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)

Patients who are chronically infected with the hepatitis B virus are at an increased risk of developing cirrhosis, hepatic decompensation and hepatocellular carcinoma. Therapeutic intervention offers the only means of interrupting this progression. Currently there are three licensed agents for the treatment of chronic hepatitis B virus infection. These are interferon-alpha, an immunomodulator, and two synthetic nucleos(t)ide analogs, namely lamivudine (Epivir, GlaxoSmithKline) and adefovir dipivoxil (Hepsera, Gilead Sciences). This review aims to summarize current experience with these drugs in the treatment and management of patients with chronic hepatitis B virus infection, their efficacy, and current problems of drug resistance. An outline of future treatment perspectives is also included.
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PMID:Current therapies for chronic hepatitis B virus infection. 1548 37

To investigate the effect of biochemical modulation on antitumor activity shown by the combination of 5-Fluorouracil (5-FU) and interferon-alpha (IFN-alpha), experimental therapy was performed on human hepatocellular carcinoma cell (HuH7, PLC/PLF/5) xenografts inoculated into nude mice, using 5-FU and IFN-alpha, either alone or in combination. These agents showed antitumor activity in different degrees. Although IFN-alpha, given as 100,000 units/mouse/3 times/week subcutaneously x 6, and 5-FU, given as 0.5 mg/mouse/3 times/week intraperitoneally, showed addititive antitumor effect against HuH7 and PLC/PLF/5, the activities of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), orotate phosphoribosyltransferase (OPRT), uridine phosphorylase (UP) and uridine kinase (UK) were not significantly influenced in the tumors treated with the 5-FU/IFN-alpha combination, compared with those treated with 5-FU or IFN-alpha alone. This suggested that antitumor activity of 5-FU and IFN-alpha in combination was not significantly involved in 5-FU metabolism in two human hepatocellular carcinoma cell lines examined.
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PMID:[Influence on 5-fluorouracil metabolism by combination of interferon-alpha and 5-fluorouracil against human hepatocellular carcinoma xenografts]. 1550 42

Persistent infection with the hepatitis B virus (HBV) represents a major health problem worldwide with over 350 million patients at risk of developing liver cirrhosis or hepatocellular carcinoma. HBV is a small, partially double-stranded DNA virus with four overlapping genes and a unique life cycle, creating an intracellular pool of covalently closed circular DNA molecules for persistence and an RNA template for replication via reverse transcription. Mutations occur frequently, and particular selection pressures, both endogenous (host immune clearance) and exogenous (vaccines and antivirals), readily select escape mutants. For example, HBeAg-negative chronic HBV infection with either basal core promoter or precore mutations is predominant in many parts of the world. Therapy of HBV infection with the nucleoside analogue lamivudine frequently leads to the selection of drug-resistant strains with polymerase mutations. Treatment options for chronic HBV infection include at present either interferon-alpha or the oral nucleos(t)ide analogues lamivudine or adefovir. However, these drugs have drawbacks, including possible serious side effects and low response rates in HBeAg-negative patients in the case of interferon or recurrence of viremia after cessation of therapy and development of escape mutants after a long period of treatment with nucleoside inhibitors. Recent advances of in vitro and in vivo models allow to study new antiviral strategies, including novel nucleoside analogues, nucleocapsid inhibitors or small interfering RNA. This review summarises the impact of clinically relevant mutations in the HBV genome on viral replication and drug sensitivity, the current status of therapy and promising future perspectives on novel drug regimens.
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PMID:Influence of mutations in the hepatitis B virus genome on virus replication and drug resistance--implications for novel antiviral strategies. 1554 68

We report a case of diffuse type advanced hepatocellular carcinoma (HCC), which was successfully treated by a combination therapy of interferon-alpha (IFN) and 5-fluorouracil (5-FU). A 74-year-old man underwent distal gastrectomy 6 years ago for gastric cancer. In April 2002, an increased serum alpha-feto-protein (AFP) level was noted and a computed tomography (CT) of the abdomen revealed a diffuse type of HCC. He was treated with a combination therapy of IFN (5x10(6) units/body i.m., days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26) and 5-FU (500 mg/body/day i.a., days 1-5, 8-12 continuously). The treatment was repeated every 4 weeks with a maximum of five cycles. After 5 cycles, serum AFP levels fell from 665 ng/ml to a normal level. CT showed a reduced size of the tumor. He has been well and continue to receive IFN (3x10(6) units/body i.m., two times a week) and 5-FU (500 mg/body/day i.a., once a week) at the outpatient clinic for the last 16 months.
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PMID:[Intrahepatic arterial chemotherapy with 5-fluorouracil and intramuscular interferon-alpha for a patient with diffuse type of hepatocellular carcinoma]. 1555 25

A 52-year-old male was admitted to our hospital with huge hepatoma of the right lobe. He underwent a right lobectomy of the liver in July 1999. After five months from the surgery, multiple recurrences in the liver and lung were revealed with Computed tomography (CT). TAE was performed for intrahepatic recurrence and a combination therapy, consisting of UFT and interferon-alpha, was started for pulmonary metastasis. Then 5-FU/CDDP/interferon-alpha therapy was given in 2001 and TS-1/interferon-beta therapy was given thereafter in 2002. Consequently, the patient survived for 31 months with no disturbance in quality of life. No intrahepatic recurrence was also detected during the survival period. It was suggested that a good prognosis may be expected, even in the HCC case with distant metastasis after hepatic resection, if the primary cite was curatively treated.
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PMID:[A case of long-term survivor with multiple pulmonary metastases of HCC after hepatic resection]. 1555 66

Hepatitis B virus (HBV) infection is an important health problem. It's believed that there are now at least 400 million carriers of HBV in the world. Infants born to HBeAg-positive carrier mothers have a 60% to 90% chance of contracting chronic hepatitis B infection and of possible subsequent progression to cirrhosis and hepatocellular carcinoma. Treatment of chronic hepatitis B is aimed at sustained suppression of HBV replication and remission of liver disease. Treatment with interferon alpha has a 36% to 45% remission rate after a four-month course of treatment in selected patients. The criteria of good response for the treatment include elevated aminotranspherase levels, the presence of HBV DNA but a level of less than 200 pg/mL, and a liver biopsy suggesting moderate or severe inflammatory activity. Interferon can be used alone or concurrently with lamivudine in chronic hepatitis patients. Although there were hopeful data about the efficacy of lamivudine therapy, the combination of more than one antiviral agent needs to be assessed to improve the actual response rate obtained with interferon-alpha. Preliminary reports suggest that 73% to 86% of patients remained HBeAg-negative after HBeAg seroconversion in clinical trials, but some responders who had early relapse were not included in these follow-up studies, so these results may be overly optimistic.
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PMID:[Treatment of chronic hepatitis B in children]. 1562 50

Hepatic arterial infusion chemotherapy (HAIC) has been often selected as a therapeutic option for advanced hepatocellular carcinoma (HCC) with intrahepatic metastases or portal vein thrombosis, which is not eligible for hepatic resection, tumor ablation, or embolization. Among various regimens, HAIC, consisting of 5-fluorouracil (5-FU) in combination with either low-doses of cisplatin (CDDP) or interferon-alpha has been reported to improve the response rates for advanced HCC. As both regimens require the use of an implanted port-catheter system, maintaining the patency of hepatic arteries is an important factor for the intrahepatic drug distribution and the efficacy of HAIC. Recently, a new product, CDDP powder has been also developed for intraarterial use, which adds a new option to HAIC. However, the long-term outcome or the survival benefit remains unclear with HAIC, and it may be significantly affected by liver function and cirrhosis. None of the regimens have been proved to be the standard for HAIC, and prospective multi-center clinical studies with standardized protocol are needed in the future.
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PMID:[Hepatic arterial infusion chemotherapy (HAIC)--hepatocellular carcinoma]. 1562 54

Chronic infection with HCV represents second most common cause of end-stage liver diseases and hepatocellular carcinoma in Korea. The introduction of new agents and regimens for the treatment of chronic hepatitis C, such as pegylated forms of interferon-alpha (Peg-IFN) and combination with oral ribavirin has resulted in substantial improvement in sustained virologic response (SVR) rates. SVR rate of Peg-IFN and ribavirin combination therapy can be 40-46% of individuals infected with genotype 1 and approximately 75-85% with genotype 2 and 3. Peg-IFN/ribavirin combination therapy represents current standard therapy of chronic hepatitis C. This article reviews the treatment objectives, outcomes, optimal regimens, efficacy and predictors of response, monitoring during treatment, adverse events, retreatment of persons who failed to respond to previous treatments, and treatment of special patient groups in chronic hepatitis C.
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PMID:[Treatment of chronic hepatitis C]. 1566 73

Hepatitis C virus (HCV) infection has emerged as the main cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals, since the introduction of antiretroviral therapy. Coinfection with both viruses may lead to end-stage liver disease (ESLD), including cirrhosis and hepatocellular carcinoma. HCV infection is altered by HIV presence, although the effect of HCV on HIV infection is still controversial. For this reason, HCV screening is recommended in all HIV-infected persons. The final goal of HCV treatment is to eradicate the virus or, in other words, to eliminate the infection, and this objective is especially important in HIV/HCV-coinfected patients, because they have more severe liver disease, achieve less frequently sustained virologic response on treatment, and have limited access to orthotopic liver transplantation with respect to HCV-monoinfected patients. Combination therapy with pegylated interferon-alpha (pegIFN) and ribavirin (RBV) has become the standard treatment for chronic HCV infection. However, when we compare coinfected with monoinfected patients, this regimen has decreased efficacy, and the rate of adverse effects is higher.
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PMID:Update on hepatitis C treatment in HIV-coinfected patients. 1571 8

The introduction of pegylated interferon-alpha (PEG-IFN-alpha) as well as lamivudine and adefovir has greatly improved the perspectives for patients with chronic hepatitis B. In addition, new nucleos(t)ide analogues are currently being evaluated and may allow the development of effective combination therapy regimens in the future. In the absence of resistance development, lamivudine reduces the risk of decompensation and hepatocellular carcinoma in patients with cirrhosis. Current standard therapy of chronic hepatitis C, PEG-IFN-alpha combined with ribavirin, results in a sustained virologic response in 20-80% of patients, depending on the viral genotype and additional factors, such as ethnicity, fibrosis stage, body mass index, viral load, alcohol consumption, and coinfections. Novel antiviral strategies are currently being explored.
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PMID:[When and how to treat hepatitis B and C?]. 1577 Aug 18


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