Fumio Sugata

Reactivation of precore mutant hepatitis B virus leading to fulminant hepatic failure following cytotoxic treatment

Three hepatitis B virus carriers who were HBeAg negative and having normal liver function developed fulminant hepatitis with evidence of HBV replication following intensive chemotherapy for non-Hodgkins lymphoma. Each was continuously negative for HBeAg. Analysis of the precore region of HBV isolated from each demonstrated that the HBV of each had a point mutation in the precore region that inhibited the synthesis and the release of hepatitis Be antigen. This observation suggests that all HB carriers receiving either immunosuppressive or cytotoxic therapy should be monitored closely even if standard assays suggest that viral replication is not present. Sudden enhanced replication of a HBV mutant as a result of such therapy can be a cause of either very severe hepatitis or occasionally fulminant hepatitis.

Prognostic value of hepatic volumetry in fulminant hepatic failure

Serial hepatic volumetry calculated from the liver area on abdominal computed tomography was performed in 19 patients with fulminant hepatic failure to determine a relationship between liver volume and prognosis. All patients received intensified artificial liver support comprised of plasma exchange and hemodiafiltration using high-performance membranes, and 10 patients survived. Liver volume was significantly larger in survivors than in nonsurvivors, both in an initial volumetry performed at the onset of coma and in subsequent volumetry performed 10–20 days after the onset of coma. The difference became more significant in the subsequent volumetry because of the recovery of liver size in some of the survivors and progressive liver shrinkage in all nonsurvivors. All patients with a liver volume greater than 656 ml at 10–20 days after the onset of coma survived, whereas all but one patient with a liver volume less than that died. Multivariate analysis revealed only liver volume in subsequent volumetry had discriminatory power upon prognosis among six prognostic factors. These observations imply that in order to obtain an accurate prediction of fulminant hepatic failure by hepatic volumetry, serial studies at least until 10–20 days after the onset of coma are necessary.

Recurrent fulminant hepatic failure in an HB carrier after intensive chemotherapy

SummaryA 56-year-old female HB carrier developed fulminant hepatic failure with propagation of precore mutant hepatitis B virus following two sessions of intensive chemotherapy for non-Hodgkins lymphoma. She was treated with interferon and cyclosporin A for the suppression of viral replication and enhanced host immune responses. She recovered from liver failure with histological evidence of marked regenerative activity.She again developed fulminant hepatic failure with reactivation of the hepatitis B virus following repeated chemotherapy for recurrent non-Hodgkins lymphoma.This case report supports the view that both enhanced viral replication and host immune responses contribute to the development of fulminant hepatitis in HB carriers. Treatment suppressing both mechanisms may be effective in this type of fulminant hepatitis.

Endoscopic Hemostasis in Hemorrhagic Gastric Ulcer—Effectiveness of the Hemoclipping, Ethanol Injections and Heat Probe—

Abstract: The hemostatic effects of hemoclipping, the pure ethanol local injection method and the heat probe methods on hemorrhagic gastric ulcers associated with exposed blood vessels, were compared. The locations of the ulcers and exposed blood vessles, as well as characteristics and the severity of the hemorrhage were discussed. The hemoclipping method was used on 59 patients, the pure ethanol local injection on 32 patients, and the heat probe methods on 26 patients. The hemoclipping and pure ethanol local injection methods were effective in all of the patients in whom the exposed blood vessels were present around the margin of ulcers. The efficacy rate was 91%, 92% and 92%, respectively, when exposed blood vessels were found at the base of the ulcer. The efficacy rate was 94%, 100% and 80% for the three hemostatic methods, respectively, when an oozing hemorrhage was present. The three methods had an efficacy rate of 100% when only blood clots were present. The efficacy rate for a spurting hemorrhage was 86%, 71% and 67%, respectively, for the three methods. The hemoclipping and pure ethanol local injection were effective in 100% of slight and moderate hemorrhage cases, while the heat probe method was effective in only 89% of moderate cases. The efficacy rate was 85%, 85% and 83%, respectively, for severe cases. Overall, the efficacy rate was 93% for the hemoclipping method, 94% for the pure ethanol local injection and 92% for the heat probe method, and there was no significant difference between the three methods with regard to the overall efficacy rate.

Ursodeoxycholic acid therapy for chronic type C hepatitis: A multicenter, dose-finding trial

Abstract Ursodeoxycholic acid (UDCA) was administered orally for 12 weeks to 40 patients with chronic type C hepatitis. Patients were randomly assigned to receive UDCA 150 mg/day (n = 20) or 450 mg/day (n = 20). In the 450-mg group, alanine aminotransferase (ALT) decreased significantly ( P P P P

ACTIVATION OF HEPATITIS C VIRUS FOLLOWING IMMUNOSUPPRESSIVE TREATMENT

To The Editor: Activation of hepatitis B virus (HBV) infection during immunosuppressive and/or cytotoxic treatment has been reported (1, 2). Although accentuation of active hepatitis consistent with type non-A, non-B (NANB) infection following such treatments has been reported (3, 4), this has not been demonstrated unequixrocally. Moreover, whether the enhanced hepatitis seen in these situations is actually due to viral activation or some other mechanism has not been documented. Recently, we have seen three patients with well-established chronic C hepatitis that occurred as a result of repeated blood transfusions administered as part of the treatment of acute leukemia. Two of these three developed fulminant hepatic failure following a rapid withdrawal of cyclosporin A (CsA) immunosuppression administered following allogenic bone marrow transplantation (Table 1). Serial determinations of HCV RNA in blood using a two-stage polymerase chain reaction (5) revealed an activation of HCV infection after the initiation of the CsA therapy. This observation suggests that replication of HCV may be influenced by immunological state of the host or at least as a consequence of cyclosporine therapy. What was particularly striking in these two cases, however, was the observation that two weeks after the termination of cyclosporine therapy, fulminant hepatic failure occurred in both cases. In only eight of the

Diagnosis of type C fulminant hepatitis by the detection of antibodies to the putative core proteins of hepatitis C virus.

Recently, ELISA tests for the determination of antibodies against hydrophilic domains of the putative capsid proteins of HCV, a 36-mer oligopeptide (CP-9)I), and a 19-mer oligopeptide (CP-IO) 2) have been developed. We measured both anti-CP-9 and anti-CP-lO antibodies in type B and NANB fulminant hepatitis (FH), and NANB late onset hepatic failure (LOHF)3), and evaluated their usefulness in the diagnosis of type C FH and LOHF. HCV RNA was determined by the previously reported two-stage PCR method4). Anti-ClO0 was measured by the 0rtho Ab ELISA test. Antibodies to CP-9 and CP-IO were not detected in any type B FH patients, nor were HCV RNA and anti-ClO0. However, 16 of 17 patients with NANB FH and LOHF were positive for anti-CP-9 or anti-CP-lO or both. Compared with those for HCV RNA and anti-ClO0, detection rates for antibodies to the core proteins were higher in every type of NANB FH, establishing a type C diagnosis in acute NANB FH in which HCV RNA and anti-HCV were not usually detected. Thus, antibodies to the putative core proteins of HCV are valuable in the diagnosis of type C FH. i) Okamoto H, et al.: Jap J Exp Med 1990, 60:223 2) Okamoto H, et al.: Jap J Exp Med 1990, 60:121 3) Gimson AES, et al.: Hepatology 1986, 6:288-94 4) 0kamoto H, et al.: Jap J Exp Med 1990, 60:215 Table Detection rate of HCV RNA, anti-C100 and the anti-core proteins in typeB and NANB FH and LOHF

Endoscopic and Histopathological Study about 25 Cases of Minute Superficial Depressed Neoplastic Lesions in the Large Intestine

Abstract: We studied 25 cases of minute (less than 5 mm in a diameter) superficial depressed neoplastic lesions during the period of March 1990 to September 1991. These depressed neoplastic lesions were recognized by colonoscopy as asteroid redness with surrounding elevation. The thickness and height of the surrounding elevations were modified by air volume. Occasionally, they seemed according to the air volume to be elevated lesions, though their fundamental form was confirmed as being superficial depressed lesions from observations of histopathological sections and using a dissecting microscope. The endoscopic figures were emphasized by sprinkling them with Methylene Blue.

Antibodies to hepatitis C virus in non-A non-B fulminant viral hepatitis

Significance of being antibody positive state with respect to HCV (anti-HCV) in cases of non-A non-B fulminant viral hepatitis (NANB FVH) was investigated using 50 consecutive serum samples from 22 patients presenting FVH and late onset hepatic failure (LOHF) 1 Anti-HCV was detected in none of 7 patients with FVH who developed coma within i0 days of the onset of hepatitis (acute type), and continued to show negative results up until 30, 35, 63 and 120 days in 4 surviving cases. Anti-HCV was detected in 7 patients including 3 seroconverted cases out of ii patients who developed coma from 14 to 43 days after the onset of hepatitis (subacute type). Two out of 4 patients with LOHF were anti-HCV positive at the time they went into coma. The above observations suggest that in Japan we have at least two types of NANB FVH. One type is characterized by negative anti-HCV, the rapid progression of liver failure and a relatively favarable prognosis. Another Table Results of anti-HCVAb investigated for 22 Japanese patients with NANB FVH and LOHF

GENOTYPE OF HEPATITIS C VIRUS IN FULMINANT HEPATITIS C

portant role during the inflammatory response to bacterial infection (3, 4). We have prospectively studied IL-6 levels in ascitic fluid and serum of 28 consecutive patients with hepatic ascites. Seven of them had SBP as defined by positive bacterial cultures of ascitic fluid (three) or an ascitic fluid neutrophil count of _>500/mm 3. IL-6 was measured by ELISA (Biermann, B~id Nanheim, Germany), and by the B9 hybridoma bioassay (5). Both assays showed a good correlation (r = 0.88, P < 0.001). Comparisons between groups and correlations were calculated by Mann-Whitney and Spearman regression analysis respectively. IL-6 levels in both infected (14,900 6890 pg/ ml; mean SEM) and not infected (1730 --466 pg/ml) ascites were much higher than the serum levels of IL-6 in these patients (79 --+ 42 pg/ml and 41 _-+ 8.9 pg/ml, respectively) (Figure 1). In patients with SBP the concentrations of IL-6 in ascites were significantly higher than in patients without SBP (P = 0.05), whereas the serum levels of IL-6 were not significantly different (P = 0.8) between these groups (Figure 1). Patients with SBP and positive bacterial ascitic fluid cultures had significantly higher IL-6 levels in ascitic fluid (32,700 _ 7420 pg/ml versus 4780 -+ 662 pg/ml, P = 0.006) and in serum (157 --. 80 pg/ml versus 48.6 ___ 7.8, P = 0.05) than patients with negative bacterial ascitic fluid culture but increased ascitic leukocyte count. In one patient with SBP, IL-6 concentrations were determined in ascitic fluid before and several days after successful antibiotic treatment. They fell from 22,600 pg/ml before treatment to 3960 pg/ml after treatment. Using a cutoff level of 10,000 pg/ml, the positive predictive value of ascitic fluid IL-6 for SBP was 100% and the negative predictive value was 85%. Our results indicate that there is a high local production of IL-6 in the peritoneal cavity of all patients with hepatic cirrhosis. This might indicate a continuous presence of bacteria or bacterial products in ascitic fluid of patients with liver cirrhosis. IL-6 synthesis is further increased during culturepositive SBP and decreases with effective treatment. Although the IL-6 ascites levels of patients with SBP are significantly higher than those of patients without SBP, our data suggest that only very high IL-6 ascites levels (> 10,000 pg/ml) increase the probability of the presence of clinically relevant SBP in an individual patient. TILO ANDUS VOLKER GROSS AXEL HOLSTEGE JORGEN SCHOLMERICH Department of Internal Medicine I University of Regensburg Franz Josef Strauss Allee W-8400 Regensburg, Germany