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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) is both the leading cause of cirrhosis and hepatic failure leading to liver transplantation and a cause of chronic hepatitis in approximately 10% of all transplant recipients. Beginning 5-10 years or more posttransplant, HCV causes progressive liver disease in a significant fraction of infected individuals and contributes to an increased incidence of opportunistic infection and hepatocellular carcinoma. The existence of multiple genotypes of HCV with differing biologic behaviors and the generation of antigenic diversity of the virus (quasispecies) during the course of infection, limit the capacity of the immune system to generate protective immunity. Antiviral therapy with interferon-alpha is effective in only a minority of transplant patients, and since allografts from HCV infected donors are quite efficient in transmitting the virus, great attention is paid to the appropriate use of organs from HCV-positive donors. At present, these organs should be particularly targeted for patients in emergent need of lifesaving heart, liver, or lung transplants. Issues requiring further investigation include the impact of viral superinfection on HCV-infected recipients of organs from HCV-infected donors and the use of such organs in seronegative patients who are older, diabetic, or highly sensitized, for whom quality of life issues may outweigh the long-term impact of HCV infection.
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PMID:Hepatitis C virus and organ transplantation. 875 8

The high worldwide prevalence of chronic viral hepatitis, as well as its progressive course, have led to the performance of multiple clinical studies. The natural history of the disease is different depending on the infecting virus; thus, the evolution to liver cirrhosis and/or hepatocellular carcinoma for the hepatitis B, C and delta (D) viruses in chronic hepatitis is 15, 20 and 75%, respectively. Different therapeutic agents have been used in attempts to modify the natural course of these diseases, interferon-alpha (IFN alpha) having proved to be the most effective. In 30 to 50% of patients, treatment with IFN alpha has achieved inhibition of viral replication, as well as normalisation of aminotransferase levels. Moreover, in a majority of patients, histological improvement is observed, principally in piece-meal necrosis and portal inflammation. The dosage currently recommended for treatment of chronic hepatitis B is 30 to 35MU weekly for a minimum of 4 months; when there is a co-existing delta virus infection, the total dosage employed should be greater. For hepatitis C, the minimum effective dosage is 9MU weekly, and a treatment duration of 12 months is recommended. The administration of IFN alpha produces a series of dose-dependent adverse effects, which are reversible on suspension of the medication. The most frequent of these adverse reactions is the 'flu-like' syndrome, which is self-limited and generally well tolerated. Secondary haematological alterations (leucopenia and thrombocytopenia) are the most frequent cause of reduction in dosage or suspension of treatment, although the latter is not normally necessary. The proportion of patients requiring dosage modification or suspension of treatment fluctuates between 5 and 15%. Taking the evolution of chronic hepatitis into account, there can be no doubt that all patients with this disease should be offered treatment. At present, the drug of choice is IFN alpha, as it slows disease progression and it is generally well tolerated.
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PMID:Risks and benefits of interferon-alpha in the treatment of hepatitis. 878 18

A meta-analysis of six randomized clinical trials involving 240 children with chronic hepatitis B treated with recombinant interferon-alpha (IFN-alpha) was performed. IFN-alpha treatment was effective in blocking viral replication. Clearance of hepatitis B virus (HBV) DNA from sera occurred in 44 of 127 treated patients (P < .00001), and clearance of hepatitis B e antigen (HBeAg) occurred in seven of 74 treated patients (P = .099). IFN-alpha normalized serum levels of alanine aminotransferase (ALT) in 33 of 85 treated patients (P = .017). At the end of the follow-up period, viral replication was still reduced in IFN-alpha-treated patients, HBV DNA clearance occurred in 36 of 126 patients (P = .014), and HBeAg clearance occurred in 29 of 126 patients (P = .026). Regarding these virological and biochemical endpoints, we found that prolonged therapy (> 6 months) was associated with a better response, whereas high dosages of IFN-alpha were not. These findings could be biased by limited follow-up. Children with high ALT levels had a better response. However, these randomized clinical trials had some methodological flaws, including the lack of information on histologic response to IFN-alpha treatment by pediatric patients and the absence of "hard outcomes" (such as survival or development of cirrhosis or hepatocellular carcinoma).
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PMID:Interferon-alpha therapy for chronic hepatitis B in children: a meta-analysis. 881 42

The ribonucleotide reductase inhibitor, hydroxyurea (HU), augments the cytotoxic effects of 5-fluorouracil (5FU) in vitro; both drugs are synergistic with interferon-alpha (IFN) in vitro. The aim of this phase I study was to determine the maximal duration of HU, 4.3 g/m2, administered as a parenteral infusion in combination with 5FU, 2.6 g/m2 administered over 24 hrs each week, + IFN, 9 MU, subcutaneously three times per week. There were 26 patients enrolled and evaluable. This included 14 patients with colorectal cancer of whom 13 had been previously treated, and 12 patients with other refractory malignancies (pancreas, cholangiocarcinoma, hepatocellular carcinoma, renal cell carcinoma, and others), of whom 10 were previously untreated. The dose-limiting toxicity of this regimen was myelosuppression. This prohibited dose escalation of HU above the starting dose (24 hrs) on a 6-weeks-on, 2-weeks-off therapy schedule. When filgrastim, 480 microg, was administered subcutaneously on days 3-6, the duration of HU could be extended to 48 hrs on a 2-weeks-on, 1-week-off therapy schedule. There were two instances of fatal infection, one in a patient with a rectovaginal fistula with neutropenic sepsis and the second in a patient with non-neutropenic Clostridium septicum sepsis. All therapy was administered in the ambulatory setting. There were three responders, all among previously untreated patients. High-dose parenteral hydroxyurea, 4.3 g/m2 administered over 24 hrs, can be safely combined with high-dose weekly 5FU, 2.6 g/m2 over 24 hrs + IFN, 9 MU subcutaneously three times per week, without filgrastim in the ambulatory setting. Parenteral hydroxyurea, 4.3 g/m2 over 24 hrs daily x 2 can also be combined with high-dose 5FU + IFN, but requires the addition of filgrastim to avoid severe myelosuppression.
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PMID:Phase I trial of high-dose infusional hydroxyurea, high-dose infusional 5-fluorouracil and recombinant interferon-alpha-2a in patients with advanced malignancies. 882 49

Efficacy and safety of therapy with lymphoblastoid interferon-alpha alone or combined with deflazacort has been investigated in 38 HBsAg-HBeAg+ patients with biopsy-proven chronic hepatitis. Group I received 5 MU/m2 interferon thrice a week for 26 weeks; group II took interferon for 26 weeks simultaneously with a 6-week course of deflazacort. Follow-up was 18-72 months (median 42). After 12 months, responses were achieved in 3 (18%) out of 17 patients on interferon alone vs 5 (26%, p > 0.05) out of 19 on combined therapy. Blind histological assessment revealed no improvement in either group or in patients who responded to therapy within the first year of follow-up ("early responders"). "Delayed" responses were observed in 4 (29%) patients who took interferon alone vs 5 (36%, p > 0.05) who took the combined therapy. Serum HBV DNA levels decreased significantly during treatment and remained low up to 24 and 36 months of follow-up in both groups. One early responder developed hepatocellular carcinoma, another had exacerbation of liver disease in long-term follow-up. No non-responders developed liver failure or hepatocellular carcinoma. These results indicate that lymphoblastoid interferon-alpha inhibits HBV replication and corticosteroids have no synergistic effect in treatment of HBsAg-HBeAg+ chronic hepatitis.
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PMID:Treatment of chronic hepatitis B (HBeAg-HBV DNA-positive) with lymphoblastoid alpha interferon with or without corticosteroids: short- and long-term follow-up. 889 47

A 60-year-old man with a chronic hepatitis C virus (HCV) infection and histological features of chronic active hepatitis was treated with interferon-alpha (IFN). He successfully responded to IFN with normalization of serum ALT and disappearance of serum HCV-RNA. His liver biochemistry profile remained normal and serum HCV-RNA was not detected throughout the entire follow-up period. One year later, a small hepatocellular carcinoma (HCC) was detected by routine ultrasonographic screening. Laparotomy revealed a small tumour with no metastasis and the non-tumorous liver demonstrated macronodular cirrhosis. Although no space-occupying lesions were detected by frequent radiological examinations prior to IFN therapy, the small size of the tumour suggested de novo development of HCC. Patients with chronic HCV infection, including those who have complete responses to IFN and lack clinical and histological evidence of cirrhosis, should be followed up for the potential development of HCC.
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PMID:Case report: development of hepatocellular carcinoma in a patient with chronic hepatitis C infection after a complete and sustained response to interferon-alpha. 891 34

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Several risk factors for HCC development have been identified, including cirrhosis, hepatitis B virus (HBV) infection, and hepatitis C virus (HCV) infection. With regard to cirrhosis, multivariate analysis indicates that alcohol abuse, HBsAg positivity, and anti-HCV seropositivity are independent variables associated with an increased risk for HCC in the cirrhotic patient. A close relationship between chronic HBV infection and HCC has been established by epidemiological studies and laboratory investigations. Evidence indicates that HCV also plays a leading role in development of HCC. Most patients with HCV-related HCC develop the tumor as a consequence of long-standing infection accompanied by chronic and progressive liver damage. In our study of 290 consecutive patients with cirrhosis, patients with persistently elevated or fluctuating ALT levels had a significantly greater rate of HCC development. The mechanism of HCC development in HCV infection remains to be elucidated. The annual cumulative risk of developing HCC is approximately 1% in patients without cirrhosis at inclusion and 3-10% in those with cirrhosis, depending on the stage of cirrhosis and presence of etiological cofactors. Although some evidence suggests that patients infected with the HCV genotype 1b are at increased risk for development of more severe liver disease, including HCC, results of our prospective study do not support a difference between cirrhotic and noncirrhotic patients in terms of the natural course of cirrhosis and the rate of developing HCC based on genotype. Strategies to prevent HCV-related HCC include blood screening and treatment of chronic HCV infection with interferon-alpha. Recent studies suggest that interferon-alpha treatment may prevent the development of HCC in HCV infection. Further research is warranted.
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PMID:Risk factors and prevention of hepatocellular carcinoma in HCV infection. 901 76

To evaluate the efficacy of methotrexate (MTX)-5-fluorouracil (5-FU), cisplatin (CDDP), and interferon-alpha-2b(IFN alpha-2b) combination therapy, we conducted a clinical pilot study in patients with locally advanced hepatocellular carcinoma (HCC). Sixteen patients, who had received no prior treatment for the HCC, with portal tumor thrombosis in the main trunk or in the major branch were enrolled in the study. IFN alpha-2b (3 x 10(6) units) was injected subcutaneously 3 times per week. After a bolus administration of MTX (30 mg/m2), CDDP (75 mg/m2) and thereafter 5-FU (750 mg/m2) were given weekly by intrahepatic arterial infusion. In 15 eligible patients, there were 1 complete response (CR) and 6 partial responses (PR) with a response rate of 46.7%. Median survival of the 15 patients was 7 months, and the 2-year survival rate of CR and PR patients was 57.1%. There was severe transient hematologic toxicity. More than grade 2 nausea/vomiting was noted in > 50%. In conclusion, the IFN alpha-2b combination chemotherapy demonstrated good response in patients with locally advanced HCC. This treatment should be tried in a controlled study.
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PMID:Clinical pilot study of intrahepatic arterial chemotherapy with methotrexate, 5-fluorouracil, cisplatin and subcutaneous interferon-alpha-2b for patients with locally advanced hepatocellular carcinoma. 942 74

Clinico-epidemiological data show that the most severe forms of hepatitis C virus (HCV) associated liver disease occur in patients with multifactorial liver damage. We found that the prevalence of hepatitis B virus (HBV) markers in anti-HCV positive patients with cirrhosis complicated by hepatocellular carcinoma (HCC) is higher than in cirrhotics with comparable age and disease history, but without HCC. HBV can persist in integrated forms in HBsAg negative, anti-HBc positive individuals and we may speculate that in such patients concurrent liver pathogens, as HCV, could cause HCC more easily than in patients without previous exposure to HBV. Analysing the relations between age at HCC diagnosis and the different risk factors in consecutive HCC patients we found that patients with single hepatitis virus infections (HBsAg and/or anti-HCV positive) were of an older median age than patients with multiple hepatitis virus infections. We also studied patients with compensated cirrhosis and hepatitis virus infections. untreated or treated with interferon-alpha. The independent effect of treatment was analysed by matching groups with regard to all the other significant HCC risk factors. The overall relative HCC risk was three times higher (risk ratio 3.1) in untreated vs treated anti-HCV positive patients and more than six times higher (risk ratio 6.2) in untreated vs treated anti-HCV positive/anti-HBc negative patients. The difference between treated and untreated patients was not statistically significant in hepatitis B surface antigen carriers and in anti-HCV positive/anti-HBc positive patients. The evidence that HBV coinfection may worsen the course of liver cirrhosis in patients with chronic hepatitis C is intriguing, but it has important practical consequences. It warrants the identification of high risk patients with chronic hepatitis C who need to be treated as early as possible and patients who can still benefit from interferon-alpha therapy once cirrhosis has already been diagnosed.
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PMID:Impact of interferon-alpha therapy on the development of hepatocellular carcinoma in patients with liver cirrhosis: results of an international survey. 942 13

Various papers reported that chronic viral hepatitis is the principal cause of chronic liver disease, as cirrhosis and hepatocarcinoma. Interferon is the only agent known to have a beneficial effect in chronic hepatitis. The response rate has been less than 10 percent in patients with genotype 1b, but in patients with genotype 2 or 3 it has been greater than 40 percent. Aim of our investigation was to study 10 patients suffering from chronic viral hepatitis HCV related, genotype 1b, non responder to interferon-alpha therapy. In these patients we administered beta-interferon at the dose of 6 million units, 3 times a week, for 3 months. A significant reduction of aminotransferase level was reported after 3 months of the start of the therapy. An higher level of beta-interferon plasma rate was found in 3 non responder patients. The interaction of beta-interferon with the immune system was demonstrated with an increase of CD8+ lymphocytes that correlated with decrease of HCVRNA. The treatment with beta-interferon have a beneficial effect in patients with chronic hepatitis HCV related, genotype 1b, no responder to interferon-alpha therapy.
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PMID:[beta-Interferon therapy of chronic hepatitis HCV+, 1b genotype]. 967 29


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