Microvasculature in the small portal tracts in idiopathic portal hypertension

Summary The morphology of the microvasculature in the small portal tracts was examined in normal livers, idiopathic portal hypertension (IPH) and other hepatic diseases. The microvasculature examined was arbitrary divided into two groups: that near the limiting plate and that within portal tracts, particularly around bile ducts. Based on comparisons of histology, immunohistochemistry and vascular casts, it is suggested that the former corresponded to inlet venules and the latter to distributing portal veins and peribiliary capillary plexus. Both of these microvasculatures were positive forUlex europaeus lectin I, and (infrequently and weakly) for factor VIII-related antigen. Morphometry disclosed that inlet venules were reduced in number in IPH compared with normal livers and that distributing portal veins, peribiliary capillary plexus and inlet venules were increased in extrahepatic portal obstruction, chronic active hepatitis and extrahepatic obstructive cholestasis. We believe that the change in the microvasculature reflects abnormal microcirculation in the small portal tracts, and that the reduction of inlet venules plays an important role in the development of portal hypertension in IPH.     

Expression of HLA-DR antigen on hepatic vascular endothelial cells in idiopathic portal hypertension.

Immunologic abnormalities have been reported in idiopathic portal hypertension, though the exact immunologic mechanism(s) leading to various portal venopathies in this disease remain unsettled. Recently, aberrant expression of HLA-DR antigen on target cells has been noted in the organ-specific autoimmune diseases. In this study the expression of HLA-DR antigen on the hepatic vasculature was surveyed immunohistochemically in idiopathic portal hypertension (n = 36) and in control livers: normal livers (n = 27), chronic active hepatitis (n = 35) and cirrhosis (n = 21). Endothelial cells of hepatic veins and hepatic arteries occasionally expressed HLA-DR antigen, and there was no difference in the expression between idiopathic portal hypertension and controls. Endothelial cells of the main portal vein, within the small and medium-sized portal tract, did not express HLA-DR antigen in idiopathic portal hypertension and controls. By contrast, endothelial cells of the smaller venous radicles, including inlet venules in these portal tracts other than the main portal vein, more frequently expressed HLA-DR antigen in idiopathic portal hypertension (78%) than in chronic active hepatitis (26%), cirrhosis (29%) and normal liver (15%). These data raise the possibility that the smaller venous radicles in the small and medium-sized portal tracts are targets of immunologic attack in idiopathic portal hypertension.     

Pathology and pathogenesis of idiopathic portal hypertension with an emphasis on the liver

Idiopathic portal hypertension (IPH) is characterized by a long-standing presinusoidal portal hypertension of unknown etiology in adults. Some unidentified agent(s) affect(s) the intrahepatic small portal veins or portal tracts. Immunological disturbance, thromboembolism, infectious etiology and/or increased fibrogenesis in portal tracts are suspected as being candidates for the primary agent(s). During the long clinical course of IPH, several pathological changes may occur, including subcapsular parenchymal atrophy, atrophy of the liver, portal and parenchymal fibrosis, and portal venous phlebosclerosis and thrombosis. The last-named of these lesions is mostly found in patients with a history of splenectomy. Subcapsular parenchymal and hepatic atrophy may result from a hepatocellular dropout via apoptosis or necrosis because of intrahepatic hemodynamic disturbances, particularly chronic portal venous blood insufficiency. Pericellular fibrosis and thin fibrous septa are also frequently found and associated with activated perisinusoidal cells positive for smooth muscle actin. At the same time, vague nodular hyperplasia of hepatocytes not surrounded by fibrous septa is not infrequently seen. It may resemble nodular regenerative hyperplasia, partial nodular transformation, or focal nodular hyperplasia. However, liver cirrhosis does not occur even at the terminal stage. Taking these findings into consideration, a new staging of IPH with a combination of hepatic parenchymal atrophy and portal venous thrombosis was proposed: non-atrophic liver without subcapsular parenchymal atrophy (stage I), non-atrophic liver with subcapsular parenchymal atrophy (stage II), atrophic liver with subcapsular parenchymal atrophy (stage III), and portal venous occlusive thrombosis (stage IV). IPH livers are likely to progress from stage I to stage III. Stage IV, which occurs relatively late, has a poor prognosis. This staging is applicable to clinical and autopsy cases without any histological data.     

Pathogenesis of portal sclerosis in the liver with idiopathic portal hypertension. Observations of 19 autopsy cases and animal experiments

The pathomorphological changes of intrahepatic portal veins were studied in 19 autopsy cases of idiopathic portal hypertension (IPH), and the pathogenesis of portal sclerosis was discussed by the observations on the human and experimental materials. The degree and morphological appearance of intimal lesions vary from vessel to vessel. Fibro-cellular proliferation of subendothelial tissue and incorporation of organized mural thrombi were suggested as the cause of intimal thickening in the portal veins. Animal experiment showed that injury of portal vein wall was followed by intimal hyperplasia and/or incorporation of mural thrombi, and resulted in portal sclerosis similar to that of IPH liver. The cause of portal phlebosclerosis in IPH can not be explained by passive congestion alone. There might be a certain possibility of direct injurious effect in the vessel wall in the pathogenesis of portal lesions of IPH. The following pathogenesis of portal sclerosis in IPH is postulated: phlebo-sclerotic changes of the portal veins are initiated by injury to the vessel wall due to unknown cause(s) and accelerated by secondary thrombosis and/or mechanical injury due to increased portal pressure.     

Induction of elastin expression in vascular endothelial cells relates to hepatoportal sclerosis in idiopathic portal hypertension: possible link to serum anti-endothelial cell antibodies

Hepatoportal sclerosis accompanied by dense elastic fibre deposition is generally regarded as the primary lesion in the development of idiopathic portal hypertension (IPH). This study was performed to clarify the mechanism of elastic fibre deposition in the peripheral portal tracts of IPH liver in relation to serum anti-endothelial cell antibodies (AECA). In-vitro experiments were performed using human dermal microvascular endothelial cells (HMVEC) and patients' sera. The presence of serum AECA was assayed by a cell-based enzyme-linked immunosorbent assay (ELISA) using HMVEC. Immunohistochemical analysis of elastin was performed using liver tissue sections of IPH patients. IPH sera contained one or more AECA that could bind to the vascular endothelial cells of the peripheral portal tracts of the liver. When the value of AECA greater than the mean ± 2 standard deviations of healthy controls was regarded as positive, the positive detection rate of either immunoglobulin (Ig)G, IgA or IgM AECA in IPH sera was 30% (10 of 33 cases). IPH sera induced the expression of elastin in HMVEC, which appeared to be associated with the presence of AECA. Apoptosis was also induced in HMVEC by the stimulation with IPH sera. In vivo, elastin expression was observed in the endothelial cells of the peripheral portal tracts of IPH livers in a proportion of cases. The disease pathogenesis of IPH seems to be heterogeneous, and this study elucidated a possible contribution of the induction of elastin expression in the portal vessels to hepatoportal sclerosis of IPH, which might be linked to serum AECA as a causative factor.     

A comparative histological and morphometric study of vascular changes in idiopathic portal hypertension and alcoholic fibrosis/cirrhosis

AIM: To examine the pathological changes of hepatic arteries in idiopathic portal hypertension (IPH) which is characterized by the obliteration of the intrahepatic portal vein branches and presinusoidal portal hypertension. METHODS AND RESULTS: Liver specimens (biopsied or surgically resected) from 20 patients with IPH, 20 patients with alcoholic fibrosis/cirrhosis (AF/C) and 20 histologically normal livers were used. The vascular lumina of arterial and venous vessels in portal tracts were morphometrically evaluated by an image analysis system. The ratio of portal venous luminal area to portal tract area (portal venous index) of IPH and that of AF/C were significantly reduced compared with normal liver. The portal venous index for IPH was significantly lower than that for AF/C. The ratio of hepatic arterial luminal area to portal tract area for AF/C was significantly higher than that in normal liver; however, that for IPH was similar to normal. The peribiliary vascular plexus was increased in AF/C but not in IPH. In AF/C, the number of mast cells and macrophages known to be the source of angiogenic substances was significantly increased in the portal tract compared with normal liver, while in IPH it was not increased. CONCLUSIONS: In AF/C, a reduction in portal venous lumen was associated with an increase of hepatic arterial lumen and of angiogenesis-related cells in portal tracts. However, such compensatory arterial changes were not evident in IPH, and this compensatory failure may be a feature of IPH.     

Idiopathic portal hypertension: a histopathological study of 26 Japanese cases

Analysis of 25 liver biopsy specimens and one autopsy specimen from 26 Japanese patients (23 women and three men) with idiopathic portal hypertension revealed findings that collectively appeared diagnostic for the condition. Changes in the portal tract included capillary dilatation, phlebosclerosis, and fibro-elastosis of the stroma. Many portal veins were dilated and had herniated into the surrounding hepatic parenchyma. Portal vein obliteration and loss of bile ducts were a rare complication. The acinar architecture was disturbed by: 1 capillary and necro-infiammatory bridging, mostly between portal tracts and terminal hepatic veins; 2 the formation of isolated megasinusoids in a random distribution; 3 displaced and abnormally large hepatic vein branches with or without phlebosclerosis and 4 slender, curved fibrous septa (hairline septa). Early nodular regeneration was found in 25% of the cases. Our review supports the contention that incomplete septal cirrhosis may be a late manifestation of idiopathic portal hypertension. It is not clear whether the biopsy findings in Japanese patients differ only in severity from those in western patients, or whether the conditions differ pathogenetically. Some histopathological findings in the Japanese cases, in particular the necroinflammatory changes, are difficult to reconcile with portal hypertension as a primary haemodynamic abn rmality.     

Portal and parenchymal alterations of the liver in idiopathic portal hypertension: a histological and immunochemical study

Idiopathic portal hypertension (IPH) is characterized by presinusoidal portal hypertension owing to the intrahepatic, presinusoidal portal venous block, whereas the primary cause and initial vascular lesions(s) remain only speculative. In this study, a total of 97 IPH livers were histopathologically and immunohistochemically examined, placing emphasis on hepatic parenchymal fibrosis and atrophy as well as on portal tract fibrosis. Alcoholic cirrhosis and normal livers were used as controls. When compared with normal livers, the expression of connective tissue growth factor (CTGF) in periductal mononuclear cells was significant. Matrix metalloproteinase (MMP)9-positive mononuclear cells were fewer in number in the portal tract of IPH liver, when compared with alcoholic cirrhosis. These findings suggest a possible pathogenesis of collagen and elastin deposition because of increased CTGF expression and decreased MMP-9 expression in portal tracts of IPH. Sinusoidal dilatation associated with hepatocellular atrophy and apoptosis occurred frequently, but focally in 20% of the IPH cases. These changes were most often found in hyperplastic hepatocellular areas and in the perivenular areas of hepatic lobules. In these areas, pericellular fibrosis and thin fibrous septa were also frequently seen. In these fibrotic areas, there were deposited not only collagen fibers, but also elastic fibers, in which alpha-smooth muscle actin-positive sinusoidal cells, reflecting activated hepatic stellate cells, were frequently detected. It is possible that in IPH cases, continuing portal venous blood insufficiency may be responsible for hepatic parenchymal damage, which may be followed by hepatocellular apoptotic dropout and then by hepatic parenchymal atrophy and fibrosis.     

Immunohistochemical analysis of adhesion molecules in the micro-environment of portal tracts in relation to aberrant expression of PDC-E2 and HLA-DR on the bile ducts in primary biliary cirrhosis

We have examined immunohistochemically the expression of adhesion molecules in the micro-environment of portal tracts and their relationship to the expression of the pyruvate dehydrogenase E2 complex (PDC-E2) and HLA-DR in liver biopsy specimens. Ten cases of primary biliary cirrhosis (PBC) and 19 controls were examined, including four cases of extrahepatic biliary obstruction, six of chronic viral hepatitis, and nine normal livers. In PBC, the damaged small bile ducts demonstrated an increased expression of PDC-E2 and an aberrant expression of HLA-DR; about half of these damaged bile ducts also expressed intercellular adhesion molecules (ICAM)-1 and a few expressed vascular adhesion molecule (VCAM)-1. In addition, lymphocyte function-associated antigen (LFA)-1 and very late antigen (VLA)-4 were expressed on infiltrating lymphocytes around these bile ducts. In contrst, in control livers, these alterations in antigen expression on the bile ducts were either not observed or were only focal and weak, when present. These findings suggest that ICAM-1/LFA-1 and also VCAM-1/VLA-4 linkages between the damaged bile ducts and lymphocytes may facilitate antigen-specific reactions such as the presentation of antigens, possibly PDC-E2, to the periductal lymphocytes in PBC. ICAM-1, VCAM-1, and E-selectin were strongly expressed on the endothelial cells of some vessels in the portal tracts in PBC, suggesting the facilitation of the recruitment of lymphocytes around the of some vessels in the portal tracts in PBC, suggesting the facilitation of the recruitment of lymphocytes around the bile ducts of PBC. VCAM-1, a member of the immunoglobulin superfamily, has not hitherto been reported on bile ducts.     

Hepatocellular prolapse of hepatic portal tracts and subendothelial space of central veins in idiopathic portal hypertension

We report a case of idiopathic portal hypertension (IPH) with unusual liver pathology. The liver showed changes similar to these previously reported in IPH and, in addition, we observed the unusual features of prolapse of hepatocytes into portal tracts and also into the subendothelial space of hepatic veins. Hepatocyte prolapse into hepatic veins has previously been reported only in patients with a history of androgenic steroid therapy and immunosuppressive therapy. We speculate that, in our case, prolapse of hepatocytes could be related to the abnormal intrahepatic blood flow or to intrahepatic vasculopathy.     

HLA-DR expression in human fetal thymocytes.

We analyzed the expression of MHC class I (W6/32) and class II (HLA-DR) antigens on human fetal and postnatal thymocytes by fluorescence-activated cell sorting. Less than 5% of prenatal thymocytes expressed HLA-DR before week 12 of gestation. However, the number of HLA-DR-positive cells significantly increased during the late second and third trimester of gestation, when greater than 50% of prenatal thymocytes expressed HLA-DR. Such high-level expressions of HLA-DR in fetal thymocytes were also demonstrated by Northern-blot analysis and immunohistochemistry. After birth, the percentage of HLA-DR-positive cells in thymocytes decreased gradually. A high-level expression of class I antigen was also observed in thymocytes from the early stages of gestation, but, in contrast to MHC class II, a majority of postnatal thymocytes maintained high levels of class I antigen after birth.     

PATHOGENESIS OF PORTAL SCLEROSIS IN THE LIVER WITH IDIOPATHIC PORTAL HYPERTENSION

The pathomorphological changes of intrahepatic portal veins were studied in 19 autopsy cases of idiopathic portal hypertension (IPH), and the pathogenesis of portal sclerosis was discussed by the observations on the human and experimental materials. The degree and morphological appearance of intimal lesions vary from vessel to vessel. Fibrocellular proliferation of subendothelial tissue and incorporation of organized mural thrombi were suggested as the cause of intimal thickening in the portal veins. Animal experiment showed that injury of portal vein wall was followed by intimal hyperplasia and/ or incorporation of mural thrombi, and resulted in portal sclerosis similar to that of IPH liver. The cause of portal phlebosclerosis in IPH can not be explained by passive congestion alone. There might be a certain possibility of direct injurious effect in the vessel wall in the pathogenesis of portal lesions of IPH. The following pathogensis of portal sclerosis in IPH is postulated: phlebosclerotic changes of the portal veins are initiated by injury to the vessel wall due to unknown cause (s) and accelerated by secondary thrombosis and/ or mechanical injury due to increased portal pressure.TA PATHOL. JPN. 35: 299–314, 1985.     

HLA-DR antigen expression and lymphocyte subsets in transitional cell carcinoma of the urinary bladder. An immunohistological study on frozen sections

Lymphocyte subpopulations (B cells, CD4, CD8), interleukin-20 receptors (IL-2), monocytes/macrophages (Leu M₅), and HLA-DR antigen expression were studied immunohistochemically on frozen sections from 38 bladder cancer specimens. T cells predominated over B cells in all tumours. CD4-positive lymphocytes predominated over CD8 in the stroma (CD4/CD8: 1·35/1), while in epithelial tumour cells CD8 was the prominent subpopulation (CD8/CD4: 1·75/1). Aberrant HLA-DR expression was found in 21·05 per cent of bladder tumours. A strong correlation between CD4 and CD8 population densities and macrophages with the other subpopulations was noticed. In HLA-DR-positive tumours, there was no correlation of the percentage of positive cells with CD4- and CD8-positive lymphocyte populations. Various parameters including IL-2 receptors, B cells, CD8- and CD4-positive cells, and macrophages did not differ significantly between the groups of tumours expressing and not expressing HLA-DR antigen. There were no statistically significant differences in the population densities of B cells, CD8- or CD4-positive cells, IL-2 receptor, monocytes/macrophages, and HLA-DR antigen expression among various clinicopathological parameters, including growth pattern, histological grade and clinical stage or patient's age and sex. These findings suggest that in transitional cell carcinoma of the urinary bladder, HLA-DR antigen expression is independent of lymphocyte subpopulations. It is therefore possible that HLA-DR expression by tumour cells reflect the existence of separate HLA-DR-positive or HLA-DR-negative tumour clones.     

Portal vein or hepatic vein? A curious aberrant vasculature in the liver with idiopathic portal hypertension

The existence of aberrant vasculatures has been described as one of the characteristic findings in the liver with idiopathic portal hypertension (IPH). In this paper, the morphological features and the genesis of aberrant vasculatures were studied on the basis of autopsy and biopsy materials of IPH and animal experiments. Aberrant vasculatures in IPH livers are characterized as thin-walled vessels located mainly adjacent to the portal tracts and at times in the hepatic lobules. Although some of them are morphologically very similar to hepatic vein branches, they are portal in nature. These aberrant vessels develop in order to compensate for portal circulatory insufficiency due to obliteration of portal vein branches, and play an important role in maintaining an adequate blood supply to the parenchyma. It is predicted that decrease of these intrahepatic collateral vessels is responsible for or related to parenchymal atrophy and deterioration of liver function in the advanced stage of this disease. We regard these vasculatures as characteristic of the intrahepatic portal venous obstruction, particularly with portal hypertension accompanied by increased portal blood flow.     

Immunology of atherosclerosis: cellular composition and major histocompatibility complex class II antigen expression in aortic intima, fatty streaks, and atherosclerotic plaques in young and aged human specimens

There is evidence that fatty streaks in arteries can transform into atherosclerotic plaques. Mononuclear cells, including both monocytes and lymphocytes, are among the first cells participating in the development of atherosclerosis of experimental animals. To investigate the roles of different cell types in human atherosclerosis, we enumerated and compared the cellular compositions of normal intima, the transition zone (the area between the normal intima and the core of fatty streaks), fatty streaks, and plaques in young (age 16-30 years) and aged (over 60 years) human specimens using double-staining immunofluorescence with a series of monoclonal and polyclonal antibodies. T lymphocytes, both T helper/inducer (70% of T cells) and T suppressor/cytotoxic (30%) phenotypes, were found in every stage of atherosclerosis, constituting 30 to 40% of total cells in fatty streaks and transition zones of young subjects, and occasionally even in normal intima. Seventy percent of these T cells were HLA-DR positive, which indicated that most of them were activated. Macrophages were most frequent in fatty streaks and around the necrotic core of plaques. Smooth muscle cells, increasing from 5 to 30% with lesion progression, were HLA-DR positive where activated T helper cells occurred in the vicinity. The intracellular presence of the invariant gamma chain confirmed that HLA-DR was actually synthesized by these smooth muscle cells. Endothelial cells were HLA-DR positive above those regions of the lesions where HLA-DR-positive cells had accumulated, but not in normal intima, again suggesting induction of HLA-DR expression by T-cell-derived gamma-interferon. Furthermore, most HLA-DR-positive cells were also identified as HLA-DP and HLA-DQ positive. This aberrant major histocompatibility complex class II antigen expression in smooth muscle and endothelial cells may participate in the perpetuation of the atherogenetic autoimmune reaction.     

A survey of liver pathology in needle biopsies from HBsAg and anti-HBe positive individuals

AIMS: To use laboratory data and liver biopsies, prospectively obtained from hepatitis B surface antigen (HBsAg) and anti hepatitis B e antigen (anti-HBe) positive patients, for the assessment of: (1) the relation between biopsy length/number of portal tracts and sampling error; (2) the relation between the severity of piecemeal necrosis and the new grading terminology (minimal, mild, moderate, and severe chronic hepatitis); and (3) liver pathology, which has not been studied in patients with this specific serological profile. METHODS: The study group (n = 174) included 104 patients with normal aminotransferase concentrations and no cases with clinically apparent cirrhosis. The specimen length and number of portal tracts were measured at light microscopy examination. Sampling error analysis was related to the discrepancies between aminotransferase concentrations versus histological grade. Detailed histological scorings were undertaken by the reference pathologist and compared with laboratory and hepatitis B virus (HBV) DNA precore sequence data. RESULTS: Sampling error seemed to be a constant feature, even for biopsies > or = 20 mm, but increased dramatically in biopsies < 5 mm long and/or containing less than four portal tracts. Between 25% and 30% of biopsies, graded as "mild" or "moderate" activity showed features of moderate and severe piecemeal necrosis, respectively. Ten per cent of the patients with normal aminotransferase values had stage III-IV hepatic fibrosis, and 20% had piecemeal necrosis. Only cytoplasmic, not nuclear, core antigen expression was a strong predictor of high hepatitis B viraemia. There was no association between precore stop codon mutations, grade/stage of liver disease, and hepatitis B core antigen (HBcAg) expression. CONCLUSIONS: The specimen available for light microscopical examination should be > 5 mm long and should contain more than four portal tracts. In addition, the new grading terminology might give the clinician an inappropriately mild impression of the severity of piecemeal necrosis. Furthermore, even in the presence of normal aminotransferase concentrations, considerable liver pathology can be found in 10-20% of HBsAg and anti-HBe positive individuals; such pathology is not associated with the occurrence of precore stop codon mutations.     

HLA-DR expression is a significant prognostic factor in laryngeal cancer. A morphometric study

HLA-DR antigen expression in tumour cells was investigated in 68 laryngeal carcinomas. The tissue sections were studied by a morphometric method using a computer image analysis system. Although the highest number of HLA-DR-positive cells was observed in the groups with the lowest clinical stage, these differences did not reach statistical significance. Analysis of survival showed a significantly different survival time of patients classified as HLA-DR positive (10% and more HLA-DR+tumour cells) compared to those classified as HLA-DR negative. There were no significant differences in survival times between patients with glottic and extraglottic cancers, or between patients with various grades of histological malignancy.     

Non-co-ordinate expression of HLA-DR antigens and invariant chain

The expression of HLA-DR and MHC class II antigen-associated invariant chain (Ii) was studied in normal colorectal mucosa, adenomas and carcinomas using monoclonal antibodies and a sensitive immunoperoxidase technique on frozen sections. In six of 15 specimens of normal mucosa, epithelial cells expressed Ii, but were unreactive for HLA-DR antigens. In 15/20 adenomas and 51/70 carcinomas, Ii-positive tumour cells clearly outnumbered HLA-DR-positive tumour cells. Expression of Ii in non-neoplastic epithelium adjacent to carcinoma was much stronger than expression of HLA-DR. The results indicate that in certain tissues expression of these two antigens is not closely associated.     

The expression of histocompatibility antigen HLA-DR in cervical squamous epithelium infected with human papilloma virus

Uterine cervices with histologic changes suggestive of human papilloma virus (HPV) infection were examined for the presence of papilloma virus capsid antigens and the Class II histocompatibility antigen HLA-DR. The purpose of this study was to determine whether papilloma virus infection could induce HLA-DR expression by squamous cells. This expression would allow squamous epithelium to function as antigen-presenting cells and perhaps initiate the immune response. In 20 cases in which HPV capsid antigens were identified, no HLA-DR expression was noted. HLA-DR expression was noted on Langerhans cells within the squamous epithelium and on mononuclear cells in the underlying lamina propria. HLA-DR-positive cells were also noted between columnar epithelial cells of the endocervix. We conclude that HPV infection does not induce HLA-DR expression in the cells it infects.     

Epithelioid cell granulomas in chronic hepatitis C: immunohistochemical character and histological marker of favourable response to interferon-α therapy

Aims : The clinicopathological significance of intrahepatic epithelioid cell granulomas in chronic hepatitis C was determined.  

Method and results

Granulomatous lesions were surveyed in 542 liver biopsy specimens and were immunohistochemically examined. We also tested whether this lesion is a marker of response to interferon-α therapy in chronic hepatitis C. Granulomatous lesions in hepatic lobules and/or portal tracts were identified in 11/542 (2%) cases with chronic hepatitis C. Granulomas were positive for HLA-DR and β2-microglobulin, and were surrounded by T-cells. Among them, three chronic hepatitis C cases showed portal granulomas with mild biliary epithelial damage. Bile ducts showing mild epithelial damage in chronic hepatitis C were positive for β2-microglobulin, but negative for HLA-DR, while both antigens were frequently expressed in damaged bile ducts in primary biliary cirrhosis (PBC). All five cases of chronic hepatitis C with granulomas who had interferon-α therapy and were followed up and were found to have responded well.  

Conclusion

Granulomas showed the same immunohistochemical phenotypes, though the expression of HLA-DR on bile ducts in PBC but not in chronic hepatitis C suggests a different pathogenesis. Granulomas may predict a favourable response to interferon-α therapy in chronic hepatitis C.