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 < or =2 x 10(4) copies/ml (competitive RT-PCR) or <100 x 10(3) copies/ml (Amplicor monitor) of HCV RNA by 468-1206 MU of IFN, but response was only 0-25% of the patients with > or =2 x 10(5.5) copies/ml (competitive RT-PCR) or >200 x 10(3) copies/ml (Amplicor monitor), even with 468-1206 MU of IFN. A high sustained rate was demonstrated in patients with 100-200 x 10(3) copies/ml of HCV RNA by 901-1206 MU of IFN, in comparison to that with < or =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 x 10(3) copies/ml of HCV RNA. Cost efficacy analysis indicated that it cost approximately $10,000, $26,000, and $50,000-227,000 for one person-viral eradication in the patients with <100, 100-200, and >200 x 10(3) 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 x 10(3) copies/ml of HCV RNA.

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

Because interferon therapy exhibits low efficacy for cirrhotic patients infected with hepatitis C virus, this prospective study was conducted to determine effective interferon regimens tailored to treatment response by monitoring HCV RNA status. A total of 157 cirrhotic patients were enrolled to receive 9 million units (MU) of interferon three times a week. The HCV RNA values were drawn 8 weeks apart and the patients were randomized to a further 16 or 32 weeks of treatment after two sequential findings of negativity for HCV RNA. A total of 73 out of 157 patients (46%) proceeded to randomization to different durations of treatment, 37 short-course and 36 long-course (duration: 38 +/- 8 and 49 +/- 13 weeks; total amount of interferon: 940 +/- 240 and 1130 +/- 390 MU, respectively). The remaining 84 patients without two sequential negative serum HCV RNA determinations received 44.8 +/- 27.4 weeks of interferon (IFN) therapy with total amount of 993 +/- 633 MU. Of these 157 patients, sustained virological and biochemical response was shown in 32 (20%) and 37 patients (24%), respectively. Sustained virological and biochemical response rate in the randomized patients was significantly higher than in nonrandomized patients (41% vs. 2%, and 38% vs. 11%; each P <.01). Of the 73 randomized patients, the rate of sustained virological response in patients with long-course treatment (50%) was significantly higher than that of patients with short-course treatment (32%) (P =.026: log-rank test), and in patients with early disappearance of HCV RNA especially within 8 weeks, in patients with low virus load (

Endoscopic papillary balloon dilation for the management of common bile duct stones: experience of 226 cases.

BACKGROUND AND STUDY AIMS: Endoscopic sphincterotomy is a widely accepted technique for the treatment of patients with common bile duct stones. However, it is still associated with occasional complications. The recently developed technique of endoscopic papillary balloon dilation seems to be a safe and effective procedure, and to have great potential for replacing endoscopic sphincterotomy. However, few reports have been published on the use of this technique for bile duct stones. The present study was undertaken to evaluate its safety and efficacy. PATIENTS AND METHODS: Endoscopic papillary balloon dilation was used to remove common bile duct stones in 226 consecutive patients including 41 patients of ASA classification III/IV, 41 elderly patients (> 80 years) 24 with liver cirrhosis, and 86 with periampullary diverticulum. After dilation of the papilla with a balloon diameter of 8 mm, the stones were retrieved. RESULTS: In conjunction with the use of a mechanical or/and electrohydraulic lithotriptor in 79 patients (35%) with large stones (> 10 mm in diameter), clearance of the common bile duct was achieved in 225 of 226 patients (99%) without serious complications, such as hemorrhage or severe pancreatitis; mild (n = 13) or moderate (n = 2) pancreatitis occurred in 7% of cases. CONCLUSIONS: Endoscopic papillary balloon dilation is a safe and effective technique for the treatment of common bile duct stones, even in high-risk patients.

[Endocrine disturbances in liver cirrhosis--focused on sex hormones].

Various endocrine disturbances are often observed in the patients with liver cirrhosis. We focused this paper on the sex hormones. Clinical features of male cirrhotic subjects are feminization(gynecomastia etc) and hypogonadism(testicular atrophy, reduced fertility, loss of libido, impotence etc). Chief abnormalities of sex hormones are a decrease in serum testosterone levels and an increase in serum estrogen levels accompanied by an increase in ratio of estrogen to testosterone in the patients with severe liver cirrhosis associated with the severity of hepatic dysfunction. Hyperestrogenization may be related with feminization of male cirrhotic subjects, whereas hypogonadism is the result of alcohol abuse per se, rather than the indirect consequence of liver cirrhosis.

Detection of alpha-fetoprotein mRNA, an indicator of hematogenous spreading hepatocellular carcinoma, in the circulation: a possible predictor of metastatic hepatocellular carcinoma.

We attempted to detect circulating hepatocellular carcinoma by demonstrating hepatocyte-associated mRNA in the nuclear cell component of peripheral blood using nested reverse transcription-polymerase chain reaction because of the extremely small number of tumor cells in the circulation. Albumin mRNA was demonstrated not only in the liver tissue (hepatocytes) and HepG2 cells but also in nuclear cells of the blood from normal healthy volunteers (neutrophils and lymphocytes) by reverse transcription-polymerase chain reaction. In contrast, alpha-fetoprotein mRNA was demonstrated in the liver tissue, as well as in HepG2 cells, but not in peripheral blood of normal healthy volunteers, indicating the possibility of using alpha-fetoprotein mRNA for detection of benign and malignant hepatocytes among the population of neutrophils and lymphocytes. alpha-Fetoprotein mRNA in peripheral blood was detected in 17 of 33 cases of hepatocellular carcinoma (52%), 2 of 13 cases of cirrhosis (15%) and 2 of 17 cases of chronic hepatitis (12%). alpha-Fetoprotein mRNA was not demonstrated in 26 cases of normal healthy volunteers (0%). Among the patients with hepatocellular carcinoma, total volume of tumor tissue, maximum size of tumor and serum alpha-fetoprotein level were markedly increased in the patients with alpha-fetoprotein mRNA in blood. In addition, alpha-fetoprotein mRNA was detected in the blood of all 6 patients showing metastasis at extrahepatic organs (100%), in contrast to 11 of 27 cases without metastasis (41%). From these results, we conclude that the presence of alpha-fetoprotein mRNA in peripheral blood may be an indicator of circulating malignant or benign hepatocytes, which might predict hematogenous spreading metastasis of tumor cells in patients with hepatocellular carcinoma.

[A chronic alcoholic patient with the development of frank diabetes after heavy drinking and perfect improvement following abstinence from alcohol].

We experienced a chronic alcoholic patient in whom a large intake of alcohol led to the development of frank clinical diabetes, and glucose intolerance and insulin deficiency improved perfectly following abstinence from alcohol. The patient was a 31-year-old male with no diabetes among his relatives. He was a heavy drinker since 12 years, and especially had a large intake of alcohol from Dec. 25 '84 to Jan. 3 '85. From the end of Jan. 1985 he complained of thirst, polydipsia, polyuria and body weight loss from 94 to 69 Kg. On June 25 1985 he admitted for the treatment of diabetes and had abstinence from alcohol. The blood glucose and HbA1 levels were 291 mg/dl and 14.7%, respectively on admission. His 75 g OGTT was diabetic in type and serum insulin response to glucose decreased markedly. Liver function tests were normal, and islet cell antibody was negative. Blood adrenaline, noradrenaline, growth hormone, glucagon, cortisol, T3 and T4 levels were normal. FBS, HbA1 and 75 g OGTT recovered to normal by dietary treatment (1800 kcal) with oral hypoglycemic agents for 8 weeks. This case report suggests that the cause of alcohol-induced diabetes is probably due to impairment of insulin secretion by either alcohol itself or alcohol metabolites.

A case report of leiomyosarcoma originating in the ligamentum teres of the liver.

A case of leiomyosarcoma that appeared to have originated in the ligamentum teres hepatis of a 66-year-old female has been presented. The case was suspected of leiomyosarcoma originating in the ligamentum teres of the liver from the findings by preoperative examinations, and definitely diagnosed as such in a laparotomy and by histological examination of the resected tissue specimen.

The diagnostic value of pneumoperitoneogram for splenomegaly in chronic liver diseases.

The splenic enlargement is an important symptoms of portal hypertension, and various attempts have been made to objectively describe it. But, endoscopic diagnosis for splenomegaly in chronic liver diseases may be sometimes difficult for these uncharacteristic appearances. The pneumoperitoneography was performed in 141 chronic liver diseases just before laparoscopic procedure, size and form of the spleen on X-ray film were measured and analysed. We have compared these results with the laparoscopic findings (the gross appearance of liver and spleen, the degree of portal hypertension, etc), the patterns on scintigram and the histological findings of the liver. There were fairely good correlation between the splenic findings on radiogram and above factors, especially the size of the spleen was gradually increased according to the degree of portal hypertension and the fibrous change of the liver specimens. In conclusion, the findings of spleen on pneumoperitoneogram were valuable for diagnosis of splenomegaly in chronic liver diseases.