Lobular Activity Research Articles

The concentration of total sialic acid in chronic hepatitis B and C.

The synthesis and glycosylation of glycoproteins and glycolipids take place in the liver. Thus, liver diseases may affect serum concentrations of some carbohydrate derivatives, especially the concentration of sialic acid which is attached to the end of oligosaccharide chains. The aim of this study was to measure and compare the serum concentration of total sialic acid in chronic hepatitis B and C. The hypothesis is that both viruses responsible for the development of inflammation work differently at the cellular level. Serum samples were obtained from 90 patients suffering from liver diseases: 50 from chronic hepatitis B and 40 from chronic hepatitis C at the time of diagnosis. The total sialic acid concentration in the serum was measured according to the enzymatic method using a colorimetric procedure. The mean total sialic acid concentration in patients with chronic hepatitis B was significantly lower than the mean concentration in the healthy group, while in patients with chronic hepatitis C, it was significantly higher than that in healthy people and in patients suffering from chronic hepatitis B. There were no significant differences in total sialic acid concentrations in patients with chronic hepatitis B and C according to the grade of portal/periportal activity, the grade of lobular activity and the stage of fibrosis. We conclude that chronic viral hepatitis affects the total serum concentration of sialic acid. Moreover, the concentration of total sialic acid may be a useful marker to differentiate between chronic hepatitis B and C but is not useful for evaluation of the progression of these diseases.

Hallmarks of liver lesions in pigs naturally infected by hepatitis E virus genotype 3

ABSTRACT: Histopathological evaluation of liver from 33 pigs slaughtered for human consumption in Amazon region, previously tested by serology and molecular techniques for hepatitis E virus infection (HEV), was analysed in three groups: Group 1, negative for both HEV-RNA and anti-HEV IgG (n=10); Group 2, positive for HEV-RNA (n=13); Group 3, positive for anti-HEV IgG (n=10). Group 2 showed a significant difference among the groups for liver lesions such as lobular activity (P=0.007), periportal interface hepatitis (P=0.004), portal inflammation (P=0.028) hepatitis with lobular, portal and periportal interface activity (P=0.001). HEV detection by immunohistochemistry was performed and 3 of 6 samples of group 2 were positive. Pigs naturally infected by HEV genotype 3 present microscopic necroinflammatory liver lesions similar to HEV in humans. Liver histopathology showed be important in the diagnosis of active asymptomatic HEV infection in pigs slaughtered for human consumption because hepatic liver lesions may present distinct profiles according to molecular and serological diagnosis and in this sense, histopathology and immunohistochemistry may be an important complementary diagnostic tool.

HIV and Autoimmune Hepatitis: A Case Series and Literature Review

Liver disease is the leading cause of non-AIDS related morbidity and mortality in human immunodeficiency virus (HIV) infected patients. There are many causes of liver disease in these patients, most commonly co-infection with viral hepatitis or alcoholic liver disease. A far less commonly described entity is autoimmune hepatitis (AIH) in HIV patients. The relationship between HIV and autoimmune diseases is well-described in a few conditions such as systemic lupus erythematosus and diffuse infiltrative lymphocytosis syndrome; however, patients with HIV who subsequently develop autoimmune hepatitis (AIH) has rarely been described in the existing literature. Managing these coexisting morbidities requires careful monitoring, as treating AIH requires the further immunosuppression of an HIV-infected individual. Herein, we present two patients who were diagnosed with and treated for AIH while receiving concurrent highly active anti-retroviral therapy. This case series provides treatment outcome data for a situation that has heretofore been rarely reported.Figure: A. Liver biopsy from case patient #1. On left, fibrous septum containing a dense lymphoplasmacytic inflammatory infiltrate with prominent interface and lobular activity. 100x; hematoxylin and eosin. On right, dense plasma cell-rich infiltrate and an area of hepatocyte drop-out at the interface. 400x; hematoxylin and eosin. Biopsy is compatible with autoimmune hepatitis. B. Liver biopsy from case patient #2. On left, dense portal lymphoplasmacytic inflammation with prominent interface and lobular activity. 100x; hematoxylin and eosin. On right, lobular lymphoplasmacytic inflammation with hepatocyte rosette formation. 400x; hematoxylin and eosin. Biopsy is typical for autoimmune hepatitis.Figure: A timeline that plots patient liver function tests in relationship to initiation of autoimmune hepatitis (AIH) targeted therapy. Both patients were started on prednisone. Patient CD4 counts (cells/mL) are also shown.Table: Table. A review of the existing literature on patients with HIV who developed AIH. CD4 count is in cells/microliter and viral load is in copies/microliter

The transferrin isoforms in chronic hepatitis

BackgroundThe aim of this study was to evaluate the effect of chronic hepatitis on the serum profile of transferrin isoforms. MethodsTested group consist of 160 patients with chronic hepatitis. The samples were analyzed by capillary electrophoresis on MINICAP electrophoretic system (Sebia, France). ResultsIn patients with chronic hepatitis tetrasialotransferrin level was increased (P=0.002) and pentasialotransferrin decreased (P=0.009). Moreover, statistical analysis revealed that trisialotransferrin level was different according to the grade of portal/periportal activity (P=0.009), the grade of lobular activity (P=0.004) and the stage of fibrosis (P=0.022). There were no differences in tetrasialotransferrin and pentasialotransferrin according to the advancement of hepatitis activity and the stage of fibrosis (P>0.05 for all comparisons). ConclusionsWe conclude that chronic hepatitis affect the serum profile of transferrin isoforms, but only trisialotransferrin level could be useful in determining progression of chronic hepatitis and the stage of fibrosis.

Acute presentation of autoimmune hepatitis: a multicentre study with detailed histological evaluation in a large cohort of patients

AimsAlthough liver biopsy is crucial to diagnose and guide treatment decisions, a detailed histological analysis of autoimmune hepatitis (AIH) with clinically acute presentations has not yet been performed. This study...

Hepatic nucleotide binding oligomerization domain-like receptors pyrin domain-containing 3 inflammasomes are associated with the histologic severity of non-alcoholic fatty liver disease.

To examine the role of nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes in the development of non-alcoholic fatty liver disease (NAFLD). Levels of mRNAs encoding NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, procaspase-1, interleukin (IL)-1β, and IL-18 were quantified by real-time polymerase chain reaction in 91 liver samples and 37 blood samples from biopsy-proven patients with NAFLD. Adiponutrin (also called PNPLA3) polymorphisms (rs738409, C>G) were determined in 74 samples by genotyping assays. Serum IL-1β and IL-18 levels were measured by enzyme-linked immunosorbent assay and liver tissue caspase-1 expression by immunostaining. Hepatic NLRP3, procaspase-1, IL-1β, and IL-18 mRNA levels were significantly higher in NAFLD patients than in controls and were significantly associated with adiponutrin G alleles. Blood procaspase-1 mRNA was significantly higher in NAFLD patients than in healthy controls. Hepatic procaspase-1 and IL-1β mRNA levels correlated significantly with lobular inflammation, hepatocyte ballooning, and NAFLD activity score. Serum IL-18 levels were significantly higher in NAFLD patients than in controls, while IL-1β levels were non-significantly higher. Serum IL-1β and IL-18 concentrations correlated significantly with steatosis, NAFLD activity score, and transaminase levels. Serum IL-1β levels were significantly associated with adiponutrin G alleles. Scattered caspase-1-positive cells were present in portal tracts and inflammatory foci and around ballooning hepatocytes. Immunofluorescence staining showed that caspase-1 colocalized with the macrophage marker CD68. The NLRP3 inflammasomes are primed in the liver, influenced by adiponutrin genotypes, and activated in Kupffer cells and/or macrophages in NAFLD, leading to histological progression through IL-1β and IL-18 production.

Development of the index of idiopathic lobular panniculitis activity on the basis of the clinical and laboratory characteristics of a series of clinical observations (the authors' own data)

Idiopathic lobular panniculitis (ILP) is regarded as a clinical and pathological variant of lobular panniculitis with typical clinical symptoms. To assess the nature of the disease and to solve therapy problems, there is a need to clarify and grade disease activity, which is the basis for this investigation. Objective: to create a rating scale for the activity of the inflammatory process in ILP on the basis of clinical and laboratory parameters. Patients and methods. 67 patients (9 men and 58 women) with a verified diagno sis of ILP, who have been followed up at the V.A. Nasonova Research Institute of Rheumatology in 2007 to 2017, were examined. The patients' age was 20 to 76 years; the mean disease duration was 78.91 [48; 540] months. Physical examination, chest computed tomography, immunological and TB tests, and pathomorphological examination of the skin biopsy of the node were carried out; the serum concentrations of α1-antitrypsin, amylase, lipase, ferritin, creatine phosphokinase, and body mass index were determined. Results. Analysis of clinical manifestations could identify four ILP forms: nodular (n=30), plague (n=10), infiltrative (n=15), and mesenteric (n=12) ones that had clinical and laboratory features. Along with lesions of the skin and subcutaneous adipose tissue, 51 (76.11%) patients complained of weakness (p<0.001); 48 (71.64%) had rising body temperatures to febrile values (p=0.0001). 31 (46.26%) patients were noted to have articular syndrome that was characterized by polyarthralgia in 90.32% of cases (p<0.0001) and by knee and/or ankle arthritis in only 3 (9.67%) patients. The examinees showed a significant increase in erythrocyte sedimentation rate (p=0.01) and C-reactive protein levels (p<0.0001). Based on these findings, the authors developed an ILP activity index (AI) that included the characteristics of the status of 7 organ systems. The maximum score for individual systems is 1 to 3 in relation to the number of estimated parameters. Conclusion. The proposed ILP AI is of practical value. There is a need for further investigations and maybe a search for new parameters of ILP activity.

The Performance of Serum Biomarkers for Predicting Fibrosis in Patients with Chronic Viral Hepatitis.

The invasiveness of a liver biopsy and its inconsistent results have prompted efforts to develop noninvasive tools to evaluate the severity of chronic hepatitis. This study was intended to assess the performance of serum biomarkers for predicting liver fibrosis in patients with chronic viral hepatitis. A total of 302 patients with chronic hepatitis B or C, who had undergone liver biopsy, were retrospectively enrolled. We investigated the diagnostic accuracy of several clinical factors for predicting advanced fibrosis (F≥3). The study population included 227 patients with chronic hepatitis B, 73 patients with chronic hepatitis C, and 2 patients with co-infection (hepatitis B and C). Histological cirrhosis was identified in 16.2% of the study population. The grade of porto-periportal activity was more correlated with the stage of chronic hepatitis compared with that of lobular activity (r=0.640 vs. r=0.171). Fibrosis stage was correlated with platelet count (r=-0.520), aspartate aminotransferase to platelet ratio index (APRI) (r=0.390), prothrombin time (r=0.376), and albumin (r=-0.357). For the diagnosis of advanced fibrosis, platelet count and APRI were the most predictive variables (AUROC=0.752, and 0.713, respectively). In a hepatitis B endemic region, platelet count and APRI could be considered as reliable non-invasive markers for predicting fibrosis of chronic viral hepatitis. However, it is necessary to validate the diagnostic accuracy of these markers in another population.

Characteristics of non-obese non-alcoholic fatty liver disease: Effect of genetic and environmental factors.

There are a considerable number of patients with non-obese non-alcoholic fatty liver disease (NAFLD). However, the clinical characteristics of non-obese NAFLD is not fully understood. We investigated genetic and other clinical parameters in non-obese and obese NAFLD. The single nucleotide polymorphism rs738409 in the patatin-like phospholipase 3 gene (PNPLA3) was genotyped by the Invader assay in 540 NAFLD patients (134 non-obese and 406 obese) and 1012 control subjects (782 non-obese and 230 obese). All NAFLD patients underwent liver biopsy. Odds ratios were calculated by multiple logistic regression analysis using age, sex, body mass index (BMI), type 2 diabetes mellitus (T2DM) and rs738409 genotype as explanatory variables. Non-obese NAFLD subjects had a higher rs738409 GG genotype than obese NAFLD. Multiple logistic regression analysis indicated that the odds ratios of T2DM and rs738409 GG genotype for NAFLD were higher in non-obese than in obese groups. In non-obese NAFLD, rs738409 GG genotype was associated with lobular inflammation, hepatocyte ballooning and NAFLD activity score. In obese NAFLD, BMI and T2DM but not rs738409 GG genotype were associated with severity of histology. We demonstrated that the risk factors for the development and progression of NAFLD were different between non-obese and obese patients and that PNPLA3 rs738409 was strongly associated with the development and progression of non-obese NAFLD.

Outcomes after curative hepatectomy in patients with non-B non-C hepatocellular carcinoma and hepatitis B virus hepatocellular carcinoma from non-cirrhotic liver.

There is controversy regarding liver function of non-B, non-C hepatocellular carcinoma (NBNC-HCC) patients, the biological behavior of their tumors, and the outcome after surgical treatment. The aims of the present study were to compare clinicopathologic data and long-term clinical outcomes between NBNC-HCC patients and hepatitis B virus HCC (HBV-HCC) patients from non-cirrhotic liver after curative hepatectomy. Data for HBV-HCC patients (n = 360) and NBNC-HCC patients (n = 103) were retrospectively reviewed. The median age of patients in the NBNC group was significantly higher than that of the HBV group (63 years vs. 53 years, P < 0.001). Tumor size in the NBNC group was greater than that in the HBV group (5.1 cm vs. 3.8 cm, P < 0.001). Regarding liver histology, the grade of lobular activity, periportal activity, and fibrosis in the HBV group was higher than in the NBNC group (P < 0.001, P < 0.001, and P < 0.001, respectively). There were no statistically significant differences in disease-free survival and overall survival between the two groups (P = 0.257 and P = 0.579, respectively). Multivariate analysis showed that increased tumor size, microvascular invasion, and intrahepatic metastasis were associated with tumor recurrence after curative liver resection. For patients with non-cirrhotic liver, clinical outcomes for NBNC-HCC were comparable to those for HBV-HCC after curative hepatectomy.

The risk factors of early recurrence after hepatectomy in hepatocellular carcinoma.

PurposeEarly recurrence after hepatectomy is a well-known poor prognostic factor in patients with hepatocellular carcinoma. This study was undertaken to identify the risk factors of early recurrence in patients with hepatocellular carcinoma after hepatectomy.MethodsOne hundred and sixty-seven patients that underwent hepatectomy for hepatocellular carcinoma from January 2005 to December 2010 were enrolled. The numbers of patients with or without early recurrence group were 40 and 127, respectively. Clinico-pathologic factors were retrospectively analyzed.ResultsPotential risk factors were classified as host, tumor, or surgical factors. Of the host factors examined, lobular hepatitis activity was found to be a significant risk factor of early recurrence, and of the tumor factors, infiltrative type of gross appearance, level of preoperative AFP and worst Edmondson-Steiner grade were significant.ConclusionThe present study shows that an infiltrative gross appearance, a high preoperative AFP level, high lobular hepatitis activity, and a poor Edmondson-Steiner grade are independent risk factors of early recurrence. Accordingly, patients with these risk factors should be followed closely after hepatectomy.

A comparative evaluation of scoring systems for assessing necro-inflammatory activity and fibrosis in liver biopsies of patients with chronic viral hepatitis.

To compare the five scoring systems in assessing grading and staging of liver biopsies from patients with chronic viral hepatitis and their problems and pitfalls. Liver biopsies from 25 patients with chronic viral hepatitis were studied. Sections were stained with Haematoxylin and Eosin, Reticulin and Masson's Trichrome stains. Van Gieson, Perl's and Shikata's Orcein stains were used as and when required. Coded histological sections were scored independently by three histopathologists using the Knodell Histology Activity Index (HAI), the Scheuer scoring system, Ishak's system, Metavir system and Ishak modified HAI. There were 15 males and 10 females. Their mean age was 51.24 years. On histological examination, hepatocytes showed degenerative changes with varying grades of necrosis (spotty and confluent). Widening of portal tracts with varying severity of mononuclear inflammatory infiltrate and interface hepatitis was observed. Fibrosis appeared as periportal, portal-portal and portal-central septa. A significant agreement was found by kappa statistics for both grading (p< 0.001) as well as staging (p < 0.001) among all the five scoring systems. Lobular activity was the only parameter that showed some discrepancy. No significant intra observer difference was observed. It is concluded that all the scoring systems are equally good for grading and staging in the hands of an experienced hepatopathologists.

Hepatitis e infection in a renal transplant recipient.

An asymptomatic 35-year-old renal transplant recipient was noted to have deranged liver function tests. Liver biopsy revealed a portal inflammatory process with mild lobular activity and portal fibrous expansion, consistent with a virally mediated process. An extensive viral screen confirmed infection with Hepatitis E virus genotype 3 (HEV-3). There is increased awareness about locally acquired Hepatitis E virus (HEV) infection in the transplant population in the UK. The important implications of this infection are becoming more apparent as progression to liver cirrhosis can occur. However, the incidence, natural history, and treatment of HEV infection in the transplant population are not well established. This report illustrates a case of delayed spontaneous clearance of the HEV infection.

Histological features of chronic hepatitis C in haemodialysis patients.

HCV infection in haemodialysis (HD) patients is still a matter of investigation. The aim of this study was to determine the histology of chronic hepatitis C (CHC) in HCV-infected HD patients within the context of a comparative analysis including non-uraemic patients with CHC. The relative importance of virological, demographic and clinical parameters on disease manifestation was examined. Sixty-one consecutive liver biopsies from HD patients and 326 from non-uraemic patients with chronic HCV infection were comparatively evaluated. Haemodialysis patients with CHC were older than control subjects (P = 0.031), showing a similar HCV genotype distribution (P = 0.328) and lower viral load (P = 0.001). CHC in HD patients was significantly milder according to stage (P = 0.033), grade and its parameters (periportal activity, portal inflammation and lobular activity) (P < 0.001). The frequency of lymphoid aggregates (10.2% vs. 50%, P < 0.001), bile duct lesions (1.7% vs. 22.1%, P < 0.001) and extent of steatosis (P = 0.022) in HD group was significantly reduced. Multivariate analysis showed that non-uraemic patients had 2.3 times higher risk of developing steatosis independently of genotype distribution and age. In HD group, genotype 3, longer HD duration and age at infection were significantly associated with steatosis, while older age at infection correlated with advanced fibrosis. Chronic hepatitis C in HD patients is usually very mild, losing its diagnostic histological features while patient's age and age at infection retain their prognostic significance. The weak inflammatory response, probably because of immunocompromised status and low viral load, may present a beneficial factor in the natural course of the disease.

Acute Hepatitis With Periportal Confluent Necrosis Associated With Human Herpesvirus 6 Infection in Liver Transplant Patients

To correlate human herpesvirus 6 (HHV-6) viral load with pathologic features in graft acute hepatitis of unknown origin. Liver frozen samples from 26 patients with graft hepatitis of unknown origin were available for HHV-6 DNA quantification. In 10 (38.5%) of 26 liver samples, HHV-6 DNA was detectable, with a median viral load of 3.84 log10 copies/10⁶ cells. Confluent periportal necrosis was observed in 4 of 10 patients and associated with high viral load. These 4 patients responded to antiviral therapy. Mild unspecific hepatitis was observed in 4 patients with low intragraft viral load and in 2 patients with high viral load in a context of deep immunosuppression. Patients with HHV-6-negative graft hepatitis disclosed lobular necrotico-inflammatory activity without periportal necrosis. Our study provides data supporting the pathogenic role of HHV-6 for liver allografts. The presence of confluent periportal necrosis could be a clue for prompt diagnosis of HHV-6-induced graft hepatitis.

Heterogeneity of fibrosis patterns in non‐alcoholic fatty liver disease supports the presence of multiple fibrogenic pathways

Adult non-alcoholic fatty liver disease (NAFLD) involves lobular necroinflammatory activity and fibrosis is typically centrilobular, whereas paediatric NAFLD has predominantly portal fibrosis. The reasons for these differences are unclear. We aimed to determine (a) how centrilobular and portal fibrosis in children relate to histological parameters; and (b) whether atypical fibrosis patterns exist in adults that are unexplained by current fibrogenesis models. Histological features of paediatric (n=38) and adult (n=56) NAFLD were assessed using conventional scoring systems. Keratin-7 immunostaining was used to assess hepatic progenitor cell numbers and the ductular reaction. Centrilobular and portal components of fibrosis were independently scored and fibrosis patterns were classified according to accepted types. Post-treatment (rosiglitazone/gastric banding) biopsies were also examined in adults. Twenty-six children (68.4%) had portal-predominant fibrosis, although the typical "adult" pattern was seen in 11 (28.9%). Portal fibrosis was associated with a ductular reaction (P=0.021) and hepatic progenitor cell expansion (P<0.001), whereas centrilobular fibrosis was associated with lobular inflammation (P=0.026) and ballooning (P=0.001). Before intervention, six adults (10.7%) had atypical fibrosis including 3 (5.4%) with a previously unrecognized pattern of very fine, non-zonal sinusoidal fibrosis. Despite improvements in steatosis and inflammation, more patients developed this unusual pattern after intervention with most having had surgery (9 of 10 adults; P<0.001). Differing associations with portal and centrilobular fibrosis in children and atypical fibrosis patterns in adults suggest that multiple fibrogenic pathways exist in NAFLD. This has implications for therapy and understanding pathogenesis.

Histopathological Causes of Late Liver Allograft Dysfunction: Analysis at a Single Institution

BackgroundWe summarize our experience in the pathological diagnosis of late complications of liver transplantation (LT) to better understand the causes of late allograft dysfunction in a population mostly composed of patients with hepatitis B virus (HBV) infection.MethodsWe reviewed 361 post-transplant liver biopsies from 174 patients who underwent LT and first presented with liver function abnormalities 3 months post-procedure. The underlying diseases included HBV-associated liver disease (77%), toxic or alcoholic liver disease (10.3%), hepatitis C virus (HCV)-associated liver disease (8.6%), primary biliary cirrhosis (1.2%), primary sclerosing cholangitis (1.2%), and metabolic disease (1.7%).ResultsThe three most common late complications were acute rejection (32.5%), recurrent disease (19.1%), and biliary complication (17.1%). Patients who underwent LT for HBV infection or for drug- or alcohol-related liver disease had a lower incidence of recurring disease than those who underwent transplantation for HCV infection. During post-transplantation months 3-12, acute rejection was the most common cause of allograft dysfunction and recurring disease was the leading cause for allograft dysfunction (p=0.039). The two primary causes of late allograft dysfunction have overlapping histological features, although acute rejection more frequently showed bile duct damage and vascular endothelialitis than recurring HBV infection, and recurring HBV infection had more frequent lobular activity and piecemeal necrosis.ConclusionsThe causes of late liver allograft dysfunction are closely associated with the original liver diseases and the period after LT. Careful attention is required for differential diagnosis between acute rejection and recurrent HBV.

Impaired renal function in morbid obese patients with nonalcoholic fatty liver disease

Obesity is a common risk factor for nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). NAFLD and CKD have been associated in many epidemiological studies. We hypothesize that more severe liver disease, namely nonalcoholic steatohepatitis (NASH), is related with further renal impairment. We aimed to evaluate if changes in renal function were present in morbid obese patients with NAFLD. Prospective and consecutive recruitment of morbid obese patients with biopsy proven NAFLD obtained during bariatric surgery. Renal function was evaluated with CKD-Epidemiology Collaboration estimated glomerular filtration rate (eGFR). Plasmatic adiponectin, leptin and active ghrelin concentrations were determined. One hundred and forty-eight patients were included of whom 25% had NASH and 75% simple steatosis. NASH patients were older, with higher body mass index and had more frequently metabolic syndrome and lower eGFR (97 ± 22 vs 106 ± 16 ml/min/1.73(2), P = 0.035). NASH conferred an odds ratio (OR) 3.0 (1.3-7.0) for eGFR < 90 and OR 9.7 (1.0-96.4) for eGFR < 60 ml/min/1.73(2). eGFR < 90 ml/min/1.73(2) associated with aspartate aminotransferase [OR 2.9 (1.1-7.6)] and γ-glutamyl transpeptidase elevation [OR 3.0 (1.3-7.2)], NASH [OR 3.0 (1.3-7.0)], any lobular inflammatory activity [OR 3.0 (1.3-7.0)] and severe fibrosis [OR 3.4 (1.1-10.8)]. Neither eGFR nor liver histology was associated with adipokines levels. In morbid obese patients, NASH, particularly lobular inflammation and advanced fibrosis, associates with mild decreases in eGFR, suggesting a common inflammatory link between liver and renal lesion.

Histological characteristics predisposing to development of hepatocellular carcinoma in patients with chronic hepatitis B

AimsLongstanding liver inflammation leads to hepatic regeneration and fibrosis, which subsequently progresses to cirrhosis in some patients with chronic hepatitis B virus (HBV) infection. It remains unclear, however, if the...

Hepatic Expression of the Proliferative Marker Ki-67 and cell cycle p53 Protein in chronic hepatitis C (A histopathological and immunohistochemical study)

Aim and background: To evaluate hepatic expression of the nuclear proliferative marker Ki-67 and the cell cycle marker p53 oncoprotein in chronic hepatitis C in relation to the advanced stages of liver fibrosis in HCV positive Egyptian patients. Material & Methods: Paraffin-embedded liver biopsy specimens were studied from 21 untreated patients with chronic HCV infection. All patients were HCV antibody positive, as determined by a commercially available enzyme-linked immunosorbent assay kit. Patients having other etiologies for chronic liver disease including HBV infection were not included in this study. Liver biopsies were obtained percutaneous. All biopsies were fixed in formalin, embedded in paraffin, and sectioned by microtome with a thickness of 5 µm. Routine specimen processing involved staining slides with hematoxylin and eosin (5 levels), Masson's trichrome stain (5 levels), for a total of 10 levels per specimen All levels were screened. All specimens were examined by two pathologists, and classified by consensus for all abnormal histological findings. The histological activity index (or histological grade) was determined using Ishak grading scheme22 expressed as a semiquantitative score for portal inflammation (0-4), lobular activity sporadic lytic foci (0-4) and parenchymal confluent necrosis (0-6), and piecemeal necrosis(0-4). The extent of fibrosis (or histological stage) was determined using Ishak score (0-6). Steatosis was scored according to Keliner et al 2005, from grade 0 to 3; where S0 = no steatosis or less than 5% (low or medium power evaluation) of parenchymal involvement by fatty changes, S1 (mild) = 5%-33%, S2 (moderate) = >33%-66% and S3 (severe) > 66% of the hepatocytes are involved by fatty changes. Expression of p53 and Ki67 were determined by immunohistochemistry, using avidin-biotin-peroxidase. Results: Liver histology: The studied group (n = 21) involved 16 males and 5 females (male to female ratio 3.3:1). The histopathological findings of HCV infection, including portal lymphoid infiltration, periportal piecemeal necrosis, lymphocyte infiltration of the lobules, hepatocellular necrosis, steatosis and fibrosis, were studies. The age ranged from 31 to 59 years old with mean of 44.86 ± 8.74, males 76.2%, females 23.8% .P53 expression was positive in 52.4% and negative in 47.6%. cytoplasmic localization dominated over nuclear expression. Ki 67 was negative in 81% of cases and positive in19% of cases, all cases in stage 6 were positive for p53 while there were no difference in the other stages of fibrosis, and this relation was statistically significant. There was no relation between the grade of necro-inflammation and the expression of p53, and this result was statistically non significant.There was a relation between the percent of steatosis and the expression of p53 as percent of positivity increases with the increase of the percent of steatosis, and this result was statistically significant using independent sample t test and regression test.All negative cases for P53 have negative Ki67 but this rule is not applied on positive cases for P53, and this relation was not statistically significant There was no relation between the grade of necro-inflammation and the expression of Ki67, and this result was statistically non significant. Conclusion: Hepatic expression of the nuclear proliferative marker Ki-67 and the cell cycle marker p53 oncoprotein in chronic hepatitis C in relation to advanced stages of liver fibrosis in HCV positive patients are expressed in a considerable present of cases which should be cansdidates for follow up for early detection of hepatocellular carcinoma.