Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis C virus (HCV) infection is an important cause of chronic hepatitis, cirrhosis, hepatocellular carcinoma and liver failure worldwide. Chronic hepatitis C virus infection is treated with interferon-a (IFN-alpha), pegylated interferon-alpha (PEG-IFNalpha) alone or in combination with ribavirin; however, a significant fraction of patients either fail to respond or relapse after cessation of therapy. Efforts to identify and develop highly specific and potent HCV inhibitors have intensified recently. Each of the virally encoded replication enzymes has been a focus of studies as well as viral receptors and the host immune system. This review summarizes recent progress in the search for novel anti-HCV agents.
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PMID:Existing and future therapeutic options for hepatitis C virus infection. 1582 6

As a leading cause of liver cirrhosis and hepatocellular carcinoma, chronic hepatitis B poses a major health care problem. Currently approved therapeutic options include interferon-alpha, pegylated interferon-alpha, lamivudine and adefovir. Interferon-alpha can induce long-term suppression of viral replication in a proportion of patients. However, treatment is associated with considerable side effects. Lamivudine and adefovir effectively suppress viral replication and induce histological improvement in the majority of patients. However, recurrence rates are high after cessation of treatment. During long-term treatment about 20% lamivudine-resistant mutants emerge annually, while currently available studies suggest that this number is about 3% for adefovir after two years of therapy. Efficacy of the respective antivirals is affected by virological and clinical parameters, thus requiring individual treatment strategies.
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PMID:[Management of chronic hepatitis B]. 1590 Aug 29

Hepatitis C virus infects an estimated 170 million people worldwide. It is a major cause of liver cirrhosis, end-stage liver disease and hepatocellular carcinoma. It is also a leading cause of liver transplant in the USA. The virus is primarily transmitted parenterally, but there is significant mother-to-child transmission. Partly due to the virus's genetic diversity, it evades the host immune response and it has been difficult to identify candidate vaccines. However, significant advances have been made in the treatment of chronic hepatitis C virus infection. Currently, the combination of pegylated interferon-alpha and ribavirin is the standard treatment for chronic hepatitis C virus infection, and leads to long-term eradication of the virus in approximately 54% of people. Treatment response is dependent on the infecting genotype, with 76 to 80% of those with genotypes 2 and 3, but only approximately 40% with genotype 1 or 4 achieving a sustained virologic response. Since treatment is expensive and associated with significant adverse effects, more effective strategies for the prevention of transmission are needed, especially in resource-limited countries, where the burden of disease is the highest.
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PMID:Hepatitis C virus infection: the new global epidemic. 1591 81

Undetectable hepatitis C virus (HCV)-specific RNA in serum six months after the end of treatment is the primary aim of antiviral therapy in patients with chronic hepatitis C. Long-term studies confirmed that viral eradication is durable in more than 95% of cases. The high chronification rate of acute hepatitis C (50 to 80%) justifies therapeutic strategies to prevent a chronic course of the infection. Monotherapy with interferon-alpha for 24 weeks can prevent chronification in more than 90% of patients with acute hepatitis C. Antiviral therapy should be considered in all patients with chronic hepatitis C, who are symptomatic, or have a considerable risk for the development of liver cirrhosis and its sequelae, if they have no contraindication for therapy. Furthermore, treatment should be considered in all patients who carry a substantial risk to infect others. Combination therapy with a pegylated interferon-alpha plus ribavirin is the current standard of care and achieves sustained virologic response rates of 54 to 61%. Patients chronically infected with genotype HCV-1 isolates should be treated for 48 weeks (independent from baseline viral load), while in patients infected with HCV-2 or -3 isolates 24 weeks of treatment are sufficient. Patients without sustained virologic response can still benefit histologically from an interferon-alpha based therapy. Possibly, interferon-alpha also reduces the risk for patients with chronic hepatitis C to develop hepatocellular carcinoma.
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PMID:[Treatment of hepatitis C virus infection]. 1593 83

Hepatitis C is an RNA virus responsible for chronic infection in at least 4 million Americans. Patients are often unaware that they have contracted the virus until the appearance of long-term consequences of the infection, primarily cirrhosis and hepatocellular carcinoma. Many patients with hepatitis C have comorbid psychiatric and/or substance abuse disorders. Treatments for hepatitis C infection are based on interferon-alfa therapy and have shown increasing effectiveness in recent years; however, interferon-alfa therapy also poses significant risks for physical and neuropsychiatric side effects. Since psychiatrists often serve as primary caregivers for patients who are at higher risk for hepatitis C infection, knowledge about the diagnosis, prognosis, and treatment of this disease is needed. In the first half of this article, the authors review the epidemiology, transmission, pathophysiology and disease course of hepatitis C, as well as the neuropsychiatric complications of hepatitis C infection. They also discuss the incidence of comorbid psychiatric disorders in patients with hepatitis C infection and consider the impact of the infection on patients' quality of life. The authors then provide an overview of the clinical management of HCV infection, including screening procedures, decision-making about treatment, available treatments (interferon-alfa, pegylated interferon-alpha, combination therapy with interferon and ribavirin) and their side effects and potential drug-drug interactions, and prediction of treatment response. The authors then discuss management of the neuropsychiatric complications of treatment with interferon-alpha and ribavirin, including depression, mania and psychosis, and cognitive and neurological complications. The final section of the article focuses on special issues related to the treatment of hepatitis C infection in patients with substance abuse or dependence and/or other comorbid psychiatric illness.
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PMID:Comprehensive review of hepatitis C for psychiatrists: risks, screening, diagnosis, treatment, and interferon-based therapy complications. 1598 20

The long-term usefulness of interferon-alpha (IFN-alpha) in chronic hepatitis B remains controversial. To investigate the long-term efficacy of IFN-alpha therapy in chronic hepatitis B, 62 Japanese patients, including 27 patients treated with IFN-alpha (IFN group) and 35 patients without antiviral therapy matched by age and sex as controls (control group), were followed up for 2-14 years. At entry, the serum alanine aminotransferase (ALT) level in the IFN group was significantly higher than that in the control group (238.6+/-250.1 vs. 142.3+/-152.1 IU/l, P < 0.05). The prevalence of genotype C was 89%, with no difference between the two groups (93 vs. 86%). There was no significant difference in the presence of the precore mutation or the dual core promoter mutations between the IFN and control groups (37 vs. 46%, 74 vs. 66%). After long-term follow-up, the rate of sustained HBeAg seroconversion was comparable in the two groups (33 vs. 31%). Normalization of serum ALT level was seen in 44% of the IFN group and 51% of the control group, with no difference. There was also no difference in the percentage of cases with loss of serum HBV-DNA by PCR assay between the two groups (33 vs. 29%). During follow-up, two patients of the control group and three patients of the IFN group developed cirrhosis, and one of the IFN- treated patients progressed to hepatocellular carcinoma. The results of this long-term follow-up study showed that no benefit of IFN-alpha treatment was detectable during long-term follow-up in Japanese patients with chronic hepatitis B.
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PMID:Long-term follow-up of Japanese patients with chronic hepatitis B treated with interferon-alpha. 1601 62

The potential anti-proliferation effect of interferon-alpha (IFN-alpha) against hepatocellular carcinoma (HCC) and its growth inhibitory mechanisms remain unclear. We examined four human HCC cell lines and every cell line had the anti-proliferative effect of IFN-alpha. The PLC/PRF/5 cell line, which expressed the IFN receptor most abundantly, responded most effectively to IFN-alpha stimulation. Here, we delineate the anti-proliferative effect of IFN-alpha via the MAPK pathway in human HCC cell lines. IFN-alpha retarded G1/S transition with no evidence of apoptosis and inhibited cell proliferation. IFN-alpha diminished the phosphorylation of both extracellular signal-regulated kinase (ERK) and mitogen-activated ERK-regulating kinase (MEK), but not Raf, within 5 min. Knockdown of signal transducers of activation and transcription1 (STAT1) or Janus kinase1 (JAK1) suppressed the reduction of phosphorylation both of ERK and MEK and diminished the growth inhibition by IFN-alpha. These results suggest that IFN-alpha induces anti-proliferative signaling via the JAK/STAT pathway downstream of IFN-alpha receptors and may reduce the growth stimulation signaling by cross-talk with the MEK/ERK pathway without IFN-alpha-induced transcription.
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PMID:Rapid inhibition of MAPK signaling and anti-proliferation effect via JAK/STAT signaling by interferon-alpha in hepatocellular carcinoma cell lines. 1605 12

We report a case of hepatocellular carcinoma (HCC) treated successfully by transarterial chemoembolization (TACE) followed by combination therapy of 5-fluorouracil (5-FU) and pegylated interferon-alpha (PEG-IFN-alpha). In the present case, the patient had massive and advanced HCC with a diameter of over 8 cm located in segment 7 (S7) of the liver. Furthermore, the tumor invaded into the major branch of the portal vein (Vp3). After TACE, combined administration of 5-FU and PEG-IFN-alpha was performed for 5 mo. HCC was totally eradicated and the serum levels of tumor markers were markedly decreased by the treatment. Although it has been reported that the combined use of conventional IFN-alpha and 5-FU showed striking effects on HCC in some cases, this case may suggest the more promising effect of PEG-IFN-alpha with a long-lasting effect, in the combined use with 5-FU for the treatment of massive advanced HCC.
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PMID:Successful treatment of advanced hepatocellular carcinoma by combined administration of 5-fluorouracil and pegylated interferon-alpha. 1614 57

Chronic liver disease, including liver cirrhosis and hepatocellular carcinoma (HCC), has been a major cause of mortality in Korea. The prevalence rates of hepatitis C virus (HCV) and hepatitis B virus (HBV) infections in the general population of Korea are approximately 1 and 5%, respectively. The most common genotypes of HCV in Korea are 1b and 2a. The sustained virological response rates after antiviral therapies, including combined interferon-alpha and ribavirin, have been reported to be 38-59%. The annual incidence of HCC among HCV-related liver cirrhosis has been estimated at 5%, and approximately 12% of HCC is attributable to HCV and 68% to HBV in Korea. The mean age of patients with HCV-related HCC at the time of diagnosis was consistently 10 years older than that of patients with HBV-related HCC. Moreover, HCV-related HCC was accompanied by more advanced liver cirrhosis than HBV-related HCC. Coinfection with HBV seemed to increase the risk of developing HCC in chronic HCV infection. After the successful program of hepatitis B vaccination, HCV infection is now emerging as an important etiology of chronic liver disease in Korea, which warrants more detailed and large-scale studies.
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PMID:Current status of hepatitis C virus infection in Korea. 1616 92

Chronic hepatitis B virus (HBV) infection by definition is persistence of hepatitis B surface antigen (HBsAg) in the serum for > or =6 months. The risk of developing chronic HBV infection ranges from 90% in neonates to <5% in immunocompetent adults. HBV acquired by perinatal infection has a prolonged immune-tolerant phase, characterized by the presence of hepatitis Be antigen (HBeAg), high HBV-DNA and normal alanine aminotransferase (ALT) levels. Efficient and multi-specific helper and cytotoxic T-cell response is essential for controlling HBV infection. Chronic HBV infection is characterized by a state of HBV-specific T-cell hyporesponsiveness. The goal of therapy in chronic HBV infection is to eliminate or significantly suppress HBV replication and prevent the progression of liver disease to cirrhosis with the potential development of liver failure or hepatocellular carcinoma (HCC). In adults, drugs currently licensed for treatment of HBV infection: are interferon-alpha (IFN-alpha), lamivudine (LMV) and adefovir dipivoxil (ADV), the first two are also licensed to use in children. IFN-alpha has the advantage of having a more durable response, fixed duration of treatment and lack of resistant mutants. The disadvantages of IFN-alpha include need for thrice-weekly injections, higher cost and more side-effects compared with the nucleoside analogues. Nucleoside analogues can be given orally and used in decompensated cirrhosis and transplant recipients. ADV and newer drugs like tenefovir can successfully treat mutants produced after prolonged LMV therapy. Current protocols exclude children with immunotolerant HBV. Periodic screening with liver ultrasound scan and alpha-fetoprotein (AFP) in all children with chronic HBV infection is recommended. The severe shortage of cadaveric donor organs has led to the use of marginal (including anti-HBc-positive) cadaveric donor livers in selected transplant candidates with high medical urgency; 5-10% of all liver transplants are because of HBV. Using hepatitis B immunoglobulin and nucleoside analogues has made the outcome following liver transplantation for hepatitis B, comparable with, if not slightly better, than that in patients with other diagnoses. Future treatments should be based on the restoration of HBV-specific T-cell responses to levels similar to that seen in subjects controlling HBV.
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PMID:Hepatitis B in children: complexities in management. 1617 31


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