Expansion of CD4(+)CD25(+)FoxP3(+) regulatory T cells in hepatitis C virus-related chronic hepatitis, cirrhosis and hepatocellular carcinoma.

AIM: Regulatory T (Treg) cells may play a pivotal role in the persistence of hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC). Therefore, we examined their frequency in peripheral blood from patients with HCV-positive chronic hepatitis (CH), cirrhosis (LC) and HCC. METHODS: Treg cells were identified as CD4(+), CD25(+) and FoxP3(+) T lymphocytes using three-color FACS. The frequency of Treg cells was expressed as a percentage of the total CD4(+) T lymphocytes, and the phenotype of Treg cells was examined using CD45RA. RESULTS: Treg cells were significantly increased in CH (5.88 +/- 0.19%, n = 76; P < 0.01), LC (6.10 +/- 0.28%, n = 40; P < 0.001) and HCC (6.80 +/- 0.30%, n = 57; P < 0.0001) compared to healthy control (5.13 +/- 0.25%, n = 31). However, Treg cells were not increased with the progression of fibrosis or the grade of inflammations. Treg cells were slightly increased in early-stage HCC (6.91 +/- 0.40%) compared with advanced-stage HCC (6.58 +/- 0.39%), but these results were not statistically significant. In a serial examination, a distinct increase in Treg cells after local therapy for early-stage HCC was a hallmark of early recurrence. Most expanded Treg cells in HCC were CD45RA(-), suggesting that a memory-type Treg population had differentiated in the periphery and not in the thymus. CONCLUSION: We observed an increase in Treg cells in HCV-related chronic liver disease, particularly in HCC, and these cells were shown to be memory-type Treg cells.

[A case of primary small cell carcinoma of the esophagus responding remarkably to carboplatin (CBDCA) + etoposide (VP-16) combination therapy and radiation therapy].

A 78-year-old man was admitted to hour hospital because of dysphagia, and primary small cell carcinoma of the esophagus was diagnosed. Carboplatin (CBDCA) + etoposide (VP-16) combination chemotherapy and radiation therapy was performed. After this therapy, endoscopic examination and computed tomographic scan showed the disappearance of the primary esophageal tumor. Endoscopic examination with biopsy confirmed the disappearance of malignant cells. Severe adverse reactions were not observed during this therapy. This patient is alive without recurrence for 6 years and 3 months. This case seems to provide suggestions on deciding on the operative indications for small cell carcinoma of esophagus.

Etiology of non-B non-C hepatocellular carcinoma in the eastern district of Tokyo.

BACKGROUND: This study was carried out to clarify the carcinogenic factors associated with nonviral hepatocellular carcinoma (HCC). METHODS: A total of 320 HCC patients diagnosed and treated from January 2000 to December 2006 were enrolled. The clinical characteristics of non-B non-C HCC patients were examined to determine possible carcinogenic factors. RESULTS: Of 320 HCC patients, 64 were classified as having non-B non-C HCC. The proportion of non-B non-C HCC increased from 17.8% in 2000 to 28.6% in 2006. Non-B non-C HCC patients had a significantly higher rate of early stage cirrhosis (Child-Pugh classification) than viral HCC patients. Significantly fewer non-B non-C HCC patients had periodic intensive medical assessments than viral HCC patients. Forty-five non-B non-C HCC patients were habitual alcohol drinkers, ten had nonalcoholic fatty liver disease (NAFLD), and seven had no apparent etiology. In habitual drinkers, the stage of underlying liver disease varied widely, while most NAFLD patients had early stage cirrhosis. On the other hand, more than half of the patients with HCC of undetermined etiology had noncirrhotic liver disease. Among habitual drinkers, the underlying liver disease was more progressive, and the T stage was more advanced in those with high daily alcohol intake than in those with low daily alcohol intake. Periodic intensive medical assessments were crucial for detecting early stage HCC. CONCLUSIONS: Alcohol consumption and NAFLD may be important etiological factors in non-B non-C HCC. Periodic medical assessments for all patients with non-B non-C cirrhosis are crucial for early diagnosis and curative therapy.

Analysis of risk factors for hepatocellular carcinoma that is negative for hepatitis B surface antigen (HBsAg).

OBJECTIVE: To clarify risk factors for hepatocellular carcinoma (HCC) other than hepatitis B surface antigen (HBsAg). PATIENTS AND METHODS: We investigated serum HBV-DNA and other factors in 146 patients with liver cirrhosis (LC) or HCC who were HBsAg negative. We analyzed the clinical background of the patients, status of hepatitis B (HBV) viral markers and platelet count as well as the presence of an HBV-DNA fragment by PCR and elucidated risk factors for HCC generation using a logistic regression model. RESULTS: Among ten factors, we determined that four represented a significant risk for HBsAg negative HCC: male gender, total alcohol consumption, total cigarettes smoked, and the presence of an HBV-DNA fragment. Multivariate analysis showed that among the four factors, the HBV-DNA fragment was an independent factor associated with HCC. CONCLUSION: The presence of an HBV-DNA fragment irrespective of the status of antibodies to either HBsAg (anti-HBs) or hepatitis B core antigen (anti-HBc) is a pivotal factor associated with the development of HCC.