Selection of prognostic factors of acute hepatitis type non-A, non-B for patient listing for liver transplantation.

The aim of this study was to select prognostic factors from information available on admission in order to list patients for liver transplantation before the onset of hepatic encephalopathy in patients with fatal hepatitis type non-A, non-B. Information regarding patient profile and biochemical data obtained on admission was analyzed by multiple stepwise logistic regression, and independent prognostic factors related to death were selected. Four parameters were selected as independent prognostic factors. Patient age (over 50 years), serum total bilirubin level (over 10 mg/dl), peripheral leukocyte count, and prothrombin time were independently related to death. Positive predictive value, negative predictive value, and predictive accuracy were 0.86, 0.79, and 0.84, respectively. Our model is able to predict a patient's fatal outcome much earlier than other currently used models. It will be helpful for early referral to a transplant center.

Serum carboxy-terminal cross-linked telopeptide of type I collagen reflects bone metastasis in hepatocellular carcinoma.

Carboxy-terminal telopeptide of type I collagen (ICTP) is a degradation product of type I collagen. In this study, we investigated the usefulness of measuring the serum ICTP concentration for diagnosing and monitoring bone metastasis from hepatocellular carcinoma (HCC). The serum concentrations of ICTP, type I procollagen carboxy-terminal propeptide (PICP), type III procollagen aminoterminal propeptide (PIIIP), type IV collagen (Ty IV), type IV collagen 7S-domain (7S), and hyaluronic acid (HA) were measured in patients with liver cirrhosis, HCC with or HCC without bone metastasis, and in healthy controls. The diagnostic efficiency of the serum ICTP and fibrosis marker levels in the HCC patients with and without bone metastasis was evaluated using receiver operating characteristic curves. We also retrospectively examined the changes in the serum ICTP levels before and after bone metastasis in the HCC patients. The serum ICTP level was significantly higher in the HCC patients with bone metastasis than in the patients with other diseases and the healthy controls. The serum PICP, PIIIP, Ty IV, 7S and HA levels of the HCC patients with bone metastasis did not differ significantly from those of the patients without bone metastasis. The diagnostic efficiency for HCC with bone metastasis was 87% for ICTP, 51% for PICP, 65% for Ty IV, 55% for PIIIP and 51% for HA. During the follow-up, the changes in the serum ICTP values paralleled the behavior of bone metastasis. These results indicate that the measurement of serum ICTP concentration is useful for detecting and monitoring HCC patients with bone metastasis.

In vitro study of neutrophil apoptosis in liver cirrhosis.

Cirrhotic patients frequently manifest neutropenia and are predisposed to bacterial infections. We examined neutrophil apoptosis to determine if neutrophil survival in cirrhotic patients is shortened. Neutrophils isolated from 10 cirrhotic patients and 10 healthy volunteers were cultured for 24 hours. The time course of neutrophil viability was assessed by the trypan blue dye exclusion test and apoptosis was determined morphologically by light and electron microscopy. Apoptotic cells were also confirmed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick and labeling (TUNEL) and DNA gel electrophoresis. Fas expression of neutrophils was examined by flow cytometry. Viabilities were significantly decreased in liver cirrhosis (p<0.0001). Neutrophils from cirrhotic patients exhibited significantly greater apoptosis. Fas expression of neutrophils was significantly reduced for cirrhotic patients (p=0.0001). Neutrophils from cirrhotic patients exhibited markedly accelerated apoptosis in vitro. Shortening of neutrophil survival via apoptosis may explain in part the mechanism of neutropenia in cirrhotic patients.

[Evaluation of serological response to Bartonella henselae by enzyme immunoassay in cat scratch disease].

The IgG and IgM titers to Bartonella henselae were determined by an enzyme immunoassay (EIA). The EIA test for detection of IgG and IgM antibodies to B. henselae concerning CSD showed that 8 (40%) of 20 patients with CSD had a serum IgG antibody titer of 12 EIA unit or more and that 5 (25%) patients had a serum IgM titer of 12 EIA unit or more. Totally 12 (60%) of the 20 patients with CSD were seropositive for B. henselae. The mean age of IgG positive patients were higher than IgM positive patients. The IgM antibodies to B. henselae disappeared within 4 to 12 weeks after onset of disease. The IgG antibodies to B. henselae disappeared within 3 to 8 weeks after onset of the symptoms in 2 cases of CSD. Another 2 cases CSD produced high levels of IgG antibodies in the acute phase of the disease. Different course of IgG and IgM antibody titers were found in sera from patients.

[Longitudinal study of serological response to Bartonella henselae by indirect fluorescence assay in cat scratch disease].

Sequential serologic testing for IgG and IgM titers to Bartonella henselae were evaluated by an indirect fluorescence assay (IFA) in patients with CSD. The IFA test for the detection of IgG and IgM antibodies to B. henselae in 52 CSD patients showed that 40 (76.9%) were positive for IgG antibody and 9 (17.3%) were positive for IgM antibody. Two or more consecutive serum samples from 30 patients with CSD were assessed. In regard to the detection of IgG antibody, 5 patients had rapidly elevated titers in the acute phase, 12 patients had high titers from the acute phase, and 5 patients had a positive titer 24 weeks after the onset. B. henselae IgM antibody kinetics varied widely between patients with CSD. The seropositive rate for the antibody to B. henselae was analyzed at overtime after the onset and we found that the IgG-seropositive rate was high from 2 weeks after the onset and low after 25 weeks. The sensitivity of the IgM IFA was low, and IgM antibody to B. henslelae was not detected from 9 weeks. The detection from consecutive serum samples of antibodies to B. henselae by IFA is very useful for diagnosis in the case of clinically suspected CSD.

[Two cases of suspected Bartonella henselae infection from a dog].

A 55-year-old male was admitted to our hospital because of fever and left submaxillary, right axillary, and left inguinal lymphadenopathy. A presumptive diagnosis of rickettsiosis was made and treatment with oral doxycycline was started. Lymphadenopathy was partialy resolved after antibiotics treatment. Ablation of the left inguinal node was done and histopathological examination showed non-Hodgkin's lymphoma. Lymphadenopathy was resolved by chemotherapy. The second patient, a 40-year-old male, developed a tender submandibular node. Excisional biopsy of the node was performed to eliminate lymphoma. Histopathological examination revealed granulomatous lymphadenitis with follicular hyperplasia. The patients had no history of cat contact, but owned a dog. Diagnosis of both cases was confirmed by the detection of IgG antibodies to Bartonella henselae with an enzyme immunoassay. Our findings suggest that dogs are implicated in B. henselae infection and can serve as a reservoir of the organism as well as cats. In the abscence of other bacterial and especially after exposure to dogs, B. henselae should be included as possible cause of lymphadenopathy.

[Five cases of erythema infectiosum in adults].

The similarities between clinical features of erythema infectiosum and collagen disease or other viral infections prompted us to investigate clinical manifestations and laboratory data of parvovirus B19 (B19) infection in adults. We diagnosed all five patients as acute B19 infection by antibody assays. The age of patients ranged from 18 to 39 years old (mean 29), and all patients were female. All five patients showed high fever, arthralgia and edema of the extremities. Four of the five patients showed skin rash of the extremities or cheeks. Two patients were diagnosed as erythema infectiosum by family physicians before coming to us. The three remaining patients were suspected to be systemic lupus erythematosus, adult Still disease or rubella indivisually and referred to our hospital. A-27-old female (case 5) visited our hospital because of polyarthralgia and butterfly rash on her face. A test for antinuclear antibodies (ANA) was positive at a dilution of 1:320. Rheumatoid factor (RF) was also detected by latex fixation test. Her AST was 51 IU/L, ALT 68 IU/L and LDH 568 IU/L. Her symptoms persisted for 3 weeks and hepatic dysfunction recovered within 3 weeks. Five months later. ANA was negative at the dilution of less than 1:40. We suggest that the similarities between some symptoms of B19 infection and clinical and serological manifestation of collagen diseases merit closer attention.

[A case of cat scratch disease identified by an elevated Bartonella henselae antibody level using enzyme immunoassay].

A 68-year-old male was admitted to our hospital because of fever and a 2-week history of inguinal adenomegaly. Since he owned a cat, cat scratch disease was suspected. But it was necessary to distinguish cat scratch disease from lymphoma type adult T-cell leukemia because he showed a high level of antibody against HTLV-1. An excisional biopsy of the inguinal node was performed. Histopathologic examination revealed abscess-forming granulomatous lymphadenitis compatible with cat scratch disease. A Warthin-Starry silver stain showed pleomorphic bacilli in the lymph node. So we confirmed a serological response to Bartonella henselae, the causative agent of cat scratch disease, using enzyme immunoassay (EIA). The IgG antibody level to B. henselae was positive at 42 EIA Unit before treatment. After treatment with intravenous cefepime and oral tosufloxacin, his physical symptoms improved and the antibody level decreased to less than 12 EIA Unit. EIA was very useful for diagnosis of this case. Serology to B. henselae may replace traditional diagnostic criteria for cat scratch disease.

[Autoimmune thrombocytopenia and erythroid hypoplasia associated with hepatitis A].

A 53-year-old woman developed fever and fatigue after eating raw oysters, and consulted a local clinic. She exhibited liver dysfunction and jaundice, and was therefore referred and admitted to our hospital. Hepatitis A was diagnosed based on virus markers, and palliative therapy was administered. After admission, the increased levels of transaminases and lactic acid dehydrogenase (LDH) normalized rapidly. However, marked thrombocytopenia was observed, and steroid pulse therapy was administered. Thereafter, idiopathic anemia developed, and a bone marrow puncture was performed. Bone marrow smears showed marked depletion of cells of the erythroblastic and megakaryocytic series. Parvovirus B19 infection was ruled out, and an additional steroid was administered. However, the patient's anemia and thrombocytopenia persisted. She suffered a prolonged period of cholestasis and died of acute renal failure. At autopsy, the bone marrow revealed severe erythroblastopenia. A diagnosis of thrombocytopenia due to an autoimmune mechanism was made on the basis of elevated levels of platelet-associated immunoglobulin G (PAIgG) and immune complex. Furthermore, the advanced anemia was complicated by concurrent hemolysis. This case may provide information useful for clarifying the pathogenesis of hematopoietic disorders complicated by hepatitis.

The significance of colocalization of plasminogen activator inhibitor-1 and vitronectin in hepatic fibrosis.

BACKGROUND: We examined the relationships among vitronectin (VN), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor beta 1 (TGF-beta 1) in liver diseases to evaluate the presence of plasmin cascade in human hepatic fibrosis. METHODS: Blood and liver tissues were obtained from 57 patients with liver disease. Plasma VN, PAI-1 antigen, and PAI-1 activity levels were evaluated. Biopsied liver specimens were observed by light and electron microscopy after immunohistochemical staining. Morphometric analysis was performed on these specimens. RESULTS: Plasma VN and PAI-1 activity levels decreased significantly with the progression of hepatic fibrosis and were particularly marked in the liver cirrhosis group. Plasma PAI-1 antigen level increased significantly. The immunolocalization of the active form of TGF-beta became more intense with the progression of hepatic fibrosis, whereas that of the dual-stained positive areas of PAI-1 and VN (PAI-1.VN) decreased. There was a positive correlation between TGF-beta and PAI-1, whereas there was a negative correlation between TGF-beta and PAI-1.VN. Immunoelectron microscopy showed the localization of PAI-1-VN in the extracellular space around the sinusoidal cells or surface of aggregating platelets, TGF-beta mainly in Ito cells, and VN in hepatocytes near the focal necrotic area or fibrous septa. CONCLUSIONS: These findings suggest that VN and PAI-1 are related to the active form of TGF-beta and that it is possible that the plasmin cascade is present in the human liver.

Prognostic factors for short-term survival in alcoholic hepatitis in Japan: analysis by logistic regression.

Prognostic factors for the outcome of patients with alcoholic hepatitis were identified by logistic regression analysis. To predict the outcome immediately after admission, clinical data from 97 patients with alcoholic hepatitis on admission were introduced to multivariate analysis. Independent prognostic factors for favorable outcome were hepaplastin time, peripheral white blood cell count, age (40 to 60 years), and serum creatinine level (below 1.4 mg/dl). Sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy were 0.78, 0.89, 0.78, 0.89, and 0.86, respectively. The resultant equation for the death rate was applied to another set of patients with alcoholic hepatitis as a validation study. Predictive accuracy estimated 0.95 in validation. The prognostic index derived was simple, accurate, and useful in the prediction of the outcome in patients with alcoholic hepatitis. Furthermore, it provides the clinician with an indication of the necessity for the intensive care of patients in a critical condition.

Serological study of Bartonella henselae in cat scratch disease in Japan.

It has become clear that Bartonella henselae is a common cause of cat scratch disease (CSD). The indirect fluorescence antibody (IFA) test for detection of IgG and IgM antibodies to B. henselae concerning CSD showed that 5 (50%) of 10 patients with CSD had a serum IgG antibody titer of 1:128 or more and that 2 (20%) patients had a serum IgM antibody titer of 1:20 or more. One of 7 asymptomatic members of patients' families (14%) had IgG antibody to B. henselae at a titer of 1:256. IgM antibody to B. henselae was not detected in sera from the patients' families. Both IgG and IgM antibodies to B. henselae were not detected in sera from the healthy control group. These data suggest that B. henselae may be a cause of CSD in Japan.