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Aims: Cytokeratin (CK) 7 and CK19 expression, present in hepatic progenitor cells (HPCs) and in cholangiocytes but not in normal hepatocytes, has been reported in some hepatocellular carcinomas (HCCs); however, the incidence and relevance of this expression in HCC in Caucasians is not known. Therefore, our aim was to study the occurrence and clinicopathological characteristics of HCC expressing CK7 and/or CK19 in 109 Caucasian patients. Methods and results: The expression of hepatocellular differentiation markers (Hepar, canalicular polyclonal carcinoembryonic antigen), biliary/progenitor cell markers (CK7, CK19), α-fetoprotein (AFP), p53 and β-catenin in HCC was semiquantitatively assessed by immunohistochemistry. Of 109 HCCs, 78 were CK7–/CK19– (72%), 13 CK7+/CK19– (12%), seven CK7–/CK19+ (6%), 11 CK7+/CK19+ (10%). CK19 expression was significantly associated with elevated serum AFP (400 ng/ml) ( P = 0.023), tumour AFP expression ( P < 0.0001), presence in serum of anti-hepatitis B core ( P = 0.016), less fibrosis in non-neoplastic parenchyma ( P = 0.009) and less nuclear β-catenin expression ( P = 0.021). CK7 expression was significantly associated with elevated serum bilirubin (> 2 mg/dl) ( P = 0.0005) and less nuclear β-catenin expression ( P = 0.003). HCC expressing CK19 had a higher rate of recurrence ( P = 0.009, hazard ratio 12.5, n = 31) after liver transplantation compared with CK19– tumours. Conclusions: In our series, 28% of HCCs contained cells expressing CK7 and/or CK19. They potentially derive from HPCs. The higher recurrence rate of CK19+ HCC after transplantation suggests a worse prognosis for these HCCs compared with CK19– HCC. [ABSTRACT FROM AUTHOR]

Provides a practical guideline on the histopathology of portal hypertension. Classification of portal hypertension; Most common cause of portal hypertension; Portal tract changes and parenchymal changes; Special features of diagnostic value.

Background: Irritable bowel syndrome developing following infective gastroenteritis accounts for approximately 1 in 10 of unselected lBS patients. Aims: To define the long term natural history of post-infective lBS (PI-lBS). Methods: A total of 436 individuals, who had previously responded to a questionnaire on their bowel habits following an acute episode of gastroenteritis, were sent a questionnaire about their current bowel habits and physical and mental health six years after their initial illness. Results: Complete data on original bowel habit, episodes of gastroenteritis, mental health history, and subsequent bowel habit at six years were obtained in 192 individuals. Of these, there were 14 cases of "post-infective lBS" (PI-lBS) and 13 who had lBS prior to infection (previous lBS). Over the six year follow up period there were 20 "new non-infective lBS cases" (new lBS). The strongest risk factor for developing any type of lBS was female sex (relative risk 2.2, p<0.05). Compared with new lBS, those with PI-lBS had significantly more days with loose stools (p<0.05) but a similar number of days with pain, urgency, and bloating. Six of 14 (43%) PI-lBS and four of 13 (31%) previous lBS patients recovered by six years (NS). Of 27 lBS patients followed for six years, only 1/8 with a history of anxiety or depression recovered compared with 9/19 without such a history (p=0.19). Conclusion: PI-lBS differs from non-infective lBS by having more diarrhoeal features. Less than half of both PI-lBS and non-infective lBS cases recover over six years. A history of anxiety and depression severe enough to warrant treatment may impair recovery but larger numbers are needed to prove this. [ABSTRACT FROM AUTHOR]

Predictive value of liver cell dysplasia for development of hepatocellular carcinoma in patients with non-cirrhotic and cirrhotic chronic viral hepatitis Aims: Hepatocellular carcinoma (HCC) frequently develops in patients with chronic viral hepatitis, especially in the cirrhotic stage. We retrospectively studied whether the presence of the putative preneoplastic lesions large liver cell dysplasia (LLCD) and/or small liver cell dysplasia (SLCD) in a needle liver biopsy of these patients are a risk factor for the development of HCC. Methods and results: The presence of LLCD and SLCD in the needle liver biopsy taken at the initial work-up of 115 patients with chronic hepatitis B or C was assessed retrospectively. LLCD and SLCD were present in the initial biopsy of, respectively, 35 (30%) and 25 patients (22%). During a mean follow-up of 107 months, 16 patients (14%) developed HCC and this occurred significantly more frequently in patients with cirrhosis, age ≥ 55 years, LLCD or SLCD. Cirrhosis and LLCD were independent risk factors for HCC development. Conclusions: Our findings indicate that the presence of LLCD in a needle liver biopsy of patients with viral-induced chronic liver disease is an independent risk factor for the development of HCC. If these results are confirmed, the presence of LLCD can be used to identify a subgroup of patients at high risk for HCC requiring more intensive screening. [ABSTRACT FROM AUTHOR]

The dendritic cells in skin biopsies from 36 fetuses (from 16 weeks' gestational age on) and neonatal infants of different ages were investigated using a number of markers for various cells of the immune system and immunohistochemistry. Epidermal Langerhans' cells were found in all cases in a predominantly basal localization. The number of OKT6-positive Langerhans' cells and the development of their dendritic processes gradually increased with age. Dermal dendritic cells were present as well. Both HLA-DR-positive and Leu-10-positive dermal dendritic cells were found in the superficial and deep dermis, often in a perivascular distribution. The OKT6-positive dermal dendritic cells were few in number and occurred only in the upper dermis.

Skin biopsies from 43 patients with a rather dense dermal lymphoid infiltrate of either inflammatory or neoplastic nature have been investigated. We studied the number, distribution and immunophenotype of epidermal Langerhans cells and dermal dendritic cells. As previously reported, differences in epidermal Langerhans cell and dermal dendritic cell numbers between skin biopsies with a B-cell infiltrate and skin biopsies with a T-cell infiltrate were found, dendritic cells being more numerous in the latter. The main finding of this study was an uneven distribution of epidermal Langerhans cells and dermal dendritic cells in skin biopsies with a T-cell infiltrate: in skin lesions with an inflammatory lymphoid infiltrate, small clusters of epidermal and dermal dendritic cells admixed with T-lymphocytes (predominantly T-helper/inducer cells) and small blood vessels were present at areas of exocytosis. In skin lesions with a neoplastic lymphoid infiltrate larger, more loosely arranged aggregates of dendritic cells and T-cells were seen. These cell aggregations composed of activated (inflammatory or neoplastic) T-cells and dendritic cells may represent the cutaneous homologue of the secondary T-nodule in the lymph node. Both types of cell aggregates may correspond to the dendritic cell-T cell clusters observed in in vitro induced immune responses. [ABSTRACT FROM AUTHOR]

The immunohistochemical findings in granulomatous lymphadenitis in patients with Crohn's disease are presented and compared with conventional light microscopic findings. The cellular composition of the granulomas in mesenteric lymph nodes was examined with a broad panel of monoclonal and polyclonal antibodies directed to B-cells, T-cells, monocytes/macrophages, dendritic reticulum cells, HLA-DR antigens and the transferrin receptor. The centre of the granulomas contains OKIa, OKM1, OKT9, DRC, To5 epithelioid cells and giant cells and OKT3 lymphocytes. In general, the majority of the small lymphocytes within the granulomas expresses the OKT3, OKT4 Leu 3a phenotype which points toward T-helper cells. Fewer OKT3 OKT8 T suppressor/cytotoxic cells are observed. At the periphery of the granulomas a lymphocytic corona composed of BA1, B1 B lymphocytes may be present. From these findings it can be concluded that the granulomas in mesenteric lymph nodes from patients with Crohn's disease are composed of centrally located T-lymphocytes and of epithelioid cells which are of monocyte/macrophage origin and have the characteristics of antigen-presenting cells. [ABSTRACT FROM AUTHOR]

Skin biopsies from 34 patients, presenting with a variety of bullous skin disorders were investigated, using routine light microscopy and immunohistochemistry. In bullous skin diseases characterized by deposition of complement factors (CF) and/or immunoglobulins (Ig), a monolayer of OKIa, OKT, OKM dendritic cells was found at the dermo-epidermal junction. Retrospectively, these cells were easily recognized on paraffin embedded, H & E stained material. In bullous skin disorders, showing no deposition of CF and/or Ig, this monolayer of dendritic cells was lacking. It is suggested that these OKIa, OKT, OKM dendritic cells at the dermo-epidermal junction represent some type of antigen presenting cells, not corresponding to Langerhans cells, veiled cells or indeterminate cells. [ABSTRACT FROM AUTHOR]

Using monoclonal antibodies on fresh frozen endoscopically obtained oesophageal biopsies the distribution of Langerhans cells, B lymphocytes, and various subpopulations of T lymphocytes was studied in the normal human oesophageal mucosa and in oesophagitis. Identification of the lymphocytes was carried out by an immunoperoxidase technique using OKT (antihuman T cell antibody), OKT (antihuman helper T cell antibody), OKT (antihuman cytotoxic T cell) and OKT (antihuman null cell antibody). Identification of the Langerhans cells was carried out using an ATPase stain and OKIa (Ia like antigen) and OKT (antihuman thymocyte). In the normal oesophageal epithelium cytotoxic T lymphocytes are found as well as Ia positive Langerhans cells. Helper T lymphocytes and B lymphocytes are present mainly in the lamina propria. In oesophagitis an increase in Langerhans cells and cytotoxic T lymphocytes within the epithelium is found. From these findings it can be concluded that the oesophagus contains a reticuloepithelial system as well as a lymphocytic population which are a part of the gut-associated lymphoid tissue. [ABSTRACT FROM AUTHOR]

Gallbladders of 12 cases with chronic cholecystitis showing pseudopyloric glands (PPG) and of 18 cases with acute cholecystitis or chronic cholecystitis but without PPG were examined by the peroxidase - antiperoxidase (PAP) method using rabbit antibody against human lysozyme (LM). LM-immunoreactivity was detected in the cytoplasm of PPG and, to a lesser extent, in the pits of epithelial crypts that gave rise to PPG. No LM was found in normal gallbladders; in cases of cholecystitis without PPG, LM-immunoreactivity was restricted to infiltrating inflammatory cells. The presence of LM in PPG suggests that PPG represent functional metaplastic areas, involved in the non-specific defence mechanisms through participation of LM. [ABSTRACT FROM AUTHOR]

By use of the indirect immunoperoxidase method, lysozyme was localized in the serous glands and serous parts of mixed mucous-serous glands of the nasal respiratory area. Histochemically, lysozyme was absent from acini containing acid mucosubstances. These findings are in agreement with localizations of lysozyme in glands at other sites. [ABSTRACT FROM AUTHOR]

ABSTRACT- Twenty specimens of focal nodular hyperplasia were studied with special attention to the histological features of chronic cholestasis (grouped under the headings of cholestasis, cholate-stasis and signs of ductular reabsorption). In all specimens, evidence was found for one or more features of cholestasis and cholate-stasis. Signs of ductular reabsorption were less constant, and apparently varied according to the developmental stage of the lesion. The cholestatic features emphasize the bile secretory capacity of the lesional parenchyma, and are apparently due to the lack of real bile ducts in the portal tract equivalents of the lesional tissue. Evidence is presented that the 'ductular component' in FNH is not due to proliferation of pre-existing ductules, but rather derives from ductular metaplasia of liver cell plates in zone 1 equivalents. This metaplastic development of a ductular network may serve the function of reabsorbing the biliary constituents produced by the lesional parenchyma, leading to periductular inflammation and progressive fibrosis, thus producing an equivalent of biliary fibrosis and biliary cirrhosis. [ABSTRACT FROM AUTHOR]

ABSTRACT- Ten liver biopsy specimens from nine patients with PBC stages II to IV were studied immunohistochemically with a broad panel of monoclonal antibodies. In areas of bile-duct proliferation, many BA1+ B-lymphocytes and OKT4+/Leu3a+ helper/inducer T-cells were observed, admixed with some C3b-receptor positive, mono-and polymorphonuclear OKM1+ cells. Numerous IgM-containing plasma cells were seen in portal tracts showing bile-duct proliferation. In contrast, areas of piecemeal necrosis and intralobular spotty necrosis consisted mainly of OKT4+/Leu3a+ helper/inducer, and OKT8+ suppressor/cytotoxic T-cells, admixed with some OKM1+ polymorphonuclear granulocytes. Almost no BA1+ B-lymphocytes or Ig-containing plasma cells were observed in areas of piecemeal necrosis and spotty necrosis. Major histocompatibility complex (MHC)-class I antigens (i.e. HLA-A,B,C) were demonstrated either on the liver cell membrane, or on sinusoidal lining cells. The latter also expressed MHC-class II antigens (i.e. HLA-DR). In two liver biopsies, an increased expression of HLA antigens was observed near areas of piecemeal and spotty necrosis. Our results indicate that several immune mechanisms each with a particular topographical distribution, are operative in PBC. Inflammatory cells, involved in humoral immunity, are present mainly in areas of bile duct proliferation. In contrast, the effector cells of antigen-specific cellular cytotoxicity are present in areas of piecemeal necrosis and spotty necrosis. In the latter areas, a pronounced expression of MHC products representing the afferent limb of the cell-mediated immune response, may permit an optimal T-cell-mediated immune effect or, eventually, result in adverse effects. [ABSTRACT FROM AUTHOR]

ABSTRACT- Deparaffinized sections of hepatitis B surface antigen (HBsAg) positive liver biopsies, when incubated in a human fibrinogen solution, reveal a strong labelling of ground-glass hepatocytes with fibrinogen. This implies an interaction between HBsAg and fibrinogen. The binding of fibrinogen to HBsAg is thought to be mediated by the protein moiety of HBsAg, since its binding capacity is destroyed by trypsin digestion, and to occur through formation of disulphide bridges because the binding can be disrupted by the reducing effect of 2-mercapto-ethanol. Not all ground-glass hepatocytes exhibit fibrinogen binding. The reason for this is at present unclear. No relationship between serum HBeAg positivity and binding of HBsAg to fibrinogen was observed. Preincubation in a fibrinogen solution did not alter the immunoreactivity of HBsAg. We conclude that there is a striking analogy between the interaction of HBsAg with polymerized human serum albumin and its interaction with fibrinogen. [ABSTRACT FROM AUTHOR]

ABSTRACT- The predictive value of piecemeal necrosis (PMN) in acute hepatitis was investigated in 62 patients (39 hepatitis B virus infection, 9 hepatitis A virus infection and 14 possible hepatitis NANB virus infection). The 62 initial biopsies were blindly recoded and classified into three groups: 1. Acute hepatitis with signs of possible transition to chronicity (AHTC) (n = 35)(i.e. a picture of acute hepatitis associated with PMN). 2. AHTC-borderline group (BL) (n = 15) (i.e. a picture of acute hepatitis with minimal PMN). 3. Uncomplicated acute hepatitis (AH) (n = 12) (i.e. a picture of acute hepatitis without PMN). Follow-up of the patients revealed an evolution to chronicity in a very high percentage of the AHTC-cases of hepatitis B (95%) and NANB (89%) etiology. Also 67% of the BL-cases of hepatitis B etiology developed chronic liver disease. In hepatitis B the immunohistochemical pattern of HBsAg is of additional help. In hepatitis A, PMN is often present (5/9) but no evolution to chronicity was observed. This study shows that PMN in acute hepatitis appears to be a useful prognostic feature for chronicity in hepatitis B and NANB. [ABSTRACT FROM AUTHOR]

ABSTRACT- A syndrome resembling human Primary Biliary Cirrhosis (PBC) and occurring spontaneously in a strain of domesticated rabbits from the Faenza region in Italy, is reported. The syndrome is characterized by histological liver changes consisting of chronic non-suppurative destructive cholangitis and copper accumulation, biochemical and immunological abnormalities mainly represented by an elevation of serum alkaline phosphatase and a positive antimitochondrial antibody test. The abnormalities were not observed in newborn rabbits from the same area nor in control rabbits from the island of Sardinia. A toxic effect related to some environmental factor may be responsible for the disease. Alternatively, a continuous process of partial inbreeding among consanguineous animals may have resulted in a selection of a strain genetically predisposed to the development of PBC. Whatever the etiology, the domesticated Faenza rabbit proves to be an interesting animal model for a chronic non-suppurative destructive cholangitis, very similar to the human disease known as PBC. [ABSTRACT FROM AUTHOR]

ABSTRACT- A new ultrastructural cytoplasmic marker designated as type 2, and distinct from type 1 previously associated with NA-NB hepatitis in chimpanzees, was found in hepatocytes of two patients and of one experimentally infected chimpanzee. These cases represent a minority of all cases we studied as presumed NA-NB viral hepatitis. Type 2 marker consists of tubular structures composed of an assembly of ring-like units coated with smaller uniform fragments, accumulated in different patterns in dilated cisternae of the endoplasmic reticulum. Preliminary data using immunofluorescence with NA-NB hepatitis convalescent serum and antiserum against fibrinogen are reported. Type 2 marker may represent a different agent or a different reaction pattern to one agent of NA-NB viral hepatitis. Its features are compared with those of hepatitis B. [ABSTRACT FROM AUTHOR]

ABSTRACT- Ultrastructural investigation of liver biopsies from two patients with non-A, non-B hepatitis revealed cytoplasmic and nuclear alterations in the hepatocytes. The lesions in both patients, one with acute and one with chronic hepatitis, were similar and distinct from those previously described in other forms of hepatitis. These findings are compared with the reported findings in chimpanzee liver after inoculation with non-A, non-B infective material. The intranuclear findings are similar to the aggregations of 20-27 nm particles described in some infected chimpanzees, and the cytoplasmic alterations seem to be similar to the cytoplasmic structures and tubular arrangements reported in other inoculated chimpanzees. A striking finding of this study is the presence of both alterations together in the same biopsy in two different patients, suggesting that they represent a different stage of viral infection or different parts of the viral agent. It still remains to be proved that the ultrastructural particles indeed contain antigen(s) of the non-A, non-B hepatitis virus. The nuclear and cytoplasmic alterations are, however, characteristic for non-A, non-B hepatitis and are useful as ultrastructural hallmarks of this form of hepatitis. [ABSTRACT FROM AUTHOR]

The expression of transferrin receptors (TfR's) has been investigated in eight liver biopsy specimens (four from patients without demonstrable iron and four from patients with iron storage due to primary hemochromatosis (HC)) using immunoelectron microscopy to demonstrate TfR's by the simultaneous application of two specific monoclonal antibodies (OKT9 and B3/25) to tissue chopper sections. In the four specimens without iron overload, hepatocytes, but not sinusoidal lining cells, stained positively and immunoreactivity was mainly localized in the cytoplasm. Positively stained cisternae of the endoplasmic reticulum indicated synthesis of the TfR. The presence of TfR's on segments and coated invaginations of the sinusoidal membrane and in small, but otherwise unidentified vesicles in the cytoplasm is compatible with endo-/exocytotic transport and recycling of TfR's as demonstrated by biochemical studies. Ocassional positively stained material in canalicular lumina together with positively stained canalicular microvilli and pericanalicular vesicles suggest that transcellular transport may be an additional pathway for TfR's. In three biopsies showing severe iron overload due to HC, TfR immunoreactivity was completely absent. The remaining specimen showing HC, exhibited relatively mild iron overload and showed only a few positively stained hepatocytes. This supports the previously reported disappearance of hepatic TfR expression in HC when iron overload is severe. [ABSTRACT FROM AUTHOR]

The enzyme and immunohistochemical features of lymphnodes showing sinus histiocytosis have been studied. Sinus histiocytes with phenotype OKM1 0KT4 Leu3a To5 OKIal showed strong acid phosphatase and non-specific esterase, weak endogenous peroxidase and no ATPase activities. In nine out of ten lymph nodes, paracortical collections of dendritic OKT6 OKIal cells were observed. In two of the four cases studied these dendritic cells showed strong ATPase activity. We suggest that the dendritic OKT6 OKIal ATPase interfollicular cells represent newly arrived veiled cells (VC) which have entered the lymph node by the afferent lymph, settled in the interfollicular area and are probably involved in the induction of a cellular immune response. OKT6 OKIal ATPase VC may subsequently transform into mature, OKT6 OKIal ATPase interdigitating reticulum cells which are involved in the negative feedback of the cellular immune response. The association with sinus histiocytosis is probably related to the fact that an increase in mononuclear phagocytes in the afferent lymph is accompanied by a relative increase in VC. Our results demonstrate that in lymph nodes showing sinus histiocytosis, two cell types increase in number, i.e. an Ia sinusoidal cell, engaged in phagocytosis of foreign material, and an Ia dendritic cell in the interfollicular area, probably involved in the induction of a cellular immune response. [ABSTRACT FROM AUTHOR]

We compared the paracortical area in 4 cases of dermato-pathic lymphadenitis (DL) with the same area in 11 cases of various other reactive conditions of the lymph node by immuno- and enzymehis-tochemical techniques. In addition, electron microscopy was performed on threee cases of DL. The paracortical nodules in DL proved to be composed of a variable number of dendritic, OKT6+ OKIa+ ATP-ase+ cells, admixed with helper T-lymphocytes. All other lymph nodes studied lacked dendritic OKT6+ cells, whereas OKIa positivity was found in the cortical (follicular centers and mantle zones) and paracortical area (lymphocytes and scattered dendritic cells). Short incubation for ATPase revealed a paracortical, pericellular staining pattern in cases of DL, whereas in all other cases this staining pattern was observed only after long incubation times. On electron microscopy, three types of dendritic cells were found in DL, namely interdigitating reticulum cells (IDRC), Langerhans cells (LC) and macrophages. Intermediate forms between IDRC and LC, containing a few Birbeck granules and a well developed rough endoplasmic reticulum, were found. It is suggested that immunoreactivity for the monoclonal antibody 0KT6 is restricted to cases of DL, and is due to the appearance of dendritic cells that have LC-characteristics. These cells either arrive from the skin along afferent lymph vessels, or are the result of a local transformation process of IDRC that acquire LC-characteristics, i.e. OKT6 immunoreactivity and Birbeck granules. [ABSTRACT FROM AUTHOR]

The effect of interferon-gamma on the expression in situ of major histocompatibility complex (MHC) products in human corneas was studied in vitro. Incubation for four days with 5 or 50 mg/l of Escherichia coli-derived recombinant human interferon-gamma resulted in the appearance de novo of MHC class II or HLA-DR antigens on variable numbers of corneal epithelial cells as well as on corneal endothelium, whereas it had no effect on the expression of MHC class I or HLA-ABC antigens. These results may help to explain the mechanism underlying the expression of HLA-DR antigens on corneal and limbal epithelium in various inflammatory eye diseases. [ABSTRACT FROM PUBLISHER]

Upper palpebral conjunctival biopsy specimens obtained from eight patients with active trachoma were examined by routine histological and immunohistochemical methods. The epithelium expressed class I major histocompatibility complex (MHC) products throughout and class II MHC products in the superficial layers. The epithelial inflammatory infiltrate consisted of polymorphonuclear leucocytes, macrophages, T lymphocytes, and dendritic cells. In the underlying stroma the inflammatory infiltrate was organised as B lymphoid follicles, and there was also a diffuse infiltrate consisting of plasma cells and scattered B lymphoid cells, dendritic cells, T cells, macrophages, and polymorphonuclear leucocytes. Each type of cell has its special location in the tissue. Plasma cells were located on a subepithelial band and as a dense infiltrate round the acini of accessory lacrimal glands. IgA+ plasma cells outnumbered IgG+ cells, whereas IgM+ and IgE+ cells were few. Our data provide good evidence for the presence of both humoral and cell mediated immune responses and a possible role for autoimmune mechanisms in the conjunctival tissues of trachoma patients. [ABSTRACT FROM PUBLISHER]

The cellular composition of the inflammatory infiltrate present in 13 patients with the limbal form of vernal keratoconjunctivitis was examined in the conjunctival scrapings and the limbic replicas by means of Giemsa stain and immunohistochemistry. Conjunctival scrapings showed the presence of mast cells, lymphocytes, plasma cells, polymorphonuclear leucocytes, and very few basophils in all the specimens. Eosinophils were present in only four scrapings. The superficial epithelium of the limbic lesion and the adjacent cornea and conjunctiva was studied by the replica technique. The limbic lesion area showed the presence of necrotic epithelial cells mixed with inflammatory cells, including eosinophils, mast cells, lymphocytes, plasma cells, and polymorphonuclear leucocytes and very few basophils. Most of the inflammatory cells were HLA-DR+. Many OKT6+ cells were present, indicating the presence of Langerhans cells. T-lymphocytes including a few helper/inducer cells and many suppressor/cytotoxic cells, were detected in the infiltrate. In addition many B-lymphocytes were observed. These findings suggest that other immune mechanisms in addition to type 1 reaction are involved in the pathogenesis of the disease. [ABSTRACT FROM PUBLISHER]

Eighteen liver biopsy specimens from patients with hepatitis B surface antigen (HBsAg) positive chronic aggressive hepatitis were studied by electron microscopy. All cases were selected on the basis of positive liver cell membrane fluorescence for HBsAg on immunohistochemical investigation. Striking changes in the morphology of the liver cell membrane were observed in nearly all cases. Furthermore, a dual aspect of hepatitis B core antigen (HBcAg) is described. HBcAg particles may occur as either 'naked' or 'cloudy' particles surrounded by semi electron dense material. The nature of the 'cloud' remains to be identified. [ABSTRACT FROM PUBLISHER]