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

A 60-year-old man with a chronic hepatitis C virus (HCV) infection and histological features of chronic active hepatitis was treated with interferon-alpha (IFN). He successfully responded to IFN with normalization of serum ALT and disappearance of serum HCV-RNA. His liver biochemistry profile remained normal and serum HCV-RNA was not detected throughout the entire follow-up period. One year later, a small hepatocellular carcinoma (HCC) was detected by routine ultrasonographic screening. Laparotomy revealed a small tumour with no metastasis and the non-tumorous liver demonstrated macronodular cirrhosis. Although no space-occupying lesions were detected by frequent radiological examinations prior to IFN therapy, the small size of the tumour suggested de novo development of HCC. Patients with chronic HCV infection, including those who have complete responses to IFN and lack clinical and histological evidence of cirrhosis, should be followed up for the potential development of HCC.
 ...
PMID:Case report: development of hepatocellular carcinoma in a patient with chronic hepatitis C infection after a complete and sustained response to interferon-alpha. 891 34

A 39-year-old man developed sequential acute mononeuropathies involving both median, both ulnar, and the right radial and left peroneal nerves. Electrophysiology demonstrated an asymmetric sensorimotor axonal polyneuropathy; nerve biopsy confirmed a vasculitis. Laboratory evaluation revealed a mixed cryoglobulinemia and active hepatitis C infection. The patient stabilized with prednisone/cyclophosphamide/interferon-alpha. Hepatitis C should be considered in the differential diagnosis of mononeuropathy multiplex. Accurate diagnosis is important, as interferon-alpha may prevent transition to chronic hepatitis/cirrhosis.
 ...
PMID:Nonsystemic vasculitic mononeuropathy multiplex, cryoglobulinemia, and hepatitis C. 894 Dec 74

Liver transplantation for cirrhosis caused by hepatitis B virus (HBV) has a poor prognosis. This is primarily a consequence of the near universal reinfection of the allograft, subsequent accelerated hepatic disease while receiving immunosuppression, and a reduced long-term survival. Because interferon-alpha has been shown to have an antiviral effect on HBV, a study was initiated in 1986 to assess the effect of interferon-alpha therapy on the course of liver transplantation in HBV-positive recipients. Twenty-eight patients with decompensated endstage liver disease caused by HBV were treated with 5, 2.5 or 1.25 million units (MU) of human recombinant interferon-alpha 2b (r-IFN-alpha 2b) daily for a minimum of 14 days prior to transplantation and continuing for 42 days post-transplantation. HBV antigens, HBV antibodies, HBV DNA and serum transaminase levels were measured throughout the treatment and post-treatment period. HBV DNA was eliminated in 10 of 19 patients, who survived 3 months or more post-transplantation, and was associated with a significant flare of hepatitis as detected by symptoms and transaminase levels (P < 0.05). Patients who cleared HBV DNA had lower HBV DNA levels (P < 0.05) at entry compared with those who did not. While four of 10 patients with hepatitis B e antigen (HBeAg) converted to hepatitis B e antibody (HBeAb), no surviving patient cleared hepatitis B surface antigen (HBsAg) on a long-term basis. Nonetheless, post-transplant survival was significantly better (P < 0.0001, median follow-up 42 months) in the IFN-alpha treated patients as compared with historical controls, and was similar to that of patients transplanted for all causes of parenchymal liver disease other than HBV cancer. Hence IFN-alpha therapy in the perioperative liver transplantation period improves short-term survival but does not prevent HBV infection of the allograft.
 ...
PMID:Interferon-alpha 2b improves short-term survival in patients transplanted for chronic liver failure caused by hepatitis B. 894 86

Approximately 50% of patients with chronic hepatitis C respond to treatment with interferon-alpha. The aim of this randomized controlled trial was to evaluate whether an increase in dose of interferon-alpha augments response rate. One hundred thirty-eight patients with newly diagnosed chronic hepatitis C received a three-month course of 3 MU IFN-alpha2b administered every two days. All patients were anti-HCV and HCV-RNA (PCR) positive. Prior to treatment, a liver biopsy was performed. Complete response was defined by normal serum ALT concentrations and disappearance of HCV-RNA. After three months, 60 nonresponders were randomized (stratified according to histology) either to continue 3 MU interferon-alpha2b every two days for another six months (group A, total dose: 410 MU) or to receive increasing doses of interferon-alpha2b (6 MU every two days for three months, followed by 10 MU every two days for three months) (group B, total dose: 870 MU). Serum ALT concentrations were measured monthly and HCV-RNA at three-month intervals. Liver biopsy was repeated six months after end of treatment. Pretreatment characteristics of the randomized patients were: group A: N = 30; male/female: 20/10; age: 54 +/- 10 years; CPH 9, CAH 8, cirrhosis 13; mean ALT 108 +/- 98 units/liter; group B: N = 30; male/female: 21/9; age: 57 +/- 15 years; CPH 10, CAH 9, cirrhosis 11; mean ALT 90 +/- 40 units/liter. At the end of treatment six patients in group B but none in group A became responders [P = 0.011 (Fisher's exact test), intent-to-treat analysis]. All six responders were noncirrhotics. High-dose interferon was not tolerated by six patients in group B. Noncompliance resulted in five dropouts in group A and one in group B. During the six-month follow-up, four of the six responders relapsed. A patient in group A with increased serum ALT concentration but negative HCV-RNA at the end of treatment became a full responder after six months. Of nonresponders to 3 MU interferon alpha2b every two days for three months, 20% responded to higher interferon doses, but none to continued standard dose. Prolonged treatment with interferon may be necessary to obtain a sustained response. However, treatment with higher-dose interferon was not tolerated in 20% of the patients.
 ...
PMID:Dose increase augments response rate to interferon-alpha in chronic hepatitis C. 901 66

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Several risk factors for HCC development have been identified, including cirrhosis, hepatitis B virus (HBV) infection, and hepatitis C virus (HCV) infection. With regard to cirrhosis, multivariate analysis indicates that alcohol abuse, HBsAg positivity, and anti-HCV seropositivity are independent variables associated with an increased risk for HCC in the cirrhotic patient. A close relationship between chronic HBV infection and HCC has been established by epidemiological studies and laboratory investigations. Evidence indicates that HCV also plays a leading role in development of HCC. Most patients with HCV-related HCC develop the tumor as a consequence of long-standing infection accompanied by chronic and progressive liver damage. In our study of 290 consecutive patients with cirrhosis, patients with persistently elevated or fluctuating ALT levels had a significantly greater rate of HCC development. The mechanism of HCC development in HCV infection remains to be elucidated. The annual cumulative risk of developing HCC is approximately 1% in patients without cirrhosis at inclusion and 3-10% in those with cirrhosis, depending on the stage of cirrhosis and presence of etiological cofactors. Although some evidence suggests that patients infected with the HCV genotype 1b are at increased risk for development of more severe liver disease, including HCC, results of our prospective study do not support a difference between cirrhotic and noncirrhotic patients in terms of the natural course of cirrhosis and the rate of developing HCC based on genotype. Strategies to prevent HCV-related HCC include blood screening and treatment of chronic HCV infection with interferon-alpha. Recent studies suggest that interferon-alpha treatment may prevent the development of HCC in HCV infection. Further research is warranted.
 ...
PMID:Risk factors and prevention of hepatocellular carcinoma in HCV infection. 901 76

The efficacy of various regimens using interferon-alpha (IFN-alpha) in the treatment of hepatitis C virus (HCV) infection was analyzed in a meta-analysis of 33 randomized clinical trials (RCTs). The results of the meta-analysis showed increased complete and sustained ALT response rates in patients receiving IFN 3 MU three times a week for six months compared with patients receiving placebo or no treatment. The dose effect (6 MU three times a week versus 3 MU three times a week) on complete ALT response rate at the end of treatment was significant, with a mean 10% improvement at both six and 12 months. There also was a significant dose effect on sustained response for 12 months treatment, with a mean 17% improvement. There was a significant treatment duration effect on sustained response rate at 3 MU three times a week and 6 MU three times a week, with a mean improvement of 16% (> or = 12 months vs six months) with 3 MU three times a week. Due to adverse events, we conclude that the best efficacy-risk ratio favors IFN treatment with 3 MU three times a week for at least 12 months. The results of our RCT comparing three IFN regimens showed that patients receiving 3 MU three times a week for up to 18 months exhibited significant improvements in histological activity score, normalization of serum ALT concentrations, and sustained response compared with patients receiving a lower dose or shorter duration of treatment with IFN. Together, these results support the conduct of another RCT to evaluate the hypothesis that long-term, continuous IFN treatment may significantly reduce the incidence of cirrhosis in patients with HCV infection.
 ...
PMID:Treatment of chronic hepatitis C by interferon for longer duration than six months. 901 84

In chronic hepatitis C (HCV), standard interferon therapy with 3 MU three times weekly for 6 months is associated with sustained response in about 10-20% of patients while another 10-15% respond only when higher dosages or/and longer periods of treatment are used. Different variables have been described that are associated with sustained response and may also identify patients requiring low- or high-dose regimens. We have analysed a large data base of 442 patients with chronic hepatitis C treated with interferon-alpha to define rates of sustained response in different patient subgroups treated with different schedules. The rate of sustained response was increased with higher dose regimens in most patient categories, defined according to age, pre-treatment liver histology and HCV genotype, while the amount of interferon per one sustained response remained the same or was reduced. The use of higher dose regimen was particularly cost-effective in patients with cirrhosis. Using the same data base, different models of prediction of sustained response in the individual patient were developed and compared. Inclusion of the HCV genotype in these models was found to increase significantly specificity and sensitivity, confirming that this parameter has a major influence on sustained response to interferon therapy in chronic HCV.
 ...
PMID:Variables that influence response to different interferon schedules in chronic hepatitis C and predictive models. 909 83

To verify its value with regard to the outcome of therapy in chronic hepatitis C, serum interferon-alpha (IFN) was measured by ELISA in 70 patients (43 male, 27 female) with chronic hepatitis C, treated with IFN 9 MU/week subcutaneously for up to one year. Serum IFN was detectable in 49/70 patients, 16 of whom had IFN values >125 pg/ml. Only 1/22 patients who maintained a sustained response six months after the end of treatment had pretreatment serum IFN > 125 pg/ml, in comparison to 15/48 patients who did not respond or who relapsed (chi2 6.1, P < 0.02). At multivariate analysis the predictive value of serum IFN was independent of age, sex, presence of cirrhosis, infection by genotype 1b (improvement chi2 7.1, P < 0.01). In patients with chronic hepatitis C, measurement of serum IFN at baseline might be useful for the selection of patients with higher probability of long-term response.
 ...
PMID:Endogenous interferon-alpha concentration and outcome of interferon treatment in patients with chronic hepatitis C. 912 46

Interferon is indicated in chronic infection by hepatitis C virus (HCV), however, cirrhosis has been reported as a bad response factor to the therapy. Fifteen cirrhotic patients with HCV, undergoing treatment with recombinant interferon-alpha, ribavirin and/or ursodeoxycholic acid were studied. They were followed-up and evaluated with dosages of alanine aminotransferase and HCV RNA investigation by PCR technique. Of the 15 cirrhotic patients, seven were negative for HCV RNA after antiviral treatment, however ALT was normal in only three of them. Of the eight patients who were not negative, two had normal ALT. Biochemical-virological discrepancy in the follow-up of the patients after antiviral treatment observed in this study has also been reported by other authors. These reports show that the criteria for response to the treatment is to be established.
 ...
PMID:Clearance of hepatitis C viral RNA in cirrhotic patients with antiviral therapy. 921 95

Response to interferon-alpha (IFN-alpha) treatment in hepatitis C is poorer when cirrhosis is present. In the third Australian multicentre hepatitis C trial, Aushep-3, we examined the efficacy and tolerability of an intensive 24-week course of interferon-alpha 2a in Child-Pugh grade A patients with chronic hepatitis C and cirrhosis. This was an open uncontrolled trial of 4.5 million units (MU) of IFN-alpha 2a daily for 24 weeks; follow-up was 48 weeks. Chronic hepatitis C and cirrhosis were confirmed histologically. HCV RNA was determined in serum by reverse transcriptase polymerase chain reaction (PCR), and viral genotyping was by line-probe assay. Treatment response was defined as a reduction of alanine aminotransferase (ALT) to less than 1.5 times the upper limit of normal (and by at least 50% of pretreatment values) at weeks 20 and 24. Sustained response was defined as normal serum ALT after treatment from trial week 28 until week 48. Among the 56 patients, a treatment response occurred in 18 (32% by intention-to-treat; 42% of those who completed treatment) and eight (14%) had a sustained response. At 24 weeks, HCV RNA was not detectable in 12 of 17 treatment responders, and remained negative at 48 weeks in six of eight sustained responders. Treatment response by genotype occurred in 75% of patients with HCV type 2, in 38% with HCV type 3a and in 12% with HCV genotype 1. Sustained response occurred in only one (4%) patient with HCV genotype 1 but in five (20%) with genotypes 2 or 3a. Among 13 patients withdrawn, nine were for adverse effects, most often haematological; 10 others underwent dose reduction for adverse effects. It is concluded that a sustained biochemical and viral response to treatment with IFN-alpha 2a can be obtained in some patients with hepatitis C and cirrhosis, particularly those with genotypes 2 or 3a. Therefore, patients with cirrhosis should be considered for interferon treatment on an individual basis. Genotyping may improve case selection, but vigilance is required for haematological complications.
 ...
PMID:Efficacy and tolerance of a 6-month treatment course of daily interferon-alpha 2a for chronic hepatitis C with cirrhosis. The Australian Hepatitis C Study Group. 931 Sep 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>