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) has been associated with acute and chronic posttransfusion and with sporadic non-A non-B (NANB) hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Cloning of the sequence encoding an antigenic component of HCV in 1989 led to the development of tests to detect antibody to HCV in serum. Viral HCV RNA can be detected and estimated with polymerase chain reaction (PCR) and branched-chain DNA (bDNA) signal amplification tests. The entire viral genome has been sequenced. The HCV envelope region varies considerably, and infections with mutant HCV have been described. Approximately 0.5-1.5% of healthy blood donors test positive, and HCV infection can be acquired by blood transfusion or i.v. drug abuse. Vertical and sexual transmission of the virus is rare, and the transmission mode remains obscure in a large group of patients. Acute hepatitis C is mild and often asymptomatic. Chronic hepatitis C has an indolent course but may progress to cirrhosis and HCC. Recombinant alpha interferon (IF) is used to treat chronic HCV disease, but no consensus has been reached on patient selection, dose, and duration of treatment. Approximately 50% of treated patients respond, but 50-80% of responders relapse over time. Liver transplantation in patients with end-stage, HCV-related liver disease is often followed by allograft infection. Short-term survival with reinfection is good, but the long-term consequences remain to be defined.
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PMID:Hepatitis C: an overview. 759 67

This study was undertaken to investigate the response rate, time to treatment failure and survival time of patients with hepatocellular cancer (HCC) treated with beta-interferon or menogaril. Sixty-nine patients with histologically confirmed, advanced, measurable hepatocellular carcinoma were randomized to receive beta-interferon or menogaril. Eligibility criteria included an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2, or 3, as well as adequate kidney and liver function and hematologic reserve. The number of patients with lethal, life-threatening, and severe toxicities on beta-interferon were 1, 3, and 12 and on menogaril 2, 5, and 10, respectively. No objective responses were documented among the 61 patients who had HCC, histologically reviewed and confirmed. The time to treatment failure was 6.7 weeks on beta-interferon and 8.6 weeks on menogaril. The median survival time was 11.1 weeks on beta-interferon and 23.1 weeks on menogaril (South African patients 10.1 weeks). The difference is not significant. Poor prognostic factors were jaundice, age, and associated hepatitis. After controlling for other covariates, beta-interferon appears to increase the relative risk of dying by 2.7. This trial reconfirms the importance, previously reported by ECOG of jaundice and age in the prognosis of patients with HCC. It shows that further trials with neither beta-interferon nor menogaril are warranted.
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PMID:Hepatocellular carcinoma. An ECOG randomized phase II study of beta-interferon and menogaril. 762 67

Chronic viral hepatitis is prevalent worldwide in the pediatric population and can be associated with significant morbidity and mortality. Acquisition of disease in early childhood may predispose children to long-term complications, including cirrhosis and HCC. Efforts should be made to recognize, control, and prevent further spread of these infections, especially in areas where hepatitis is endemic. Alpha interferon therapy hastens disease remission in a proportion of patients with chronic hepatitis B. Further studies are needed to define the role of interferon in chronic HDV and HCV infection in children.
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PMID:Management of chronic viral hepatitis in children. 763 78

The therapeutic effect of the fibroblast-mediated human interferon (IFN alpha) gene therapy in combination with interleukin-2 (IL-2) activated killer cells (AK)/doxorubicin (i.e., adoptive chemoimmunotherapy) on nude mice bearing the human hepatocellular carcinoma (HCC) was investigated. A fibroblast cell clone (NIH3T3-IFN alpha+) secreting 1024 U/ml human IFN alpha was obtained from 14 positive clones by BMGNeo-IFN alpha DNA transfection, G418-resistant selection, limiting dilution and assay of IFN alpha activity. After i.p. implantation of NIH3T3-IFN alpha+ encapsulated into collagen, serum human IFN alpha activity could be detected from 12 h to day 15 with a peak at 72 h. AK were prepared from human peripheral mononuclear cells costimulated in vitro by IL-2 and inactivated human SMMC 7721 HCC cells. When the NIH3T3-IFN alpha+ cells were i.p. implanted into the HCC-bearing nude mice, the grown of HCC was inhibited and the survival time of the mice was extended. The growth of HCC was inhibited more obviously when AK was i.v. injected and IL-2 was i.p. injected after the NIH3T3-IFN alpha+ cells had been implanted. The best therapeutic effect was achieved when NIH3T3-IFN alpha+ cells were used in combination with IL-2/AK/doxorubicin. All these results suggested that the fibroblast-mediated human IFN alpha gene therapy could be used to treat the human hepatocellular carcinoma effectively and that when used in combination with IL-2-based adoptive chemoimmunotherapy, the therapeutic effect would be better.
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PMID:Treatment of human hepatocellular carcinoma by fibroblast-mediated human interferon alpha gene therapy in combination with adoptive chemoimmunotherapy. 764 87

Vaccine therapy is now used in various infectious diseases. The hepatitis B virus (HBV) leads to chronic infection in around 5% of patients with a high risk of chronic active hepatitis which may result in cirrhosis and hepatocellular carcinoma. The partial efficacy of antiviral therapies (40% of sustained inhibition of HBV replication), their cost, the numerous side effects and the immune-mediated pathology of HBV infection explain the emergence of new immune therapies in treating HBV infection. Experimental and clinical arguments are in favor of vaccine therapy in HBV chronic infection. Thirty-two consecutive chronic HBsAg carriers with chronic hepatitis and detectable serum HBV DNA were given 3 standard injections of the GenHevac B vaccine at one month intervals. Six months after the first injection, 12 patients (37.5%) had undetectable HBV DNA while 3 others showed significant decrease in HBV DNA titers. Eight of these 15 responders received a standard course of alpha-interferon (5 MU thrice weekly subcutaneously for 4 months) and all still had undetectable HBV replication. By contrast, among 13 (of the 17) non responders to vaccine who were given alpha-interferon, only 3 stopped HBV replication. In summary, serum HBV DNA disappeared in 18 of the 32 patients (53.1%) who were given vaccine therapy, with or without interferon. Vaccination was uneventful. Active immune therapy against HBV appears as efficient and less expensive than antiviral therapies in stopping HBV replication. Such a result should be confirmed by controlled randomized trials.
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PMID:Immunotherapy of chronic hepatitis B by anti HBV vaccine. 764 80

Hepatitis C virus infection is a common disease with a high propensity to progress towards chronicity. Alpha interferon has been proposed to halt progression of the disease and prevent the development of more severe liver diseases such as cirrhosis and hepatocellular carcinoma. Unfortunately, less than 20% of treated patients show a long-lasting ALT normalization and HCV-RNA negativity. Factors which might be predictive of a long term response to interferon are debated. Univariate analysis of data collected in randomized clinical studies, has shown that IFN dose, age, duration of disease, cirrhosis and early response (primary) to IFN were all predictors of a sustained response to IFN, but with differences in different studies. When data were analyzed by a multivariate analysis, short duration of the disease and absence of cirrhosis were found to predict long-term response to interferon. Finally, many evidences indicate that response rates to therapy may be better in patients with low pretreatment levels of HCV-RNA measured either by polymerase chain reaction (PCR) or the branched-DNA assay (b-DNA).
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PMID:Alpha interferon treatment of chronic hepatitis C. 764 81

To characterize the role of serum soluble interleukin-2 receptor (sIL-2R) in hepatitis C virus (HCV) infection, the level of sIL-2R was measured by ELISA in 117 subjects with chronic HCV infection and in 23 healthy controls. HCV RNA was detected by polymerase chain reaction in all subjects with HCV infection. Forty-seven patients with chronic hepatitis and 10 with liver cirrhosis were treated for six months with natural interferon-alpha. The sIL-2R levels of 40 asymptomatic HCV carriers (632 +/- 340 units/ml), 47 patients with chronic hepatitis (547 +/- 204 units/ml), 10 with cirrhosis (679 +/- 239 units/ml, and 20 with hepatocellular carcinoma (1145 +/- 487 units/ml) were significantly higher than those of healthy controls (380 +/- 191 units/ml) (P < 0.05, respectively). The levels of sIL-2R increased, as did the histological activity index scores (r = 0.348, P < 0.01). The level of sIL-2R rose after the initial administration of interferon in all 57 patients. In patients whom HCV RNA was eliminated from the sera within a six-month follow-up after cessation of treatment, the level of sIL-2R reverted to basal values, but in patients in whom HCV RNA was not eliminated the value was significantly higher than that before treatment. These results suggest that monitoring serum sIL-2R in patients with chronic HCV infection treated with interferon may provide information concerning the possibility of the elimination of HCV RNA.
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PMID:Serum levels of soluble interleukin-2 receptors and effects of interferon-alpha for patients with chronic hepatitis C virus. 764 88

We studied the potential of alpha-interferon (IFN-alpha) to enhance alpha-fetoprotein (AFP) and thus alter the localization of 125I-labeled antibody to the human hepatoma xenograft in athymic mice using monoclonal antibody (MAb) 19F12, which recognized AFP on the surface of human hepatoma cells. Treatment of the human hepatoma cell NuE with IFN-alpha increased the surface expression of AFP 2.4-fold in an IFN-dose-dependent manner. The IFN-alpha treatment substantially increased (2.7-fold) the localization of 125I-labeled 19F12 to NuE xenografts in athymic mice. The increase in localization of 125I-labeled 19F12 was dependent on the circulating plasma IFN levels. Our experimental results suggested that IFN-alpha could act as a potent modulator of the cellular antigen AFP, and be used to enhance the targeting of a conjugated MAb to hepatoma cell populations.
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PMID:Effect of alpha-interferon on anti-alpha-fetoprotein-monoclonal-antibody targeting of hepatoma. 767 54

We have previously reported depressed gamma-interferon production and depressed lymphokine-activated killer and natural killer activity in patients with relatively large hepatocellular carcinomas. These parameters were normal in cirrhosis. Some evidence had suggested a gamma-interferon production defect as the main cause of depressed lymphokine-activated killer activity in hepatocellular carcinoma, (i.e., gamma-interferon enhances lymphokine-activated killer and natural killer activity and gamma-interferon antibody inhibits lymphokine-activated killer induction). However, we were unable to clinically define the precise mechanism operating here because gamma-interferon production and lymphokine-activated killer activity were both defective in advanced hepatocellular carcinoma. In recent years, it has become possible to detect even small hepatocellular carcinomas on ultrasonography and to confirm them by fine-needle biopsy. In this study, we assessed those immune parameters in 48 patients with hepatocellular carcinomas less than 2 cm in diameter to confirm depressed immune function and to clarify the mechanism of these defects. Lymphokine-activated killer activity was defective in 31 patients (64.6%), whereas gamma-interferon production was defective in only 1 of these patients (2.1%). This observation argues against the hypothesis that defective gamma-interferon production is the primary defect and provides new insight into the mechanism of progression of defective immune function in hepatocellular carcinoma. Thirty-one of the 48 hepatocellular carcinoma patients were treated surgically, and these immune parameters were followed for 6 mo. The recovery of lymphokine-activated killer activity in all hepatocellular carcinoma patients with low lymphokine-activated killer activity suggests the tumor burden as the cause of defective lymphokine-activated killer activity.
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PMID:Assessment of lymphokine-activated killer activity and gamma-interferon production in patients with small hepatocellular carcinomas. 768 18

Adults with a healthy immune system who are exposed to hepatitis B virus (HBV) usually suffer from a mild acute infection. The likelihood of chronicity is only 5%, but climbs as high as 90% in newborns and n the immunocompromised. Acute HBV infection can cause fulminant liver failure (case fatality rate of 80%). People with chronic infection tend to have no symptoms, normal liver enzymes, and normal or almost normal liver histology, making diagnosis difficult. Active viral replication occurs in most people with active liver disease. People with persistent active replication are at higher risk of death from liver disease or hepatocellular carcinoma (HCC) than those with inactive disease. HBV transmission occurs via sexual intercourse or blood or needle contact. In the US, iv drug use is the major risk factor for HBV infection in adults. Prevention of HBV infection is through patient education and vaccination. Some people advocate universal HBV vaccination because it is often difficult to vaccinate high risk populations and to identify risk factors. Universal vaccination is not cost effective in low risk areas, however, e.g., the US and Europe. Treatment for chronic HBV infection is limited. Response to interferon therapy depends on low HBV DNA levels, high transaminase levels, and a history of acute hepatitis. Short- and longterm response rates tend to be low, however ( 40% short term and much lower for longterm). Experimental drugs are thymosin and nucleoside analogues. Standard treatment for patients with end-stage chronic liver disease or fulminant hepatic failure is liver transplantation. High dose immune globulin is the best means to delay and prevent recurrent HBV infection in transplantation patients. Some problems with management of chronic HBV are prevention of HCC and recurrent HBV after transplantation. Variant viruses are mutations of the precore or of a surface gene. HIV/AIDS is often associated with HBV and hepatitis delta virus infection.
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PMID:Clinical aspects of hepatitis B virus infection. 769 23


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