ABSTRACT
BACKGROUND: Alpha-fetoprotein (AFP) messenger RNA (mRNA) may be a potential marker of the dissemination of hepatocellular carcinoma (HCC) cells into the circulation. The aim of this prospective pilot study was to assess the prognostic value of quantitative levels of AFP mRNA in patients undergoing ablative treatment for HCC. METHODS: Peripheral blood samples were taken from seven patients before and after treatment for measurement of AFP mRNA levels by reverse-transcriptase polymerase chain reaction (RT-PCR). Patients were treated with percutaneous radiofrequency thermal ablation (n=3) or transarterial chemoembolization (n=4). The level of AFP mRNA in blood was serially determined, and the time course was related to the clinical course and disease outcome. The median duration of follow-up was 14 months (range, 9-16 months). RESULTS: HCC recurred locally in four patients, and lung metastases developed in two of them. Patients were divided into three groups on the basis of the pre- and post-treatment AFP mRNA status. Group 1 included four patients with consistently high serum AFP and AFP mRNA levels (pre- and post-treatment). These patients developed distant and local recurrence. Group 2 included a patient with serum-negative AFP mRNA and normal AFP levels at entry. Although serum AFP remained within normal range, mean AFP mRNA increased from 10 to 95 copies/microg RNA. This patient had no distant metastases, but his tumor markedly increased in size. In Group 3, AFP mRNA and serum AFP remained within normal range before and after treatment. These two patients did not develop either local or distant metastases during the follow-up period. CONCLUSIONS: Although this is a small sample size pilot study these findings imply that quantitative measurement of AFP-expressing cells in peripheral blood may serve as a marker of HCC recurrence.
Subject(s)
Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/blood , Liver Neoplasms/diagnosis , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/diagnosis , RNA, Messenger/blood , alpha-Fetoproteins/analysis , Aged , Carcinoma, Hepatocellular/secondary , Carcinoma, Hepatocellular/therapy , Catheter Ablation , Embolization, Therapeutic , Female , Humans , Liver Neoplasms/therapy , Male , Pilot Projects , Prognosis , Prospective Studies , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Giant cell hepatitis (GCH) in adults is a rare event. The diagnosis of GCH is based on findings of syncytial giant hepatocytes. It is commonly associated with either viral infection or autoimmune hepatitis type I. A patient with GCH due to autoimmune hepatitis type II (LKM1+) is described, a combination that has not been previously reported. Corticosteroid therapy was effective in decreasing serum liver enzymes; however, the patient deteriorated rapidly and developed subfulminant hepatic failure. Although an emergency orthotopic liver transplantation was performed, the patient died because of reperfusion injury. Interestingly, only a few giant hepatocytes were noted in the explanted liver. This case stresses the association of GCH with autoimmune disorders, the possible immune mechanism involved in the formation of giant cell hepatocytes, and illustrates the rapidly progressive course and unfavorable prognosis that these patients can develop.
Subject(s)
Autoantibodies/analysis , Giant Cells , Hepatitis, Autoimmune/diagnosis , Liver Failure/diagnosis , Adult , Diagnosis, Differential , Fatal Outcome , Female , Giant Cells/pathology , Hepatitis, Autoimmune/pathology , Humans , Liver/pathology , Liver Failure/pathology , Liver Function Tests , Liver Transplantation , Middle AgedABSTRACT
The mechanism of hepatitis C virus (HCV) -induced hepatotocellular carcinoma (HCC) is still unknown, but in vitro studies clearly suggest that HCV proteins exert a direct effect on liver carcinogenesis. HCV NS3 serine protease is known to play a key role in the life cycle of the virus and may interact with the host cellular regulatory proteins. The aim of the present study was to conduct a genetic analysis of the HCV NS3 gene coding for the serine protease isolated from serum, tumor, and nontumor tissue of HCC patients. RNA was extracted and HCV cDNA was amplified by nested reverse transcriptase-polymerase chain reaction (RT-PCR). Sequence comparison yielded unique changes at the vicinity of the catalytic sites of the NS3 clones isolated only from HCC tissue. These changes included the insertion of a "large" and charged amino acid, substitution of a polar with a hydrophobic amino acid, and substitution of a charged with a polar amino acid. Those changes affect the electrostatic charge around the active site, and thus the activity and substrate specificity of the serine protease. This is the first study to define significant amino acid changes at the catalytic domain of the NS3 serine protease gene isolated from HCC tissue.