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)

To evaluate the efficacy and safety of human lymphoblastoid interferon treatment (interferon alfa) for patients with compensated cirrhosis caused by hepatitis C virus (HCV) infection, we randomly assigned 82 cirrhotic patients with chronic HCV infection (44 men, 38 women; mean age, 58.6 years) to two groups: 41 patients were treated with interferon alfa (480 million U over 6 months), and the other patients received no drug treatment. HCV RNA genotypes were determined by polymerase chain reaction (PCR) testing using type-specific primers. HCV RNA levels were measured by competitive PCR testing. No untreated patients eliminated HCV RNA from the serum or had a decrease in the level of alanine aminotransferase to normal during the observation period. Of the 34 patients who completed interferon alfa treatment, 6 (17.6%) who were considered complete responders eliminated HCV RNA from the serum by the end of treatment and sustained this elimination throughout a 6-month follow-up period. Complete responders constituted 6 (46.2%) of 13 patients with HCV RNA levels < or = 10(5) copies/50 microL, but none of the 21 patients with levels > 10(5) copies/50 microL were complete responders. Two (7.1%) of 28 patients with genotype 1b infection and 4 (66.7%) of 6 with genotype 2a were complete responders. Five patients withdrew because of interferon alfa-induced side effects (1 for thrombocytopenia, 3 for severe general malaise, and 1 for impotence), and 2 withdrew after being diagnosed with hepatocellular carcinoma. Hepatic failure did not occur in any treated patient in the present study. These findings indicate that interferon alfa treatment is useful for compensated cirrhosis caused by HCV infection if the HCV RNA levels are low and the infection is of genotype 2a.
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PMID:Human lymphoblastoid interferon treatment for patients with hepatitis C virus-related cirrhosis. 944 45

During the course of long-term follow-up, we examined the efficacy of interferon (IFN) in the improvement of liver function and prevention of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) associated cirrhosis patients. Fifty-five cirrhotic patients, in whom HCC nodules in the liver were not detected by ultrasonography (US) or computed tomography (CT), received 3 or 6 million units of human lymphoblastoid IFN daily for two weeks and 3 times a week for 22 weeks. Complete response (CR) was defined as normalization of serum alanine aminotransferase (ALT) together with negative HCV RNA at 6 months after IFN therapy completion. Any other pattern of response was defined as non-response (NR). After IFN therapy the patients were followed up every 1-3 months for at least 1 year (average follow-up period, about 40 months) with serological tests and US or CT. In the 8 CR patients, the serum ALT levels remained normal and HCV RNA remained negative. Platelet count, white blood cell count, serum albumin and zinc turbidity test have recovered to the normal range at final follow-up. Ten of the 47 patients with NR have developed HCC, whereas no patients with CR has developed HCC during follow-up. We conclude that IFN improves the liver function and may prevent the development of HCC even in cirrhotic patients who show CR to IFN therapy.
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PMID:Long-term evaluation of interferon therapy in hepatitis C virus-associated cirrhosis: does IFN prevent development of hepatocellular carcinoma? 945 23

Chronic hepatitis C is a major health care problem throughout the world. The disease may progress to cirrhosis, with complications such as hepatocellular carcinoma. The usual primary goal of therapy is viral eradication, as patients with long-term remission are generally regarded as unlikely to develop cirrhosis or hepatocellular carcinoma. Another primary goal should be the reduction in liver fibrosis progression. Interferon-alpha (IFN-alpha) is the only drug approved for the treatment of hepatitis C in Europe and North America. Its effectiveness appears to be related to dose and duration of therapy. The best efficacy/risk ratio seems to be in favour of 3 million units (MU) IFN-alpha three times per week on a 12-month schedule. With this regimen, a sustained alanine aminotransferase (ALT) response is achieved in nearly 35% of patients. Ribavirin has emerged as potentially the second most effective drug. While it appears unsatisfactory when given alone, it seems much more effective in combination with IFN. Combining them seems to exert a synergistic effect between the two drugs and sustained remission might be achieved in nearly 50% of patients with combination therapy. Controversy persists concerning the long-term benefit of therapy in transient responders and non-responders. It is possible that IFN therapy, in comparison to natural history, might reduce liver fibrosis progression and prevent hepatocellular carcinoma, even in non-responders, and have greater efficacy if used in long-term treatment. Whatever the treatment schedule, prolonged viral eradication may not be achieved in all patients and new drugs should be sought to improve the results of therapy.
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PMID:Management of hepatitis C. 957 31

To elucidate the risk factors for liver carcinogenesis and to examine the incidence of hepatocellular carcinoma (HCC) after interferon therapy, 1,022 chronic hepatitis C patients treated with interferon were followed by ultrasonography for 13 to 97 months (median 36 months). Sustained response with prolonged alanine aminotransferase normalization was found in 313 patients, transient response with alanine aminotransferase relapse after therapy in 304, and no response in 405. Forty-six developed HCC, of whom 5 were sustained responders, 9 were transient responders, and 32 were nonresponders. The cumulative incidence of HCC in transient responders was almost equal to that in sustained responders, and it was significantly higher in nonresponders than in sustained and transient responders (P=.0009). The seventh-year cumulative incidence rates of HCC in sustained responders, transient responders, and nonresponders were estimated to be 4.3%, 4.7%, and 26.1%, respectively. However, there was no significant difference in the cumulative incidence of HCC between patients with HCV subtype 1 and 2 (P=.14). Cox regression analysis showed that the risk of HCC development was not elevated in transient responders compared with sustained responders, but that the risk was 7.90-fold higher in nonresponders than in sustained responders (P=.008). Patients > or =55 years of age had a significantly higher risk ratio (4.65) than did those under 55 years of age (P=.006). The risk of HCC development in men was 4.35 times higher than the risk in women (P=.02). However, the degree of fibrosis was not a significant risk factor for the development of HCC (risk ratio, 3.16; P=.052). These results suggest that patients in the high-risk group of HCC after interferon therapy were those who showed no response, those who were older, and those who were male, and that such patients should be carefully followed using ultrasonography.
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PMID:Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Osaka Liver Disease Study Group. 958 5

Patients with chronic hepatitis C virus (HCV) infection are often asymptomatic with few clinical signs of liver disease. Recognition of the presence of fibrosis or cirrhosis is difficult without liver biopsy, but with the availability of effective treatments, such as interferon, and the potential for progression to hepatoma in some cases, an accurate measure of the stage of disease is important. Serum hyaluronic acid (HA) has been identified as a potential marker of fibrosis or cirrhosis in other settings. In a prospective study in 130 chronic HCV carriers therefore, serum HA concentrations were compared with conventional liver function tests (including alanine aminotransferase (ALT), a-glutathione-S transferase (GST) and serum HCV RNA in order to determine which identified the stage of liver fibrosis as assessed by liver biopsy most accurately. The median HA concentrations according to the stage of fibrosis 0, 1 & 2, 3 and 4 & 5 were 17 g l-1 (range 5-37), 17 g l-1 (5-80), 30 g l-1 (10-105) and 350 g l-1 (20-800) respectively. The median HA concentration in stage 4 & 5 was significantly greater than in stages 0, 1 & 2 or 3. Serum HA concentration rose with age, but even when adjusted for age the median HA at stage 4 & 5 was greater than all other groups (95% CI of difference between the medians exceeded 0). Thus, serum HA gave a sensitivity and specificity for stage 4 & 5 fibrosis of 85% and 88% respectively, exceeding those for ALT or GST. In contrast, serum ALT or GST levels were not correlated with the stage of fibrosis although ALT was significantly greater in the cirrhotic group when compared to the group with no fibrosis (stage 0). There was no correlation between serum HA and either the grade of inflammatory changes or serum HCV RNA. These results suggest that serum hyaluronic acid is a useful marker of liver fibrosis in patients with chronic HCV infection. It could therefore be used to monitor patients at risk of progressive fibrosis, in controlled clinical trials, as a measure of response to antifibrotic therapy and in those in whom liver biopsy is difficult or contraindicated.
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PMID:Serum hyaluronic acid is a useful marker of liver fibrosis in chronic hepatitis C virus infection. 965 72

The association of viremia, elevated serum alanine aminotransferase (ALT) levels, and hepatocyte inflammatory activity in hepatocellular carcinoma (HCC) patients was studied. Serum samples from 114 HCC patients undergoing surgery were assayed for hepatitis B, C, and D viral nucleic acids by polymerase chain reaction (PCR) prior to surgery. Of these patients, 65 had HBV infection alone, 15 had HCV infection alone, 4 had HDV infection, 20 had HBV and HCV superinfection, 1 had triple viral infection, and 9 were negative for HBV and HCV infections. The prevalence of active viral replication was significantly higher in HCV than in HBV (92% versus 70%; P = 0.006) patients, and significantly higher mean serum ALT levels were also noted in the HCV group than in the HBV group (P = 0.02). The incidence of marked ALT elevation (>200 U/l) was highest in the HCV (27%) and the HDV (25%) groups. Patients in the HCV group were 10 years older than those in the HBV group. Viral superinfection did not accelerate the development of HCC. Viral replication persisted in a significant portion of HCC patients and a higher prevalence of hepatic inflammation was noted in patients with HCV- and, possibly, HDV-related HCC.
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PMID:Detection of serum hepatitis B, C, and D viral nucleic acids and its implications in hepatocellular carcinoma patients. 971 53

This is a study of the differences in the risk factors for being either hepatitis B surface antigen positive [HBsAg(+)] or antibody to hepatitis C virus positive [Anti-HCV(+)] in A-Lein, a rural area in southern Taiwan, an area which also has a high hepatoma mortality rate. Three hundred eighty-five patients age > or =40 years participated in hepatoma screening at the A-Lein Community Health Center during 1995. Those who were HBsAg(-) and anti-HCV(-) or had coinfection of HBsAg(+) and anti-HCV(+) were excluded, leaving 293 patients: 109 HBsAg(+) and 184 anti-HCV(+). The anti-HCV(+) patients had a lower socioeconomic status (as defined by level of education and type of occupation) and were older than HBsAg(+) patients (P < 0.05). Those with higher alanine aminotransferase levels (ALT) also had a higher anti-HCV(+) to HBsAg(+) odds ratio (OR), and a dose response relationship was found, P < 0.0001. Anti-HCV(+) patients were more likely than HBsAg(+) patients to have a spouse who shared the infection, OR = 5.11; 95% CI, 2.30-11.28. Anti-HCV(+) patients were more likely than HBsAg(+) patients to have had blood transfusions (OR = 2.66; 95% CI, 1.20-5.89), frequent medical injections (OR = 2.64; 95% CI, 1.62-4.31), or injections by non-licensed medical providers (OR = 1.91; 95% CI, 1.18-3.09). Multiple logistic regression analysis showed that the significant factors for anti-HCV(+) patients vs. HBsAg(+) patients are drinking habit (OR = 3.45; 95% CI, 1.02-11.60), age (OR = 6.33; 95% CI, 2.93-13.68), and frequent medical injections (OR = 2.88; 95% CI, 1.65-5.03). The transmission of hepatitis C in A-Lein is closely related to low socioeconomic status, age, alcohol abuse, spouses being anti-HCV(+), and frequent medical injections, especially from non-licensed medical providers, including both pharmacists and those with no medical licensing whatsoever. These nonlicensed medical providers sometimes reuse needles to save money, which is a likely route of infection.
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PMID:Differences in risk factors for being either a hepatitis B carrier or anti-hepatitis C+ in a hepatoma-hyperendemic area in rural Taiwan. 973 21

This study was performed to evaluate the long-term effects of interferon-alpha 2a (IFN-alpha 2a) vs no treatment in patients with chronic hepatitis B and to determine whether viral clearance, following therapy or occurring spontaneously, was sustained. Patients originating from three previously published multicentre, randomized, controlled trials were analysed. Information about survival and response during long-term follow-up was available in 340 (73%) and 308 (66%) of 469 randomized patients respectively. Response to therapy (viral clearance) was defined as: loss of hepatitis B virus (HBV) DNA and loss of hepatitis B e antigen (HBeAg) and improvement in alanine aminotransferase level. Scheduled treatment-free follow-up was 12 months in all studies. Median long-term follow-up time after inclusion in the individual studies was 4.7 years (range: 0.2-7.5 years). Viral clearance after IFN-alpha 2a, or occurring spontaneously, was sustained in 70 out of 80 evaluable patients (88%) who were responders at the end of the original trials and 21 (30%) lost hepatitis B surface antigen (HBsAg). A total of 80 patients received (re)treatment during the long-term follow-up period and 33% of them responded, irrespective of previous treatment category. Overall response rate was not significantly affected by gender, sexual inclination or ethnic origin. Durability of response did not depend upon ethnic origin or presence of cirrhosis. At the end of the original trial periods, 253 patients were histologically evaluated and 22 (9%) had histologically confirmed progression to cirrhosis. During long-term follow-up an additional five patients developed cirrhosis. Hepatocellular carcinoma developed in three patients (1%): in one patient during the follow-up period of the original trial and in two patients (one untreated) during the long-term follow-up period. Ten of 25 deaths were liver-related (hepatocellular carcinoma in three, gastrointestinal bleeding in two and liver failure in five). The distribution of clinical events (progression to cirrhosis, hepatocellular carcinoma and liver-related deaths) was unrelated to original treatment category and response to treatment. Hence, 90% of responding patients will, irrespective of treatment category, have a sustained response. At least 30% of responding patients will eventually lose HBsAg. For a number of reasons, the present patient population and observation period are insufficient to establish a presumed beneficial effect of IFN-alpha 2a on disease progression and survival.
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PMID:The long-term effect of treatment with interferon-alpha 2a in chronic hepatitis B. The Long-Term Follow-up Investigator Group. The European Study Group on Viral Hepatitis (EUROHEP). Executive Team on Anti-Viral Treatment. 985 48

To investigate the association between GB virus C/hepatitis G virus (GBV-C/HGV) infection and the development of hepatocellular carcinoma (HCC) in H city, in the inshore area of the Yangtze River, where high prevalence of HCC has been reported, we determined hepatitis B virus (HBV) and hepatitis C virus (HCV) markers, GBV-C/HGV-RNA and GBV-C/HGV E2 antibody (anti-HG E2) among 114 HCC patients and the same number of age- and sex-matched controls. There were no significant differences in the clinical and demographic characteristics between them, except for serum alanine aminotransferase level and history of liver diseases. There was a significant difference of hepatitis B virus surface antigen (HBsAg) prevalence between the HCC patients (75.4%) and the controls (20.2%; P<0.01). Hepatitis C virus antibody was detected in 4.4% of the HCC patients, compared with 1.7% of the controls. GB virus-C/HGV-RNA and anti-HG E2 were detected in 14.9 and 1.7% of the HCC patients, respectively, compared with 7.0 and 1.7% of the controls, respectively. Nucleotide sequences and molecular evolutionary analysis showed the strains of GBV-C/HGV-RNA were classified into genotype 2 and 3 (HG and ASIA type). An effect analysis showed an odds ratio (OR) for developing HCC from GBV-C/HGV infection among HBsAg-positive subjects was 14.9, with a 95% CI of 4.9-45.4. HBsAg infection alone was 13.83 (95% CI 7.4-25.9) and GBV-C/HGV infection alone, 3.74 (95% CI 1.1-13.1), respectively. These data indicate that HBV infection is considered to be one of the major risk factors in patients with HCC and although GBV-C/HGV infection was observed in both the HCC and the control groups, it might not play an important role in the development of HCC in this area.
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PMID:GB virus C/hepatitis G virus infection among patients with hepatocellular carcinoma in the inshore area of the Yangtze River, China. 991 33

In patients with chronic hepatitis C, the influence of the genetic heterogeneity of the hepatitis C virus (HCV) on the progression of liver disease and on the responsiveness to interferon therapy is a matter of controversy. In this study we evaluated the genetic complexity of HCV by single-strand conformation polymorphism (SSCP) analysis of amplicons from the hypervariable region 1 (HVR1) in 168 patients with chronic genotype 1b HCV infection, of whom 122 received a single course of interferon therapy (3 MU, three times weekly for 6 months). No correlation was observed between the degree of genetic complexity of HCV (indicated by the number of bands in the SSCP assay) and patient age, serum alanine aminotransferase activity, or serum HCV-RNA concentration, measured by competitive polymerase chain reaction. HCV genomic complexity was not related to gender nor to the presumed source of infection. The number of SSCP bands detected in serum samples from patients with chronic hepatitis, either mild (8.1 +/- 3.9), moderate (8.0 +/- 3.3), or severe (9.2 +/- 3.3), and in patients with liver cirrhosis, either compensated (8.0 +/- 2.9), decompensated (6.3 +/- 2.9), or with superimposed hepatocellular carcinoma (9.5 +/- 2.9), was similar. The number of SSCP bands detected in patients with sustained response (7.5 +/- 3. 9), transient response (8.3 +/- 2.9), or no response (8.2 +/- 3.6) to interferon administration was similar as well. These observations suggest that the genetic complexity of hypervariable region (HVR1) of HCV, as estimated by SSCP analysis, is not related to the severity of liver injury nor to the type of response to interferon therapy. Thus, information offered by SSCP analysis of HVR1 of HCV in chronic HCV genotype 1b infection does not appear to be useful in the clinical management of these patients. (HEPATOLOGY 1999;29:897-903.)
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PMID:Relationship of the genomic complexity of hepatitis C virus with liver disease severity and response to interferon in patients with chronic HCV genotype 1b infection [correction of interferon]. 1005 95


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