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Background: Percutaneous radiofrequency ablation (RFA) has been widely accepted as an alternative to surgery for small hepatocellular carcinoma (HCC). In RFA, a portion of liver tissue surrounding tumour is also ablated to achieve a safety margin. The intrahepatic bile duct may be injured and result in chronic bile duct dilatation upstream of the injured site. However, the impact of such an injury on the overall prognosis has been unclear. Methods: Patients who showed bile duct dilatation following RFA were identified by a retrospective review of imaging studies. Each dilatation was classified as mild (limited to one hepatic subsegment) or severe (affecting two or more subsegments). The relation between the incidence of intrahepatic bile duct dilatation and HCC recurrence or survival was analysed using proportional hazard models. Results: Among 589 consecutive HCC patients treated with RFA, 70 (11.9%) and 21 (3.6%) patients showed mild and severe bile duct dilatation respectively. Patients with severe dilatation, but not those with mild dilatation, had lower survival and higher HCC recurrence than patients without dilatation. Severe dilatation, but not mild dilatation, was significantly associated with death [hazard ratio (HR) 2.17, P=0.035] and recurrence (HR 2.89, P

One of the characteristics of hepatitis C virus (HCV) infection is the unusual augmentation of oxidative stress, which is exacerbated by iron accumulation in the liver, as observed frequently in hepatitis C patients. Using a transgenic mouse model, the core protein of HCV was shown previously to induce the overproduction of reactive oxygen species (ROS) in the liver. In the present study, the impact of iron overloading on the oxidant/antioxidant system was examined using this mouse model and cultured cells. Iron overloading caused the induction of ROS as well as antioxidants. However, the augmentation of some antioxidants, including heme oxygenase-1 and NADH dehydrogenase, quinone 1, was compromised by the presence of the core protein. The attenuation of iron-induced augmentation of heme oxygenase-1 was also confirmed in HepG2 cells expressing the core protein. This attenuation was not dependent on the Nrf2 transcription factor. Thus, HCV infection not only induces oxidative stress but also hampers the iron-induced antioxidant activation in the liver, thereby exacerbating oxidative stress that would facilitate hepatocarcinogenesis.

Overwhelming lines of epidemiological evidence have indicated that persistent infection with hepatitis C virus (HCV) is a major risk for the development of hepatocellular carcinoma (HCC). In addition, heavy alcohol use has been linked with earlier progression to HCC in chronic hepatitis C patients. However, in the pathogenesis of HCV-associated HCC, it still remains controversial as to whether the virus plays a direct or an indirect role, and as to how alcohol operates in the acceleration of HCC development. Several studies using transgenic mouse models, in which the core protein of HCV has an oncogenic potential, indicate that HCV is directly involved in hepatocarcinogenesis, although other factors such as continuous inflammation or environmental factors seem also to play a role. The downstream events of the HCV core protein expression in the transgenic mouse HCC model are segregated into two pathways. One is the augmented production of oxidative stress in the absence of inflammation along with the attenuation of some scavenging systems in the putative preneoplastic stage with steatosis in the liver. The other pathway is the alteration in cellular gene expression and intracellular signaling, including the mitogen-activated protein kinase cascade. The combination of these pathways would explain the unusually high incidence and multicentric nature of HCC development in HCV infection. In addition, alcohol feeding in this animal model further activated the two pathways synergistically with HCV, leading to an earlier development of HCC. Such a synergy would reveal the molecular basis for the acceleration of HCC development by alcohol in HCV infection.

Patients with HIV infection are frequently infected with hepatitis viruses, which are presently the major cause of mortality in HIV-infected patients after the widespread use of highly active antiretrovirus therapy. We previously reported that approximately 20% of HIV-positive Japanese patients were also infected with hepatitis C virus (HCV). Hepatitis B virus (HBV) infection may also be an impediment to a good course of treatment for HIV-infected patients, because of recurrent liver injuries and a common effectiveness of some anti-HIV drugs on HBV replication. However, the status of co-infection with HIV and HBV in Japan is unclear. We conducted a nationwide survey to determine the prevalence of HIV-HBV co-infection by distributing a questionnaire to the hospitals belonging to the HIV/AIDS Network of Japan. Among the 5998patients reported to be HIV positive, 377 (6.4%) were positive for the hepatitis B surface antigen. Homosexual men accounted for two-thirds (70.8%) of the HIV-HBV co-infected patients, distinct from HIV-HCV co-infection in Japan in which most of the HIV-HCV co-infected patients were recipients of blood products. One-third of HIV-HBV co-infected patients had elevated serum alanine aminotransferase levels at least once during the 1-year observation period. In conclusion, some HIV-infected Japanese patients also have HBV infection and liver disease. A detailed analysis of the progression and activity of liver disease in co-infected patients is needed.

BACKGROUND: Recent studies have revealed that HBV may not be cleared even after the disappearance of serum HBsAg. The purpose of this study was to investigate whether the replication of HBV persists in HBsAg-negative blood donors who lack apparent liver disease. STUDY DESIGN AND METHODS: Serum HBV was examined by using PCR coupled with Southern blotting in 50 blood donors who were identified to be HBsAg negative but anti-HBc positive. RESULTS: HBV DNA was detected in the sera from 19 (38%) of 50 donors. In 11 of the 19, HBV existed exclusively as immune complexes, while HBV presumably did not exist as immune complexes in the remaining eight. The levels of HBV DNA were similar to those in patients who had recovered from acute HBV. Some nucleotide substitutions, which did not confer amino acid changes in the major epitope of HBsAg, were found in the preS-S regions. CONCLUSION: The replication of HBV is ongoing in a substantial proportion of healthy blood donors who have anti-HBc. Blood from such donors may contain very low levels of HBV free of immune complex formation and should be excluded for transfusion. The fact that such blood donors apparently lacked liver disease suggests no pathogenicity of such “occult” HBV.

BACKGROUND Recently, it has been reported that hepatitis B virus (HBV) DNA is detected in cancerous liver tissues in some hepatitis B surface antigen negative chronic hepatitis C patients with hepatocellular carcinoma (HCC). However, the significance of HBV DNA detected in such cases remains unclear. METHODS The authors determined the presence or absence and the titers of HBV DNA in the liver tissue of anti-hepatitis C virus (HCV) positive/HBs antigen negative patients with HCC by polymerase chain reaction (PCR) and Southern hybridization, and correlated them with clinicopathologic parameters. RESULTS HBV DNA was found in cancerous liver tissues from 12 (50.0%) of the 24 patients studied. However, Southern hybridization of genomic DNA in the cancerous liver tissues led to detection of HBV DNA in only 3 (12.5%) of the 24 patients, suggesting that the copy number of HBV DNA may be very low in most cases. Indeed, the titration of HBV DNA in cancerous liver tissues performed by the end point dilution method revealed that most contained less than one copy of HBV DNA per cell, although cells of monoclonal origin carrying integrated HBV DNA should have at least one copy of it. There was no significant difference in HBV DNA positivity between the HCC patients with and without underlying cirrhosis. CONCLUSIONS The results of this study corroborate previous reports of frequent detection of HBV DNA in the liver tissue of anti-HCV positive/HBs antigen negative patients with HCC, but do not support an essential role of HBV in hepatocarcinogenesis in patients with chronic hepatitis C and occult HBV infection. Cancer 2000;88:2478–86. © 2000 American Cancer Society.

Hepatic steatosis has been reported as one of the characteristics which discriminates hepatitis C from other forms of hepatitis, besides lymphoid follicles and bile duct damage. However, it is unclear whether or not the presence of hepatitis C virus (HCV) itself is associated with the development of steatosis. The possibility that the HCV itself is directly related to the development of steatosis was examined. The intrahepatic core protein levels, as a marker of the HCV load, were correlated with the presence of steatosis in 43 patients with chronic hepatitis C. Among 43 patients studied by Western blotting, the core protein was detected in the liver in 27 (62.8%). On the other hand, hepatic steatosis was observed in 21 (48.8%) of the 43 patients. Importantly, the core protein was detectable in 19 (90.4%) of the 21 patients with steatosis, while it was detected in only 8 (36.4%) of the 22 patients without steatosis (P = 0.008). However, serum HCV-RNA levels as determined by the Amplicor monitor were not significantly different between patients with and without steatosis. Multivariate analysis showed that the serum alanine aminotransferase level (P = 0.013), body mass index (P = 0.038), and intrahepatic HCV core protein positivity (P = 0.038) were the independent parameters best predictive of steatosis. These results indicate a close relationship between intrahepatic HCV and the development of steatosis, and suggest a possible role of the HCV itself or core protein in the pathogenesis of steatosis in human chronic hepatitis C. J. Med. Virol. 59:141–145, 1999. © 1999 Wiley-Liss, Inc.