Junichi Tazawa

Radiation therapy in combination with transcatheter arterial chemoembolization for hepatocellular carcinoma with extensive portal vein involvement

The aim of this study was to examine the effectiveness and toxicity of radiation therapy in combination with transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with extensive portal vein tumor thrombus (PVTT).

Diabetes mellitus may be associated with hepatocarcinogenesis in patients with chronic hepatitis C.

It is unknown whether diabetes mellitus is a risk factor of the hepatocarcinogenesis in patients with chronic hepatitis C. Three hundred eleven anti-hepatitis C virus (HCV) -positive patients who had undergone liver biopsies were studied. Patients with histologically proven cirrhosis or withdrawing within 12 months were excluded. Thus, the remaining 279 patients were followed-up for 65.9 ± 29.4 months until the occurrence of hepatocellular carcinoma (HCC). During the observation period, HCC developed in 13 patients. Diabetes, age, sex, habitual alcohol intake, history of blood transfusion, serum α-fetoprotein level, histological findings, HCV genotype, viral load, and interferon therapy were assessed as potential risk factors. The Cox proportional hazard model identified that diabetes mellitus, histological staging, and age were independently associated with the occurrence of HCC. With multivariate analysis, only diabetes mellitus and age were associated with the occurrence of HCC. Diabetes mellitus may be associated with hepatocarcinogenesis in patients with chronic hepatitis C.

Efficacy of endoscopic clipping for bleeding gastroduodenal ulcer: comparison with topical ethanol injection.

Objective:Although endoscopic clipping is used widely for the treatment of bleeding gastroduodenal ulcers, clinical trials on its efficacy are scarce. The aim of this study is to assess the efficacy and safety of endoscopic clipping for hemostasis from bleeding gastroduodenal ulcers.Methods:The present study was designed as a retrospective study using historical controls. One hundred consecutive patients with bleeding gastroduodenal ulcers were treated by endoscopic clipping. The preceding 91 consecutive patients treated by endoscopic pure ethanol injection were regarded as controls. Forty-nine of the clipping group and 41 of the ethanol group had lesions at sites difficult to perform endoscopic manipulation. Hemostatic rates, rebleeding rates, amounts of blood transfusion, and durations of hospital stay were analyzed.Results:The hemostatic rate was 96% in both clipping and ethanol groups, whereas the rebleeding rate was lower (15%vs 29%, p= 0.023) in the former than the latter. In technically difficult cases, the hemostatic rate was comparable (96 vs 90%).Conclusion:In patients with bleeding gastroduodenal ulcers, endoscopic clipping may be a choice of therapy because of a low rebleeding rate compared with pure ethanol injection.

Expression of gap junction protein connexin 32 and E-cadherin in human hepatocellular carcinoma

The expression of connexin 32, a major gap junction protein, and E-cadherin, an intercellular adhesion molecule that is supposed to be involved in the regulation of gap junctional intercellular communications, was examined immunohistochemically in seven specimens of human hepatocellular carcinoma and surrounding non-carcinomatous tissues. We found that the number of connexin 32-positive spots per mm2 was significantly less in hepatocellular carcinoma tissues than in the surrounding non-carcinomatous cirrhotic tissues (4360 +/- 3390/mm2 vs 10,030 +/- 3690/mm2; p < 0.01). The number in the latter was also significantly less than that in normal controls (23,560 +/- 4170/mm2). E-cadherin was expressed in all non-carcinomatous hepatocytes as well as carcinomatous cells, except for one case of Edmondsons grade III hepatocellular carcinoma. These results suggest an impairment of cell-to-cell communications in human hepatocellular carcinomas.

Choledochocele with obstructive jaundice: A case report and a review of the Japanese literature

A case of a 57-year-old farmer with a rare type of choledochal cyst (choledochocele; Alonso-Lejs type III) is described. The patient was admitted because of obstructive jaundice and acute biliary infection. Abdominal computed tomography scan showed a cystic lesion in the head of the pancreas, and endoscopic retrograde cholangiopancreatography disclosed cystic dilatation of the terminal portion of the common bile duct. It was suspected that the choledochocele could swell and compress the common bile duct, causing obstructive jaundice and acute cholangitis; therefore, it was surgically resected. We also reviewed 61 cases of choledochocele reported in Japan; the findings were similar to those reported in the English literature.

Overexpression of interferon γ -inducible protein 10 in the liver of patients with type i autoimmune hepatitis identified by suppression subtractive hybridization

OBJECTIVE:To clarify gene expression profiles in the liver may elucidate the pathogenesis of type I autoimmune hepatitis (AIH). Using suppression subtractive hybridization (SSH), we identified genes overexpressed in the liver of AIH.METHODS:A small liver biopsy sample from a patient with definite AIH was available to be analyzed in our system. By mixing cDNA synthesized from this sample as a ‘tester’ and cDNA from a normal liver as a ‘driver,’ we subtracted cDNA to enrich genes overexpressed in AIH. After polymerase chain reaction (PCR) amplification and subcloning, we identified subtracted genes by sequencing 50 randomly selected clones.RESULTS:Only one cDNA fragment, which is identical to interferon inducible protein 10 (IP-10), was overexpressed by >10 times in the liver of AIH, as compared with control. We confirmed IP-10 overexpression in all eight patients with AIH by reverse transcription PCR. Immunohistochemical analysis demonstrated increased IP-10 expression in hepatocytes in the liver of AIH. Reverse transcription PCR analysis of 63 liver biopsy samples with various liver diseases revealed that IP-10 expression was significantly higher in AIH (p = 0.025) and chronic hepatitis C (p = 0.0043) than in other liver diseases. Interestingly, the amount of IP-10 mRNA expression was correlated with serum ALT values in AIH (p = 0.0006), but not in chronic hepatitis C (p = 0.43).CONCLUSION:These results indicate the IP-10 expression in the liver might be used as a preferential marker of AIH, and that IP-10 has some pathophysiological roles in the liver damage of AIH.

Long-term observation after transjugular intrahepatic portosystemic stent-shunt in two patients with hepatocellular carcinoma.

Two patients with hepatocellular carcinoma (HCC) were treated with transjugular intrahepatic portosystemic stent-shunt (TIPS) and followed for 22 and 58 months thereafter. HCC was well controlled by transcatheter arterial chemoembolization. Hepatic failure or metastasis, especially in the lung, was not observed in the long-term observation. TIPS seems to be useful even in patients with HCC, provided HCC is controlled.

Characteristics of Anti-HCV Antibody-Positive Patients with Hepatocellular Carcinoma on Chronic Hemodialysis: Recommendation of Periodic Ultrasonography for Early Detection

We analyzed 10 patients (male:female 9:1, mean age 64.2 years) who developed hepatocellular carcinoma during the observation period of 2 years among 2,164 chronic hemodialysis patients in 23 dialysis centers. Among them, 409 patients were positive for serum anti-HCV antibodies (19%). They were all positive for serum anti-HCV antibodies but negative for HBs antigen. None of the anti-HCV antibody-negative patients developed hepatocellular carcinoma during this period. Although liver function tests of the patients were almost normal, pathological examination of the liver revealed chronic active hepatitis or cirrhosis. Periodic ultrasonographic examination is necessary for early detection of hepatocellular carcinoma in chronic hemodialysis patients with positive anti-HCV antibodies even if liver function tests are within normal ranges.

CD81 nucleotide mutation in hepatocellular carcinoma and lack of CD81 polymorphism in patients at stages of hepatitis C virus infection

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. J. Med. Virol. 63:22–28, 2001.

Collaboration between Hepatologists and Primary Care Physicians in Treating Patients with Chronic Hepatitis C

Objective: The purpose of this study was to assess the treatment outcome in patients with chronic hepatitis C (CHC) using the current standard antiviral therapy when patient were treated in collaboration between hepatologists and primary care physicians (PCPs). Patients and Methods: One hundred and ten patients with CHC were treated with a combination therapy of peginterferon-alpha 2b and ribavirin. Among them, 25 patients were treated by a collaboration between hepatologists and PCPs (collaboration group), whereas 85 patients were treated with exclusively by hepatologists (noncollaboration group). The duration of the therapy was 48 weeks for 58 ‘difficult- to-treat’ patients (genotype 1 with a high load of HCV-RNA; 1H patients) and 24 weeks for the remaining 52 patients (non-1H patients). In the collaboration group, antiviral therapy was initiated and adjusted, if needed, by hepatologists (visits every four weeks), whereas the weekly administration of peginterferon-alpha 2b was performed by PCPs. Clinical characteristics and the treatment outcome were compared between these two groups. Results: The two groups had similar baseline characteristics. By intention to treat, the two groups showed similar rates of treatment-related serious adverse effects (0% vs. 1%, respectively) and dropout rates for adverse effects (8% vs. 13%, respectively). Sustained virologic response rates were also similar between the two groups, being 42% vs. 39% in the 58 1H patients (NS) and 62% vs. 64% in the 52 non-1H patients (NS), respectively. Conclusions: Collaboration between hepatologists and PCPs may be a valid treatment alternative to treat patients with CHC using the current standard antiviral therapy.