Cyanamide hepatotoxicity. Incidence and clinico-pathological features

Ground-glass hepatocytes resembling those seen in HBsAg carriers on hematoxylin and eosin and on trichrome stained sections, but giving a negative reaction to orcein and a positive one to PAS, were found in liver biopsy specimens from nine asymptomatic former alcoholics who were on treatment with cyanamide, in one of four who had been treated with cyanamide several months before the liver biopsy procedure, in none of 15 treated with disulfiram, and in one of eight who had apparently not received aversive drugs. Portal and periportal inflammatory changes and fibrosis were more frequently observed in biopsy specimens containing PAS-positive ground-glass hepatocytes than in those without, but cirrhosis was found with a similar frequency. It is concluded that periportal PAS-positive ground-glass hepatocytes are a histological marker of cyanamide treatment.     

Cyanamide-Induced Liver Dysfunction After Abstinence in Alcoholics: A Long-Term Follow-Up Study on Four Cases

Background: Cyanamide, an aversive agent widely used in Japan, is known to induce various degrees of hepatic lesion with ground-glass inclusion bodies. When cyanamide-treated alcoholics relapse into drinking, more severe inflammation develops in the liver. However, it is controversial whether progressive hepatic lesions develop in complete abstainers as a result of long-term cyanamide treatment. Case Reports: Case 1: A 53-year-old male alcoholic received cyanamide treatment for 4.5 months and completely abstained without cyanamide treatment for 6 years. A liver biopsy shortly after abstinence showed extensive pericellular fibrosis, but a biopsy after 6 years showed very mild fibrosis. Case 2: A 43-year-old male alcoholic remained completely abstinent with cyanamide treatment for 5 years and complained of general fatigue. His serum transaminases were slightly elevated and hepatic hyperechogenicity was observed on ultrasonography. Only mild pericellular fibrosis was present in the liver biopsy specimen obtained shortly after abstinence, but after 5 years the second liver biopsy showed that thin septum-like fibrosis that formed portal-to-portal and portal-to-central linkage had developed and ground-glass hepatocytes had emerged extensively. Case 3: A 29-year-old female alcoholic complained of general fatigue and a slight fever after 1.5 years of abstinence with cyanamide treatment. Slight elevation of serum transaminases and hepatic hyperechogenicity were observed. The liver biopsy showed extensive ground-glass hepatocytes and thin septum-like fibrosis that formed portal-to-portal linkage. Case 4: A 61-year-old male alcoholic who remained completely abstinent while taking cyanamide for 3 years showed slight elevation of serum transaminases. Liver biopsy showed extensive ground-glass hepatocytes and extension of thin septum-like fibers from portal tract to the lobule. Ultrasonography revealed hepatic hyperechogenicity. Conclusion: In some abstainers who take cyanamide for several years, thin septum-like liver fibrosis progresses along with the emergence of ground-glass hepatocytes. Hepatic hyperechogenicity on ultrasonography and slight elevation of serum transaminases might erroneously lead to a diagnosis of hepatic steatosis without liver histology.     

Cyanamide-Associated Alcoholic Liver Disease: A Sequential Histological Evaluation

This is the first study that we are aware of that followed the his-topathological progression of the liver disease that was caused by the combination of both chronic alcohol use and cyanamide, an an-tidipsotropic agent. Two sequential liver biopsy specimens were obtained on 29 alcoholics who relapsed with varying histories of cyan-amide treatment. Cyanamide induced ground-glass inclusions (GGIs) in the hepatocytes. Two groups were identified, depending on whether GGIs proliferated or regressed, which was, in turn, found contingent on the duration of cyanamide treatment and the drug-free period. Group 1 included 14 cases in which GGIs either emerged only in the second biopsy specimen or else were increased in the second specimen as compared in the initial specimen. Group 2 composed of 15 cases in which GGIs were either not observed in either specimen or decreased in the second specimen as compared in the initial specimen. Acidophilic bodies were sequentially increased in five cases (36%) of group 1 and in none of group 2. The severity of portal inflammation worsened in 10 cases (71%) of group 1 but in 2 cases (13%) of group 2, although the changes in fibrotic process did not differ between two groups. These differences could not be explained on the basis of the daily ethanol consumption and the length of relapses of the two groups. Thus, when cyanamide-treated alcoholics relapsed, the combined effect of cyanamide and alcohol produced the development of acidophilic bodies and portal inflammation along with the emergence of GGIs.     

Comparison of Cyanamide and Disulfiram in Effects on Liver Function

Background: Cyanamide, an aversive drug widely used in Japan, develops ground-glass inclusion bodies in the hepatocytes at high incidences, which may be associated with portal inflammation and fibrosis. When cyanamide-treated alcoholics relapse drinking, the combined effect of cyanamide and alcohol produce more severe portal inflammation along with the emergence of ground-glass inclusions. Disulfiram also causes hepatitis, but there have been no comparative studies of effects of cyanamide and disulfiram on liver function. Methods: We reviewed the laboratory data of 408 alcoholics admitted for a 3 month course of alcohol detoxification and rehabilitation. Patients tested negative for hepatitis virus markers and were diagnosed as not having cirrhosis. Among the subjects, 222 patients received cyanamide treatment (a daily dose of 70 mg) without a history of disulfiram treatment, and 186 received disulfiram (a daily dose of 200 mg) without a history of cyanamide treatment. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels obtained at 0, 4, 8, and 12 weeks of administration of each aversive drug were compared between the two alcoholic groups. Results: Elevation of serum transaminases (AST, > ALT) probably due to alcoholic liver disease quickly fell after abstinence. In patients who took cyanamide, the ALT levels were significantly higher at 4 and 12 weeks than in those who took disulfiram. Reelevations of ALT after alcohol detoxification were more frequently observed in those who took cyanamide than in those who took disulfiram (19.4% vs. 5.9%, p < 0.001). The reelevations of ALT were slight to moderate, being more than 3-fold in three (1.4%) patients who took cyanamide and four (2.2%) who took disulfiram. The reelevations occurred more frequently in those with a history of cyanamide treatment before the present treatment than in those who took cyanamide for the first time (31.1% vs. 16.4%, p < 0.05). Conclusions: Cyanamide, compared with disulfiram, was more frequently associated with elevations of ALT that persisted after abstinence.     

Adult polyglucosan body disease: a rare presentation with chronic liver disease and ground-glass hepatocellular inclusions

Liver involvement in genetic and metabolic disorders may result in intrahepatic accumulation of specific precursors or byproducts, which have distinctive features on light microscopy. The "polyglucosan disorders" are diseases in which polyglucosan (abnormal glycogen with decreased branching) is formed and deposited in various tissues because of decreased or absent glycogen branching enzyme activity. These disorders include Lafora disease (myoclonus epilepsy) and type IV glycogen storage disease. Polyglucosan deposits in both conditions result in ground-glass hepatocellular inclusions resembling those seen in chronic hepatitis B virus infection. In the present report, we describe a case of the rare, adulthood form of glycogen branching enzyme deficiency, adult polyglucosan body disease (APBD), in which abnormal serum liver tests prompted a liver biopsy. The pathologic findings of periportal ground-glass hepatocellular inclusions, mild chronic portal inflammation, and periportal fibrosis are not well described in APBD, but resemble the chronic changes that have been reported in Lafora disease. The differential diagnosis of ground-glass hepatocytes and the genetic basis of APBD are discussed.     

Are there diagnostic histologic features of porphyria cutanea tarda in liver biopsy specimens?

In a blind review of 485 consecutive liver biopsy specimens, 16 from patients with porphyria cutanea tarda (PCT) and 469 from patients with other diseases, we have evaluated the frequency of the following features: a) needle-shaped cytoplasmic inclusions in liver cells, b) lobular aggregates of histiocytes laden with ceroid and iron, and c) the simultaneous presence of portal inflammation, hemosiderosis and fatty change, in order to ascertain their usefulness in the diagnosis of PCT. Cytoplasmic inclusions and lobular aggregates of macrophages were only found in two specimens, both of them from patients with PCT. The simultaneous presence of portal inflammation, hemosiderin and fat was found in nine patients (56%) with PCT and in nine (1.9%) of those without PCT. The localization of hemosiderin deposits differed between the two groups, being observed in periportal hepatocytes in cases with PCT, whilst it was predominantly found in Kupffer cells with a diffuse lobular distribution in cases without PCT. Thus, the finding in a liver biopsy specimen of hemosiderin in periportal hepatocytes, fatty changes and portal inflammation should alert one to the possible diagnosis of PCT and encourage the utilization of tests to confirm this diagnosis.     

肾移植后纤维化淤胆性肝炎的临床病理特点

目的 探讨纤维化淤胆性肝炎（fibrosing cholestatic hepatitis,FCH)临床病理特点和拉米夫定的防治效果。方法 回顾性分析我院794例肾移植后发生的17例重度黄疸性肝炎，其中6例经肝活检证实，2例有发病前后组织病理对比。结果 肾移植者中慢性HBV感染者为9.3%，其中FCH发生率为22.9%，肝活检证实的6例发病时间在移植后的1.5-22个月中，2例经拉米夫定治疗后缓解，4例慢性乙肝患者移植前后服用拉米夫定未发生纤维化淤胆性肝炎，移植后应用极大剂量多种免疫抑制剂，逐渐发生淤胆性肝炎和迅速进展肝功能衰竭，血清HBVDNA达极高水平；组织学表现独特的病变组合；肝细胞广范围气球样变性，毛玻璃样肝细胞不少见，区域性肝细胞溶解消失，淤胆，而炎症浸润轻微，并由汇管区发展的广范围纤维化。结论 肾移植后可发生纤维化淤胆性肝炎，拉米夫定对FCH有明显的即时治疗效应。     

Ground-glass, polyglucosan-like hepatocellular inclusions: A "new" diagnostic entity

BACKGROUND & AIMS: Ground-glass (GG) inclusions within hepatocytes are an important histopathologic marker of chronic hepatitis B virus (HBV) infection but may also be seen in Lafora's disease (myoclonus epilepsy), cyanamide alcohol aversion therapy, and type IV glycogenosis. We have noted a recent increased incidence of liver biopsy and postmortem specimens with GG inclusions associated with none of these etiologic factors. This study was undertaken to further delineate the clinical and liver pathologic features in such cases and their possible pathogenesis. METHODS: Ten cases with GG inclusions (8 biopsy, 2 postmortem) were examined by light and electron microscopy, and the patients' clinical records were reviewed. RESULTS: Light microscopy demonstrated pale pink, oval to crescentic intracytoplasmic inclusions with a predilection for periportal hepatocytes but sometimes present throughout the lobules. The inclusions were intensely positive on periodic acid-Schiff stain and digested with diastase. Transmission electron microscopy of two cases showed non-membrane-bound cytoplasmic collections of granules with mild-to-moderate electron density, consistent with abnormal glycogen granules. The patients included 7 transplant recipients (liver, hematopoietic stem cell), 3 with type 2 diabetes and a child on chronic parenteral nutrition for short bowel syndrome. Medications included immunosuppressive agents, antibiotics, and insulin. CONCLUSIONS: GG hepatocellular inclusions may be seen in individuals without HBV infection or other recognized etiologies, appear to be composed of abnormal glycogen and closely resemble polyglucosan bodies described in humans, animals, and experimental models. The possible pathogenetic roles of disturbed glycogen metabolism and polypharmacotherapy are stressed.     

Hepatic expression of intercellular adhesion molecule-1 (ICAM-1) in viral hepatitis B

The in situ distribution patterns of intercellular adhesion molecule-1 and human leukocyte antigen-DR antigens were studied in serial sections of 61 liver biopsy specimens from patients with hepatitis B virus infection using immunohistochemical techniques. In addition, the topographical relationship between the display of HBcAg on one hand and the expression of intercellular adhesion molecule-1 by hepatocytes on the other was analyzed with a double-staining immunohistochemical procedure in 14 selected liver biopsy samples showing chronic persistent or chronic active hepatitis and signs of active hepatitis B virus replication as reflected by the presence of variable amounts of HBcAg in a nuclear or cytoplasmic pattern of immunoreactivity. Coexpression of intercellular adhesion molecule-1 and human leukocyte antigen-DR antigens by hepatocytes correlated positively with the site and extent of the inflammatory infiltrate, which was composed of lymphocytes expressing lymphocyte function-associated antigen-1. In healthy HBsAg-positive carriers without inflammatory liver disease, no intercellular adhesion molecule-1 or human leukocyte antigen-DR expression was found on hepatocytes; in acute hepatitis, intercellular adhesion molecule-1 and human leukocyte antigen-DR were strongly expressed throughout the liver parenchyma on liver cell membranes and on sinusoidal lining cells. In chronic persistent and chronic active hepatitis and in active cirrhosis, intercellular adhesion molecule-1 and human leukocyte antigen-DR showed membranous positivity on focal clusters of hepatocytes in areas of periportal or intraacinar inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antibodies to a human liver membrane lipoprotein (LSP) in primary biliary cirrhosis.

Antibodies reacting with a human liver-specific membrane lipoprotein (LSP) have been detected using a sensitive and specific radioimmunoassay in 19 (51%) of 37 patients with primary biliary cirrhosis. The anti-LSP antibodies were found only in the later stages of the disease as judged by histological criteria, being present in 73% of those in stage IV, 44% of those in stage III, and none of those in stage I or II. Although there was no relationship between percentage binding and standard liver function tests, there was a close correlation between percentage binding of 125I-LSP by serum and the extent of piecemeal necrosis of periportal hepatocytes on liver biopsy. The timing of the anti-LSP response makes it very unlikely that it is involved in the pathogenesis of the early bile duct damage but the results of this and other studies suggest that antibodies to this hepatocyte membrane lipoprotein may be an important cause of periportal liver cell necrosis in both primary biliary cirrhosis and chronic active hepatitis and could be one of the factors determining progression to cirrhosis in both these conditions.     

Survey of copper granules in liver biopsy specimens from various liver abnormalities other than Wilson's disease and biliary diseases

Copper granules in hepatocytes were examined by the p-dimethylaminobenzylidene rhodanine method in 965 liver biopsy specimens obtained from patients with various liver abnormalities other than Wilson's disease and biliary diseases. The granules were found in chronic active hepatitis (incidence of positive cases: 17.2%) and alcoholic fibrosis (22%) with lobular disarray and fibrosis, nonbiliary liver cirrhosis (28%), and drug-induced cholestasis (15%). Copper granules were present in the periportal or periseptal hepatocytes where the granules were mainly found in the perinuclear cytoplasm. These intracellular and intralobular distribution patterns of copper granules resembled those of primary biliary cirrhosis. These data suggest that hepatic fibrosis and lobular disarray with fibrosis in these chronic liver disease may lead to distortion or interruption of small biliary branches followed by disturbance of bile flow and deposition of copper granules. Copper stain seems to provide a valuable information for assessment of progression of these chronic liver diseases. Impaired biliary excretion seems important in deposition of copper granules in drug-induced cholestasis.     

Ultrastructural and biochemical liver analyses in Fabry's disease

Ultrastructural and biochemical analyses were made of liver biopsy material from a patient with longstanding Fabry's disease. Both hepatocytes as well as periportal macrophages showed lipid accumulations consisting of amorphous material as well as stacks of lamellar leaflets. Lipid inclusions in periportal macrophages were much larger than in hepatocytes. Furthermore, small round spheres were found exclusively in periportal macrophages. The biochemical analysis showed an increased content of ceramide -3, with only minor elevated concentrations of other glycosphingolipids. The almost normal hepatic architecture and the presence of well-preserved hepatocytic organelles are in agreement with the observation that liver involvement in Fabry's disease has only minor clinical significance.     

Immunohistochemical study of adhesion molecules in liver inflammation

Using monoclonal antibodies and in situ immunohistochemistry, we studied the distribution of "accessory" adhesion molecules (i.e., intercellular adhesion molecule-1 and leukocyte function-associated antigen-3) in 114 liver biopsy specimens with various inflammatory liver diseases and in 12 control liver biopsy samples without inflammation. The distribution of these adhesion molecules was compared with the presence on inflammatory cells of their natural ligands, lymphocyte function-associated antigen-1 and cluster of differentiation antigen-2, respectively. In normal liver, intercellular adhesion molecule-1 and leukocyte function-associated antigen-3 reacted weakly with sinusoidal lining cells, portal vessel endothelium and scattered mononuclear inflammatory cells, whereas hepatocytes were constantly negative. In contrast, all 114 biopsy samples of acute or chronic liver diseases revealed strong expression of intercellular adhesion molecule-1 and leukocyte function-associated antigen-3 on sinusoidal lining cells and on hepatocytes in areas of inflammation. Hepatocellular membrane positivity resulted in a "honeycomb pattern" of staining , which was panacinar in acute hepatitis and focal in chronic persistent or aggressive hepatitis. In various other chronic liver diseases, a multifocal periportal and intraacinar honeycomb pattern was detected. In all cases, a close topographical correlation was found between hepatocellular expression of intercellular adhesion molecule-1 and leukocyte function-associated antigen-3 on one hand and the presence of inflammatory cells expressing lymphocyte function-associated antigen-1 and cluster of differentiation antigen-2 on the other.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vascular adhesion molecules in acute and chronic liver inflammation.

Adhesion to and penetration through the sinusoidal vascular endothelium is a mandatory step for leukocyte migration and accumulation at sites of liver inflammation. This leukocyte trafficking is controlled by interactions between adhesion molecules on leukocytes and corresponding ligands on endothelial cells. We have analyzed the in situ distribution of two recently described vascular adhesion molecules (i.e., endothelial leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1) and of the lymphocyte "homing" receptor cluster of differentiation antigen-44 in normal and inflamed liver biopsy specimens. Endothelial leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1 were absent from normal liver tissue, but they were strongly expressed on sinusoidal lining cells in inflammatory liver disease. Endothelial leukocyte adhesion molecule-1 expression predominated diffusely throughout the liver parenchyma in acute hepatitis; in contrast, vascular cell adhesion molecule-1 was mainly expressed in areas of periportal and intralobular inflammation in chronic active and persistent hepatitis. The "homing" receptor cluster of differentiation antigen-44 was weakly expressed on scattered mononuclear cells and on sinusoidal lining cells in normal liver tissue, but it was strongly up-regulated on mononuclear inflammatory cells and sinusoidal lining cells in acute and chronic hepatitis. In addition, reactivity for the cluster of differentiation antigen-44 was found on the membranes of variously sized clusters of hepatocytes in biopsy specimens with acute hepatitis. De novo or up-regulated expression of these adhesion molecules on sinusoidal lining cells in inflamed liver biopsy specimens indicates that these cells actively modulate their phenotype in response to environmental factors, thus playing a key role in the recruitment of leukocytes in acute and chronic liver inflammation.     

Epithelioid granulomas in chronic hepatitis C: A transient pathological feature

Multiple hepatic granulomas in chronic hepatitis C patients treated with alpha interferon were recently observed. To assess the presence of hepatic granulomas in chronic hepatitis C, and to determine whether their presence is related to interferon therapy or primarily related to chronic hepatitis C viral (HCV) infection, 446 liver biopsy specimens from 239 Japanese patients with chronic hepatitis C were reviewed. Well-formed non-caseating epithelioid granulomas were found in five (1.1%) of 446 liver biopsy specimens from five (2.0%) of 239 patients. All five patients had been followed up for 1 to 3 years, having between one and six liver biopsy specimens taken at intervals of 6 months to 1 year. Four of these five patients received alpha interferon therapy during the follow-up period. Hepatic granulomas were found in one of the pretherapy liver biopsy specimens in four patients and in one of the post-therapy specimens in one patient. Extensive investigation of the aetiology of hepatic granulomas yielded no conclusive findings. The presence of hepatic granulomas could not be demonstrated in follow-up liver biopsy specimens taken from the four patients who had undergone alpha interferon therapy. These findings suggest that hepatic granulomas may appear as an expression of non-specific reaction in HCV-related chronic hepatitis, and are not related to alpha interferon therapy.     

Localization of Protein-Acetaldehyde Adducts on Cell Surface of Hepatocytes by Flow Cytometry

Acetaldehyde, a highly reactive intermediate of ethanol metabolism, has been shown to form adducts with liver proteins (e.g., a cytosolic 37 kDa protein and the microsomal cytP450IIE1) in rats fed alcohol chronically. In this study, flow cytometry was utilized to test for the presence of protein-acetaldehyde adducts (-AAs) on the surface of hepatocytes and immunotransblot was used to detect for the 37 kDa protein-AA in cytosol as was previously described. For flow cytometric analysis, rabbit anti-hemocyanin-AA IgG and fluorescein isothiocyanate-conjugated goat anti-rabbit serum IgG were used as the primary and secondary antibodies to label surface protein-AAs on hepatocytes at 0 degrees to 4 degrees C. After labeling and washing, hepatocytes were fixed with paraformaldehyde-cacodylate and analyzed with a flow cytometer. In an experiment wherein hepatocytes isolated from rats pair-fed liquid diets with and without ethanol were treated by adding both the primary and secondary IgGs, some hepatocytes from both alcohol-fed and control rats exhibited positive fluorescence but no significant difference in fluorescence intensity was noted. In another experiment, hepatocytes were isolated from rats pair-fed cyanamide (a selective aldehyde dehydrogenase inhibitor) with and without ethanol. The number of hepatocytes showing positive fluorescence in the presence of both primary and secondary IgGs was significantly higher in rats fed cyanamide plus ethanol than in rats fed cyanamide only. Of note, the 37 kDa protein-AA could be detected by immunotransblot in liver cytosol of alcohol-fed rats but not in the controls of both experiments with and without cyanamide supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Histological findings in the livers of patients with neonatal intrahepatic cholestasis caused by citrin deficiency

Aim: To characterize the histological features of the livers of patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), we studied specimens from 30 patients diagnosed with NICCD by genetically analyzing the SLC25A13 gene. Methods: Liver biopsy specimens were subjected to hematoxylin–eosin, Azan, and Berlin‐blue staining. Results: Most specimens showed varying degrees of fibrosis. The degree of inflammation varied among the specimens, with half showing moderate or severe inflammatory changes. Fat deposition in hepatocytes was observed in almost all of the specimens, and severe fatty liver was noted in 20 (67%) of them. There was a mixture of two types of hepatocytes with macrovesicular or microvesicular fat droplets, and cholestasis was observed at a rate of 77%. Hemosiderin deposition, mostly mild and localized in periportal hepatocytes and macrophages in portal areas, was observed in 57% of the specimens. Conclusion: A combination of mixed macrovesicular and microvesicular fatty hepatocytes and the above‐described findings, such as fatty liver, cholestasis, necroinflammatory reaction and iron deposition, are almost never observed in other liver diseases in infants and adults. We believe that NICCD is a disease with characteristic hepatopathological features.     

Ultrastructural liver pathology in patients with minimal liver disease and alpha 1-antitrypsin deficiency: a comparison between heterozygous and homozygous patients

A light and electron microscopic investigation of liver tissue from three homozygous (Pi-type ZZ) and three heterozygous (Pi-type MZ) alpha 1-antitrypsin deficiency patients is presented. All had slightly elevated levels of serum amino transferases as the only signs of liver damage. Light microscopical investigation showed minor periportal fibrosis and periodic acid-Schiff-positive globules in the homozygous patients, but no specific findings besides fatty changes were seen in the heterozygous patients. Electron microscopical investigation was performed on periportal and centrilobular areas separately. In the three homozygous patients, dilatation of endoplasmic reticulum was found in many periportal liver parenchymal cells. In these cells, a marked increase in peroxisomes was also noted and in some instances they showed signs of cell necrosis. Evidence of Kupffer cell heterophagy of such cells was also found, thus indicating that they had died. Only in one liver parenchymal cell from one of the three heterozygous patients was evidence of a dilated endoplasmic reticulum found. No increase in peroxisomes was found and no apparent signs of liver cell necrosis were noted. An increased amount of lipofuscin-like material in the lysosomes was encountered in liver cells both from patients with homozygous and heterozygous alpha 1-antitrypsin deficiency. Based on these findings, it is suggested that cell death occurs in cells with a dilatation of the endoplasmic reticulum. If these findings are important for the pathogenesis in liver disease in alpha 1-antitrypsin deficiency, the present study suggests that the risk to develop liver disease is less in heterozygous patients since, with one exception, alterations of the same nature were not found in their hepatocytes.     

Immunotherapy of chronic active viral hepatitis B with propionibacterium granulosum KP-45 (a 5-year follow-up report).

In the period 1982 to 1984, 14 HBS-AG-positive patients with chronic active hepatitis B were treated monthly with a cell wall preparation (5 or 10 mg) of Propionibacterium granulosum KP-45 (PG), intravenously administered for a period of 6 to 10 months. All 14 patients were monitored by serological and biochemical tests as well as liver biopsy two, three and five years after completing immunotherapy with PG. During this period the patients received neither a specific antiviral, corticosteroid or interferon therapy, nor PG. Re-appearance of HBSAG or HBeAG was never seen in patients who were already free from the antigens one year after completing PG immunotherapy. During the 5-year follow-up, spontaneous improvement in serological and morphological (liver biopsy) parameters of chronic virus B hepatitis occurred in six patients. Five years after completion of PG immunotherapy, only four of the 14 patients showed trace amounts of serum HBSAG (carriers), and in two low levels of anti-HBeAG were present, while the whole group showed a decreasing tendency and serum anti-HBc was still detectable in six patients. HBeAG- and DNA-polymerase-positivity was absent in all patients. Microscopic examination of liver biopsies 5 years after PG immunotherapy showed mild symptoms of chronic hepatitis with inflammatory infiltration, non-active cirrhosis, but without massive periportal and/or multilobular necrosis and trace amounts of HBsAG and HBcAG in hepatocytes only in the four carriers. The remaining 10 patients were free of symptoms of active hepatitis and/or active cirrhosis, but all the patients had moderate to intensive fibrosis in their liver biopsies.     

Fas、FasL在慢性乙型肝炎肝组织中的表达

探讨Fas、FasL在慢性乙型肝炎肝组织中的表达特点。对 30例慢性乙型肝炎患者进行肝穿刺肝组织病理检查及免疫组化法检测肝组织中的Fas/FasL表达强度。 (1)Fas、FasL在肝组织肝细胞膜及胞浆均有不同程度表达 ,其表达阳性细胞主要位于汇管区小叶内及周边碎屑状坏死区 ,呈弥漫分布 ,在其周围浸润的淋巴细胞上多为FasL阳性细胞 ,亦可见到Fas阳性细胞。 (2 )肝组织中Fas、FasL表达随着慢性肝炎程度即炎症和纤维化程度加重而加强 (P均 <0 0 0 1)。Fas-FasL系统介导的细胞凋亡 ,确实参与了慢性乙型肝炎的发病机制 ,且在慢性乙型肝炎的发生发展中起重要作用。