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)

Clinical and experimental data show that beta-IFN enhances the effect of tamoxifen on advanced breast cancer. There is a similarity between breast and liver as far as the proliferating effect on normal and neoplastic tissue of estrogen and progestin receptors is concerned. The authors tested this pharmacological association in unresectable liver neoplasms. They considered 76 (not randomized) patients affected with HCC; 38 were treated by trans-arterial chemoembolization (TACE) and 38 to beta-INF and tamoxifen (the 2 groups were comparable according to age, sex, Child-Pugh score, Okuda and TNM stages, cirrhosis etiology). The treatment response (positive when a tumor diameter decreased or stabilization was observed) was similar in the two groups; in the TACE group, the presence of a peritumoral capsula had a significant influence on survival (p < 0.02); on the other hand, in the patients treated with beta-INF and tamoxifen important factors for a better prognosis were the TNM stage (I and II, p < 0.02) and a symptom-free condition (p < 0.04). The authors believe the beta-INF and tamoxifen treatment could represent an effective alternative in the management of unresectable HCC. A better knowledge of the presence and meaning of estrogen and progestin receptors in the neoplastic tissue may allow a better selection of patients.
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PMID:[The palliative treatment of hepatocarcinoma: chemoembolization vs. the combination of tamoxifen plus beta-interferon]. 751 97

To evaluate the effect of interferon alfa (IFN-alpha) on the hepatic extracellular matrix, we investigated the changes in serum N-terminal propeptide of type III procollagen during and after 4 months of INF-alpha treatment in 178 treated and 45 nontreated patients with chronic hepatitis C. Serum pretreatment levels in nonresponders were significantly higher than those in long-term and short-term responders, but those levels were not different in the latter two groups. Serum propeptide levels decreased significantly during and after IFN-alpha therapy in the treated patients, although those levels were unchanged in the nontreated patients. This decrease was sustained for 12 months after IFN-alpha was completed not only in long-but also in short-term responders and nonresponders. Serum propeptide levels decreased in those with elevated pretreatment levels, but not in those with normal initial levels, whereas serum transaminase levels decreased similarly in both groups. The changes in serum propeptide levels during and after treatment were more closely correlated with the initial levels compared with those in serum transaminase levels. These results suggested that IFN-alpha treatment induces the long-term suppression of active fibrogenesis in chronic hepatitis C independent of antiviral and anti-necroinflammatory effects, thus preventing progression to cirrhosis.
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PMID:Long-term decrease in serum N-terminal propeptide of type III procollagen in patients with chronic hepatitis C treated with interferon alfa. 763 9

To analyse the incidence and risk factors of clinical rebound and hepatic decompensation during or upon withdrawal of prednisolone pretreatment before interferon (IFN) therapy, two series of Taiwanese patients with chronic viral hepatitis from two independent randomized controlled trails were compared. Group 1 included 41 patients with chronic hepatitis B who were pretreated with daily prednisolone (30 mg) for 3 weeks, 15 mg for 1 week and no prednisolone for 2 weeks prior to lymphoblastoid IFN therapy. Group 2 consisted of 59 patients with chronic hepatitis B who were pretreated with daily prednisolone (40 mg) for 2 weeks, 30 mg prednisolone for 2 weeks, 20 mg prednisolone for 2 weeks and no prednisolone for 2 weeks prior to INF alpha-2a therapy. Clinical rebound developed more frequently in group 2 (67.8%) than in group 1 patients (41.5%; P < 0.01). The peak serum transaminase levels of group 1 and 2 patients during clinical rebound were similar. Icteric and symptomatic clinical rebound occurred in four (one cirrhotic) group 2 patients. The incidence of hepatic decompensation was 3.4% in group 2 patients, or 5.0% in group 2 patients with clinical rebound. Patients pretreated with a higher dose (40 mg) of prednisolone (odds ratio 3.0; 95% CI 1.3-6.6; P < 0.01) and non-cirrhotic patients (odds ratio 6.2; 95% CI 1.2-32.1; P < 0.02) tended to suffer from clinical rebound more frequently. However, once clinical rebound develops in cirrhotic patients, the relative risk of decompensation is 16 times that of non-cirrhotic patients. These results suggest that clinicians should be cautious in prescribing a short course of corticosteroids for patients with chronic viral hepatitis, because hepatic decompensation might occur in Oriental people with or without cirrhosis.
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PMID:Severe clinical rebound upon withdrawal of corticosteroid before interferon therapy: incidence and risk factors. 867 59

The inducible nitric oxide synthase (iNOS) gene is expressed by hepatocytes in a number of physiologic and pathophysiologic conditions affecting the liver including septic and hemorrhagic shock. The molecular regulation of iNOS expression is complex and occurs at multiple levels in the gene expression pathway. The cytokines TNF-alpha, IL-1beta, and INF-gamma synergistically activate iNOS expression in the liver, and the human iNOS gene was first cloned from cytokine-stimulated hepatocytes. iNOS expression requires the transcription factor NF-kappaB and is down-regulated by steroids, TGF-beta, the heat shock response, p53, and nitric oxide (NO) itself. In vivo, hepatic iNOS induction is differentially regulated from the typical acute-phase reactants and is not expressed as a mandatory component of the acute phase response. Thus, numerous mechanisms have evolved to regulate iNOS expression during hepatocellular injury. Studies of the effects of NO in the liver demonstrate that induced NO synthesis plays an important role in hepatocyte function and protects the liver during sepsis and ischemia reperfusion. Its cytoprotective role is best exemplified in a rodent model of endotoxemia. Here the addition of the nonspecific NOS inhibitors significantly increased hepatic damage. NO exerts a protective effect through its ability to prevent intravascular thrombosis by inhibiting platelet adhesion and neutralizing toxic oxygen radicals. NO also exerts a protective effects both in vivo and in vitro by blocking TNF-alpha-induced apoptosis and hepatotoxicity, in part by a thiol-dependent inhibition of caspase-3-like protease activity. These studies demonstrate the cytoprotective effects of NO in the liver and suggest hepatic iNOS expression functions as an adaptive response to minimize inflammatory injury. In addition, NO has anti-tumor effects as well as known mutagenic effects, is involved in the systemic vasodilatation of cirrhosis, and has potent antimicrobial properties.
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PMID:Inducible nitric oxide synthase in the liver: regulation and function. 972 29

The health care burden caused by hepatitis C is projected to increase significantly in the next 20 years, on the basis of modeling estimates of cirrhosis, hepatic decompensation, and HCC likely to be seen in this population in the future. The number of cases of HCV-induced liver decompensation and mortality in the United States is projected to be approximately 4 times higher by the year 2018 than is currently seen, because of the aging of those presently infected. HCV also poses a significant quality-of-life decrement in the majority of individuals with chronic infection. Quality-of-life assessment in these patients has shown substantial reductions in both somatic and physical functioning compared with the general population, regardless of disease severity. The impact of chronic HCV on quality-of-life issues has been equated to that of non-insulin-dependent diabetes. Thus, HCV imparts a considerable toll on individual level of functioning and on overall health care resources. Hepatitis C evolves into a chronic infection in approximately 85% of individuals exposed to the virus, and progression to cirrhosis occurs in 20% to 30% of patients, with a disease duration up to 20 years. Hepatic decompensation will occur in approximately 20% and HCC in about 10% of those with HCV-related cirrhosis within 5 years of the determination of cirrhosis. End-stage liver disease caused by HCV is now the most common indication for liver transplantation in this country. Patients in whom liver decompensation develops should be considered for liver transplant evaluation, with referral to appropriate centers if these complications arise. Individuals with decompensated disease should not be treated with any of the current regimens available for HCV eradication, because these agents can accelerate hepatic dysfunction and will not mitigate the clinical outcome after the onset of decompensation. Available treatment options for HCV are rapidly changing, with INF as the standard and combination therapy with INF plus ribavirin rising to prominence as the optimal option. The need for abstinence from alcohol cannot be underestimated, given its documented synergistic effects on hepatotoxicity when combined with chronic HCV. Patients must be counseled in this regard and provided with the rationale for this recommendation. The benefits of therapy from a medical resource standpoint have recently been defined through analyses of cost-effectiveness. Bennett et al. used a mathematical model to estimate the cost-effectiveness of INF in the treatment of mild chronic HCV (no bridging fibrosis or cirrhosis). Therapy was found to be cost-saving for patients aged 20 to 35 years and was found to increase life expectancy by 3 and 1.5 years, respectively, at the spectrums of this age range. Kim et al. found the cost-effectiveness of a 12-month course of INF to compare favorably to other accepted medical interventions in the United States in patients younger than 60 years. Similar data for combination therapy has not yet been reported but would be expected to be comparable. Interferon monotherapy for 12 months is the current standard treatment recommendation for individuals with chronic HCV and elevated ALT levels. The explosive expansion of information now available to, and frequently quoted by, HCV patients seeking treatment will increasingly make this option less acceptable to a great many of this group. Combination therapy has emerged as the most efficacious option to date, both as initial treatment and for patients who relapse after standard INF. Unless data appear to the contrary, combination therapy should be considered first-line treatment in these groups. A suggested treatment algorithm for chronic HCV is outlined in Figure 2. Patients intolerant to ribavirin should be considered for continuation of INF to complete a 12-month course, dependent upon the assessment of HCV PCR status at week 12 of therapy. (ABSTRACT TRUNCATED)
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PMID:Advances in the treatment of hepatitis C. 1063 46

Liver cirrhosis main related to hepatitis C virus constitutes the main indication of liver transplantation in Europe and the USA, representing as many as 50% of the indications in adults, while cirrhosis associated with hepatitis B virus represents around 10%. The indications for transplantation in patients with infection by both viruses are fulminant hepatitis, decompensated cirrhosis and hepatocellular carcinoma. Both injections may relapse after transplantation. The evolution of the relapse in the graft is variable and can include non-significant alterations of the liver junction tests, chronic active hepatitis and cirrhosis. Less frequently, a particularly severe form called "fibrosing cholestatic hepatitis" can develop, which rapidly evolve to graft failure. The immunoglobin against the B virus and lamivudine reduce the risk of reinfection. The principal factor associated with reinfection is active viral replication before the transplantation, thus it is considered a contraindication for liver transplantation. INF-alpha has been used in the treatment of hepatitis B virus reinfection with discouraging results. More recently, lamivudine and adefovir have been used. Post-transplantation recurrence of hepatitis C is universal and its evolution towards cirrhosis is more rapid than in immunocompetent patients, with graft dysfunction being the most frequent cause of mortality and of indication for retransplantation. Different factors have been related to the severity of the recurrence including factors related to the donor, the recipient, the virus, immunosuppression and surgery. There are no preventive treatments against recurrence of post-transplantation hepatitis C. In the treatment of the hepatitis C virus recurrence, INF-alpha and rivabirin have been used in single form or in combination with variable results, with the combined therapy being more effective. Recently, encouraging results have been described with the combination of pegylated interferon and rivabirin without a higher incidence of rejection. Finally, the results of retransplantation in patients with recurrent hepatitis B or C have not been encouraging.
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PMID:[Liver transplantation in patients with cirrhosis secondary to hepatitis B virus and hepatitis C virus infections]. 1538 47

Suppressor of cytokine signaling (SOCS) is a new family of proteins produced in cells. It may play an important role in classic negative feedback loop to regulate cytokine signal transduction. SOCS-1 was observed and confirmed firstly. Expression of SOCS-1 can inhibit cytokine signal transduction of some cytokines, such as IL-6, LIF, OSM, INF-gamma, GH, and so on, many immune responses are regulated by them in vivo. Abnormal expression of SOCS-1 is closely related to some human diseases. It plays an important role in the development of leukemia, rheumatoid arthritis, liver cirrhosis and liver cancer. In this review, the advances of research on the relationship between SOCS-1 and cytokine, and its correlation with some diseases were summarized.
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PMID:[Progress of study on suppressor of cytokine signaling-1 - review]. 1749 65

Since 2004, pegylated interferon (P-IFN) in combination with ribavirin has become the optimal choice of therapy for chronic hepatitis C virus (HCV) infection. IFN a-2b suppresses HCV replication and restores elevated serum aminotransferase levels, leading to improvements in the histological changes in the livers of patients with chronic hepatitis C. Unfortunately, P-IFN has several adverse effects, including pneumonitis. This complication has been reported in the treatment of malignant diseases and CHC. We report a patient with interstitial pneumonitis thought to be caused by an IFN-based treatment in an unusual scenario of a patient with HCV-related Child-Pugh stage A cirrhosis, who experienced dyspnea, fever, and cough after 12 months of treatment with P-IFN a-2b. Her lung injury and pulmonary symptoms did not disappear despite discontinuation of IFN and the administration of corticosteroid. We concluded that the patient developed a fatal interstitial pneumonitis associated with P-INF a-2b therapy.
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PMID:Interstitial pneumonitis associated with pegylated interferon alpha-2b therapy for chronic hepatitis C: case report. 1837 74

Recurrent hepatitis C after liver transplantation is universal. Graft reinfection occurs rapidly, with chronic hepatitis and rapid evolution from end-stage liver disease. Within 5 years until 30% of patients with recurrent disease ultimately progress to cirrhosis, and survival of transplanted patients with recurrent hepatitis C virus has been shown to be lower than of patients transplanted for other indications. Antiviral therapy in this patient population is generally recommended, but indication, optimal timing, dose and duration of therapy are not clearly defined. There are two major indications of therapy in that patients: pre-transplant antiviral therapy aiming to prevent reinfection, and post-transplant therapy with the goal of eradicating the recurrent infection. The first is limited by poor tolerance and drug side effects, and the second achieves only sustained virologic response in 25-45% of patients. Combination therapy with PEG INF and ribavirin showed the better results. Dose reduction and interruption of therapy occurs in 30 to 60% by side effects. There are no prospective randomized trials with confidence of results. More efficacious and better tolerable antiviral therapies are needed.
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PMID:Treatment of recurrent hepatitis C post-liver transplantation. 2071 2

The characteristics and response rate to pegylated interferon and ribavirin (PEG-INF + RBV) of patients with chronic hepatitis C infected with genotype 5 are poorly documented. A meta-analysis of two large phase III/IV prospective randomized clinical trials conducted in Belgium in patients with chronic hepatitis C (n = 1,073 patients) was performed in order to compare the response to antiviral therapy of hepatitis C virus (HCV) genotype 5 with that of other HCV genotypes. A subset of HCV-1 infected patients selected from within the study database were selected to match the HCV-5 sample for known prognostic factors. In Belgium HCV-5 is responsible for a significant minority of cases of chronic hepatitis C CHC (4.5%) and is characterized by a more advanced age (58.4 years), a high frequency of cirrhosis (27.7%), a specific mode of HCV acquisition, and a particular geographic origin (66.7% of patients from West Flanders). The primary comparative analysis showed that response to treatment with PEG-INF + RBV of HCV-5 is similar to HCV-1 and lower compared to HCV-2/3. The analysis of the matched patient subgroup demonstrates that the HCV-5 "intrinsic sensitivity" to PEG-IFN + RBV therapy is identical to HCV-1, with a sustained virological response of 55% in both groups. In contrast to previous publications, this meta-analysis suggests that HCV-5 response to treatment is closer to HCV-1 than to HCV-2/3 and suggests that in Belgium HCV-5 infection should be treated with the same antiviral regimen as HCV-1.
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PMID:Efficacy of interferon-based antiviral therapy in patients with chronic hepatitis C infected with genotype 5: a meta-analysis of two large prospective clinical trials. 2141 90


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