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)

Primarily TTV has been thought as an etiologic agent of post transfusion non-A to -G hepatitis. TTV can replicate in liver and bone marrow cells. The presence of TTV has been found in the serum of patients with acute as well as chronic hepatitis of known etiology. Patients with acute hepatitis A, B, C and hepatitis caused by EBV or CMV all have TTV viremia in a frequency up to 60%. In chronic viral hepatitis TTV was present in a wide range of 7-94.4%. Treatment of viral hepatitis patients with interferon alfa and rybawiryn leads to eradication of TTV viremia in 50% cases. TTV infection in hepatocellular carcinoma ranged from 8.1% up to 100% patients. In hepatitis of unknown etiology TTV infection was observed in 26% to 71% cases. In liver cirrhosis TTV infection has been evidenced in 10% to 66% patients. Some authors postulated that the frequency of TTV increased with the number of blood or blood products transfusions. Coinfection of TTV has been found in 34.9%-76% of HIV positive persons. The study of medical staff revealed no difference in TTV viremia with healthy individual control. TTV is widespread in healthy general population. Therefore based on so far published results the association between TTV infection and hepatitis is questionable.
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PMID:[Role of TT virus in pathogenesis of liver diseases--the prevalence of TTV in patients and healthy individuals]. 1215 53

Recent discovery of a novel DNA virus from the serum of a Japanese patient (T.T.) has prompted further studies directed on possible role of TT virus in the development of cryptogenic hepatitis. The TT is an unenveloped and circular DNA virus. TTV possesses single stranded DNA genome and comprises 3537 to 3853 nucleotides. TTV is similar to the Circoviridae and possesses three open reading frames. Phylogenetic analysis revealed up to 30% nucleotide sequence divergence in the 16 virus genotypes. TTV infection can be detected by polymerase chain reactions, in situ hybridization and by specific antibodies to TTV. TTV DNA has been identified in the serum of patients with cryptogenic hepatitis, hepatitis B and C, hepatocellular carcinoma as well as in healthy individuals. TTV has been found also in the peripheral blood leukocytes, bone marrow cells, liver biopsies as well as in feces and breast milk. Some animals including cattle, sheep, pigs and chicken appeared to have TTV viremia. Recent detection of TTV in nonblood products, such as saliva and feces suggest in addition to parenteral also nonparenteral routes of TTV transmissions including sexual and fecal-oral.
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PMID:[TT virus--characteristics, occurrence and routes of transmission]. 1215 72

In this report, we examine two patients with chronic hepatitis B virus (HBV) infection that had been diagnosed as precirrhosis or liver cirrhosis more than a decade previously. These patients had been cleared of HBsAg and had developed anti-HBs at a later time, yet hepatocellular carcinoma (HCC) eventually occurred. Both patients had been found negative for HBV DNA, using sensitive methods. Interestingly, a nontumor specimen of the liver obtained at surgical resection showed a marked reduction of fibrosis when compared to the histology observed when the patient was diagnosed as precirrhosis. Our findings suggest that the fibrosis from liver cirrhosis had been absorbed to a large extent during the long-term absence of active viremia and the normalization of alanine aminotransferase (ALT) levels. However, the cancer-prone biological characteristics of liver cirrhosis remained. Thus, patients with liver cirrhosis due to past chronic hepatitis B should be monitored carefully for the development of HCC even if HBV infection has been serologically resolved.
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PMID:Remote development of hepatocellular carcinoma in patients with liver cirrhosis type B serologically cured for HBs antigenemia with long-standing normalization of ALT values. 1235 45

Acute hepatitis chronic C is usually anicteric and asympntomatic. Chronic viraemia occurs in 85-90% of infected individual. 70% of whom develop some degree of chronic liver injury and face the potential risk of progression to cirrhosis and hepatocellular carcinoma. Approximately 20% of individual with chronic hepatitis C infection develop cirrhosis within 20 years.
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PMID:[Natural history of chronic hepatitis C]. 1271 46

The effect of genetic polymorphisms for glutathione S-transferase ( GST) M1, GSTT1, GSTP1-1( GSTP1), cytochrome P450 2E1 ( CYP2E1) and aldehyde dehydrogenase 2 ( ALDH2) on the risk of hepatocellular carcinoma (HCC) was observed in 78 Japanese patients with HCC and 138 non-cancer hospital controls. We found a positive association between cumulative amounts of alcohol consumption (>/=600,000 ml in a lifetime) and the risk of HCC (OR=4.52, 95% CI 2.39-8.55). However, cigarette smoking was not significantly related to the risk of HCC (OR=1.23, 95% CI 0.57-2.68). The allelic frequencies of GSTM1, GSTT1, GSTP1, CYP2E1and ALDH2of HCC patients were not significantly different from those of controls when odds ratios were only adjusted for age and gender except for any 2 alleles of ALDH2in drinkers (OR=2.53, 95% CI 1.21-5.31). However, the frequency of any C2 alleles of CYP2E1and any 2 alleles of ALDH2were significantly higher than those of controls (OR=5.77, 95% CI 1.24-27.39, OR=9.77, 95% CI 1.63-58.60) when covariates including viremia were selected by using stepwise logistic regression analysis. We conclude that habitual alcohol drinking is likely to lead to an increased risk of HCC, and any C2alleles of CYP2E1as well as any two alleles of ALDH2were also associated with an increased risk of HCC.
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PMID:Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and the risk of hepatocellular carcinoma. 1275 47

The core promoter mutants of hepatitis B virus (HBV) emerge as the dominant viral population at the late HBeAg and the anti-HBe stages of HBV infection, with the A1762T/G1764A substitutions as the hotspot mutations. The double core promoter mutations were found by many investigators to moderately enhance viral genome replication and reduce hepatitis B e antigen (HBeAg) expression. A much higher replication capacity was reported for a naturally occurring core promoter mutant implicated in the outbreak of fulminant hepatitis, which was caused by the neighboring C1766T/T1768A mutations instead. To systemically study the biological properties of naturally occurring core promoter mutants, we amplified full-length HBV genomes by PCR from sera of HBeAg(+) individuals infected with genotype A. All 12 HBV genomes derived from highly viremic sera (5 x 10(9) to 5.7 x 10(9) copies of viral genome/ml) harbored wild-type core promoter sequence, whereas 37 of 43 clones from low-viremia samples (0.2 x 10(7) to 4.6 x 10(7) copies/ml) were core promoter mutants. Of the 11 wild-type genomes and 14 core promoter mutants analyzed by transfection experiments in human hepatoma cell lines, 6 core promoter mutants but none of the wild-type genomes replicated at high levels. All had 1762/1764 mutations and an additional substitution at position 1753 (T to C), at position 1766 (C to T), or both. Moreover, these HBV clones varied greatly in their ability to secrete enveloped viral particles irrespective of the presence of core promoter mutations. High-replication clones with 1762/1764/1766 or 1753/1762/1764/1766 mutations expressed very low levels of HBeAg, whereas high-replication clones with 1753/1762/1764 triple mutations expressed high levels of HBeAg. Experiments with site-directed mutants revealed that both 1762/1764/1766 and 1753/1762/1764/1766 mutations conferred significantly higher viral replication and lower HBeAg expression than 1762/1764 mutations alone, whereas the 1753/1762/1764 triple mutant displayed only mild reduction in HBeAg expression similar to the 1762/1764 mutant. Thus, core promoter mutations other than those at positions 1762 and 1764 can have major impact on viral DNA replication and HBeAg expression.
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PMID:Genome replication, virion secretion, and e antigen expression of naturally occurring hepatitis B virus core promoter mutants. 1276 80

The lifetime cumulative risk of developing cirrhosis and hepatocellular carcinoma is the rationale for treating patients with chronic hepatitis C with antivirals. The standard treatment is combination therapy with interferon-alfa and ribavirin. In patients with high transaminases and histologic signs of chronic hepatitis, 6- to 12-month therapy with 3 mega units (MU) interferon-alfa thrice weekly, combined with ribavirin, yielded up to 30% sustained responders, and this was increased to 50% with pegylated interferon combined with ribavirin. Favorable predictors of response to the former treatment were genotype 2 or 3, less than 2 million copies of hepatitis C virus (HCV), no portal fibrosis at biopsy, age less than 40 years, and female sex. The same was true for the latter treatment; however, with body weight less than 82 kg replacing female sex. A 98% cure of community-acquired acute hepatitis C was achieved with early treatment with daily doses of 5 MU interferon, compared with a calculated 30% HCV-RNA clearance in untreated patients. More cost-effective strategies for ceasing treatment, based upon early clearance of HCV, are under investigation, with cutoff equal to or more than a 2 log decrease in serum HCV-RNA at week 12. This approach has 100% negative predictive value and 80% positive predictive value. Treatment can also be optimized by combination retreatment of relapsers and nonresponders to monotherapy, which yielded sustained responses of 50% and 25%, respectively. There are difficult-to-treat patients who have high viremia, genotype 1 and 4, or coinfection with HIV or HBV, or carry an organ graft, and those who did not respond to combination therapy. Extended treatment of the latter patients with pegylated interferon might slow down the progression of fibrosis.
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PMID:Treatment of chronic hepatitis C in Europe. 1450 51

Chronic hepatitis C entails a life-long risk of developing cirrhosis and hepatocellular carcinoma and eradication of the hepatitis C virus (HCV) is the only realistic approach for lowering the risk of disease progression. Treatment is indicated for patients with high transaminases and histologic signs of chronic hepatitis: 6-12 month therapy with 3-6MU interferon alfa thrice weekly combined with 1-1.2 grams ribavirin yielded up to 30% sustained virological responses (SVR). SVR raised up to 50% with pegylated interferons combined with ribavirin. Favourable predictors of response to the former treatment are genotype 2 or 3, less than 2 million copies of HCV, no or portal fibrosis at biopsy, age less than 40 yr and female gender. The same was true for the latter treatment, however, with body weight less than 82 kg replacing female gender. Six month treatment is enough for treating genotype 2 or 3 patients whereas 12-month therapy is indicated for the more resistant patients with genotype 1 or 4.98% cure of community-acquired acute hepatitis C was achieved with early treatment with daily doses of 5MU interferon, compared to a calculated 30% virus clearance occurring in untreated patients. Cost-effective stopping rules based upon early clearance of serum HCV-RNA, are under investigation. A cut-off equal or more than 2 log decrease in serum HCV-RNA at week 12, has 97% negative predictive value and 60% positive predictive value. Treatment could be optimized also by retreatment with combination therapy of relapsers and non-responders to monotherapy, with SVR rates of 50% and 25%, respectively. Difficult-to-treat patients include patients who have high genotype 1 and 4 viremia or coinfection with HIV or hepatitis B virus as well as patients who carry an organ graft. Extended treatment of virological non responders with pegylated interferons might slow down progression of hepatic fibrosis and prevent hepatocellular carcinoma.
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PMID:Treatment of chronic hepatitis C. 1451 11

The role of quantitative viral load in development of hepatocellular carcinoma (HCC) among chronic hepatitis B virus (HBV) carriers was evaluated using real-time PCR (TaqMan PCR), a highly sensitive method for quantitative detection of HBV DNA. Serum samples collected at study entry from HCC cases and matched controls were chosen separately from ongoing prospective cohort studies in Senegal, West Africa, and Haimen City, China. For 14 HCC cases and 28 controls from Senegal, the relative risk (RR, 95% CI) of HCC was 15.6 (2.0-124.3) for those positive by the TaqMan PCR assay. Average length of follow-up (study entry to death from HCC) among cases was 2.8 (+/-1.6) years. The paired median difference between cases and controls was 3.8 x 10(4) virions/ml, with cases higher (P = 0.09). In order to clarify the relationship with lower-titer viremia, we selected 55 cases and 55 matched controls from the Chinese cohort all negative for serum HBV DNA by conventional dot blot hybridization. In this group, the RR associated with HBV DNA positivity by TaqMan PCR was 3.1 (1.1-9.2), with an average duration of follow-up of 3.3 (+/-2.1) years. The median difference in quantitative viremia between cases and controls was 6.0 x 10(4) virions/ml, with cases higher (P < 0.0001). Increased risk appeared to be confined to subjects with viral loads >2.3 x 10(4) virions/ml. In conclusion, HBV viremia, except perhaps at extremely low levels, is associated with increased risk for HCC in prospective studies of chronic carriers in two disparate populations.
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PMID:Hepatitis B viremia is associated with increased risk of hepatocellular carcinoma in chronic carriers. 1463 8

Both hepatitis B virus (HBV) and hepatitis C virus (HCV) are more common in HIV-infected individuals than in the general population as a result of shared risk factors for viral acquisition. Populations of injecting drug users are at particularly high risk for HIV/HCV co-infection. Co-infection with HIV results in greater likelihood of chronicity and enhanced viral replication in the setting of both HBV and HCV infections. Current evidence suggests that HIV infection may have a negative impact on HBV-related liver disease progression, although the mechanisms for this are unclear. HBV seems to have little impact on the progression of HIV disease. HIV co-infection hastens HCV-related liver disease with faster progression to cirrhosis, end-stage liver disease and occurrence of hepatocellular carcinoma. There is still conflicting evidence on the impact of HCV on HIV progression with inconsistent results from cohort studies. Long-term follow-up of highly active antiretroviral therapy (HAART)-treated patients will help elucidate this further. Antiretroviral agents have little long-term impact on HCV viraemia, although some have significant anti-HBV activity. Morbidity and mortality from end-stage liver disease in HIV-infected individuals is increasing and every effort should be made to identify, educate and treat as appropriate those with HBV or HCV co-infection.
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PMID:The epidemiology and natural history of HIV/HBV and HIV/HCV co-infections. 1467 4


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