Low incidence of hepatitis B virus reactivation and subsequent hepatitis in patients with chronic hepatitis C receiving direct-acting antiviral therapy.

To determine the clinical characteristics of hepatitis B virus (HBV) reactivation in patients undergoing interferon-free antihepatitis C virus (HCV) therapy, we examined HBV DNA in 25 HBV co-infected patients and 765 patients with resolved HBV infection during and after treatment with direct-acting antiviral agents (DAAs). Among those with HCV genotype 1, asunaprevir plus daclatasvir was administered to 160 patients, sofosbuvir (SOF) plus ledipasvir to 438 patients and paritaprevir plus ombitasvir and ritonavir to 25 patients. In total, 167 patients with genotype 2 were treated with SOF plus ribavirin. Three patients with an HBV DNA level ≥2000 IU/mL were treated with entecavir before anti-HCV therapy, without reactivation of HBV. In 3 of 22 (12%) HBV surface antigen (HBsAg)-positive patients with an HBV DNA level <2000 IU/mL, the viral load increased during treatment. However, hepatitis flare did not occur in these patients. There was no significant difference in clinical history between patients with and without HBV reactivation. Among 765 patients with resolved HBV infection, HBV reactivation occurred in 1 (0.1%) patient after initial resolution, whose HBV DNA level spontaneously decreased after DAA therapy. We compared anti-HBs titres at baseline with those at post-DAA therapy in 123 patients without HBsAg. There was no significant difference in anti-HBs levels between the two points (P = .79). In conclusion, HBV reactivation was rare in HBsAg-negative patients treated with DAA therapy. Additionally, hepatitis did not occur in HBV-reactivated patients with a baseline HBV DNA level <2000 IU/mL before DAA therapy.

Peliosis hepatis associated with idiopathic restrictive cardiomyopathy.

A rare case of peliosis hepatis associated with idiopathic restrictive cardiomyopathy is reported. A 75-year-old man was admitted for evaluation of marked edema and jaundice. Serum total bilirubin was elevated above 20 mg/dl. The liver biopsy under laparoscopy revealed marked sinusoidal dilatation and retention of red blood cells, which was consistent with a diagnosis of peliosis hepatis. Cardiac catheterization revealed right ventricular filling disturbance without specific findings on endomyocardial biopsy, suggesting idiopathic restrictive cardiomyopathy. The level of serum total bilirubin decreased in association with improvement of edema after drip infusion of furosemide therapy.

Study on the mechanism of an experimental immunological intrahepatic cholestasis model.

Tuberculin-sensitized guinea pigs were intravenously injected with heat-killed Propionibacterium acnes followed by an intravenous injection of purified protein derivatives 7 day later, resulting in the induction of intrahepatic cholestasis. Using this experimental model, the following results were obtained: (1) Both uptake and release of bile acid were inhibited in the hepatocytes prepared from the cholestasis guinea pigs. (2) The results of the erythritol clearance method indicated that the decrease in bile flow observed in the cholestasis guinea pigs was mostly attributable to the reduced bile excretion from the canaliculi. (3) The decrease in the formation of bile acid independent bile flow was the cause of the decrease in bile flow observed in the cholestasis guinea pigs. (4) There was no change in the permeability of the interhepatocellular tight junction in the cholestasis guinea pigs.

Effects of ursodeoxycholic acid on intrahepatic cholestasis.

Ursodeoxycholic acid (UDCA) was administered to 16 intrahepatic cholestasis patients with severe jaundice, and its clinical effects were studied. As a result, it was remarkably effective in 6 patients, significantly effective in 5 patients, slightly effective in 2 patients and unchanged in 3 patients. As for the dose, when 600 mg/day was administered, it was effective in all patients, but even when only 150 mg/day was administered, it was effective in one patient (50%). Duration of treatment was 15 to 177 days with a mean of 55.3 days. These results suggested that while there is no adequate treatment for intrahepatic cholestasis with severe jaundice, UDCA should be considered as a possible method of treatment.

Choleretic effects of ursodeoxycholic acid on experimentally-induced intrahepatic cholestasis.

When a lymphokine, the cholestatic factor, is intravenously injected into rats through a mesenteric vein, remarkable reductions in bile flow and bile acid excretion are observed. Using this experimentally-induced intrahepatic cholestasis model, the choleretic effects of ursodeoxycholic acid (UDCA) were studied. When UDCA was injected with the cholestatic factor, the reductions in bile flow and bile acid excretion were significantly suppressed. Remarkable choleretic effects were also noted, when UDCA was administered to normal rats. These results suggested that UDCA may be effective in the treatment of intrahepatic cholestasis.

Possible involvement of platelet-activating factor in the induction of liver cell injury.

In order to examine whether the platelet-activating factor (PAF) plays a role in the induction of liver cell injury, the effects of a PAF antagonist were studied in an experimental model of mice with acute liver cell injury induced by intravenous injection of heat-killed Propionibacterium acnes (P. acnes) and lipopolysaccharide. As a result, an intravenous injection of the PAF antagonist was shown to improve the histological changes in the liver, reducing the degree of focal tissue necrosis. In addition, liver adherent cells isolated from normal mice and from those pretreated with P. acnes were shown to produce PAF by stimulation with calcium ionophore A 23187. These results suggested that PAF produced by liver adherent cells may be involved in the induction of liver cell injury.

[Effect of glycyrrhizin on the production of platelet-activating factor from rat peritoneal exudate cells].

We examined the effect of glycyrrhizin (GL) on the production of platelet-activating factor (PAF) from rat peritoneal exudate cells. GL was shown to significantly suppress the production of PAF from the rat peritoneal exudate cells stimulated with calcium ionophore A23187. This result suggests that GL have an anti-inflammatory or allergic action by the suppression of PAF production.

[Effects of the cholestatic factor and the prostaglandin E1 derivative on the level of cAMP in isolated hepatocytes of rats].

It has been reported that cAMP in hepatocytes plays an important role in bile discharge. Therefore, in order to examine the action mechanism of the cholestatic factor, we studied the effect of the cholestatic factor and prostaglandin E1 derivative which inhibits the activity of the cholestatic factor on the cAMP level in hepatocytes. As a result, the cAMP level in hepatocytes was decreased by treatment with the cholestatic factor, but was increased by the prostaglandin E1 derivative. Furthermore, the cAMP level which was decreased by the cholestatic factor returned to the original level by treatment with the prostaglandin E1 derivative. Because the increase in the cAMP level in hepatocytes promotes the bile acid independent bile discharge, it is suggested that the cholestatic factor reduces the bile flow by the decrease in the cAMP level in hepatocytes, and that the prostaglandin E1 derivative competes with the action of the cholestatic factor through the increase in the cAMP level in hepatocytes.

[Choleretic effects of taurine on experimentally-induced intrahepatic cholestasis].

When a lymphokine, the cholestatic factor, is intravenously injected into rats through a mesenteric vein, remarkable reductions in bile flow and bile acid excretion are observed. However when taurine was injected with the cholestatic factor, the reduction in bile flow and bile acid excretion were significantly suppressed. Moreover, injection of taurine with cholestatic factor resulted in the decreases of both bile acid-dependent bile flow and vesicular transport but not bile acid-independent bile flow. Not significant choleretic effects were noted when taurine alone was administered to normal rats.

[A study of hypertriglyceridemia occurring in patients with chronic hepatitis C during administration of interferon beta].

The prevalence and risk factors of hypertriglyceridemia during the administration of interferon (IFN) were examined in 78 patients with chronic hepatitis C who were treated with 6 MU of IFN-beta once or 3 MU of IFN-beta twice a day for 6 weeks. Hypertriglyceridemia (serum triglyceride (TG) above 150 mg/dl) was found before the start of IFN treatment in 9% of the patients. During the administration of IFN, elevation of serum TG above 150 mg/dl was found in 82% of patients. In addition, serum TG level exceeded 500 mg/dl at least once during the administration of IFN in 13% of patients. On stepwise multiple regression analysis, three risk factors, high serum TG value before the administration of IFN, high ALT value before the administration of IFN, and divided administration of IFN-beta twice daily were found to be associated with hypertriglyceridemia during IFN administration.

[Changes in production of platelet activating factor by adherent hepatocytes of mice with experimental liver failure].

It is thought that the platelet activating factor (PAF) enhances the immune response and inflammatory reaction. We studied the production of PAF from liver adherent cells. As a result, liver adherent cells produced PAF, when they were stimulated with calcium ionophore. In addition, when mice were treated with heat-killed Propionibacterium acnes and the mononuclear cells were infiltrated into the liver, a significantly larger amount of PAF was produced compared to normal mice.

[Percutaneous microwave coagulation therapy for hepatocellular carcinoma--study on its therapeutic effect in surgical cases].

Six patients with hepatocellular carcinoma were subjected to percutaneous microwave coagulation therapy (PMCT) by ultrasonic guiding. The size of the main tumor in the present cases was limited to not more than 2 cm. From 18 to 48 days after PMCT, each patient was subjected to surgery and pathological examination. By macroscopic observation, the PMCT area including both non-tumor and tumor regions looked yellowish white, and the boundary was clearly recognized. In the histological examination, the coagulation area surrounded by fibrous capsule was found, and deletion of nuclei and changes in stainability were observed in the marginal region. These changes indicated obvious coagulation necrosis, but the changes became less intense toward the center in the area, and in some portions, the tissue was indistinguishable from viable cells by light microscopy. In 2 cases out of the 6, part of the tumor remained outside the coagulation area. Since only the area determined by the microwave electrode is coagulated to cause necrosis on PMCT, sufficient safety margin should be required.