suppression with lamivudine offers a means of disease improvement and immunological control in chronic hepatitis B.
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PMID:Profound suppression of hepatitis B virus replication with lamivudine. 1086 48

Chronic hepatitis C virus (HCV) infection affects 170 million individuals worldwide. These individuals are at risk of developing both hepatological and non-hepatological manifestations. HCV is usually only fatal when it leads to cirrhosis, the final stage of liver fibrosis. Therefore, an estimate of fibrosis progression represents an important surrogate end-point for the evaluation of the vulnerability of an individual patient. In untreated patients, the median expected time to cirrhosis is 30 years; 33% of patients have an expected median time to cirrhosis of less than 20 years and 31% will only progress to cirrhosis after more than 50 years, if ever. Several factors are associated with fibrosis progression rate: duration of infection, age, male gender, consumption of alcohol, HIV co-infection and low CD4 count. Non-hepatological manifestations are frequent with more than 70% of HCV patients experiencing fatigue or at least one extrahepatic clinical manifestation involving primarily the joints, skin and muscles. Several immunological abnormalities are frequently observed, including cryoglobulins (40%),anti-nuclear antibodies (10%) and anti-smooth muscle antibodies (7%). In contrast severe extrahepatic manifestations are rare, with 1% for systemic vasculitis.
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PMID:Natural history of HCV infection. 1089 Mar 17

Estimates of the extent of hepatic fibrosis and the rate of fibrosis progression represent important surrogate end points for evaluation of the vulnerability of an individual patient and for assessment of the impact of treatment on natural history in chronic hepatitis C. Using the median fibrosis progression rate, the median expected time to cirrhosis in untreated patients is around 30 years. However, one third of patients have an expected median time to cirrhosis of less than 20 years and one third will only progress to cirrhosis in more than 50 years, if ever. Factors independently associated with fibrosis progression are duration of infection, age, male gender, consumption of alcohol, human immunodeficiency virus co-infection, and low CD4 count. Evaluation of fibrosis progression is useful to decide treatment. Among patients with sustained viral response, fibrosis regresses. Evaluation of fibrosis progression has permitted validation of the concept of suppressive therapy. Among patients without viral clearance, interferon alone or in combination with ribavirin significantly reduces fibrosis progression rate in comparison with progression before treatment and to control groups. There is a major need for noninvasive markers of liver fibrosis. None are clearly useful today for the diagnosis of early stages of fibrosis.
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PMID:Fibrosis in patients with chronic hepatitis C: detection and significance. 1089 31

Virus-specific CD4(+) T-cell response at the site of inflammation is believed to play a decisive role for the course of viral disease. In hepatitis C virus (HCV) infection, the majority of studies focused on the peripheral blood T-cell response. In this study we analyzed intrahepatic virus-specific CD4(+) T-cell response and compared this with that in the peripheral blood. Liver and blood-derived T-cell lines were studied in 36 patients (18 with chronic hepatitis C and 18 with HCV-associated cirrhosis). Virus-specific interferon gamma (IFN-gamma) production at a single cell level to various HCV-proteins (core, nonstructural [NS] 3/4, NS5) were determined by enzyme-linked immunospot (ELIspot). Phenotyping was done by fluorescent-activated cell sorter analysis. In approximately half (16 of 36 [44%]) of intrahepatic T-cell lines a significant number of IFN-gamma spots were observed, whereas this was the case in only 19% (7 of 36 T-cell lines) in the blood. In relative terms, core and nonstructural proteins were recognized with the same frequency in both compartments, but HCV-specificity was significantly more often detected in liver tissue compared with the blood. Hepatitis activity index, viral load, and alanine transaminase levels did not correlate with the detection of HCV-specific CD4(+) T cells. All T-cell lines were dominated by CD4(+) T cells. In conclusion, HCV-specific CD4(+) T cells are multispecific, compartmentalize to the liver, and produce IFN-gamma. We speculate that our data would support the concept of compartmentalization of specific T cells at the site of inflammation and that a low frequency of specific T cells is associated with failure to clear the virus and a chronic course of disease.
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PMID:Liver-derived hepatitis C virus (HCV)-specific CD4(+) T cells recognize multiple HCV epitopes and produce interferon gamma. 1096 Apr 55

Data on the bone metabolism of human immunodeficiency virus (HIV)-infected patients are still extremely rare. To investigate the influence of HIV infection on the calciotropic hormones and markers of bone metabolism, we therefore performed a cross-sectional study on 100 patients (65 males and 35 females) with proven HIV infection. The following criteria were used for exclusion from the study: age less than 20/more than 50 years, confinement to bed, wasting symptoms, treatment with agents containing ketoconazole, renal or hepatic insufficiency, clinical or echographic signs of liver cirrhosis, endocrine diseases, or treatment with medications known to influence bone metabolism. Bone mineral content (BMC) was determined by single-photon absorptiometry on the left forearm. Reduced BMC was found among the male and female HIV-infected patients. Additional long-term use of heroin resulted in a severe loss of mineralization in the respective females. The markers of bone metabolism were determined in urine and serum samples. Significantly lower osteocalcin concentrations were found, indicating a reduced bone formation rate whose severity showed a significant correlation with the progressive loss of CD4 helper cells and was independent of low vitamin D3 levels (1,25-dihydroxycholecalciferol) and alterations of protein metabolism. Increased urinary excretion of cross-links as an expression of enhanced bone resorption was likewise significantly correlated with the loss of CD4 helper cells and independent of the vitamin D concentration and protein metabolism. It is therefore concluded that the changes in bone metabolism are mainly due to mechanisms of the impaired immune defense of HIV-infected patients.
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PMID:Changes in calciotropic hormones and biochemical markers of bone metabolism in patients with human immunodeficiency virus infection. 1101 93

Iron and its binding proteins have immunoregulatory properties, and shifting of immunoregulatory balances by iron excess or deficiency may produce severe, deleterious physiological effects. Effects of iron overload include decreased antibody-mediated and mitogen-stimulated phagocytosis by monocytes and macrophages, alterations in T-lymphocyte subsets, and modification of lymphocyte distribution in different compartments of the immune system. The importance of iron in regulating the expression of T-lymphocyte cell surface markers, influencing the expansion of different T-cell subsets, and affecting immune cell functions can be demonstrated in vitro and in vivo. The poor ability of lymphocytes to sequester excess iron in ferritin may help to explain the immune system abnormalities in iron-overloaded patients. Iron overload as seen in hereditary hemochromatosis patients enhances suppressor T-cell (CD8) numbers and activity, decreases the proliferative capacity, numbers, and activity of helper T cells (CD4) with increases in CD8/CD4 ratios, impairs the generation of cytotoxic T cells, and alters immunoglobulin secretion when compared to treated hereditary hemochromatosis patients or controls. A correlation has recently been found between low CD8+ lymphocyte numbers, liver damage associated with HCV positivity, and severity of iron overload in beta-thalassemia major patients. Iron overload, with its associated increases of serum iron levels and transferrin saturation, may cause a poor response to interferon therapy. Iron overload with hyperferremia is associated with suppressed functions of the complement system (classic or alternative types). High plasma ferritin content in patients with chronic, diffuse diseases of the liver (cirrhosis, chronic hepatitis), beta-thalassemia major, dyserythropoiesis, and hereditary hemochromatosis may induce the development of anti-ferritin antibodies with the production of circulating immune complexes. Increased body stores of iron in various clinical situations may tip the immunoregulatory balance unfavorably to allow increased growth rates of cancer cells and infectious organisms, and complicate the clinical management of preexisting acute and chronic diseases.
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PMID:Effects of iron overload on the immune system. 1104 59

Hepatitic C virus (HCV) viremia is universal after orthotopic liver transplantation (OLT) for HCV cirrhosis. 2. At 5 years post-OLT, approximately 20% of patients have cirrhosis caused by recurrent hepatitis C. 3. Progression of disease is related to immunosuppression, immune response (CD4(+) lymphocytes), HCV genotype, and HCV quasispecies homogeneity. 4. Whether a therapeutic strategy of pre-OLT or early (preemptive) antiviral therapy is better than treating a clinically important hepatitis and the duration of treatment are not known. 5. Monotherapy with recombinant interferon-alpha or ribavirin is not useful in the long term. 6. Combination therapy (interferon and ribavirin) has given better results, but long-term data are not available. 7. HCV recurrence will benefit from randomized studies.
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PMID:Posttransplantation prevention and treatment of recurrent hepatitis C. 1108 83

A total of 204 patients with liver biopsy-proven hepatitis C virus (HCV) infection, 84 with and 120 without human immunodeficiency virus (HIV) coinfection, were studied, to evaluate variables possibly associated with the stage of liver fibrosis. All patients were injection drugs users, with a mean age of 32 years and an estimated duration of HCV infection of 12 years. Twenty-four patients (11%) had many fibrous septa with (5%) or without (6%) cirrhosis, 56 (27%) had few fibrous septa, and 124 (60%) had no fibrous septa. In all patients, an association was found between CD4 cell counts <500 cells/mm(3)and the presence of many fibrous septa (odds ratio, 3.2; P=.037), independent of HIV infection and other factors. These results suggest that HIV infection-induced CD4 depletion is independently associated with the severity of liver fibrosis in chronic HCV infection.
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PMID:Liver fibrosis progression is related to CD4 cell depletion in patients coinfected with hepatitis C virus and human immunodeficiency virus. 1108

In patients with chronic hepatitis C and HIV infection, responsiveness to the standard schedule of alpha-interferon (IFN) is unsatisfactory. To quantify the effectiveness of tailoring IFN dosage according to HCV viral load under treatment, we enrolled 41 patients (M/F 32/9) chronically coinfected by HCV and HIV with chronic liver disease. All were former i.v. drug addicts, with a mean age of 32+/-4 years, and had clinical and histological evidence of chronic hepatitis (10% with cirrhosis). The CDC stage was A1 in five, A2 in 14, A3 in eight, B2 in eight, B3 in three and C3 in three. Twenty four patients were on triple therapy with protease inhibitors, 11 were on two-drug anti-HIV regimens and three were untreated. IFN (alphan1 interferon) was started at 3 MU tiw and increased at 6 MU tiw at 4 weeks if serum HCV-RNA had not dropped by at least 50%. IFN was stopped at 24 weeks in non-responders. Eleven patients received a dose increase (total IFN dose at 24 weeks 396 MU), while 16 did not increase the initial dose (total IFN dose at 24 weeks 216 MU). Fourteen subjects stopped within the first weeks due to relapse of drug abuse (ten) or subjective intolerance (four). ALT and HCV-RNA levels were markedly decreased at week 4, and this reduction lasted up to 24 weeks. However only one patient had a complete biochemical and virological end-of-treatment response, which was maintained over a 24 weeks post-therapy follow-up. All other patients relapsed to baseline ALT and HCV-RNA values after stopping IFN. HIV viral load was slightly reduced under IFN therapy, while CD4 counts were unaffected. We conclude that raising the dose of IFN dose not eradicate HCV in most HIV-infected patients, even when HIV is well controlled by treatment. HCV viraemia and necroinflammation are temporarily suppressed by IFN, but the relevance of these surrogate endpoints to progression of liver disease and to survival cannot be assessed.
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PMID:Response-adjusted alpha-interferon therapy for chronic hepatitis C in HIV-infected patients. 1109 Oct 68


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