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Biomedical subjects

Kojiro Michitaka

Publications and source records attributed to Kojiro Michitaka.

At least 55 records · Page 3Linked to original sources

Spontaneous closure of intrahepatic portovenous shunt in a noncirrhotic patient with recurrent encephalopathy.

A 70-year-old man was admitted to our hospital with recurrent encephalopathy. Liver function tests, abdominal computerized tomography, ultrasonography, angiography, and laparoscopy revealed an intrahepatic portovenous shunt in a noncirrhotic liver. During follow-up, the intrahepatic portovenous shunt closed spontaneously. Subsequent liver function tests were markedly improved, with resolution of the patient's previously disturbed consciousness. In the elderly, intrahepatic portovenous shunt that can be managed with conservative therapy may spontaneously close, suggesting that management options should include watchful waiting.

Aged↗

Drug-induced hepatitis due to repeated use of hair dye.

A 27-year-old Japanese man with no past history of liver disease was admitted to our hospital due to liver abnormalities. The patient was diagnosed with drug-induced hepatitis, as the three episodes of hepatitis occurred just after repeated use of hair dye. After cessation of the hair dye use, abnormal liver function tests improved to within the normal range. Although hair dyes contain various hepatotoxic compounds, hair dye is not known to cause drug-induced hepatitis. Thus, in cases of liver abnormality of unknown origin, the history of hair dye use should be investigated.

Adult↗

Acute-onset autoimmune hepatitis treated with living donor-liver transplantation.

A 50-year-old woman was diagnosed with acute-onset autoimmune hepatitis. She did not respond to steroid therapy including pulse therapy, and was subsequently treated with living donor-liver transplantation 36 days after the beginning of steroid therapy. Except for a period of transient mild acute rejection, her liver function tests remained within a normal range for 2.5 years after the operation. The courses of autoimmune hepatitis patients treated with living-donor liver transplantation have not been previously documented to our knowledge. Living donor-liver transplantation is thought to be one of the therapy options for severe autoimmune hepatitis.

Acute Disease↗

Autoimmune hepatitis associated with Graves' disease.

A 31-year-old woman with Graves' disease with a 12-month-history of propylthiouracil intake and autoantibodies in the sera was admitted to our hospital. The differential diagnosis between autoimmune hepatitis and propylthiouracil-induced hepatitis was intractable. Steroid therapy was started and she showed a complete response to the treatment. Liver biopsy demonstrated acute hepatitis and plasma cell infiltration. A second liver biopsy, which was performed 10 months after starting steroid therapy, showed some inflammatory cells in the portal tracts. These findings suggest that she had been suffering from autoimmune hepatitis.

Adult↗

Decompensated hepatitis B virus-related cirrhosis successfully treated with lamivudine allowing surgery for hepatocellular carcinoma.

A 39-year-old man was diagnosed with hepatitis B virus-related cirrhosis, and because of hepatic exacerbations with icterus and ascites, he had been repeatedly hospitalized. He was treated with lamivudine. Several months later, his ascites disappeared and his liver function was improved from class C to A according to the Child-Pugh classification. Two years later, one small hepatocellular carcinoma was detected, and he underwent a successful hepatectomy. From this case, we consider lamivudine to be useful for improving hepatic function in decompensated liver cirrhosis type B and lamivudine might enable surgical resection of hepatocellular carcinoma.

Adult↗

Drug-induced hepatitis with autoimmune features during minocycline therapy.

A 25-year-old woman with no history of liver disease developed liver dysfunction associated with severe jaundice and general malaise following a prolonged therapy with minocycline for acne vulgaris. Serum anti-nuclear antibody was detected and immunoglobulin G level was elevated. Symptoms resolved and liver function normalized following minocycline discontinuation and corticosteroid administration. Our diagnosis was drug-induced hepatitis with autoimmune features, as liver histology revealed acute hepatitis. Drug-induced hepatitis should be considered when liver dysfunction or systemic symptoms develops during long-term minocycline therapy.

Acne Vulgaris↗

Impaired function of antigen-presenting dendritic cells in patients with chronic hepatitis B: localization of HBV DNA and HBV RNA in blood DC by in situ hybridization.

Antigen-presenting dendritic cells (DCs), which play a major role in the triggering of primary anti viral immune reactions, may also contribute, in some viral models, to the pathogenesis of persistent viral infection. In fact, impaired immune response to hepatitis B virus (HBV)-encoded antigens is seen in patients with chronic hepatitis B (CH-B). The aim of this study was to check the function of DCs in these patients and to investigate the underlying mechanism. DCs were enriched from peripheral blood mononuclear cells by culturing with interleukin (IL)-4 and granulocyte-macrophage colony stimulating factor for 7 days. The stimulatory capacity of DCs were checked in allogenic mixed leukocyte (MLR) reaction. The levels of IL-12 in the culture supernatants were measured by an enzyme-linked immunosorbent assay. HBV DNA and HBV RNA were localized in DCs by polymerase chain reaction (PCR) in situ hybridization and reverse-transcriptase (RT)-PCR in situ hybridization. The stimulatory capacity of DCs in allogenic MLR was significantly lower in patients with CH-B (36321+/-12523 cpm, n=18) compared to that of normal controls (65678+/-11174 cpm, n=18) (p<0.0001). Significantly lower levels of IL-12 were detected in cultures containing DCs from patients with CH-B than normal controls (46.7+/-25.6 versus 122.4+/- 37.1 pg/ml, p<0.0001). In situ hybridization revealed the localization of HBV DNA and HBV RNA in DCs from patients with CH-B. These results indicate that chronic infection by HBV is associated with functional defects of DCs. Localization of HBV DNA and HBV RNA indicates that DCs may constitute an extra hepatic reservoir and possibly of replication of HBV.

Adult↗

Increased serum levels of macrophage inflammatory protein-3alpha in hepatocellular carcinoma: relationship with clinical factors and prognostic importance during therapy.

Macrophage inflammatory protein (MIP-3alpha) is a CC chemokine that attracts immature dendritic cells and lymphocytes and is thought to play a role in the pathogenesis of inflammation and carcinogenesis. However, nothing is known about the clinical significance or prognostic importance of this chemokine in patients with cancer. The aim of this study was to assess the clinical factors influencing the levels of serum MIP-3alpha and to evaluate any possible prognostic importance of this chemokine. We further checked the possible source of MIP-3alpha in hepatocellular carcinoma (HCC). The levels of serum MIP-3alpha from 45 patients with HCC, 12 patients with liver cirrhosis (LC) and 45 patients with chronic hepatitis (CH) were measured by an enzyme immunoassay. A correlationship between different clinical parameters and the serum levels of MIP-3alpha was analyzed. Production of MIP-3alpha by human cancer cell lines and peripheral blood mononuclear cells (PBMC) was also estimated. The levels of serum MIP-3alpha were significantly higher in HCC than in LC (p=0.0214) and CH (p<0.0001). Cancer-related factors such as size of cancer nodules, levels of differentiation of HCC and the levels of alpha-fetoprotein were related with increased MIP-3alpha levels in HCC. Human cancer cell lines, but not PBMC from HCC patients, produced very high levels of MIP-3alpha in culture. The rate of recurrence of HCC after radio frequency ablation (RFA) was fewer in patients having lower pre-therapeutic levels of serum MIP-3alpha. An impact of cancer-related factors on the levels of serum MIP-3alpha in HCC is shown. Pre-therapeutic levels of serum MIP-3alpha may be used as a marker of prognosis of RFA therapy.

Adult↗

Drug-induced hepatitis with hepatic granuloma due to saridon.

A 38-year-old Japanese woman with no past history of liver disease developed liver dysfunction associated with fever, anorexia, and general malaise following the prolonged administration of saridon. A liver biopsy demonstrated multiple noncaseating epithelioid granulomas within hepatic lobules, with an inflammatory cell infiltrate of the lobular parenchyma and portal tracts. Viral markers and autoantibodies were negative. Lymphocyte stimulation tests for saridon and for isopropylantipyrine, one of the constituents of saridon, were positive, and therefore a diagnosis of drug-induced hepatitis due to administration of saridon was made. Her symptoms resolved and liver function test results returned to normal following discontinuation of the drug. The possibility of drug-induced hepatitis must be considered when liver dysfunction or systemic symptomatology develops during saridon therapy.

Adult↗

Dendritic cell subtypes in autoimmune liver diseases; decreased expression of HLA DR and CD123 on type 2 dendritic cells.

In order to dissect the role of different subsets of antigen-presenting dendritic cell (DC) in autoimmune liver diseases, we analyzed the frequencies and phenotypes of DC1 and DC2 from patients with primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH). The numbers of DC, DC1 and DC2 in a fixed amount of peripheral blood (20 ml) from 14 patients with PBC (therapy [-]: 5, therapy [+]: 9), seven patients with AIH (therapy [-]): 4, therapy [+]: 3), nine patients with chronic hepatitis due to hepatitis C virus and 12 healthy subjects were estimated using three-color flow cytometry. The mean fluorescence intensities of HLA DR, CD11c and CD123 on DC subsets were evaluated from the flow cytometric profiles. The numbers of DC1 and DC2 did not differ significantly among patients and controls. The expression of HLA DR was lower on DC1 from patients with AIH, but not on PBC. However, the levels of HLA DR and CD 123 on DC2 were significantly decreased in patients with PBC (therapy [-]) and AIH (therapy [-]) compared with healthy subjects (P<0.05). Defective phenotype of DC2 in both AIH and PBC may have a relevance to the breakdown of tolerance to self antigen in these autoimmune diseases. Functional study of DC2 in autoimmune liver diseases is warranted.

Journal Article↗

Activation and maturation of antigen-presenting dendritic cells during vaccine therapy in patients with chronic hepatitis due to hepatitis B virus.

BACKGROUND/AIMS: The function and phenotype of antigen-presenting dendritic cells (DC) have been checked in patients with chronic hepatitis (CH) undergoing vaccine therapy to have insight about the mechanism of this immune therapy. SUBJECTS AND METHODS: Eleven patients with CH due to hepatitis B virus (HBV) were injected with vaccine containing 20 &mgr;g of hepatitis B surface antigen (HBsAg) once at every 2 weeks for 12 consecutive times. The serum interluekin-12 levels were estimated and the function and phenotype of peripheral blood DC were checked before, during and after the vaccine therapy. RESULTS: Sustained normalization of DNA-polymerase activity and alanine aminotransferase were seen in six patients (complete responders [CR]) due to vaccine therapy. The levels of serum interleukin-12 (P<0.01), the stimulatory capacity of peripheral blood DC (P<0.05) and the numbers of CD83-positive mature DC and CD86-positive activated DC (P<0.05) were significantly increased due to vaccination in CH-B patients, especially in younger patients. CONCLUSIONS: A role of DC during vaccine therapy is shown. This study also indicates that more effective vaccine therapy can be developed by upregulating the function of DC in situ in younger patients.

Journal Article↗

Morphometric analysis of lymphatic vessels in primary biliary cirrhosis.

The purpose of this study was to elucidate the morphometric changes occurring in hepatic lymphatics in primary biliary cirrhosis (PBC). The lymphatic vessels were stained intensely by enzyme-histochemistry for 5'-nucleotidase while blood vessels stained well for alkaline phosphatase (ALP). We performed a morphometric analysis to estimate the number of lymphatic and blood vessels and their areas, using computer graphics software (NIH Image). Both the number of lymphatics and their areas in specimens in patients with PBC at an early stage were found to have increased. Neither the number nor the areas of the blood vessels showed any obvious relationship with the degree of fibrosis of PBC. Our results clarified that the sizes and number of lymphatics are increased even in the early stage of PBC. This is thought to be due to increased lymph production, which is caused by disturbance of the microcirculation associated with portal hypertension.

Journal Article↗

Clinical characteristics of autoimmune hepatitis with histological features of acute hepatitis.

The number of patients with autoimmune hepatitis with histological features of acute hepatitis (AIH-AH) has been increasing recently. Here, the clinical features of patients with AIH-AH have been compared with those of patients with AIH with histological findings of chronic hepatitis (AIH-CH) and liver cirrhosis (AIH-LC). The levels of total serum bilirubin (P<0.05) and serum transaminases (P<0.05) were significantly higher in patients with AIH-AH than in patients with AIH-CH and AIH-LC. However, the serum levels of gamma-globulin (P<0.05) and immunoglobulin G (P<0.05) were significantly lower in AIH-AH than in patients with AIH-CH and AIH-LC. The aggregate score according to the criteria of the International Autoimmune Hepatitis Group in 1999 was also significantly lower in AIH-AH patients than in patients with AIH-CH and AIH-LC (P<0.05). Eleven patients with AIH-AH were treated with corticosteroids, however, the clinical response was insignificant in three patients. In summary, it is difficult to diagnose of patients with AIH-AH using the criteria of the International AIH scoring system. We wish that this scoring system would be modified in the near future.

Journal Article↗

Existence of TT virus DNA and TTV-like mini virus DNA in infant cord blood: mother-to-neonatal transmission.

The route of transmission of TT virus (TTV) was studied by examining the existence of TTV DNA in different body fluids from the new born infants and their mothers. A total of 52 pregnant women with normal serum alanine aminotransferase levels were enrolled in this study. TTV DNA was examined using a polymerase chain reaction method using Takahashi's primers which can detect all genotypes of TTV and Okamoto's primers which detect only some of the genotypes of TTV. TTV DNA was detected in the sera from 40/52 (77%), in the breast milk from 35/52 (67%), and in the amniotic fluid from 6/6 (100%) pregnant mothers using Takahashi's primers TTV DNA was also detected in the sera from 8 of 11 (73%) and in the cord blood from 25/52 (48%) new born infants using Takahashi's primers. However, TTV DNA was detected in only 5/52 maternal blood (10%) and 4/52 breast milk (8%) using Okamoto's primers. All samples positive for TTV DNA by Takahashi's primers, were also positive for TTV-like mini virus (TLMV) DNA. Our data suggest that intrauterine transmission or transmission via breast milk may contribute to maintaining the global TTV and TLMV reservoir.

Journal Article↗

Chronological changes of causes of death and distant metastasis in hepatocellular carcinoma.

The diagnostic approaches, mode of therapies, frequencies of distant metastasis and causes of death in 139 patients with hepatocellular carcinoma (HCC) between 1976 and 1998 were studied by dividing the total study duration into three periods. The period between 1976-1980 (period I) was characterized by the absence of periodic follow-up of the patients with chronic liver diseases, and operation was the only therapeutic choice for HCC. During 1981-1986 (period II), periodic screening of patients with chronic liver diseases was started using ultrasonography, and transarterial embolization became a second choice of therapy along with operation. Period III (1986-1998) was characterized by the availability of facilities to make definitive diagnosis of HCC using small-gauge cutting needle biopsy under sonographic guidance. Data from our study show that along with the advancement of new and invasive diagnostic and therapeutic approaches, the frequency of death due to gastrointestinal bleeding decreased, whereas, the frequency of death due to respiratory failure resulting from pulmonary metastasis increased. Patients treated with transcatheter arterial embolization were more prone to develop pulmonary metastasis. These data show that patients with HCC undergoing invasive therapies should be checked for distant metastasis in addition to intrahepatic recurrence of HCC.

Age Factors↗

Influencing factors for recurrence of hepatocellular carcinoma treated with radiofrequency ablation.

Radiofrequency ablation (RFA), a new local therapy, has recently been developed for hepatocellular carcinoma (HCC). In this study, we have checked for the factors influencing the recurrence of HCC following RFA. We gave special emphasis to complete coagulation. The study population was comprised of 47 patients (80 tumors) with HCC with tumor size of <3 cm in maximal diameter. The patients were observed for a period of 2-3 years (average 865 days). The local recurrence rate was 19% at the end of 1 year, and 21% by the end of 2 years. The patients with local recurrence received significantly fewer RFA sessions (P<0.05) compared to patients with no recurrence. The frequencies of complete coagulation were significantly less (P<0.05) in patients with local recurrence than patients without local recurrence. The distant recurrence rate was 38% at 1 year, and 60% at 2 years. Patients with distant recurrence had significantly increased number of tumors (2.0+/-1.4) (P<0.05) compared to patients without distant recurrence (1.2+/-0.4). In conclusion, obtaining complete coagulation is an important factor to prevent local recurrence and the number of tumors predicted the distant recurrence in patients with HCC undergoing RFA.

Adult↗