Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Viral hepatitis features with an incidence of 500 Mio infected individuals worldwide. Chronification of the infection as seen in hepatitis C, B, and D may lead to liver cirrhosis and its associated complications in later stages of the disease. Especially the chronification of acute hepatitis C is observed in a majority of cases (50-80%). Chronic Hepatitis C (cHC) should be treated in generally when elevated serum concentrations of liver enzymes are found or symptoms of disease occur. Treatment goals are viral elimination, improve in histology, prevention of HCC, and a better quality of life for the patients. As HCV and HIV share the same transmission routes, a relatively high rate of HCV-HIV co-infection is observed. Co-infection is characterized by a more progressive natural course of HCV-infection, leading to an increased mortality due to liver failure in the afflicted patients. The development of treatment options for anti-HCV-specific therapy in dually infected patients is urgently needed. The European Conference on Infectious Diseases and Tropical Medicine, EuCID 2001, which took place in May 3-6, 2001, in Leipzig covered aspects of viral hepatitis and its treatment in several sessions and gave latest results on treatment with interferon-alfa, lamivudine, and adefovir in hepatitis B as well as interferon-alfa, pegylated interferon-alfa, and ribavirin in hepatitis C and HCV-HIV co-infection respectively.
 ...
PMID:Therapy of chronic hepatitis B and C and treatment options in HCV-HIV co-infection--European Conference on Infectious Diseases and Tropical Medicine, EuCID 2001, 3-6 May 2001, Leipzig. 1143 99

The annual rate of progression to cirrhosis in patients with chronic HBV is 0.4 to 14.2% and that of death 4 to 10%. HCC risk increases in parallel with the severity and duration of infection, with an annual incidence less than 0.5% in carriers and 6% in patients with cirrhosis. The main aim of antiviral therapy for chronic "wild-type" HBV infection is to suppress viral replication before cirrhosis and HCC develop. Two drugs are approved: IFN alpha and lamivudine. IFN alpha is costly, has a narrow range of efficacy, safety, and tolerability. Lamivudine is active, cheaper, and better tolerated but has limited efficacy, being associated with increasing resistance and loss of clinical response in the long term. IFN may be the first choice treatment in HBeAg-positive patients with a favourable profile and compensated liver disease. Patients with HBeAg-negative active disease can benefit from 12-24 months IFN treatment if early response is observed. Lamivudine should be started only after considering the uncertainties about duration of therapy and risks of stopping it. In patients with slowly progressive liver disease, treatment is better postponed until effective combination regimens are available. Lamivudine is of paramount importance in end-stage chronic liver disease to suppress HBV replication and allow successful transplantation. The role of interferon in preventing HCC is controversial. In two studies comparing the incidence of HCC in patients with HBeAg-negative chronic hepatitis treated with IFN, HCC developed less frequently in sustained responders than in non-responders in Greece (2 vs. 10%, P = 0.045), but not in Milan (7 vs. 10%, P = ns).
 ...
PMID:Recent progress and new trends in the treatment of hepatitis B. 1211 46

Although controversy persists about the influence of cirrhosis on the incidence of portal vein invasion and other prognostic indicators of recurrence and survival (e.g., histologic grade, mitotic activity, multiplicity), it is clear that the degree of cirrhosis is important for the long-term survival of patients with HCC. Multicentricity is especially important because it reflects the field carcinogenesis associated with viral hepatitis and particularly chronic HCV infection [59]. A better understanding of the different mechanisms linked to tumor recurrence will help select the best candidates for curative surgery and help tailor adjuvant therapy, such as interferon therapy, to each patient [60]. Finally, the importance of vascular invasion, number of tumors, and tumor size of HCCs in addition to the effect of fibrosis has led Vauthey et al [20] to propose a simplified staging of HCC with better prognostication of survival.
 ...
PMID:Pathologic spectrum and prognostic significance of underlying liver disease in hepatocellular carcinoma. 1273 26

The quasispecies nature of hepatitis C virus (HCV) is thought to play a central role in modulating viral functions. Recent work has linked NS5A protein with viral replication, resistance to interferon (IFN), and control of cellular growth, probably through the interaction of its protein kinase R (double stranded RNA-activated protein kinase, PKR) binding domain (PKR-bd) with cellular PKR, but knowledge of how PKR-bd viral population evolves during disease progression is limited. Since we have previously described an association between amino acid composition of the PKR-bd and the presence of HCC, in this report we further investigated the dynamic behavior of viral population parameters by sequencing an average of 20 clones per sample in 27 samples from 19 untreated patients with different degrees of liver disease, 8 of whom were followed over time. Viral population parameters varied widely from patient to patient, but no differences were observed in the complexity, diversity, types of nucleotide changes, or evolutionary pattern of the quasispecies according to the stage of liver disease. In five samples, we detected "quasispecies-tails"; that is, clones whose minimum genetic distance to the remaining clones of their own quasispecies were higher than the maximum genetic distance found between any other two clones of the same sample. In summary, independent of the degree of liver disease, or the mutations detected within the consensus sequence of the PKR-bd, the NS5A of HCV presents a flexible and variable quasispecies structure that remains largely stable during the natural course of an HCV infection, highlighting the central role of NS5A protein in viral life cycle.
 ...
PMID:Characterization and evolution of NS5A quasispecies of hepatitis C virus genotype 1b in patients with different stages of liver disease. 1293 93

Hepatocellular carcinoma, a common malignancy globally, has been increasing in incidence in the United States, mostly due to the rising incidence of Hepatitis C viral (HCV) infection. The prognosis of patients with this cancer has been poor and even tumor resection has rarely been curative. However, orthotopic liver transplantation (OLT) has been associated with long-term survival benefit and cures, provided rigorous patient-selection criteria were adhered to. Liver cirrhosis is the most common precursor for HCC, and attempts have been made to prevent the progression from liver cirrhosis to HCC. Post resection adjuvant therapies have included interferon, polyprenoic acid, and adoptive immunotherapy. Finding effective systemic treatments for non-resectable HCC has been challenging and quite frustrating. The presence of liver cirrhosis and the associated volume expansion, electrolyte imbalances, decreased liver synthetic and metabolic reserve, and portal hypertension has made the design of systemic therapy for HCC a major challenge. Additionally staging of HCC using the Tumor Node Metastases (TNM) system, but ignoring the underlying liver disease made it extremely difficult to compare results of different trials. However by and large it would seem, that the more aggressive chemotherapy agents and combinations were associated with median survival times of 3-5 months. Considering the vascular nature of HCC it may be reasonable to combine tolerable chemotherapy with newly released agents with angiogenesis inhibiting properties. Thus, systemic therapy of HCC is a work in progress that calls for additional trials of tolerable newer agents and combinations.
 ...
PMID:Novel systemic therapy options for hepatocellular carcinoma. 1513 Feb 69

Hepatitis C virus chronic infection is currently the most common cause of end-stage liver disease. The benefit of antiviral therapy on liver histology and its impact on the long-term course of the disease has been extensively studied. However, the results are still equivocal and the overall assessment of treatment effect remains difficult to evaluate. Although the conclusions of the last National Institute of Health Consensus Development Conferences on Hepatitis C have recently been published, several important issues still remain unanswered. We review the available data by an evidence-based approach and conclude that: 1) peginterferon alfa is more effective than conventional interferon in improving liver histology; 2) monotherapy with PEG-interferon induces a marked reduction in staging in virological sustained responders and to a lesser degree in relapsers, but provides no benefit to nonresponders after 24-48 weeks of treatment; 3) maintenance therapy aiming to improve histology in virological nonresponders should be considered experimental and of unproven benefit; 4) although the reduction in the number of events in sustained responders suggests a long-term benefit of IFN therapy, available evidence is still insufficient to confirm that IFN prolongs life in HCV infected patients. Data of the long-term benefit of subjects treated with IFN plus ribavirin are still not available; 5) pooling of published data suggests a slight preventive effect of IFN on HCC development in patients with HCV-related cirrhosis. The magnitude of this effect is low and the observed benefit might be due to spurious associations. The preventive effect is more evident among sustained responders to interferon.
 ...
PMID:The impact of antiviral treatments on the course of chronic hepatitis C: an evidence-based approach. 1527 51

Although low-grade elevations of AFP are associated with benign liver disease including acute and chronic hepatitis and cirrhosis, AFP values above 400 ng/mL are often used as a surrogate marker for HCC. The case of a 45-year-old Caucasian woman, who while receiving interferon therapy for HCV, was found to have a marked elevation of her serum AFP level, is reported. Her baseline AFP of 7.0 ng/mL increased progressively over three months to a peak value of 734.5 ng/mL. Initial imaging was normal. Three months later, a CT scan detected two focal lesions in the dome of the liver. A post-ethiodol hepatic CT scan revealed persistent uptake at this site but fluoroscopy-guided liver biopsy failed to identify a HCC. Normalization of her AFP level occurred while she continued to receive IFN for HCV. The patient has remained stable over more than three years of follow-up. While others have reported AFP elevations in cirrhotics with HCV without evidence of HCC, to our knowledge there are no reports of an individual receiving IFN treatment for hepatitis C with AFP levels that rose over several months in the absence of a HCC.
 ...
PMID:Markedly elevated alpha-fetoprotein levels without hepatocellular carcinoma. 1553 3

Sodium butyrate is a short-chain fatty acid produced by fermentation in the gastrointestinal tract. It induces differentiation of several kinds of cancer by inhibiting histone deacetylase activity. We have reported that butyrate stimulates hepatocellular carcinoma cells into their normal phenotype. Since sodium butyrate affects both differentiation and apoptosis, we investigated expression of bcl-2-related genes in a human hepatocellular carcinoma cell line HCC-T. The expression of anti-apoptotic Bcl-2 and Mcl-1/EAT was up-regulated 4 h after the treatment, while pro-apoptotic Bax expression did not change. Gene expressions in the early stage of butyrate-stimulation were investigated by the differential display assay and the cDNA expression array. Laminin and keratin 18 were increased 6 h after the stimulation with sodium butyrate. The results of cDNA expression array revealed up-regulation of cell cycle inhibitory genes such as cyclin-dependent kinase 4 inhibitor, and interferon-related genes such as STAT2 and 3, while down-regulation of cyclin-dependent kinase 2 and cyclin E. Up-regulated production of p21WAF-1 and Mcl-1/EAT was also confirmed by Western blotting. The cytoskeletal change indicated by up-regulation of laminin and keratin 18 may be an important factor in the decrease in malignant phenotype of cancer cells. Up-regulation of interferon-related genes indicated that butyrate-treatment might induce a similar phenotypic change to that induced by type 1 interferons. This study suggests several target genes for the future gene therapy of cancer or genes preventing cancer development from pre-malignant tissues.
 ...
PMID:Gene expression associated with the decrease in malignant phenotype of human liver cancer cells following stimulation with a histone deacetylase inhibitor. 1558 45

Lack of effective treatment for surgically unresectable hepatocellular carcinoma has made this disease dismal. Although, systemic and/or locoregional chemotherapy and chemo-embolization are among the established treatment options, the results of these modalities are still far from being satisfactory. Systemic interferon administration is also used for the treatment of this disease however it has high toxicity rates. We conducted a pharmacology guided phase I/II study with the aim to explore the effect of hypoxy and interferon alpha-2a in vitro using the HepG2 Hepatoma cell line. We then translated the in-vitro results to the clinical setting and designed a treatment protocol. This schema consisted of lipiodol embolisation via a hepatic artery port in between two sets of seven loco-regional injections of IFNalpha-2a, 3 MU every other day. The in-vitro study revealed the best sequence of hypoxy and IFN as IFN-Hypoxy-IFN. Based on this finding, ten patients with HCC were treated with loco-regional IFN and lipiodolisation. Seven of them achieved partial response and the mean duration of response was 10 months. There was no Grade 4 toxicity. In conclusion, our preliminary clinical results suggest that the combined use of IFN and lipiodolisation in the optimal sequence may provide a new therapeutic option for patients with HCC.
 ...
PMID:Bioembolisation for unresectable hepatocellular carcinoma: preliminary results of a translational research study. 1559 28

One hundred and twenty-one chronic hepatitis C patients were administered interferon (IFN) and divided into two groups: 31 complete responders (CR) with prolonged HCV-RNA negative 1 year after treatment and 90 non-complete responders (non-CR), including partial responders (PR) with transiently negative HCV-RNA and non-responders (NR) with continuously positive HCV-RNA. Liver biopsy specimens were classified into four grades and stages according to the degree of severity and the extent of fibrosis, respectively. No correlation was observed between the rate of IFN efficacy and grading. By staging, however, a difference in the efficacy of IFN was observed between F1 or F2 and F3 (0.05 < p < 0.1 and 0.01 < p < 0.025, respectively). Of the CR, 0% (0/5) were at F0 and 27.9% (24/86) at F1, 42.9% (6/14) at F2, and 6.3% (1/16) at F3. Another group of 118 chronic hepatitis patients (31 CR, 41 PR and 46 NR) followed up for over 2 years after IFN treatment were analyzed. By staging, 7 cases were at F0, 76 at F1, 18 at F2, and 17 at F3. HCC occurred in 1 of the 31 CR cases (representing an annual incidence rate of 1.21%), in 4 of the 41 PR cases (4.08%), and in 4 of the 46 NR cases (3.55%). HCC did not occur in any of the 7 cases at F0 (representing an annual incidence rate of 0%); it occurred in 2 of the 76 cases at F1 (1.01%), in 1 of the 18 cases at F2 (2.28%), and in 6 of the 17 cases at F3 (16.57%). These results suggest that the new classification would be conducive to roughly predicting the efficacy of IFN treatment and the occurrence of HCC after IFN treatment.
 ...
PMID:Prediction of efficacy of interferon treatment of chronic hepatitis C and occurrence of HCC after interferon treatment by a new classification. 1578 90


<< Previous 1 2 3 4 5 6 7 Next >>