[Acute exacerbation by reactivation of HBV in steroid withdrawal therapy].
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Adult↗
Biomedical subjects
Y Arase
Publications and source records attributed to Y Arase.
[Prognosis of anti-HBe positive chronic hepatitis B].
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Hepatitis B Antibodies↗
Serial hemodynamic measurements in well-differentiated hepatocellular carcinomas.
We performed serial hemodynamics in 15 patients with 21 well-differentiated hepatocellular carcinomas. The total length of the observation period ranged from 129 to 678 days (median, 368). We investigated both arterial and portal blood flow at intervals of at least 4 months. Arterial blood flow was measured with carbon dioxide-enhanced ultrasonography (US), and portal blood flow was measured with computed tomographic arterial portography (CTAP). None of the tumors were hypervascular on the initial study; however, by the final study nine nodules (42.9%) had become homogeneously hypervascular, two (9.5%) had become partially hypervascular, and the others did not change. Of 10 nodules without portal blood supply on any study, 8 became hypervascular by the final study. Of 11 nodules with portal blood supply on the initial study, a follow-up study showed no change in portal flow in 6 and the loss of portal flow in 5. Four of these five became hypervascular, with a documented loss of portal flow before the increase in arterial flow. The doubling time of tumors with a homogeneous increase in arterial blood flow ranged from 89 to 333 days (median, 172), whereas the doubling time of other tumors ranged from 227 to 607 days (median, 392). Thus, growth rate and vascularity in well-differentiated hepatocellular carcinoma are closely correlated. When the well-differentiated hepatocellular carcinoma has portal blood flow and is not hypervascular, it grows slowly. On the other hand, when it loses portal blood flow and becomes hypervascular, it grows rapidly.
Adult↗
Serum des-gamma-carboxyprothrombin concentration determined by the avidin-biotin complex method in small hepatocellular carcinomas.
BACKGROUND: Des-gamma-carboxyprothrombin (DCP) is a useful tumor marker for hepatocellular carcinoma (HCC). The present method for measurement of DCP concentration, however, does not have adequate sensitivity to detect small HCCs. METHODS: The serum DCP concentration was investigated by the avidin-biotin complex (ABC) method in patients with an HCC smaller than 20 mm in maximum dimension. A serum DCP concentration greater than 4.0 arbitrary units per liter using the ABC method was considered abnormal. RESULTS: Of 115 patients with small HCC, 45 (39.1%) had an abnormal DCP concentration. Ten of 141 patients with chronic hepatitis (7.1%), 18 of 115 (15.7%) with cirrhosis, and 0 of 30 normal control patients had abnormal DCP concentrations. This method yielded a sensitivity of 39.1%, a specificity of 89.1%, a positive predictive value of 61.6%, and a negative predictive value of 76.5% for detection of small HCC. The detectability of HCC increased to 56.5% when alpha-fetoprotein (AFP) was was measured (> 40 ng/ml). Abnormal DCP concentrations were seen in 8 of 34 (23.5%), 24 of 42 (57.1%), and 5 of 7 (71.4%) patients with Edmondson's Grade I, II, and III tumors, respectively. There was a significant relationship between DCP concentrations and histologic grade (P = 0.0017), but there was no association between DCP concentration and other patient characteristics. Elevation of serum AFP concentrations in patients with hepatitis B surface antigen positivity, however, was more frequent than that in patients who were antihepatitis C virus (HCV) positive. Therefore, the measurement of serum DCP concentrations may be more useful than that of serum AFP concentrations in patients with anti-HCV positivity. CONCLUSIONS: The measurement of serum DCP concentrations by the ABC method is a useful diagnostic tool for the monitoring of small HCC.
Adult↗
Interferon retreatment of nonresponders with HCV-RNA-positive chronic hepatitis C.
Interferon has been shown to be an effective treatment for some patients with chronic hepatitis C. In this study, the value of retreatment of nonresponders to interferon was investigated. Thirty-eight patients with hepatitis C virus (HCV)-RNA-positive chronic hepatitis C who had been treated with beta-interferon but still showed an alanine aminotransferase (ALT) level > 50 KU upon completion of therapy were retreated with alpha-interferon. Eight patients (21.1%) had normalization of ALT levels for at least 6 months after the completion of retreatment. The factors related to normalization of ALT levels after interferon retreatment were studied. Of 16 patients with transient HCV-RNA negativity 1 month after the initial interferon therapy, 7 (43.8%) had a complete response, with normalization of ALT levels and undetectable HCV-RNA, more than 6 months after interferon retreatment. On the other hand, of the 22 patients with HCV-RNA activity 1 month after the initial interferon therapy, only 1 (4.5%) had a complete response. Multivariate analysis, using a multiple logistic model, indicated that a complete response to readministration of interferon was most strongly correlated to transient negative conversion for HCV-RNA after the initial course of treatment.
Alanine Transaminase↗
Prevalence of HCV genotype among patients with chronic liver diseases in the Tokyo metropolitan area.
We examined 613 Toranomon Hospital patients with HCV RNA-positive chronic liver disease to elucidate the viral genotype in the Tokyo metropolitan area. An epidemiological and clinical study was conducted in the 565 patients whose HCV genotype could be determined. The HCV genotypes found were type II, in 414 patients (67.5%); type III, in 103 (16.8%); type IV, in 37 (6.0%); type V, in 4 (0.7%); mixed genotype II and III, in 5 (0.8%); and mixed genotype II and IV, in 2 (0.3%). The HCV genotype could not be determined in 48 patients. Type II was most prevalent. The HCV genotype I was not found at all. There were no significant differences between genotypes in relation to sex, age, history of blood transfusion, or the progression of the disease. It was uncommon to find a history of blood transfusion in the patients with mixed genotypes; however, a high incidence of hepatic disorders was noted among the family members of these patients. Ninety-two percent of the patients with HCV genotype II tested positive for C100-3, while 70.9% of those with type III, and 43.2% of those with type IV tested positive for this antibody. HCV genotype II was most prevalent, and the positivity rate for anti C100-3 in patients with this HCV genotype was significantly higher (P < 0.00001) than that in patients with the other genotypes.
Adolescent↗
Imaging diagnosis of small hepatocellular carcinoma.
To elucidate the detectability of small hepatocellular carcinoma by various imaging modalities, we performed digital subtraction angiography, computed tomographic arterioportography and carbon dioxide-enhanced ultrasonography. Of 76 patients with a small hepatocellular carcinoma of 2 cm or less in maximum diameter, 61 underwent digital subtraction angiography, computed tomographic arterioportography and enhanced ultrasonography at the same time. Concerning the 61 patients undergoing all the procedures, the characteristics of hepatocellular carcinoma were found in 57.4% (35 of 61) by digital subtraction angiography, 75.4% (46 of 61) by computed tomographic arterioportography and 72.1% (44 of 61) by enhanced ultrasonography. Among them, four hepatocellular carcinomas were detected only by enhanced ultrasonography, three were diagnosed only by computed tomographic arterioportography and two were diagnosed by both of them. Except for six hemangioma nodules that were easily diagnosed only with angiography, four of 55 benign hepatic nodules (7.3%) showed false-positive findings suggestive of hepatocellular carcinoma with either computed tomographic arterioportography or enhanced ultrasonography. In conclusion, computed tomographic arterioportography and enhanced ultrasonography could complementarily detect a small hepatocellular carcinoma more sensitively than digital subtraction angiography.
Adult↗
Nucleotide sequence of hepatitis C virus (type 3b) isolated from a Japanese patient with chronic hepatitis C.
The genomic sequences of many hepatitis C virus (HCV) isolates have been reported and a variety of virus genotypes have been classified based on homology in the conserved regions. We have previously identified five distinct genotypes (1a, 1b, 2a, 2b and 3b) in Japanese patients with chronic HCV infection by comparing the sequences of the NS5 region. The complete nucleotide sequence for five genotypes (1a, 1b, 1c, 2a and 2b) have already been reported and we report here the complete nucleotide sequence of genotype 3b. The isolate (HCV Tr) was 9439 nucleotides long, excluding the poly(U) tract at its 3' end, and encodes a single long open reading frame of 3023 amino acids. Total nucleotide sequence homologies were 68.4 to 68.7%, 68.3 to 69.0%, 67.2%, 65.8% and 65.6% compared with type 1a, 1b, 1c, 2a and 2b genomes, respectively. The amino acid sequences of these five genotypes were highly homologous in the core, NS3 and NS5B regions, but the E2/NS1 region, which contains hypervariable regions 1 and 2, and the NS5A region were poorly conserved. Although it was possible to detect antibody against the relatively homologous core and NS3 regions by ELISA, the presence of divergent protein structures must be taken into account in the development of a vaccine.
Amino Acid Sequence↗
Small hepatocellular carcinoma: evaluation of portal blood flow with CT during arterial portography performed with balloon occlusion of the hepatic artery.
PURPOSE: To evaluate portal blood flow in small hepatocellular carcinomas (HCCs) by means of computed tomography during arterial portography (CTAP) and CTAP with hepatic arterial obstruction (CTP-HAO) achieved by means of balloon occlusion. MATERIALS AND METHODS: Thirteen patients with small HCC (< 20 mm in diameter) underwent CTAP, CTP-HAO, carbon dioxide-enhanced ultrasound (CEUS), and digital subtraction angiography (DSA). The imaging findings were correlated with histologic features. RESULTS: The first group of patients (n = 3) had tumors with portal blood flow at both CTAP and CTP-HAO and no hypervascularity at CEUS. The second group (n = 3) had tumors with portal blood flow at CTP-HAO but not at CTAP and hypervascularity at CEUS only. The third group (n = 7) had tumors without portal blood flow at CTAP or CTP-HAO and hypervascularity at DSA and CEUS. The first and second groups had well-differentiated HCCs; six of seven patients in the third group had moderately differentiated HCCs. CONCLUSION: Lack of portal blood flow was reversible in well-differentiated HCCs but irreversible in the other tumors.
Carcinoma, Hepatocellular↗
[The diagnosis of hepatocellular carcinoma determined by pattern of AFP bands separated by Con A affinity electrophoresis].
We analyzed the Con A affinity of serum AFP in patients with a serum AFP concentration greater than 50ng/ml by antibody affinity electrophoresis and Western blotting to distinguish hepatocellular carcinoma (HCC) from benign chronic liver diseases (CLD). Of 164 patients with HCC, 48 (29.3%) had a single band, while 116 (70.7%) had multiple bands. All but three of 65 patients with cirrhosis had a single band. All but one of 32 patients with chronic hepatitis had a single band. We concluded that multiple AFP bands are diagnosis of HCC. This method is a useful assay for distinguishing HCC from CLD.
Adult↗
Risk factors for tumor recurrence and prognosis after curative resection of hepatocellular carcinoma.
METHODS: Eighty-three patients with hepatocellular carcinoma (HCC) were treated with curative surgical resection during the past 8 years. RESULTS: No operative deaths occurred. The cumulative recurrence rates after resection at the ends of years 1, 2, and 3 were 37.0%, 57.1%, and 71.6%, respectively. After adjusting the imbalance in clinical factors among patients by using a Cox proportional-hazards model, it was shown that multiplicity, histologic classification, and absence of antibody to hepatitis C virus were associated significantly with recurrence after resection. The size of the tumor did not affect the incidence of recurrence. Thirty-eight of 41 patients with intrahepatic tumor recurrence had undergone at least one of the following three therapies against HCC: surgical reresection, percutaneous ethanol injection (PEI), and transcatheter arterial embolization (TAE). The most significant factor affecting the survival time of patients with tumor recurrence was the total number of tumor nodules at the time of recurrence. Although surgery and PEI were thought to be more effective treatments than TAE in prolonging life, multivariate analysis showed that they were not significant factors of survival time because choices in the method of treatment were correlated closely with the number of cancer nodules. A 65.3% 5-year survival rate from the time of first surgery was accomplished through vigorous therapy when tumors recurred. CONCLUSION: In conclusion, despite the high recurrence rate after resection of HCC, the use of multiple therapies can achieve increased survival rates.
Adult↗
Effect of lymphoblastoid alfa-interferon in patients with chronic hepatitis C having different genotypic subtype of hepatitis C virus.
Five subtypes of hepatitis C virus (Pt[I], K1[II], K2a[III], K2b[IV] and Tr[V]) have been suggested based on the nucleotide sequence of the non-structural five region. To assess the susceptibility of each subtype to interferon therapy, we developed a one-step method which allows quick determination of subtype using polymerase chain reaction with a mixed primer set deduced from the sequence of each subtype. We were able to determine the subtype of 69 of 80 (86.3%) Japanese patients who received natural alfa-interferon treatment. The incidence of each subtype was K1: 53 (76.8%), K2a: 14 (20.3%), K2b: 3 (4.3%) and Tr: 1 (1.4%). Interferon was administered to these patients and found to be effective in 28 of 51 (54.9%) patients with K1 subtype and in 16 of 18 (88.9%) patients with other subtypes (P < 0.01). These data show that K1 is a major subtype in Japan and relatively resistant to interferon treatment.
Adult↗
A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis.
To elucidate the appearance rates of hepatocellular carcinoma in cirrhosis and to assess the risk factors for hepatocellular carcinogenesis, we prospectively studied 795 consecutive patients with viral or alcoholic cirrhosis for 2 to 17 yr (median of 5.8 yr). During the observation period, hepatocellular carcinoma developed in 221 patients. Cumulative appearance rates of hepatocellular carcinoma were 19.4%, 44.3% and 58.2% at the end of the fifth, tenth and fifteenth years, respectively. When classified by the type of hepatitis virus infection, the appearance rates of hepatocellular carcinoma in 180 patients with only HBsAg and in 349 patients with only antibodies to hepatitis C virus were 14.2% and 21.5% at the fifth yr, 27.2% and 53.2% at the tenth yr and 27.2% and 75.2% at the fifteenth yr, respectively. Cox proportional hazard model identified that alpha-fetoprotein levels (p = 0.00001), age (p = 0.00067), positive hepatitis C virus antibodies (p = 0.00135), total alcohol intake (p = 0.00455) and indocyanine green retention rate (p = 0.04491) were independently associated with the appearance rates of hepatocellular carcinoma. Whereas age and indocyanine green retention rate were independent predictors for the appearance rate of liver tumor in the subgroup of HBsAg-positive patients, alpha-fetoprotein levels, age and past alcohol consumption were independent predictors in the group of hepatitis C virus antibody-positive patients. These epidemiological results suggest that some differences exist in the activity and modes of cancer promotion between hepatitis B virus infection and hepatitis C virus infection.
Adult↗
Diagnosis and follow-up of small hepatocellular carcinoma with selective intraarterial digital subtraction angiography.
To clarify the angiographic features of small hepatocellular carcinoma, we performed digital subtraction angiography in 91 patients with hepatocellular carcinomas of 2 cm or less. Repeated digital subtraction angiography studies were performed in 25 patients whose first angiograms showed no tumor staining. Digital subtraction angiography showed hypervascular tumor staining in only 51 patients (56.0%). We found that the smaller a tumor nodule was, the lower the detection rate of tumor stain on digital subtraction angiography. The detection rate of hypervascularity was closely correlated with the grading of histological differentiation of the tumors: well-differentiated hepatocellular carcinomas more often showed negative tumor staining. Repeated digital subtraction angiography studies showed alteration of tumor staining from isovascular to hypervascular in 6 of 6 patients with tumors that became larger than 2 cm and in 12 of 19 patients with tumors that remained 2 cm or smaller. Conversion of vascularity is commonly found in the early stage of small hepatocellular carcinoma, and the process is usually slow, taking approximately 1 yr.
Adult↗
Alanine aminotransferase and HCV-RNA responses following interferon therapy of HCV-RNA positive chronic hepatitis.
Interferon (IFN) has been shown to be effective for chronic hepatitis C. This study investigated changes of alanine aminotransferase (ALT) and HCV-RNA in chronic hepatitis C patients treated with alpha-IFN. IFN was given to 73 patients with HCV-RNA positive chronic hepatitis C. The pattern of changes in ALT activity after IFN administration was classified into five types. Type 1 was characterized by normalization of ALT (< or = 25 K.U) during IFN administration and sustained normalization after the IFN therapy. Type 2 involved a rebound of ALT after termination of IFN therapy and subsequent normalization. Type 3 had no ALT normalization during IFN administration, with normalization after the completion of the therapy. Type 4 involved transient normalization of ALT level during IFN therapy, with a subsequent reversion to abnormal levels after the termination of IFN therapy. Type 5 showed sustained abnormally high levels of ALT activity both during and after treatment. Twenty four patients (32.9%) had sustained normalization ALT (< or = 25 K.U) after the termination of IFN treatment. The HCV-RNA negative rate at 6 months after IFN therapy in patients with sustained normalization of ALT was 87.5% (21/24).
Adult↗
[A case of intrahepatic cholangiocarcinoma with liver cirrhosis presenting atypical images].
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Adenoma, Bile Duct↗
Effect of repeated transcatheter arterial embolization on the survival time in patients with hepatocellular carcinoma. An analysis by the Cox proportional hazard model.
One hundred fifty-eight patients with hepatocellular carcinoma (HCC) were treated by transcatheter arterial embolization (TAE) as repeatedly as possible. Survival rates at the end of the first, second, and third year were 76.5%, 54.5%, and 41.1%, respectively. In 142 patients with repeated TAE, a significantly increased number of patients with complete necrosis of tumor was observed after repetition of the therapy. Adjusting the imbalance in prognostic factors among patients by using Cox proportional hazard model, it proved that the best response during the repeated therapy, rather than the first response, was significantly associated with survival period of the patients. Aside from the factor of response to the treatment, tumor size was the worst prognostic factor at the time when diagnosis was made. Other significant factors were portal vein invasion by HCC and bilirubin. The survival period of patients with HCC treated by repeated TAE was, therefore, affected by cancer factors, liver cirrhosis factors, and therapy-responsiveness factors. It is concluded that even if complete necrosis of tumor is not obtained after the first trial, repetition of TAE is an effective measure for prolonging of survival time in patients with HCC.
Adult↗
Effect of interferon administration on serum hepatitis C virus RNA in patients with chronic hepatitis C.
Hepatitis C virus RNA as detected by reverse transcription and nested polymerase chain reaction was monitored in 16 patients with chronic hepatitis C treated with interferon. Hepatitis C virus RNA became undetectable after 4 to 8 wk of interferon administration in 13 of the 16 patients. During 6 mo of follow-up, 5 of the 13 patients who became negative for hepatitis C virus RNA after interferon administration remained negative, and all five continued to have normal ALT levels. Repeat liver biopsy in these five patients revealed histological improvement. Antibody to hepatitis C virus, which was initially positive in all treated patients, fell to undetectable levels in three of the five patients. In contrast, aminotransferase levels rose again in all eight patients who had become hepatitis C virus RNA negative but had again exhibited hepatitis C virus RNA after completion of therapy. In 16 untreated patients, hepatitis C virus RNA remained detectable. These results indicate that detection of hepatitis C virus RNA may be useful as a marker of viral replication in chronic hepatitis C; they also suggest that interferon should again be administered to patients who become hepatitis C virus RNA negative on treatment but again exhibit this marker of viral replication when treatment is stopped.
Adult↗