Biomedical subjects

H Saisho

Publications and source records attributed to H Saisho.

At least 55 records · Page 3Linked to original sources

PubMed2000

Clinical evaluation of sonoelasticity measurement in liver using ultrasonic imaging of internal forced low-frequency vibration.

The aim of this study is to evaluate liver elasticity noninvasively. We have already proposed an ultrasonic imaging system that can reconstruct vibration maps inside tissue under forced mechanical vibration. With this system, shear elastic properties of soft tissue can be evaluated as vibration velocities. Theoretically, these velocities increase with the increase of tissue elasticity. Sonoelasticity imaging was performed on 236 patients with chronic hepatitis and liver cirrhosis, and 50 healthy volunteers. The average of the velocities was 598.8 +/- 151.7 cm/s in healthy volunteers, 984.4 +/- 362.5 cm/s in chronic hepatitis and 1189.0 +/- 411.7 cm/s in liver cirrhosis. The average velocity of Child C group was statistically faster than those of Child A and B groups. Fibrotic rate from biopsy specimens statistically had the strongest positive correlation with velocities. With our system, the degree of liver fibrosis and function can be estimated objectively and noninvasively.

Adult↗

PubMed2000

PCR-SSCP analysis of 5'-nontranslated region of hepatitis A viral RNA: comparison with clinicopathological features of hepatitis A.

The recent development of the sensitive reverse transcription-polymerase chain reaction (RT-PCR) method allowed us to detect the presence of hepatitis A virus (HAV) RNA in sera from hepatitis A patients. To determine whether differences in HAV are related to the wide range of clinical severity, we used PCR-single strand conformation polymorphism (SSCP) to analyze the amplified product of the 5'-nontranslated region (5'NTR), where relatively homologous sequences are reported and the internal ribosomal entry site is considered to exist, from these various levels of hepatitis A. Twenty-seven patients admitted to Chiba University Hospital (between 1988 and 1997) were examined for HAV RNA in their sera by RT-PCR with primers located at 5'NTR of HAV RNA. The nucleotide (nt) sequence of a central part (nt 277-551) of 5'NTR was amplified and the product was examined by PCR-SSCP. HAV RNA was detected in all 27 hepatitis A patients examined: in 3 with fulminant hepatitis, 2 with severe acute hepatitis, and 22 with self-limited acute hepatitits. The amplified sequence revealed by PCR-SSCP showed that samples from fulminant and severe acute hepatitis patients had similar mobility in the gel, whereas that from acute hepatitis patients demonstrated a considerable variety in mobility patterns. From the analysis of the amplified product of 5'NTR of HAV, the bands are likely to be similar in the more severe forms of hepatitis A compared to those from uncomplicated self-limited acute hepatitis.

Acute Disease↗

PubMed2000

Impaired tumorigenicity of human pancreatic cancer cells retrovirally transduced with interleukin-12 or interleukin-15 gene.

We examined the antitumor effect of locally secreted interleukin (IL)-12 or IL-15 on human pancreatic cancer cells (AsPC-1). We subcutaneously inoculated AsPC-1 cells retrovirally transduced with IL-12 or IL-15 cDNA into nude mice. Tumors derived from these cells showed retarded growth compared with those from wild-type (wt) cells. Nude mice inoculated intraperitoneally with the cytokine producers survived longer than those injected with wt cells. These cytokine producers were also tested for their tumor growth in severe combined immunodeficient mice. The tumor growth of IL-12 producers was similarly suppressed as found in nude mice, but the average tumor volumes of IL-15 producers were not statistically different from those of wt tumors. In nude mice that were administered anti-asialo GM1 antibody before the inoculation of the tumor cells, growth retardation of tumors of IL-12 producers remained the same as in untreated animals, but that of IL-15 producers was markedly reduced. Immunohistochemical analysis revealed that CD11b+ cells migrated into the tumors of cytokine producers and that the number of CD31+ endothelial cells within the tumors was not different between IL-12 producers and wt cells. Taken together with other data, it is possible that granulocytes are candidate cells for the IL-12-mediated antitumor effect, and that natural killer cells and gammadelta T cells are involved in the IL-15-induced antitumor effect. We did not observe synergistic effects of these cytokines to suppress subcutaneous tumors.

Animals↗

PubMed2000

Accumulation of copper in the liver and hepatic injury in chronic hepatitis C.

BACKGROUND AND AIMS: Relationships between chronic liver disease and trace metals have not been clearly understood. To examine connections between severity of hepatic fibrosis in chronic hepatitis C and copper, iron and zinc we measured the contents of these metals in liver tissue and serum in the patients. METHODS: Forty-one patients (26-62 years), 13 with fibrosis representing grade F1, 16 with F2, seven with F3, and five with F4, entered this study. Metals were quantified in needle liver-biopsy specimens by particle-induced X-ray emission. In serum, metals were measured by flameless atomic absorption spectrometry. RESULTS: Hepatic copper content increased with progression of hepatic fibrosis (P < 0.05). The copper content correlated positively with bilirubin (r = 0.466, P = 0.0023), and with type IV collagen (r = 0.402, P = 0.0086) and correlated negatively with albumin (r = -0.404, P = 0.080). However, hepatic iron and zinc contents did not show a significant differences between grades of fibrosis. CONCLUSIONS: Copper accumulation in fibrotic livers caused by chronic hepatitis C may contribute to hepatic injury. The real mechanism is not known at present, but excess copper may damage the liver by oxidative stress.

Adult↗

PubMed2000

Sequence-motif analysis of 5'-untranslated region of GB virus-C in Japanese patients.

BACKGROUND: GB Virus C (GBV-C) is considered to belong to the Flaviviridae; however, the structures of the N-terminal end of its putative polyprotein are not well known. The internal ribosomal entry site (IRES) at the 5'-untranslated region of GBV-C and an initiating codon at nucleotides (nt) 552-554 have been proposed. We investigated the validity of this proposal. METHODS: The 5'-untranslated region of GBV-C was amplified from serum samples of 17 Japanese patients. Polymerase chain reaction-amplified products were directly sequenced and the obtained sequences were analysed by comparing them with the IRES structure of other viruses. RESULTS: Fifteen of the 17 (88%) GBV-C strains in our patients were classified as being Asian type. The box-A-like sequence (UUUC) and box-B-like sequence (AUCAUGG) observed in the IRES of picornaviruses were highly conserved in all the strains. Based on pair-wise comparisons with the multiple alignment data, overall sequence divergence for the 5'-terminus was 2.9-12%. When compared with the proposed secondary structure of the IRES model, the sequence divergences of the Asian-type GBV-C were higher at the regions of loop structures and lower at the regions of double-stranded RNA. The AUG codons, except for the one located at nt 552-554, produced truncated polyproteins or were not in-frame with the putative protein. CONCLUSIONS: Our examination of the sequence motif of GBV-C supports the proposal that the GBV-C has common structural motifs for IRES at its 5'-untranslated region and the AUG codon at nt 552-554 may be an initiating codon.

5' Untranslated Regions↗

PubMed2000

Origin of giant cells in osteoclast-like giant cell tumors of the pancreas.

To clarify the origin of giant cells in osteoclast-like giant cell tumors (OGCTs) of the pancreas, we performed microscopical, immunohistochemical, and K-ras gene mutation analyses with a microdissection approach in 3 cases, featuring 4 cellular components (osteoclast-like giant cells [OGCs], pleomorphic large cells [PLCs], mononuclear cells, and ductal carcinoma cells). Two cases had abundant OGCs, and 1 case contained large number of both OGCs and PLCs. In each, none of the microdissected OGCs contained any K-ras gene mutation while they were positive for a histiocytic marker (CD-68). In contrast, PLCs, when present, frequently harbored K-ras gene mutations and were negative for CD-68. In all cases, mononuclear cells, a mixture of histiocyte-like and atypical, from microscopic and immunohistochemical viewpoints, also frequently showed K-ras alteration. Histiocyte-like mononuclear cell was equipped with a regular and oval nucleus similar to those in OGCs and was positive for CD-68. Atypical mononuclear cell showed an irregular, pleomorphic, or sometimes bizarre nucleus similar to those in PLCs and was negative for CD-68. All of the K-ras gene mutations found in PLCs and mononuclear cells were the same as in the ductal carcinoma cells within the same tumor. Thus, OGCs differ in origin from ductal cells and are strongly suggested to be nonneoplastic and of mesenchymal origin, whereas PLCs, which harbor K-ras gene mutations, are neoplastic and presumably derived from ductal carcinoma cells. Moreover, mononuclear cells may be classified into 2 types, histiocyte-like and atypical.

Carcinoma, Pancreatic Ductal↗

PubMed2000

K-ras gene mutations and loss of heterozygosity at the p53 gene locus relative to histological characteristics of mucin-producing tumors of the pancreas.

Mucin-producing tumors (MPTs) of the pancreas accompanied by carcinomas usually include various grades of dysplasia in the ductal epithelium, and invasive areas are histologically similar to those of common invasive ductal carcinomas, suggesting that MPTs provide a good tool to investigate early stages of pancreatic carcinogenesis. Thus, to clarify genetic alterations in the early stage of pancreatic carcinogenesis, we analyzed K-ras gene mutations and loss of heterozygosity (LOH) at the p53 gene locus using 37 cases of MPTs harboring dysplastic epithelium. Further, we conducted an extended, multifocal microdissection analysis focusing on the histological features of ductal epithelium and the distribution of genetic alterations for 3 cases of MPT positive for LOH of the p53 gene to determine the relation to tumor progression. K-ras gene mutations were detected with high frequency in 50% or more cases of the adenomas (14 of 19), borderline tumors (4 of 7), and carcinomas (8 of 11), whereas LOH of the p53 gene was limited to carcinomas (3 of 5 informative cases, 60%) and always accompanied by K-ras gene mutation. Investigation of a total of 126 microdissection sites from 3 cases showed the presence of K-ras gene mutations in mild dysplasia and all (100%) regions of moderate or more marked dysplasia, whereas LOH of the p53 gene showed more gradual tendency to increase with grade from moderate dysplasia. In addition, the multifocal genetic analysis showed K-ras gene mutations to be widely distributed throughout tumors, whereas LOH of the p53 gene was localized to 1 or a few areas. Further, topographically delimited areas with the same histology in the same tumor did not always show the same genetic alteration. In conclusion, we could confirm that both the K-ras and p53 gene alterations occur in the intraductal stage of MPT, and the latter is superimposed on the former during the course of tumor progression. However, the pattern of association of histological features with genetic alteration differs from tumor to tumor.

Adult↗

PubMed2000

Peroral pancreatoscopy in the diagnosis of mucin-producing tumors of the pancreas.

BACKGROUND: Mucin-producing tumor of the pancreas is an increasingly recognized clinical entity. However, the differentiation of benign from malignant mucin-producing tumors of the pancreas is challenging. Peroral pancreatoscopy as recently developed may have potential for the diagnosis of mucin-producing tumors of the pancreas. METHODS: The subjects were 41 patients with clinically diagnosed mucin-producing tumors of the pancreas, 40 of whom underwent surgical resection. Autopsy findings were available in another patient with unresectable disease. Histologically, hyperplasia was identified in 3 patients, mildly atypical adenoma in 11, severely atypical adenoma in 16, and adenocarcinoma in 11. Peroral pancreatoscopy was performed before surgery or pathologic examination. The findings were retrospectively evaluated and compared with the histopathologic diagnosis. RESULTS: Pancreatoscopic observation was successful in 30 patients (73.2%). Elevated lesions were identified in 22 (73.3%). Villous or vegetative elevations and red color markings were frequently found in severely atypical adenoma or adenocarcinoma. Tumor location (main or branch duct type) did not correlate with survival after resection. Partial resection was performed in 7 of 30 patients with nonmalignant tumors and resulted in favorable outcomes. CONCLUSION: Peroral pancreatoscopy can be used to differentiate benign mucin-producing tumors of the pancreas (hyperplasia and mildly atypical adenoma) from the more dysplastic lesions (severely atypical adenoma and adenocarcinoma) and may provide useful information for determining the type of surgery to be performed.

Adenocarcinoma↗

PubMed2000

Long-term follow-up after treatment of Mirizzi syndrome by peroral cholangioscopy.

BACKGROUND: The standard treatment for Mirizzi syndrome is surgical, although endoscopic and percutaneous management have also been described. The aim of this study was to evaluate the usefulness of shock wave lithotripsy combined with peroral cholangioscopy and its long-term outcome in patients with Mirizzi syndrome. METHODS: The records of 25 patients with Mirizzi syndrome who underwent endoscopic treatment between April 1990 and November 1998 were retrospectively reviewed. Shock wave lithotripsy was performed under direct vision with a "mother-baby" endoscope system in 2 patients with type I and 23 with type II Mirizzi syndrome (12 men and 13 women, mean age 60 years). Follow-up data were obtained from clinical records or through telephone interviews. RESULTS: In the two patients with type I, the cholangioscopic approach failed and both patients underwent open cholecystectomy. The 23 patients with type II were all successfully treated with shock wave lithotripsy alone. The cholangioscopic approach was unsuccessful in the treatment of residual gallbladder stones. Follow-up data were obtained in all but one patient (mean 43.6 months, range 4 to 103 months). Of the 23 patients with type II, 12 with no gallbladder stones had remained asymptomatic during the follow-up period. Of the 6 patients with type II with large residual gallbladder stones, 4 had acute cholangitis due to stone migration 6, 9, 28, and 34 months after endoscopic treatment. Two patients died during the follow-up period, one of non-biliary causes and the other of coexistent gallbladder carcinoma. CONCLUSIONS: Endoscopic treatment of Mirizzi syndrome using peroral cholangioscopy is a safe and effective alternative to surgery, especially in patients with the type II syndrome. A favorable long-term outcome depends on the absence of large residual gallbladder stones.

Adult↗

PubMed2000

EUS changes predictive for recurrence of esophageal varices in patients treated by combined endoscopic ligation and sclerotherapy.

BACKGROUND: Recurrence of varices is still common after endoscopic treatment of esophageal varices. In this study, predictive signs of variceal recurrence were investigated by ultrasonic (US) miniature probe in patients treated by combined endoscopic ligation and sclerotherapy. METHODS: Detectability of vessels by US miniature probe was evaluated first in rats. In 41 patients treated by combined therapy, the esophagus and the cardia region were examined by US miniature probe. In 25 patients examined by percutaneous transhepatic portography, the relationship between US miniature probe and percutaneous transhepatic portography findings was evaluated. RESULTS: The smallest vessel detected by US miniature probe was 0.3 mm in diameter in the study using intra-abdominal vessels of rat. After variceal eradication, US miniature probe showed intramural vessels in the cardia that were classified as follows: grade I, a few vessels (19 patients, 46%); grade II, uniformly scattered vessels (11, 27%); grade III, abundant vessels resembling a honeycomb (11, 27%). As the sonographic grade increased, the rate of variceal recurrence increased. As the venographic grade of staining in the distal esophagus increased, the esophageal wall became thicker and the sonographic grade at the cardia increased. CONCLUSIONS: Endosonographic evaluation of the distal esophagus and cardia is predictive of variceal recurrence.

Adult↗

PubMed2000

Inactivation of a hepadnavirus by electrolysed acid water.

Glutaraldehyde is used as a disinfectant for endoscopes, but is an irritant and so should be replaced by an alternative. Electrolysed acid water (EAW) has a bactericidal effect, and an endoscopic washing device using EAW has been developed in Japan. To investigate the effect of EAW on the infectivity of viruses, we treated duck hepatitis B virus (DHBV), which has similar properties to hepatitis B virus, with EAW, and determined the number of remaining infectious virus particles in a bioassay system. One-day-old Pekin ducks were inoculated with duck serum containing 10(5.5) ID(50) DHBV; the serum had previously been incubated with 100 volumes of EAW or ion-exchanged water at room temperature for 7 min. DHBV infection was indicated by detection of viral DNA in duck serum samples 1-8 weeks after inoculation. Treatment of serum with EAW diminished DHBV infectivity whereas treatment with ion-exchanged water did not. The virus load was estimated to have been reduced to 10(1)-10(3) ID(50) during the first 1 min and to <10(0.5) ID(50) in the next 6 min of incubation when compared with the control. Thus, EAW directly inactivates DHBV and its clinical application is recommended.

Animals↗

PubMed2000

Quantitative analysis of bowel gas using plain abdominal radiograph in patients with irritable bowel syndrome.

OBJECTIVE: Ideally, the diagnosis of irritable bowel syndrome (IBS) would be achieved using a minimal number of procedures. It is presumed that bowel gas is related to IBS, and it is easily visualized by plain abdominal radiograph. In the present study, to clarify the relationship between IBS and the quantity of bowel gas, the measured bowel gas volume using plain abdominal radiographs was compared with the pathology of IBS. METHODS: Plain abdominal radiographs were digitized and transmitted to a computer (computed radiography) in 30 IBS patients and 30 normal controls. The quantity of bowel gas, determined as the pixel value on images and standardized by physique, was defined as the gas volume score (GVS). Using the mean +/- 2SD of GVS in the control group as the normal score, IBS patients were divided into three groups: high, normal, and low. To examine the sequential reproducibility of a similar quantity of bowel gas, a second plain abdominal radiography was performed about 2 months later, and the GVS were compared. The colonic transit time was determined using radiopaque markers. RESULTS: There was a strong correlation between the quantities of bowel gas measured by two independent gastroenterologists. The mean GVS of IBS patients was significantly higher than that in the control group (p < 0.001). The sequential reproducibility was recognized in all 10 IBS patients. There was no significance between colonic transit time and GVS, nor between symptoms and GVS. CONCLUSIONS: Abdominal gas was analyzed objectively by using GVS, and GVS was considered to represent a useful tool for the diagnosis of IBS.

Adult↗

PubMed2000

[The general rules for the study of pancreatic cancer from the viewpoint of internal medicine].

Useful nonsurgical treatments like chemoradiotherapy have been developed for the management of patients with unresectable pancreatic cancer. The General Rules for the Study of Pancreatic Cancer (Japan Pancreas Society) should therefore take diagnostic imaging techniques into account in order to deal with nonsurgical cases under the classification system as well as with surgical ones. The anatomic extent of disease based on preoperative dynamic CT images was evaluated in comparison with the results of pathology in a total of 35 patients with pancreatic cancer. The CT findings accurately represented the pathology for peripancreatic invasion, including vascular involvement, with a diagnostic accuracy ranging from 72% to 88%. However, it failed to detect almost half of lymphatic metastases. The staging of pancreatic cancer with dynamic CT was accurate in 66% of the patients, was underestimated in 25%, and was rarely overestimated. The detection of minute metastases is a crucial problem in the CT staging of tumors. The significant correlation of the RP factor (retroperitoneal tumor invasion) with lymphatic metastases as noted in this study offers a clue to solving this problem.

Humans↗

PubMed1999

Acquired immunity in nude mice induced by expression of the IL-2 or IL-4 gene in human pancreatic carcinoma cells and anti-tumor effect generated by in vivo gene transfer using retrovirus.

We have examined the anti-tumor effect in nude mice caused by human pancreatic cancer cells (AsPC-1) modified to secrete IL-2 or IL-4. Loss of tumorigenicity of cytokine-producing, but not wild-type, cells was observed despite their unaltered in vitro proliferation rates; and these anti-tumor effects were dependent on the amount of cytokine released. Wild-type cells inoculated into mice which had rejected IL-2- or IL-4-producer cells showed significant growth retardation, while no retardation was detected when unrelated human colon carcinoma cells were inoculated. Histological examination of regressing IL-2- or IL-4-producing AsPC-1 tumors in nude mice revealed infiltration by CD11b-, but not CD90-, positive cells around the tumors. Treatment of nude mice with anti-asialoGM(1) antibody did not affect loss of tumorigenicity. Mice injected i.p. with IL-2- or IL-4-producing AsPC-1 cells did not die, in contrast to mice inoculated with wild-type cells. Injection of retrovirus-bearing IL-2, but not beta-galactosidase, gene into mice which had wild-type cells in the peritoneal cavity also significantly prolonged survival. Thus, expression of the IL-2 or IL-4 gene in AsPC-1 cells may generate tumor-specific acquired immunity, even in mature T cell-deficient conditions. An anti-tumor response can be induced by in vivo transfer of the IL-2 gene.

Animals↗

PubMed1999

Quantification of hepatitis C virus by TaqMan PCR: comparison with HCV Amplicor Monitor assay.

The quantitation of serum levels of hepatitis C virus RNA in chronic hepatitis C has been regarded as one of the most important indicators for the outcome of interferon therapy. A new method was used for quantitating the copy number of hepatitis C virus RNA using TaqMan polymerase chain reaction and for comparing the ability and usefulness of this assay with Amplicor Monitor assay in 138 patients. The detection range of hepatitis C virus RNA by TaqMan polymerase chain reaction was from 2 x 10(3) to 2 x 10(8) copies/ml. Hepatitis C virus RNA was detectable in 128 cases (92.8%) and undetectable in 10 cases (7.2%) by this method. The RNA levels measured by Amplicor Monitor assay correlated significantly with those measured by TaqMan polymerase chain reaction assay and the sensitivity of the two assays was almost equal. Thus, TaqMan polymerase chain reaction assay appears sufficiently sensitive for the evaluation of hepatitis C virus RNA and would be useful for the diagnosis and management of hepatitis C virus infection.

Adolescent↗

PubMed1999

Early detection of radiation-induced liver injury in rat by superparamagnetic iron oxide-enhanced MR imaging.

The detectability of early liver injury induced by irradiation was studied using magnetic resonance (MR) imaging enhanced with superparamagnetic iron oxide (SPIO), a tissue-specific contrast agent against the reticuloendothelial system (RES). In rat, 3 days after focal irradiation (0-10 Gy), MR imaging was performed and specimens were obtained to observe the phagocytic function of RES. The irradiated portion of the liver was visualized with a clear demarcation from the nonirradiated part by SPIO-enhanced MR images as a decrease in negative enhancement reflecting the function of RES (P < 0.05), whereas this was impossible with nonenhanced MR images. Significant regression was observed as a dose-related change of the signal intensity in the irradiated portion on SPIO-enhanced MR images (R = 0.867, P < 0.0001). SPIO-enhanced MR imaging was reliable for detecting the range and extent of liver injury a few days after low-dose irradiation, and it may be a useful procedure for verifying the target area in clinical cases of radiation therapy.

Animals↗

PubMed1999

The role of TT virus infection in acute viral hepatitis.

Recently, transfusion-transmitted virus (TTV) was discovered to be a potential causative agent for non-A-E hepatitis. Little is known about the relation between TTV and the clinical courses of various types of acute viral hepatitis. One hundred twenty-five patients with acute viral hepatitis who were admitted to the Chiba University Hospital between 1984 and 1998 and 100 persons with normal liver function tests were tested for the presence of TTV in their sera. Serum samples were tested for TTV DNA and genotype by polymerase chain reaction (PCR). TTV DNA was detected in 15 of 35 patients (43%) with non-A-E hepatitis, 14 of 33 patients (42%) with hepatitis C, 8 of 28 patients (29%) with hepatitis A, 7 of 29 patients (24%) with hepatitis B, and 37 of 100 subjects with normal liver function tests (37%). The detection rate did not differ statistically between non-A-E hepatitis and hepatitis A, B, C, or controls. The distribution of TTV genotypes was similar in non-A-E, A, B, C types, and controls. The clinical characteristics of the acute illnesses were similar for patients with or without TTV in hepatitis non-A-E, A, B, or C. Although TTV was detected frequently in non-A-E acute hepatitis, no etiologic role for TTV could be established.

Adult↗

PubMed1999

Spontaneous negativation of serum hepatitis C virus RNA is a rare event in type C chronic liver diseases: analysis of HCV RNA in 320 patients who were followed for more than 3 years.

BACKGROUND/AIMS: The natural course of hepatitis C virus (HCV) replication in type C liver diseases has not yet been elucidated. The aim of the study was to investigate the spontaneous outcome of the viremia by examining the changes in HCV RNA in patients with chronic type C liver diseases. METHODS: Among patients who visited our liver clinic between June 1981 and December 1993, 320 patients with chronic type C liver diseases were followed for at least 3 years and had no history of interferon treatment. HCV RNA was examined by a highly specific reverse transcription-polymerase chain reaction method in paired serum samples obtained from these patients at the beginning and end of follow-up. RESULTS: Among the 320 cases, HCV RNA was seropositive in 310 (97%) cases at the beginning of follow-up. Of these 310, HCV RNA remained seropositive in 304 (98%) and became seronegative in six (2%) cases by the end of follow-up. All of these six patients had liver cancer. HCV RNA became seronegative after the patients entered the state of liver failure because of the development of tumors or portal thrombosis. The remaining 10 cases who were seronegative for HCV RNA at the beginning were seropositive at the end of follow-up. Among the 320 cases, serum alanine aminotransferase normalized and remained normal for more than 12 months until the end of follow-up in 11 cases (0.6%/year/case), but none became negative for HCV RNA. CONCLUSIONS: Thus, during the natural course of chronic HCV infection, spontaneous negativation of serum HCV RNA seems extremely rare, at least in patients with chronic active hepatitis or cirrhosis of the liver, and may occur primarily at the terminal stage when tumors cause liver failure.

Aged↗