Submassive Necrosis Research Articles

Hepatoprotective effect of Fe-TPEN on carbon tetrachloride induced liver injury in rats.

Fe(II)-tetrakis-N,N,N',N'(2-pyridylmethyl) ethylenediamine (Fe-TPEN) catalyzes the dismutation of superoxide, and blocks the toxic effect of paraquat on Escherichia coli growth and survival. We examined antioxidative effects of Fe-TPEN on lipid peroxidation and t-butyl hydroperoxide induced cell damage. Fe-TPEN inhibited the FeSO4/H2O2 induced lipid peroxidation in the rat liver homogenates with an IC50 value of 30.2 microM, and protected Ac2F cell damage by t-butyl hydroperoxide in a dose-dependent manner (EC50 value is 2.6 microM). Also, hepatoprotective effect of Fe-TPEN (5 mg/kg, i.p.) was investigated using CCl4 induced liver injury in rats. This complex inhibited the elevation of serum alanine aminotransferase (AST) and aspartate aminotransferase (ALT) levels in CCl4 induced liver injuries, and improved submassive necrosis and fatty degeneration of the hepatocytes. Fe-TPEN also prevented the loss of total and nonprotein SH contents, glutathione peroxidase and glutathione-S-transferase activity in cytosol of rat liver. Although the exact mechanism of action is not clear, antioxidative properties as well as attenuation of hepatocellular defense systems by Fe-TPEN seem to be important on its potent hepatoprotective effect in CCl4-intoxicated rat.

Hepatocellular carcinoma: Clinicopathological aspects

The histopathology and clinical picture of hepatocellular carcinoma (HCC) varies between individual patients and regions. These variations are perhaps due to differences in the genetic alterations that precede hepatocarcinogenesis. In this study, the clinicopathological features of HCC were compared between southern African blacks and Japanese, indicating large differences in the frequency of underlying cirrhosis, grade of cancer cell differentiation and clinical course. Intra-abdominal bleeding and febrile, rapidly progressive HCC are more common among blacks. Such a difference is accounted for, in part, by frequent encapsulation of the tumour which is well differentiated, and grows slowly in an expanding fashion in Japan. Encapsulated HCC was not seen among the black patients studied. Other distinct clinicopathological types discussed in this paper include diffuse-type HCC which is usually caused by multiple portal spread occurring almost simultaneously; the clinical course is fulminant. Sclerosing carcinoma is frequently associated with hypercalcaemia in the United States, but not in Japan. Fibrolamellar carcinoma is nearly non-existent in Asia, whereas it is common among young adults in the West. Its prognosis is generally better than ordinary HCC. Hepatocellular carcinoma has a strong propensity to invade vessel and duct systems. Portal invasion does not produce distinct clinical signs although it may aggravate portal hypertension. Patients with tumour occlusion in the major portal vein may give rise to ischaemic hepatitis when blood pressure drops suddenly in the preterminal stage. Liver parenchyma develops submassive necrosis and clinically there is an acute rise in alanine aminotransferase (ALT). Invasion into a major hepatic vein and the inferior vena cava also occurs, but less frequently compared with portal invasion. The patient can live even with a tumour thrombus in the atrium crossing the tricuspid valves. Intraductal invasion causes acute jaundice as well as an occasional haemobilia with pain. We recently found that a distinct pathological type called 'extrahepatic growth' or 'pedunculated HCC' develops as a result of fusion of right-sided adrenal metastasis of HCC and the liver, perhaps through the 'adreno-hepatic fusion' which is rather common in cirrhotic livers.

ACUTE LIVER FAILURE IN INFANCY

Acute liver failure in childhood is associated with > 90% mortality if INR is ≥4, unless liver transplant (LT) is performed. Prognosis is particularly severe in younger children. To assess etiology and prognosis of acute liver failure in infancy, we have reviewed retrospectively the case notes of 57 infants referred to our Unit between 1983-96. Acute liver failure was diagnosed on the basis of submassive liver cell necrosis and coagulopathy (INR >2), with or without encephalopathy, which may be absent or a late event in this age group. Age was <1 month in 22, 1 month-1 year in 25, 1-2 years in 10. Etiology was haemophagocytic lymphohistiocytosis (HLH) in 10, cryptogenic in 16, metabolic in 16 (10 neonatal haemocromatosis, 3 tyrosinaemia, 1 ornithine transcarbamylase deficiency, 1 fatty acid oxidation defect, 1 mitochrondial defect), toxic in 4 (1 Amanita phalloides, 1 paracetamol, 1 isoniazid, 1 copper), infective in 8 (4 post septic shock, 2 hepatitis B, 1 Herpes simplex Type II, 1 Herpes simplex Type I), autoimmune in 3 (all liver-kidney microsomal positive). Maximum INR was ≥4 in 45. Overall 13 of 57 patients (23%) survived, 9 after LT, 4 patients without LT; 1 tyrosinaemia treated with NTBC, 1 HLH, 1 fatty acid oxidation defect, and 1 with Amanita phalloides. LT was not indicated in 10 with HLH and was not available for 10 patients referred before 1990. Of the remaining 37 patients 9 of 19 (47%) transplanted survived compared to 3 of 18 (16.6%) without LT (p<0.02). All the transplanted survivors are well (median(range) age at LT: 4.3 months(16 days - 1.99 years); follow up: 1.4 years (4 months-5.3 years). In conclusion: a) acute liver failure in infancy has a poor prognosis; b) is associated with a particularly severe coagulopathy; c) is often caused by HLH; d) is treatable by LT even in very young infants, but the 47% survival after LT is considerably less satisfactory than reported survival in older children with fulminant hepatic failure (60%).

Treatment with a novel lipid A analogue, FS-112, and partial hepatectomy causes submassive liver necrosis and impaired liver regeneration in mice.

A novel experimental model of submassive liver necrosis with impaired regeneration has been established. A novel lipid A analogue, FS-112, was injected intravenously into male BALB/c mice, followed 2 days later by a 70% partial hepatectomy. Over the next 9 days, mice became severely jaundiced, with a peak total bilirubin (TBil) concentration of (mean +/- s.d.) 12.9 +/- 2.1 mg/dL 7 days postoperatively. In contrast, the TBil concentration in vehicle-treated mice remained less than 2 mg/dL. Significant elevations of L-alanine:2-oxoglutarate aminotransferase (ALT) were also observed 3-7 days after the operation in mice pretreated with FS-112, compared with mice pretreated with the vehicle. Submassive liver necrosis was observed with extensive mononuclear cell infiltration in mice treated with FS-112 and subjected to partial hepatectomy. Furthermore, both the BrdU and the proliferating cell nuclear antigen (PCNA) labelling index (LI) 1 day following partial hepatectomy in mice pretreated with FS-112 (8.6 +/- 4.3 and 7.9 +/- 4.2%, respectively) were significantly lower than levels in vehicle-treated mice (25.8 +/- 3.8 and 26.5 +/- 10.5%, respectively). The time course of changes in the BrdU LI in liver specimens from mice treated with both FS-112 and partial hepatectomy did not increase, even 3, 5, and 7 days postoperatively. Excellent liver regeneration with a PCNA LI 10-fold higher than the resting level was observed in mice treated with D-galactosamine hydrochloride. These results strongly suggest that this animal model of submassive liver necrosis may be suitable for clarifying the mechanisms of impaired liver cell regeneration often seen in fulminant hepatitis.

Recent-onset autoimmune hepatitis. Biopsy findings and clinical correlations.

Whereas the histologic findings in clinically "chronic" autoimmune hepatitis have been well established, with piecemeal necrosis as a hallmark lesion, the histologic findings of clinically "acute" or recent-onset autoimmune hepatitis remain undefined. The goal of this study was to define more fully the liver histomorphology in patients with recent-onset autoimmune hepatitis. Twenty-six patients were identified at our institution who had well-characterized autoimmune hepatitis and had undergone a liver biopsy within 6 months of clinical presentation. A detailed histologic evaluation revealed evidence of chronic liver disease in 25 (of 26) patients despite the lack of correlating clinical chronicity. The histologic evidence of chronicity included, in addition to a portal lymphoplasmacytic infiltrate, bridging (septal) fibrosis (11 patients) and overt cirrhosis (four patients). Eighteen of these 25 cases with evidence of chronicity also showed zone 2 and 3 lobular hepatitis, including disarray and hepatocyte necrosis. A single case showed lobular hepatitis with confluent hepatocyte necrosis (submassive hepatocellular necrosis), but no evidence of chronic liver disease. Although autoimmune hepatitis remains in the differential diagnosis of lobular hepatitis, these data show that most patients with autoimmune hepatitis who undergo biopsy early in its clinical course will have histologic evidence of chronic liver disease. Most of these patients probably have a lobular "flare" in disease activity, which likely precipitated the clinical presentation. The findings herein reinforce the concept that autoimmune hepatitis is by definition a chronic disease and supports the proposal that the modifier "chronic" be eliminated from autoimmune hepatitis.

Fulminant Hepatic Failure After Methotrexate and PUVA Therapy for Psoriasis

Acute hepatic failure developed after 8-methoxypsoralen and ultraviolet irradiation for psoriasis in a patient with prior methotrexate-induced cirrhosis. Review of the literature and the temporal relationship between 8-methoxypsoralen and hepatic injury in our patient suggests it may be a direct hepatotoxin. In our report, submassive necrosis superimposed on cirrhosis appears to have produced hepatic failure.

Reactive human bile ductules express parathyroid hormone‐related peptide

Various cholestatic liver diseases as well as regeneration after submassive necrosis are accompanied by a striking increase in the number of bile ductules. These reactive bile ductules are thought to arise either from proliferation of pre-existing bile ductules or bile ductule-related facultative stem cells, or from ductular metaplasia of hepatocytes. Recently, we found that reactive bile ductules display neuro-endocrine features, and speculated that the substance(s), produced in the neuro-endocrine granules, might play a role in their growth and/or differentiation through an autocrine or paracrine pathway. Parathyroid hormone-related peptide has been shown to be encoded by a growth factor-regulated gene that may play a role in cell growth and differentiation. We studied the immunohistochemical expression of this peptide in human liver, including three normal biopsies, 11 cases of cholestatic liver disease, six cases of focal nodular hyperplasia and three cases of regenerating liver. In regenerating liver, primary biliary cirrhosis, primary sclerosing cholangitis and partial or intermittent obstruction, the majority of reactive ductular cells expressing neuro-endocrine markers also expressed parathyroid hormone-related peptide. In focal nodular hyperplasia, a smaller number of bile ductular cells expressed the peptide. These findings suggest that parathyroid hormone-related peptide is localized in bile ductular cells and may indicate a role for this hormone in the growth and/or differentiation of human reactive bile ductules.

Effect of anti-basic liver protein antibody-induced liver injury on hepatic drug-metabolizing enzymes in C57 BL/6J mice.

We attempted to produce a model mouse with a liver injury resulting from an immunological mechanism in C57BL/6J mice, and the effect of hepatitis on the hepatic microsomal mixed-function oxidase system was studied. An experimental immunological liver injury model was caused by the intravenous injection of an anti-basic liver protein (BLP) antibody in mice which had been previously immunized with normal rabbit IgG (RGG) and complete Freund's adjuvant. C57BL/6J strain mice showed the highest susceptibility to the immunological liver injury. Typical histopathological changes in the liver included submassive hepatocellular necrosis and infiltration of lymphocytes into the portal tract and sinusoid area in a necrotic lesion. The liver injury in this model was markedly inhibited by the administration of prednisolone (20 mg/kg, p.o.), cyclophosphamide (15 mg/kg, i.p.), levamisole (10 mg/kg, p.o.), glycyrrhizin (50 mg/kg, i.p.) and cepharanthine (10 mg/kg, i.p.), which act on the immune system. Twenty-four hours after the injection of anti-BLP antibody, the activities of aminopyrine N-demethylase, aniline hydroxylase and NADPH-cytochrome c reductase and the content of cytochrome P-450 were mostly reduced, whereas cytochrome b5 and NADH-ferricyanide reductase were not. These results suggest that the experimental liver injury model in C57BL/6J mice is useful as a model of liver injury model, and its hepatitis was shown to inhibit the cytochrome P-450-dependent biotransformation of drugs in the mouse.

Detection of proliferating hepatocytes by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) in patients with acute hepatic failure.

This study evaluated whether liver regeneration could take place after massive or submassive necrosis of liver cells in 25 patients with several kinds of hepatic failure by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). PCNA positivity was significantly higher (P less than 0.01) in the patients who survived than in the patients who died. Furthermore, PCNA-positive hepatocytes were recognized diffusely in the lobule of the liver in survivors. There was positive correlation between PCNA positivity and plasma concentration of AFP (alpha-fetoprotein), (r = 0.77, P less than 0.01). These results show that liver regeneration could take place after massive necrosis of liver cells in survivors from acute hepatic failure and that immunohistochemical staining for PCNA is useful for prognostic evaluation.

Immunolocalization of regenerating cells after submassive liver necrosis using PCNA staining.

Little data exist on the proliferative state of liver cells and its relationship with various morphological findings in acute liver failure (ALF) in man. In this study we used the monoclonal antibody NCL-PCNA (clone PC-10) against the proliferating cell nuclear antigen (PCNA) to detect cycling cells in paraffin sections of 3 normal livers, 14 post-mortem needle-specimens of submassive hepatic necrosis (SHN) due to paracetamol overdosage (POD), and 10 hepatectomy specimens obtained at transplantation in patients with acute or subacute liver failure of presumed viral aetiology. In normal livers, only occasional sinusoid-lining cells were stained, whereas in SHN following POD or presumed viral hepatitis, hepatocytes of variable morphology showed significant immunoreactivity. Following POD, immunoreactivity was higher in samples taken within 5-6 days than in those obtained at 9-11 days, a pattern reminiscent of the decrease in the rate of regeneration, previously documented after partial hepatectomy in humans. Immunolabelled hepatocytes were aggregated in multiacinar 'nodules' in cases with a map-like distribution of collapsed and non-collapsed parenchyma. Ductules demonstrated comparatively less staining, but extensive labelling was exceptionally found in areas of complete hepatocellular dropout. In these areas, small elongated cells with strongly PCNA-positive ovoid nuclei, forming periportal sprouting cords or incorporated into the lining of ductules, were most remarkable in that they closely resembled 'oval cells' described in animal studies.

Fulminant hepatic failure after repeated exposure to isoflurane anesthesia: A case report

A previously healthy but obese 26-yr-old woman was diagnosed as having hepatic dysfunction 17 days after the third of three consecutive exposures to isoflurane anesthesia for paranasal sinus surgery. Serum laboratory findings included elevated aminotransferases and bilirubin. Radiographical evaluations showed no evidence of extrahepatic disease. Serological studies were negative for acute viral infections, and serum copper was normal. The patient's condition deteriorated over the ensuing 17 days, with hyperreflexia, hypoglycemia and a rapid fall in serum aminotransferases with a concomitant rise in bilirubin level and prothrombin time despite maximal medical support. The liver volume as shown by computed tomography fell from 1,290 cm3 to 680 cm3 over 6 days. The patient underwent successful orthotopic liver transplantation 25 days after onset of symptoms. Histopathological examination of the resected liver showed submassive and massive necrosis, with a few foci of microvesicular steatosis and ultrastructural evidence of mitochondrial abnormalities. Although we found insufficient evidence to prove that this case was caused by isoflurane anesthesia, the clinical course and histopathological findings are similar to those in hepatic injury caused by halothane anesthesia. Therefore we report this as a possible case of fulminant hepatic failure resulting from isoflurane anesthesia.

Outcomes of liver allograft transplantation in hepatitis B surface antigen positive (HBSAg+) Recipients

Between 1985 and 1990, the Queensland Liver Transplant Service undertook liver transplantation in 8 HB S Ag + patients. Indications for transplantation were end-stage cirrhosis (6), hepatocellular carcinoma (HCC) (3) and acute liver failure (1). Morphological findings in the resected livers and post-transplant liver biopsies were studied and correlated with serological and clinical data. Resected livers showed chronic active hepatitis (CAM)/cirrhosis in 7, 3 with coexistent HCC, and Wilson's disease with massive necrosis in 1. Six patients received Hepatitis B (HB) immune globulin perioperatively but per-mament postoperative clearance of virus was rare. One patient died of recurrent HCC 550 days post-transplant without HB recurrence, 1 died perioperatively with positive serology only and 1 with positive serology is alive 2 years post-transplant with normal liver function and minimal biopsy changes. Tissue from 4 patients 112-230 days post-transplant showed acute hepatitis. One died at 112 days of recurrent HCC; the others progressed to massive and submassive necrosis (2, deaths at 152 and 210 days) and CAH/cirrhosis (1, alive at 18 months). Another patient died at 306 days with early cirrhosis after a hepatitic illness. Acute hepatitis was associated with extensive hepatocellular nuclear and cytoplasmic HB core antigen and variable cytoplasmic HB s Ag. HB antigen expression decreased with disease progression, HB recurred in the grafts of most HB S Ag + patients and was associated with significant morbidity and mortality. Improved perioperative treatments are required to prevent HB recurrence.

Hepatotoxicity of Diethyldithiocarbamate in Rats

Hepatotoxicity of diethyldithiocarbamate (DDC) was investigated in rats. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were markedly elevated 24 hr after subcutaneous administration of DDC and histologically, the liver showed submassive necrosis. A sustained inhibition in the liver of Cu,Zn-superoxide dismutase (Cu-SOD) activity was observed following DDC treatment. DDC produced a significant loss in liver reduced glutathione (GSH) level after 1 hr, but the nadir was observed later than that of Cu-SOD. Catalase activity decreased gradually from 7 hr. Thiobarbituric acid reactive substances (TBARS) in the liver were significantly increased from 15 hr. Hepatic haemodynamics were scarcely changed up to 15 hr. Desferrioxamine (a chelator of iron) and piperonyl butoxide (an inhibitor of cytochrome P-450) prevented DDC-induced increases of both ALT and TBARS, but GSH did not, DDC hepatotoxicity was not changed by phenobarbital induction. Thus, we have shown that subcutaneous dose of DDC caused hepatotoxicity in rats. Although the exact sequence of its hepatotoxic factors is unproven, it seems likely that lipid peroxidation through the dysfunction of antioxidant defence factors and a toxic metabolite contribute to the formation of this liver injury.

Effect of OKY-046 and ONO-3708 on liver injury in mice.

The effects of OKY-046, a selective thromboxane A2 (TXA2) synthetase inhibitor, and ONO-3708, a novel TXA2 receptor antagonist, on liver disease were investigated in mice. The liver injury was induced by either an injection of antibasic liver protein (BLP) antibody into DBA/2 mice that had been previously immunized with rabbit IgG or by an injection of bacterial lipopolysaccharide (LPS) into Corynebacterium parvum (C. parvum) pretreated DDY mice. 1) In both injury models, clear elevation of glutamate transaminase (GOT and GPT) activity due to extensive liver parenchymal cell damage was observed; this was confirmed by significant histopathological changes in the liver. 2) Typical histopathological changes in the liver were submassive hepatocellular necrosis in the anti-BLP antibody-induced injury model and focal necrosis in the LPS-induced model. Inflammation and increased cell infiltration in portal connective tissue were observed in both cases. 3) Administration of OKY-046 (50 mg/kg) and ONO-3708 (0.5, 1.0 and 2.0 mg/kg) suppressed the elevation of serum GOT and GPT levels and histopathological changes in both experimental liver injury models. 4) Indomethacin inhibited the development of liver disease caused by anti-BLP antibody but not by bacterial LPS. Prostaglandin I2 inhibited the elevation of serum GOT and GPT levels and histopathological changes of the liver in the mice treated with anti-BLP antibody and showed the tendency to inhibit the development of liver injury caused by bacterial LPS.

Effect of OKY-046 and ONO-3708 on Liver Injury in Mice

The effects of OKY-046, a selective thromboxane A2 (TXA2) synthetase inhibitor, and ONO-3708, a novel TXA2 receptor antagonist, on liver disease were investigated in mice. The liver injury was induced by either an injection of anti-basic liver protein (BLP) antibody into DBA/2 mice that had been previously immunized with rabbit IgG or by an injection of bacterial lipopolysaccharide (LPS) into Corynebactehum parvum (C. parvum) pretreated DDY mice. 1) In both injury models, clear elevation of glutamate transaminase (GOT and GPT) activity due to extensive liver parenchymal cell damage was observed; this was confirmed by significant histopathological changes in the liver. 2) Typical histopathological changes in the liver were submassive hepatocellular necrosis in the anti-BLP antibody-induced injury model and focal necrosis in the LPS-induced model. Inflammation and increased cell infiltration in portal connective tissue were observed in both cases. 3) Administration of OKY-046 (50 mg/kg) and ONO-3708 (0.5. 1.0 and 2.0 mg/kg) suppressed the elevation of serum GOT and GPT levels and histopathological changes in both experimental liver injury models. 4) Indomethacin inhibited the development of liver disease caused by anti-BLP antibody but not by bacterial LPS. Prostaglandin I2 inhibited the elevation of serum GOT and GPT levels and histopathological changes of the liver in the mice treated with anti-BLP antibody and showed the tendency to inhibit the development of liver injury caused by bacterial LPS.

Liver Injury Model in Mice for Immunopharmacological Study

Experimental liver injury was produced in mice by the immunological technique. The utility of these models as an immunopharmacological method was investigated. The first model was produced by the injection of anti-basic liver protein (BLP) rabbit antibody into DBA/2 mice that had been previously immunized with rabbit IgG. The second liver injury was caused by injection of anti-liver specific protein (LSP) rabbit antibody into DBA/2 mice. The third model was produced by the injection of bacterial lipopolysaccharide (LPS) into Corynebacterium parvum pretreated ddY mice. In all injury models, extensive liver parenchymal cell damage was estimated by elevation of glutamate transaminase (GOT and GPT) activity. These were confirmed by histopathological studies of the liver. Typical histopathological changes in the liver from injured mice were submassive hepatocellular necrosis and infiltration of granulocytes and lymphocytes into the portal tract and sinusoid in the necrotic lesion. Administration of prednisolone and cyclophosphamide for 10 days prior to injection of eliciting antibodies or LPS suppressed the elevation of serum transaminase levels in all experimental liver injury models. Cianidanol and sylibin inhibited the elevation of GOT and GPT in anti-BLP induced liver injured mice. These evidences suggest that the above models are suitable for investigating the remedy for liver diseases.

Liver injury model in mice for immunopharmacological study.

Experimental liver injury was produced in mice by the immunological technique. The utility of these models as an immunopharmacological method was investigated. The first model was produced by the injection of anti-basic liver protein (BLP) rabbit antibody into DBA/2 mice that had been previously immunized with rabbit IgG. The second liver injury was caused by injection of anti-liver specific protein (LSP) rabbit antibody into DBA/2 mice. The third model was produced by the injection of bacterial lipopolysaccharide (LPS) into Corynebacterium parvum pretreated ddY mice. In all injury models, extensive liver parenchymal cell damage was estimated by elevation of glutamate transaminase (GOT and GPT) activity. These were confirmed by histopathological studies of the liver. Typical histopathological changes in the liver from injured mice were submassive hepatocellular necrosis and infiltration of granulocytes and lymphocytes into the portal tract and sinusoid in the necrotic lesion. Administration of prednisolone and cyclophosphamide for 10 days prior to injection of eliciting antibodies or LPS suppressed the elevation of serum transaminase levels in all experimental liver injury models. Cianidanol and sylibin inhibited the elevation of GOT and GPT in anti-BLP induced liver injured mice. These evidences suggest that the above models are suitable for investigating the remedy for liver diseases.

Delta‐agent infection in Taiwan

Based on observations of a limited number of patients, delta (δ) infection has been reported to be infrequent in Taiwan. To further evaluate the role of δ‐infection in patients with hepatitis B virus (HBV) infection, serum samples of 493 subjects with acute and chronic HBV infections collected in 1976–85 were studied for anti‐δ by radioimmunoassay. Intrahepatic δ‐antigen was also studied by immunofluorescence in 12 anti‐δ‐positive patients. The overall prevalence of δ‐infection was 4.7%, consistent with previous studies. δ‐Infection had an even yearly distribution in the last decade. However, there were four groups with significantly higher frequencies: (i) 24% of 41 anti‐HBe‐positive patients with chronic active hepatitis (CAH); (ii) 21% of 14 HBsAg carriers with prominent lobular hepatitis; (iii) two of three HBsAg carriers with intravenous drug abuse; and (iv) two of seven with fulminant hepatitis. On the other hand, δ‐infection was uncommon in patients with chronic persistent hepatitis, cirrhosis, hepatocellular carcinoma, classical type B hepatitis, submassive necrosis and asymptomatic HBsAg carriers. δ‐Antigen was found in only two patients with CAH; one progressed to cirrhosis, and the other had disease regression on follow‐up. Overall, at least half of the δ‐superinfected HBsAg‐positive patients had a non‐progressive course on follow‐up.It was concluded that δ‐agent was introduced to Taiwan before 1976. Although it has played a role in some clinical settings of HBV infections, it is generally infrequent in Taiwan. The δ‐superinfection apparent in half the patients studied seems to have a non‐progressive course.

免疫学的機序による肝障害モデル

An experimental liver injury was produced in mice by injection of a sub-hepatotosic dose of anti-basic liver protein (BLP) antibody after immunization of rabbit IgG (RGG) . Strain DBA/2 mice indicated the highest susceptability to the disease. Typical histopathological changes in the liver were submassive hepatocellular necrosis and infiltration of granulocytes and lymphocytes into the portal tract and sinusoid in necrosis lesion. Administration of either prednisolone (10 and 20mg/kg), cyclophosphamide (5 and 10mg/kg) or cianidanol (500 and 1000mg/kg) for 10 days prior to injection of anti-BLP antibody suppressed development of liver injury. These results suggest that the experimental liver injury model in DBA/2 mice is useful for immunopharmacological studies of liver diseases.

The morphologic spectrum of halothane-induced hepatic injury: analysis of 77 cases.

Hepatic histopathology and clinical-pathologic correlations were studied in 77 patients who met clinical criteria for halothane hepatotoxicity. They were divided into groups based on the type of surgery (minor or major) and outcome (nonfatal, biopsy group or fatal, autopsy group). The two nonfatal groups (minor surgery and major surgery) and the two fatal groups (minor surgery and major surgery) were comparable with regard to age, time of onset from exposure, peak aminotransferase values and peak bilirubin determinations. A spectrum of histologic patterns was identified in these patients. It ranged from panlobular and multifocal spotty necrosis resembling viral hepatitis through submassive confluent zonal necrosis to massive necrosis. Progression of severity of injury from spotty to massive necrosis was more closely related to multiple exposures to halothane (and especially repeated exposure within less than three months), than to the extensiveness of the associated surgical procedures.