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 hepatitis C virus (HCV) is a small enveloped RNA virus belonging to the family flaviviridae and genus hepacivirus. The HCV RNA genome is 9,600 nucleotides in length and encodes a single polyprotein that is post-translationally cleaved into 10 polypeptides including t3 structural (C, E1, and E2) and multiple nonstructural proteins ([NS] NS2 to NS5). The NS proteins include enzymes necessary for protein processing (proteases) and viral replication (RNA polymerase). The virus replicates at a high rate in the liver and has marked sequence heterogeneity. There are 6 genotypes and more than 90 subtypes of HCV, the most common in the United States being 1a and 1b (approximately 75%), 2a and 2b (approximately 15%), and 3 (approximately 7%). Acute hepatitis C is marked by appearance of HCV RNA in serum within 1 to 2 weeks of exposure followed by serum alanine aminotransferase (ALT) elevations, and then symptoms and jaundice. Antibody to HCV (anti-HCV) tends to arise late. In acute resolving hepatitis, HCV RNA is cleared and serum ALT levels fall to normal. However, 55% to 85% of patients do not clear virus, but develop chronic hepatitis C. Chronic hepatitis C is often asymptomatic, but is usually associated with persistent or fluctuating elevations in ALT levels. The chronic sequelae of hepatitis C include progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Extra-hepatic manifestations include sicca syndrome, cryoglobulinemia, glomerulonephritis, and porphyria cutanea tarda. Knowledge of the course and outcome of hepatitis C is important in developing approaches to management and therapy.
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PMID:Course and outcome of hepatitis C. 1240 73

Chronic hepatitis C virus (HCV) infection develops in 85% of exposed individuals and 20% develop cirrhosis. However, the pathogenesis of this process is not well-understood. The objective of this study was to determine whether HCV-reactive T cells play a role in the process of development of cirrhosis during chronic HCV infection. We analyzed 21 human leukocyte antigen (HLA)-A2 patients with chronic HCV infection (9 with histology of inflammation and 12 with histology of fibrosis/cirrhosis). The frequency of CD8(+) T cells reactive to 12 HCV-derived epitopes was determined by an interferon-gamma enzyme-linked immunospot (ELISPOT) assay. The frequency of CD4(+) Th1 and Th2 cells reactive to the HCV core antigen was determined by interferon-gamma and interleukin-5 ELISPOT assays, respectively. Patients with histology of inflammation showed a significantly higher CD8(+) T-cell response to five HCV-derived epitopes (YLLPRRGPRL [core], CINGVCWTV [NS3], LLCPAGHAV [NS3], ILAGYGAGV [NS4B], and GLQDCTMLV [NS5B]) as compared with patients with histology of fibrosis/cirrhosis. Also, patients with histology of inflammation showed a significantly higher CD4(+) Th1 response to the HCV core antigen as compared to patients with histology of fibrosis/cirrhosis. These results indicate that a lack of an optimal T-cell response to HCV is associated with the development of cirrhosis during chronic HCV infection.
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PMID:Lack of optimal T-cell reactivity against the hepatitis C virus is associated with the development of fibrosis/cirrhosis during chronic hepatitis. 1255 24

Chronic hepatitis C virus is a major worldwide cause of hepatitis, cirrhosis, end-stage liver disease, and hepatocellular carcinomas. Combination therapy of ribavirin with short- or long-acting interferon-alpha is now the standard treatment of chronic hepatitis C. This therapy is associated with a wide range of side effects. Although hemolysis is almost an invariable result of ribavirin, black urine due to hemoglobinuria has never been previously reported. We recently encountered two cases of black urine (hemoglobinuria) in patients treated with combination therapy. Based on reports of dark urine in many of our patients, we suggest that this phenomenon may be more common than is currently appreciated. It indicates a marked degree of hemolysis, which prompts immediate measurement of hemoglobin level.
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PMID:Hemoglobinuria with ribavirin treatment. 1264 48

Chronic hepatitis C progresses to cirrhosis within 20 years in an estimated 20-30% of patients, while running a relatively uneventful course in most others. Certain HCV proteins, such as core and NS5A, can induce derangement of lipid metabolism or alter signal transduction of infected hepatocytes which leads to the production of reactive oxygen radicals and profibrogenic mediators, in particular TGF-beta1. TGF-beta1 is the strongest known inducer of fibrogenesis in the effector cells of hepatic fibrosis, i.e. activated hepatic stellate cells and myofibroblasts. However, fibrogenesis proceeds only when additional profibrogenic stimuli are present, e.g. alcohol exposure, metabolic disorders such as non-alcoholic steatohepatitis, or coinfections with HIV or Schistosoma mansoni that skew the immune response towards a Th2 T cell reaction. Furthermore, profibrogenic polymorphisms in genes that are relevant during fibrogenesis have been disclosed. This knowledge will make it possible to identify those patients who are most likely to progress and who need antiviral or antifibrotic therapies most urgently. However, even the best available treatment, the combination of pegylated interferon and ribavirin, which is costly and fraught with side effects, eradicates HCV in only 50% of patients. While the suggestive antifibrotic effect of interferons (IF-gamma>alpha,beta), irrespective of viral elimination, has to be proven in randomised prospective studies, additional, well tolerated and cost-effective antifibrotic therapies have to be developed. The combination of cytokine strategies, e.g. inhibition of the key profibrogenic mediator TGF-beta, with other potential antifibrotic agents appears promising. Such adjunctive agents could be silymarin, sho-saiko-to, halofuginone, phosphodiesterase inhibitors, and endothelin-A-receptor or angiotensin antagonists. Furthermore, drug targeting to the fibrogenic effector cells appears feasible. Together with the evolving validation of serological markers of hepatic fibrogenesis and fibrolysis an effective and individualised treatment of liver fibrosis is anticipated.
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PMID:Hepatitis C and liver fibrosis. 1265 47

Chronic hepatitis C virus (HCV) infection is common and often results in slowly progressive liver disease. Although acute hepatitis C is now uncommon, most patients with acute infection have developed chronic hepatitis, and, therefore, the pool of infected patients is large. We used a modification of a previously described natural history model for HCV infection to project the number of cases of HCV infection, cirrhosis, and liver failure over the next 40 years. The model estimated the prevalence of HCV infection in the United States was 3.07 x 10(6) in 1993 (compared with an adjusted National Health and Nutrition Evaluation Survey (NHANES) III estimate of 2.8 to 3.5 x 10(6)). A gradual decline in the prevalence of infection should occur by year 2040 because of aging and natural deaths among the infected pool. However, as the duration of infection increases in the surviving cohort, the proportion with cirrhosis will increase from 16% to 32% by 2020 in an untreated population. Complications of cirrhosis also will increase dramatically over the next 20 years: hepatic decompensation (up 106%), hepatocellular carcinoma (up 81%), and liver-related deaths (up 180%). Although current treatment regimens eradicate HCV in over 50% of cases, many more patients would need to be treated to significantly impact disease progression. Identification and treatment of every case of HCV infection (with or without cirrhosis) would reduce the number of cases of decompensated cirrhosis by almost half after 20 years. Despite the declining incidence of acute HCV infection, chronic hepatitis C is common. The prevalence of cirrhosis and the incidence of its complications will increase over the next 10 to 20 years, because the duration of infection increases among those with chronic hepatitis C. These data emphasize the need for greater access to transplantation by expansion of the donor pool, increasing use of split livers and living donors, and novel options such as xenotransplantation.
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PMID:Projecting future complications of chronic hepatitis C in the United States. 1268 82

Hepatitis C in patients with chronic renal failure. Infection with hepatitis C virus (HCV) is a common complication in those patients under chronic dialysis. Prevalence varies from 8% to 65 percent. Immunization against hepatitis A and B for renal patients is always recommended, especially in countries with high prevalence of this type of hepatitis. Interferon as the only antiviral treatment is recommended for patients with chronic renal failure and chronic hepatitis who depend on dialysis. Viral hepatitis is the first cause of morbidity and mortality among renal recipients. Prevalence varies between 4 and 38%, depending on the geographic area. Infection with HCV usually begins before the transplant, although the patient is sometimes infected during the transplant because the donor organs carry the virus. The chronic HCV infection dosen't seem to affect the survival rate of the patient or the organ, compared to the survival rate in patients without the infection. Chronic hepatitis C without cirrhosis is not a contraindication for renal transplant, but cirrhosis is. Liver failure is the cause of death in 8-28% of renal transplant recipients infected with hepatitis C virus.
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PMID:[Viral hepatitis C in patients with renal disease]. 1271 63

Chronic hepatitis C patients with genotype 1 infection, liver cirrhosis, high viral load, or those who have not responded to anti-viral treatment in the past have limited chances of clearing the virus, even with pegylated interferon-ribavirin therapy. In this study we treated such patients with a treatment schedule that combines high dose induction Interferon (IFN), prolonged daily IFN and ribavirin treatment. Twenty-four consecutive patients were included in this study with either genotype 1 infection, cirrhosis, previous non-response to IFN or a combination of these poor-response characteristics. Patients were treated with 10 million units (MU) of IFN daily for 4 weeks followed by 5 MU/day until week 24, 3 MU/day until week 52 and 3 MU thrice weekly until week 76 in combination with 1-1.2 g ribavirin daily. HCV RNA levels were assessed weekly until week 4 and at least once every 3 months thereafter, by a validated assay with a detection limit below 500 copies/mL. Both intention to treat (ITT) and per protocol (PP) analysis showed a high sustained virological response (ITT 67%, PP 80%). A virological response occurred rapidly (before 8 weeks of treatment) in all patients with a sustained response. Relapse after stopping therapy was observed in only 5%. Side-effects were observed frequently, and six patients had to be hospitalized. With this new treatment regimen that combines induction- and prolonged daily interferon treatment with ribavirin it seems possible to eliminate hepatitis C virus in the majority of patients that have an a priori limited chance of sustained response. Further clinical evaluation of intensive interferon and ribavirin combination therapy (now also including PEG-interferon) is recommended in centres that can provide close patient monitoring and experienced hepatological support.
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PMID:High sustained virological response in chronic hepatitis C by combining induction and prolonged maintenance therapy. 1275 39

Chronic hepatitis C virus (HCV) infection results in the development of liver fibrosis and cirrhosis in 20 to 25% of patients. The main task of the physician when examining a patient with a verified HCV infection is to identify the activity of inflammatory and necrotic processes in the liver, as well as the stage of fibrosis, and the reversibility of detected changes. Along with other clinical and laboratory parameters, this plays a major role in forecasting the course of hepatitis, as well as determines the therapeutic approach in each specific case. Liver biopsy remains the best way to assess the severity of chronic hepatitis C. The risk of developing cirrhosis depends on the stage (degree of fibrosis) and the grade (degree of inflammation and necrosis) observed in the initial liver biopsy. Non-invasive diagnostic approaches attempt to evaluate the serum markers of fibrogenesis. Biochemical markers of fibrosis scoring include thrombocyte counts, the prothrombin time, ratio of alaninaminotransferase (ALT) and aspartataminotransferase (AST) levels, the level of g-glutamyl transferase and the quantity of blood serum albumin. Another set of markers is based on the detection of molecular junctions that activate fibrosis, or participate in the generation of the liver extracellular matrix. The most applicable include hyaluronic acid (HA), type IV collagen (IV-C), N-terminal propeptide of type III procollagen (PIIIP), metalloproteinases (MMP), inhibitors of metalloproteinases (TIMP), and growth-transforming factor betta (GTFbeta). The review discusses the clinical significance of each of the criteria and possibility of their combination in the non-invasive monitoring of liver fibrosis.
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PMID:Invasive and non-invasive monitoring of hepatitis C virus-induced liver fibrosis: alternatives or complements? 1276 63

Chronic hepatitis C virus (HCV) infection is a major health problem worldwide. The natural history of HCV infection is not fully understood. For years, there has been an overestimation of the rate of chronicity in acute HCV. Similar high rates of progression to cirrhosis in chronic HCV were reported. The source of confusion stems from the fact that most acute HCV infections are asymptomatic and never come to medical attention. The consequence of this is that most early studies of natural history reflect the more severe end of the spectrum of the disease. Recent studies reported 43-45% rate of chronicity as opposed to the old rates of 77-85%. Also, the rate of progression to cirrhosis and hepatocellular carcinoma was found to be much lower than previously reported. Multiple factors contribute to the chronicity and progression to cirrhosis, the most important being male gender, age, alcohol intake, and the degree of liver fibrosis on initial biopsy. At least 38% of patients with HCV will manifest symptoms of at least one extrahepatic complication. The most important extrahepatic manifestation is mixed cryoglobulinemia. Other extrahepatic manifestations and their response to antiviral therapy are discussed.
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PMID:The natural history of hepatitis C virus infection. 1289 3

Chronic Hepatitis C can progress to end-stage liver cirrhosis or hepatocellular carcinoma. Interferon (IFN) therapy is effective in clearing the hepatitis C virus and in improving liver histology, however, few patients maintain a sustained response (SR) after IFN withdrawal. Immediate retreatment with IFN is therefore considered to be both effective and necessary, especially for patients who do not respond to the initial course of IFN therapy. All 145 patients included in the present study underwent liver biopsy, followed by a first treatment course with various IFNs (alpha2a, alpha2b, alpha, OIF or beta). If hepatitis C virus (HCV) RNA was positive after the first treatment, the patient was assigned to one of 3 groups, depending on whether his or her alanine transaminase (ALT)level was normalized (incomplete response, IR), partially responsive(PR), or non-responsive (NR). After an observational interval of 6 to 76 months, a second IFN treatment was initiated with a higher dose or the same dose of the same IFN for the IR group, and with a different IFN for the PR and NR groups. At 6 months after retreatment with IFN, the overall efficacy of the retreatment was 29.7.% In the case of the IR group, who received the same IFN, the overall efficacy was 45.2%. In patients identified as non-SR after the first treatment, who received a different type of IFN for retreatment, the overall efficacy was 18.6%. Anti-IFN antibody was not detected in most of the breakthrough cases. For some IR patients, retreatment with the same IFN was effective. Anti-IFN antibody was mostly negative, indicating that the same IFN can be used in both the first treatment and retreatment to obtain an SR. Switching to a different IFN was effective for some PR and NR patients, suggesting that changing IFN for such cases is a good therapeutic choice.
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PMID:Efficacy of interferon retreatment on interferon-resistant patients with chronic hepatitis C. 1290 13


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