Yasuyo Uchimura

Serum vascular endothelial growth factor levels in various liver diseases

The clinical significance of circulatingvascular endothelial growth factor (VEGF) in patientswith various liver diseases was investigated. Twenty-onepatients with acute hepatitis (AH), 40 with chronic hepatitis (CH), 34 with cirrhosis (LC), 16 withfulminant hepatitis (FH), 10 with primary biliarycirrhosis (PBC), 12 with autoimmune hepatitis (AIH), and120 healthy individuals were included. Serum VEGF levels were measured by a chemiluminescenceenzyme-linked immunosorbent assay. The mean values ofserum VEGF levels in the patients with AH, CH, LC, FH,AIH, PBC, and control were 172.7, 58.0, 44.1, 37.3, 49.7, 74.9, and 65.0 pg/ml, respectively. Thepatients with AH had a level of serum VEGF significantlyhigher than that of the control group (P < 0.001).The serum VEGF levels in survivors of FH weresignificantly increased, but not in the nonsurvivors in therecovery phase compared with the levels on admission (P< 0.05). In the LC patients, serum VEGF levels weresignificantly lower than those of the control group (P < 0.05). These findings suggest thatserum VEGF level may be associated with hepatocyteregeneration grade.

Hepatitis C virus infection in patients with clinically diagnosed alcoholic liver diseases

Summary To determine the incidence of hepatitis C virus (HCV) infection in patients with alcoholic liver disease (AID), serum samples from 252 patients with AID were tested for anti‐HCV and HCV RNA. Serial sera of these patients were collected and stored under optimal conditions to allow exact quantification of HCV RNA. Fifteen patients who visited our hospital during the same period of time with chronic HCV infections served as controls. In those with AID, anti‐HCV and HCV RNA were positive in 55.5% and 41.2%, respectively. Patients with histologically diagnosed chronic hepatitis and hepatocellular carcinoma had much higher prevalence rates of HCV RNA (84% and 100%, respectively) compared to those with fatty liver (4.3%), hepatic fibrosis (10.1%) and alcoholic hepatitis (22.2%) (P < 0.01). Although no difference in serum HCV RNA levels was observed between the patients with both AID and chronic HCV infection and those with chronic HCV infection alone, HCV RNA levels significantly (10‐fold) dropped after abstinence in nearly half of the patients (P < 0.01). These data indicate that HCV infection in patients with AID promotes progression of liver disease, and abstinence from alcohol is associated with a reduction in serum HCV RNA levels.

Hepatic iron stainings in chronic hepatitis C patients with low HCV RNA levels : A predictive marker for IFN therapy

OBJECTIVES Interferon (IFN) therapy is ineffective in about 20-30% of chronic hepatitis C (CH-C) patients who have low HCV RNA levels. Besides the serum HCV RNA level or HCV genotype, hepatic iron concentrations are thought to be correlated with the subsequent response to IFN therapy. Our objective in the present study was to evaluate serum iron, ferritin, and hepatic iron staining in patients with low HCV RNA levels, as predictive markers for IFN therapy. METHODS We evaluated 75 CH-C patients whose serum HCV RNA levels were below 1 million genome equivalent (mEq)/ml as shown by a bDNA assay. RESULTS There were no significant differences in age, sex, serum aminotransferase levels, or serum iron concentrations between responders and nonresponders. The total iron scores (TIS) were significantly higher in responders (p < 0.01). The TIS was an independent factor relating to the response to IFN therapy by multivariate analysis (p = 0.0062). The TIS significantly correlated with serum ferritin levels (r = 0.637, p < 0.001), but not with any other parameter. bi] CONCLUSIONS Among CH-C patients within the limits of low HCV RNA levels, TIS of the liver may be used as a predictive marker for IFN therapy.

Erythropoietic protoporphyria with fatal liver failure.

Abstract: A 33-year-old woman with a history of photosensitivity, persistent abdominal pain, and liver dysfunction was admitted to our department because of abdominal pain and progression of liver dysfunction. On admission, levels of protoporphyrin and coproporphyrin within erythrocytes were markedly increased. Autofluorescent erythrocytes were also detected, leading to a diagnosis of erythropoietic protoporphyria. A liver biopsy specimen revealed cirrhosis with dark brown granules filling hepatocytes, bile canaliculi, and bile ductules. Transfusion of washed erythrocytes, hemodialysis, and administration of cholestyramine and beta-carotene transiently improved levels of porphyrins and liver function. The patient died of rupture of esophageal varices followed by multiple organ failure. However, the treatments were believed to have extended survival.

Intraspousal transmission of GB virus C/hepatitis G virus in an hepatitis C virus hyperendemic area in Japan

ObjectiveAn immunoassay for antibodies against an hepatitis G virus (HGV) protein (anti-E2) was recently developed that might serve as a useful marker for diagnosing recovery from HGV infection.MethodsWe investigated the intraspousal transmission of GB virus C/hepatitis G virus (GBV-C/HGV) using both reverse transcription hemipolymerase chain reaction (RT-hemi-PCR for the 5′ untranslated region) and a recently developed anti-E2.ResultsThirty-two GBV-C/HGV-infected index subjects were selected from an hepatitis C virus hyperendemic area in Japan. Of the 32 subjects, seven (6.4%) were GBV-C/HGV RNA-positive, 24 (21.8%) were anti-E2-positive, and one (0.9%) was both GBV-C/HGV RNA- and anti-E2-positive. Among the 32 spouses of these subjects, GBV-C/HGV RNA, anti-E2, and both GBV-C/HGV RNA and anti-E2 positivity were detected in 0, 6, (18.8%), and one (3.1%) spouses, respectively (the total prevalence of GBV-C/HGV was 7 spouses [21.9%]). Thus, the intraspousal transmission of GBV-C/HGV was undeniable in these seven couples. The respective positive rates of 175 sex- and age-matched controls were 7 (4.0%), 26 (14.9%), and 0 (the total prevalence of GBV-C/HGV was 34 [19.4%]). No significant difference in positive rates was observed between the subjects/spouses and the controls. Five spouses among the seven couples who were positive for any of GBV-C/HGV markers had parenteral risk factors such as blood transfusion, acupuncture, and major surgery.ConclusionsBased on these observations, we cannot draw a definitive conclusion that intraspousal transmission of GBV-C/HGV had occurred among these seven couples.

Transmission routes and clinical courses in sporadic acute hepatitis C

Summary. Between March 1994 and March 1996 we studied transmission routes and clinical courses in eight patients with sporadic acute hepatitis C (two men, six women). Of the eight patients, three were treated for another illness 1–2 months before the onset of hepatitis, one was a parenteral drug abuser, one had an accidental needlestick injury and two had sexual contact with a partner with chronic hepatitis C virus (HCV) infection. Clinical courses included four women whose HCV RNA and alanine aminotransferase (ALT) became persistently negative without treatment, and four men and two women with the same results following interferon (IFN) treatment. It is thought that IFN therapy may prevent the progression to chronic liver disease. Results from this study might be useful in the future management of patients with sporadic acute hepatitis C.

Characteristics of complete responders to interferon among patients with chronic hepatitis C with high serum levels of RNA

Patients with chronic hepatitis C with high serum levels of HCV RNA are less likely to show a complete response to IFN therapy than those with a low serum levels of HCV RNA. The characteristics of patients with high serum levels of HCV RNA who show a complete response to IFN therapy have not been evaluated in detail. We retrospectively analyzed the 121 patients with high serum levels of HCV RNA (≥ 1.0 Meq/ml) before IFN therapy to determine the characteristics of complete responders. A complete response to IFN was observed in 12 (9.9%) of 121 patients. There was no difference between complete responders and non-responders in age, the result of liver function tests, or liver histology. In all complete responders, pretreatment serum level of HCV RNA was less than 5.0 Meq/ml, which was significantly lower than the level in the non-responders (P < 0.01). The fluctuation of HCV RNA level less than 0.5 Meq/ml was observed in ten of the 12 complete responders. The frequency of serotype 2 was significantly higher in the complete responders compared with the non-responders (P < 0.05). These findings suggest that complete responders are rare among patients with serum levels of HCV RNA ≥5.0 Meq/ml. In planning IFN therapy, fluctuations in the HCV RNA level, as well as the serotype, should be considered.

Change in cerebral blood flow in an acute hepatitis C patient with depressive state while receiving interferon

Abstract Regional cerebral blood flow (rCBF) was measured with single photon emission computed tomography (SPECT) using N-isopropyl-p-[123I] iodoamphetamine (123I-IMP) in a patient with acute hepatitis C who showed depressive state during interferon therapy. During his depressive state the rCBF was decreased markedly in the inferior frontal cortex. This case suggests that psychotic symptoms during IFN therapy may result from decreased rCBF.

Long-term improvement of hepatic fibrosis in chronic hepatitis C treated with interferon-α

Abstract We examined the changes of hepatic fibrosis for several years following interferon- α (IFN- α ) treatment in patients with chronic hepatitis C. This study included 37 complete responders (CR) and 37 non-responders (NR) to IFN- α treatment. The period of post-treatment was 6–50 months. The scores for periportal necrosis, intralobular inflammation, portal inflammation and fibrosis before and after treatment were compared. Furthermore, the serum fibrosis markers (hyaluronic acid (HA), N-terminal amino peptide of type III procollagen (PIIIP), Type IV collagen) before and after treatment were compared in 11 CR and 14 NR. In the CR, the scores for histological findings were significantly decreased compared to those before treatment. Especially, in five of the 37 CR, the hepatic fibrosis disappeared and improved to almost normal after treatment. In the CR, the serum levels of HA and PIIIP after treatment were also significantly decreased compared to those before treatment. In the NR, however, the grade of fibrosis after treatment was more severe than that before treatment. These findings suggest that liver histology containing hepatic fibrosis is improved in patients who are continuously negative for hepatitis C virus (HCV) RNA through several years after IFN- α treatment.