UMLS:C0019204 - FACTA Search

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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 (HCV) infection occurs in as many as 33% of the patients with human immunodeficiency virus (HIV) infection. In view of their improved survival, liver disease will become more clinically significant in patients coinfected with HIV/HCV. Several studies in patients with hemophilia have shown that coinfected patients develop earlier and more severe liver disease, including hepatocellular carcinoma. In nonhemophilic cohorts, lower CD4 counts are associated with an increased prevalence of cirrhosis. However, HCV infection does not seem to alter the natural history of HIV infection in most cases. Human immunodeficiency virus coinfection in pregnant women increases the risk of perinatal HCV transmission 2-fold, with more than 25% of occurrences involving transmission of both viruses: cesarean delivery significantly decreases this risk. The expanded use of highly active antiretroviral therapy may lead to further improvement in morbidity and mortality from HIV infection. Thus, the management of coexistent HCV liver disease will need to be formulated. We suggest that alcohol be disallowed. Interferon and ribavirin in combination are likely to become the therapy of choice, particularly in coinfected patients with higher CD4 counts, lower HCV viremia, and non-1 genotype. During treatment, complete blood cell counts need to be closely monitored. Future controlled trials will determine the efficacy and safety of long-acting interferon preparations. Administration of highly active antiretroviral therapy, with the intent to prevent decreases in CD4 counts, seems crucial in stemming liver disease progression. However, some drugs have clear-cut hepatotoxic potential and patients with known liver disease should be closely monitored. Arch Intern Med. 2000;160:3365-3373.
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PMID:Hepatitis C in patients with human immunodeficiency virus infection: diagnosis, natural history, meta-analysis of sexual and vertical transmission, and therapeutic issues. 1111 28

Mechanisms determining the chronicity or the pattern of clinical course of hepatitis C virus (HCV) infections have not been clarified. Recently, CD81 was reported to bind the E2 protein of HCV and was suggested to function as a cellular receptor for HCV. Accordingly, the hypothesis was examined that CD81 polymorphism, if it exists, might correlate with certain clinical courses of HCV infection. CD81 cDNA sequences were determined from peripheral blood mononuclear cells (PBMCs). Twenty-four Japanese subjects were enrolled initially as follows: patients with chronic hepatitis C without cirrhosis (n = 3), patients with cirrhosis (n = 3), patients with cirrhosis complicated by hepatocellular carcinoma (HCC) (n = 3), patients with persistent HCV viremia without ALT elevation (n = 3), those with positive anti-HCV antibodies without evidence of HCV viremia (n = 3), and healthy volunteers (n = 9). In all PBMCs samples analyzed, no polymorphism was found in the CD81 cDNA sequence. The sequence was different, however, from the one reported previously at three nucleotide positions: a transversion to thymine instead of cytosine at nt 1130, a deletion at nt 1206, and a guanine insertion at nt 71. Subsequently, CD81 cDNA sequences from PBMCs and HCC tissue were compared among the other 6 patients with chronic hepatitis C bearing HCC. A comparative study of the CD81 sequences from HCC and PBMCs revealed that various nucleotide mutations existed only in the HCC samples in 3 out of 6 patients. Several mutations in the 3' non-coding region of CD81 cDNA were observed exclusively in HCC tissue suggesting its possible role in hepatocarcinogenesis. Because of the absence of polymorphisms, however, CD81 is unlikely to affect the progression of chronic hepatitis C in terms of chronicity, hepatitis activity, or disease stage.
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PMID:CD81 nucleotide mutation in hepatocellular carcinoma and lack of CD81 polymorphism in patients at stages of hepatitis C virus infection. 1113 Aug 83

Interferon (IFN) therapy decreases the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV). One hundred and fifty-nine consecutive patients who underwent liver resection for HCV-related HCC were studied. In 17 (group 1) of the 159 patients, HCC was detected during or after IFN therapy. The incidences of recurrence after surgery in the group 1 patients and the other 142 patients (group 2) were compared. Eight patients had a complete response to IFN, 4 had a partial response, and 5 had no response. The proportion of patients without HCV viremia was significantly higher in the group 1 patients (P < 0.0001). The tumor-free survival rate was significantly higher in the group 1 patients (P = 0.0010). By multivariate analysis of various risk factors for recurrence, no previous IFN was a significant independent risk factor for recurrence (risk ratio = 6.336; 95%CI, 1.512 - 26.50). The patients with HCC who underwent IFN therapy previously are good candidates for liver resection because recurrence after the operation was rarely observed.
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PMID:Influence of previous interferon therapy on recurrence after resection of hepatitis c virus-related hepatocellular carcinoma. 1117 45

Although there have been many studies of the risk factors for recurrence after resection of hepatocellular carcinoma (HCC), the subjects were patients with various viral status in the previous studies, and hepatitis C viremia has not been evaluated. We investigated risk factors, including hepatic C viremia and histologic findings of noncancerous hepatic tissue, for recurrence after resection of hepatitis C virus (HCV)-related HCC. A total of 223 patients who underwent liver resection for HCV-related HCC were studied. HCV viremia, laboratory data, degree of HCC malignancy, histologic findings in noncancerous hepatic tissue, preoperative interferon therapy, and operative methods were evaluated for recurrence risk by univariate and multivariate analyses. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin, and the proportion of patients with a high histologic activity score (mild to severe active hepatitis) were significantly higher in patients with HCV viremia than in those without viremia. Serum albumin was significantly lower in patients with HCV viremia. By univariate analysis, older age (> 65 years old), HCV viremia, elevated AST (> 40 IU/L) and ALT (> 45 IU/L), large tumors (> 40 mm), multiple HCCs, moderately or poorly differentiated HCC, portal invasion, mild to severe active hepatitis, and lack of preoperative interferon therapy were risk factors for recurrence. Multivariate analysis showed that older age, HCV viremia, high AST, multiple HCCs, and portal invasion were independent risk factors. For HCV-related HCCs, not only the degree of malignancy of the HCC but also HCV viremia and active hepatitis are risk factors for recurrence.
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PMID:Risk factors for recurrence after resection of hepatitis C virus-related hepatocellular carcinoma. 1119 23

Hepatitis C virus (HCV) infection is a major problem associated with hemodialysis. The extent of liver damage in hemodialysis patients with chronic HCV infection has not been thoroughly documented. The aim of this study was to evaluate liver damage of hemodialysis patients infected with HCV. A total of 233 hemodialysis patients were categorized into two groups at entry: group X, 80 positive for serum HCV RNA, and group Y, 153 negative for serum HCV RNA. All were tested for serum alanine aminotransferase (ALT) serially from 1989 to 1998, and serum hyaluronic acid (HA), serum type-IV collagen (IV-C), platelet counts, and ultrasonographic examination of the liver was done in 1998. In group X, 61.3% had continuously abnormal ALT levels for over six months followed by normal ALT levels. Of the group X patients, 11.3% had abnormal ALT levels in 1998, and in three, hepatocellular carcinoma occurred. Mean HA and IV-C levels in group X (648.8 and 188.7 ng/ml, respectively) were significantly higher than in group Y (213.1 and 165.5 ng/ml, respectively) (P < 0.05). Ultrasonographic findings significantly correlated with serum HA level and platelet counts and showed significantly more abnormalities in group X than in group Y (P < 0.05). From these findings, a combined examination with ultrasonography and serum fibrogenesis markers is useful for detection of liver damage in hemodialysis patients with HCV viremia.
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PMID:Liver damage in hemodialysis patients with hepatitis C virus viremia: a prospective 10-year study. 1121 43

The L-nucleoside analog beta-L-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine (beta-L-Fd4C) was first shown to exhibit potent activity against hepatitis B virus (HBV) in tissue culture and then to significantly inhibit viral spread during acute infection in the duck HBV model (F. Le Guerhier et al., Antimicrob. Agents Chemother. 44:111-122, 2000). We have therefore examined its antiviral activity in a mammalian model of chronic HBV infection, the woodchuck chronically infected with woodchuck hepatitis virus (WHV). Side-by-side comparison of beta-L-Fd4C and lamivudine administered intraperitoneally during short-term and long-term protocols demonstrated a more profound inhibition of viremia in beta-L-Fd4C-treated groups. Moreover, beta-L-Fd4C induced a marked inhibition of intrahepatic viral DNA synthesis compared with that induced by lamivudine. Nevertheless, covalently closed circular (CCC) DNA persistence explained the lack of clearance of infected hepatocytes expressing viral antigens and the relapse of WHV replication after drug withdrawal. Liver histology showed a decrease in the inflammatory activity of chronic hepatitis in woodchucks receiving beta-L-Fd4C. An electron microscopy study showed the absence of ultrastructural changes of hepatic mitochondria, biliary canaliculi, and bile ducts. However, a loss of weight was observed in all animals, whatever the treatment, as was a transient skin pigmentation in all woodchucks during beta-L-Fd4C treatment. There was no evidence that lamivudine or beta-L-Fd4C could prevent the development of hepatocellular carcinoma with the protocols used. These results indicate that beta-L-Fd4C exhibits a more potent antiviral effect than lamivudine in the WHV model but was not able to eradicate CCC DNA and infected cells from the liver at the dosage and with the protocol used.
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PMID:Antiviral activity of beta-L-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine in woodchucks chronically infected with woodchuck hepatitis virus. 1125 17

The number of persons infected with hepatitis C virus(HCV) is estimated to be about one to two million in Japan. Recently researchers have shown a growing interest in HCV, since the virus infection may cause liver cirrhosis and hepatocellular carcinoma. The examinations for HCV can be divided into host factor and virus factor detection methods. Classification and cost of HCV tests are shown. Antibody tests as host factor detection are used to screen for infection, for auxiliary diagnosis of viremia and for choosing treatment. Virus factor tests, such as the measurement of the viral load can be used for choosing treatment and determining the response to therapy. We describe that usage of laboratory tests for HCV and discuss medical insurance coverage.
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PMID:[The examinations associating with hepatitis C virus and medical reimbursement]. 1157 84

Infection with hepatitis C virus (HCV) accounts for 40% of cases of chronic liver disease in the United States and is now the most common indication for liver transplantation. Estimates suggest that 4 million people (1.8%) of the American population are or have been infected with HCV. Currently, the treatment of choice for patients with chronic HCV infection is recombinant interferon alfa with ribavirin. Pegylated interferons are a promising new development, and in combination with ribavirin, they will rapidly become the standard of care. The goals of therapy are to slow disease progression, improve hepatic histology, reduce infectivity, and reduce the risk of hepatocellular carcinoma. Sustained virologic response, which generally implies the absence of viremia for 6 months or more following completion of therapy, is increasingly being regarded as a cure, with evidence of slowing or even regression of fibrosis on follow-up liver biopsy. A number of factors have been shown to be predictive of a sustained response, including viral genotype other than 1, low serum HCV RNA levels, absence of cirrhosis, younger age, female gender, and shorter duration of infection. Disease severity as assessed by liver biopsy, comorbidities, and possible contraindications to therapy should be weighed in the decision to begin treatment. Counseling patients regarding transmission, natural history, and drug and alcohol abstinence also should be included in management. Close monitoring should be done during treatment for side effects of interferon, including depression and bone marrow suppression. Hemolytic anemia is the major side effect of ribavirin.
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PMID:Chronic Hepatitis C. 1169 76

As documented in the recent literature, there are more than 50 million people infected with HIV worldwide to date since the emergence of HIV and AIDS in the Western world in 1981. More importantly, about 7000 people die of AIDS daily with 2.5 and 2.6 millions total deaths in 1998 and 1999, respectively. On the other hand, human hepatitis B virus (HBV) is the leading cause of chronic hepatitis in the world. According to WHO executive summary, over 350 millions (approximately 5% of the world s population) people are chronically infected with HBV. There are about 1 million chronic HBV carriers in the United States. Although safe and effective vaccination for HBV is available for developing countries, there is still no effective treatment for the millions of chronically infected individuals. Consequently, long term infection with chronic HBV could lead to cirrhosis, and hepatocellular carcinoma. In light of these facts, it is evident that the discovery and development of novel antiviral agents for the treatment of HIV and HBV is an extremely important undertaking.The interest in L-nucleosides was spurred in recent years by the findings that L-nucleosides are generally endowed with lower host toxicity while maintaining good antiviral activity in comparison to their respective D-nucleosides. The recent FDA approval of Lamivudine [L-BCH 189 (3TC)] for the treatment of HIV and HBV further supports these notions. Since the discovery of Lamivudine, a large number of 2 ,3 -dideoxy (dd)- and 2 ,3 -didehydro-2 ,3 -dideoxy (D4)-L-nucleoside analogs have been synthesized and evaluated in hopes of identifying even better antiviral agents. As a result, 2 ,3 -Dideoxy-2 ,3 -didehydro-beta-L-fluorocytidine (beta-L-Fd4C) was found to be a promising new lead. The first synthesis and antiviral activity assessment of L-Fd4C were reported by Lin and Cheng et al. in 1996. Recent disclosures from several laboratories clearly demonstrated that L-Fd4C was the most potent anti-HBV agent reported to date (vs. 3TC, L-FddC, L-FMAU, etc.). In fact, L-Fd4C proved to be at least 10 times more potent than Lamivudine on HBV DNA synthesis in the hepatoma cell line HepG2 2.2.15. Compared with L-Fd4C, D-Fd4C showed similar anti-HIV activity yet reduced anti-HBV activity. 2 F-L-Fd4C exhibited excellent acid stability but reduced antiviral activity and cytotoxicity. Although L-Fd4C is converted intracellularly by cytoplasmic deoxycytidine kinase to its mono-, di- and triphosphate metabolites,43 the newly prepared bis(SATE)-L-Fd4CMP proved to be more potent against HBV yet less cytotoxic than L-Fd4C itself. The chemically synthesized L-Fd4CTP was found to be a poor substrate for human polymerase gamma. A recent report from Zhu and Cheng et al. indicated that L-Fd4C had no inhibitory effect on mitochondrial DNA synthesis at concentrations up to 10 microM. An in vivo study involving HBV-infected ducks showed that longer administration of L-Fd4C induced a sustained suppression of viremia (>95%) and of viral DNA synthesis in the liver. The same study also demonstrated that L-Fd4C is more potent than 3TC in vivo. In summary, on the basis of the data presented in this chapter, it is evident that L-Fd4C is endowed with exceptional anti-HBV activity (both in vitro and in vivo) as well as an acceptable toxicity profile, thus rendering it a very promising development candidate.
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PMID:Comparative evaluation of L-Fd4C and related nucleoside analogs as promising antiviral agents. 1196 52

The TT virus (TTV) load was estimated in sera obtained from 237 patients with hepatitis C virus (HCV)-related chronic liver disease including 42 patients with hepatocellular carcinoma (HCC), by real-time detection PCR using primers and a probe derived from the well-conserved untranslated region of the TTV genome, which can detect all known TTV genotypes. Of the 237 patients studied, 18 (8%) were negative for TTV DNA, 87 (37%) had low TTV viremia (1.3 x 10(2)-9.9 x 10(3) copies/ml), and 132 (56%) had high TTV viremia (1.0 x 10(4)-2.1 x 10(6) copies/ml). Various features were compared between the patients with high TTV load (n = 132) and those with no TTV viremia or low viral load (n = 105). High TTV viremia (> or =10(4) copies/ml) was significantly associated with higher age (P < 0.05), past history of blood transfusion (P < 0.001), complication of cirrhosis (P < 0.05) or HCC (P < 0.0005), lower HCV RNA titer (P < 0.05), and lower platelet count (P < 0.01). On multivariate logistic regression analysis, high TTV viral load was a significant risk factor for HCC (P < 0.05), independent from known risk factors such as complication of liver cirrhosis (P < 0.0001) and high age (> or =65 years, P < 0.05), among all 237 patients. Furthermore, high TTV viral load was an independent risk factor for HCC among the 90 cirrhotic patients (P < 0.05). These results suggest that a high TTV viral load is associated independently with the complication of HCC and may have prognostic significance in patients with HCV-related chronic liver disease, although whether high TTV viremia mediates the progression of HCV-related chronic liver disease remains to be defined.
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PMID:High TT virus load as an independent factor associated with the occurrence of hepatocellular carcinoma among patients with hepatitis C virus-related chronic liver disease. 1211 95

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