Masashi Ihori

Different turnover rate of hepatitis C virus clearance by different treatment regimen using interferon-beta.

BACKGROUND/AIM Since patients with high viral load and HCV subtype 1b are known to respond poorly to interferon (IFN) therapy, the viral dynamics of HCV RNA after initiation of interferon therapy were examined in the present study with respect to two different administration regimens, once vs. twice a day. METHODS Twenty-two patients with chronic hepatitis C confirmed by liver biopsy and with >1 Meq/ml of HCV RNA and HCV subtype 1b were randomly assigned to two different IFN administration regimens (6 million units of IFN once a day or 3 million units of IFN twice a day), and the serum HCV RNA level was serially measured. RESULTS Graphs of HCV RNA levels vs. treatment time showed an initial rapid fall, followed by a slower clearance phase. Fitting the data to a model for HCV decay proposed by Neumann et al. showed that the treatment efficacy was significantly higher with twice daily administration. Negativity for HCV RNA measured by Amplicor assay in the twice-a-day administration group was 18%, 73% and >89% at 1, 2 and 3 weeks, respectively, in contrast to 0%, 0%, and 18%, respectively, with once-a-day administration. However, a significant reduction of platelet count and albumin level, a marked increase in serum aspartate aminotransferase/alanine aminotransferase, and a high incidence of renal toxicity (proteinuria) were found in patients receiving IFN twice a day in comparison with those receiving it once a day. CONCLUSION The twice-a-day administration of IFN accelerated the clearance of HCV RNA from serum, leading to a more efficient virological response for patients with chronic hepatitis C, but with a high rate of renal toxicity.

Sustained viral response is rarely achieved in patients with high viral load of HCV RNA by excessive interferon therapy

Adequate dosing of interferon (IFN) and its cost-effectiveness for sustained virological response were evaluated in relation to viral load and subtype. Prospective analysis of IFN therapy on 326 patients with chronic hepatitis C free from cirrhosis was performed using 9 or 6 million unit (MU) of IFN for six months daily and/or three times a week. Sustained virological response was achieved in 50–94% of patients with ≤2 × 104 copies/ml (competitive RT-PCR) or <100 × 103 copies/ml (Amplicor monitor) of HCV RNA by 468–1206 MU of IFN, but response was only 0–25% of the patients with ≥2 × 105.5 copies/ml (competitive RT-PCR) or >200 × 103 copies/ml (Amplicor monitor), even with 468–1206 MU of IFN. A high sustained rate was demonstrated in patients with 100–200 × 103 copies/ml of HCV RNA by 901–1206 MU of IFN, in comparison to that with ≤900 MU of IFN. Multivariate analysis showed that IFN dose had a significant value for the efficacy of IFN therapy in patients presenting 100–200 × 103 copies/ml of HCV RNA. Cost efficacy analysis indicated that it cost approximately

Periportal Stellate Cells in Subjects with Chronic Hepatitis C with a Varied Serum Alanine Aminotransferase Level

10,000,

Analysis of sustained responders in the treatment of chronic hepatitis C with interferon: viral clearance is more associated with genotype III or IV (2a, 2b) than genotype II (1b)

26,000, and

Clinical effects and complications of diuretic therapy in patients with cirrhosis

50,000–227,000 for one person-viral eradication in the patients with <100, 100–200, and >200 × 103 copies/ml, respectively. High-dose IFN is only cost effective in patients with intermediate viral loads, and IFN therapy could be recommended in patients with <200 × 103 copies/ml of HCV RNA.

Study on the lipid metabolism in cholelithiasis

Recently it has been reported that HCV-related cirrhotic patients with persistently high serum levels of alanine aminotransferase (ALT) activity have higher risk of development of hepatocellular carcinoma (HCC) than those with persistently low levels of ALT activity [1]. Vitamin A has been demonstrated to have many biological functions in regulation of growth and differentiation of normal and cancer cells. Hepatic stellate cells (SCs) are the main storage site of vitamin A and regulate homeostasis of vitamin A. To analyze cellular and molecular mechanism in the relationship between persistent high serum level of ALT and HCC development from the viewpoint of vitamin A handling, this study was performed.

A clinical study of superficial carcinoma

Abstract Eighty-three patients with chronic hepatitis C were treated with interferon (IFN) for 6 months and followed up for another 6 months. Fifteen (18%) showed sustained normalization of serum alanine-aminotransferase (ALT) levels throughout the 6-month follow-up period. Hepatitis C virus (HCV) RNA was tested in sera from these ‘sustained responders (SR)’ at the end of the follow-up period, and was positive in nine and negative in six. All of the six RNA-negative SR cases had viral genotype III (2a) or IV (2b) in pretreatment sera, whereas most of the RNA-positive SR cases (7 of 9) had genotype II (1b). Our results thus suggest that HCV genotype III or IV is more effectively eradicated by IFN, compared with genotype II.

Detection of α‐fetoprotein mRNA, an indicator of hematogenous spreading hepatocellular carcinoma, in the circulation: A possible predictor of metastatic hepatocellular carcinoma

Conclusion1)Fluid retention disappear in some cases in early stage of liver cirrhosis without diuretic therapy.2)Diuretices have little effect and may accelerate the heavy electrolyte disturbance in already seriously ill patients.3)Sever ill patients with cirrhosis and intractable ascites should not be treated too vigorously.

Increased renin release evoked by mesencephalic stimulation in the dog.

Cholel i thias is is one of the diseases very f requent ly seen th roughout the world and untill now many invest igat ions were reported, bu t pathogenesis and growth of the gall-stone were not fully unders tand. Now, the a t tempts were made for c lar i fy the lipid metabol ism in choleli thiasis . 1) We were compared the nut r i t ive in takes wi th the autopsy incidence of gell-stone in three typical d i s t r ic t s of Japan (Tokyo, Tohoku and Kyushu district) . During 7 years period f rom 1958 to 1964, the average intake of animal protein were increased, the ra t io of an imal fa t f i sh fa t and vesi table f a t + f i s h f a t were increased f rom 0.21 to 0.34. And we found the closely correra t ion between the incidence of gall-stone and the unsatura ted fa t ty acid in diet. 2) The fa t ty acid pa t te rns of the human serum and the gal lbladder bile has been analysed by gas-liquid ch romatography in cholel i thiasis , gas t r i c diseases and l iver diseases. In cholel i thiasis , the ra t io of phospholipid to cholesterol was decreased to 0.94, and the lowering of the ra t io of sa turated fa t ty ac id /unsa tura ted fa t ty acid and linoleic acid/oleic acid (L/ ratio) in cholesterol es ter were also observed. The fa t ty acid pa t t e rns in phospholipid and neu t ra l fa t were s imilar to tha t of cholesterol. In l ivar diseases, the decrease of L/O ratio was eminent . While, the P /C rat io of gal lbladder bile was remarkably decreased to 1.9, and saturated fa t ty ac id /unsa tu ra ted fa t ty acid rat io in cholesterol was also decreased. But L/O ra t io was not changed. 3) The composit ion of the bile acide of gall-bladder bile was examined by thin-layer chromatography: in cholel i thiasis the percentage of the glycodihydrocholic acid, glycocholic acid, taurodihydrochol ie acid and taurochol ic acid were 32.1%, 29.0%, 23.4%, and 16.5%. The ra t io of glycine compounds to taur ine compounds was 1.59 in choleli thiasis , and 1.47 in s tomach diseases as control. 4) Af te r the adminis t ra t ion of linoleic acid, v i tamin B-6 and v i tamin E for the pat ients of cholel i thiasis , the abnormal findings of B-bile were improved in some cases. In conclusion, we supposed tha t the genesis of the gall-stone format ion is related to the unsa tura ted fa t ty acid, bu t accompanied l iver damage have an impor tan t effect upon the lipid metabol ism in cholel i thiasis .

Prospective study of interferon therapy for compensated cirrhotic patients with chronic hepatitis C by monitoring serum hepatitis C RNA

Abrasive sponge method was applied in 83 cases of gastr ic carc inoma and 11 cases of gastr ic ulcer under fibergastroscopic control, and obtained specimens were examined cytologically. The resul ts were as follows: Cancer cells were posit ive in 77 out of 83 cases of gastr ic carc inoma including 17 cases of ear ly cancer. According to the site of cancer, cancer cells were found in 100% of cases with cancer of gast r ic body, 96% of angle, 92% of an t rum and 67% of pylorus respectively. Cancer cells were posit ive in 54 out of 56 cases of adenocarcinoma, but only in 20 out of 24 cases of carcinoma s implex. Two cases of pyloric carcinoma and one case of antral carcinoma were false negative and in the latter the connective t issue proliferated and cancer cells were scat tered in it. There were no false positive cases in gas t r ic ulcer. It was concluded tha t fibergastroscopic abrasive sponge method was an excellent technic in the cytologic diagnosis of gast r ic cancer, especially early cancer.