Expression of cytokeratin 7 as a histological marker of cholestasis and stages of primary biliary cirrhosis.

UNLABELLED: The aim of this study was to estimate cytokeratin 7 (CK-7) expression in biopsy specimens of patients with different stages of primary biliary cirrhosis and clinicopathological patterns (cholestatic and hepatitic) and its correlation with some biochemical and pathological parameters and to examine a diagnostic value of CK-7 expression. MATERIAL AND METHODS: A total of 82 biopsy specimens of patients with primary biliary cirrhosis were analyzed. CK-7 expression was graded by 4 grades depending on the extent into parenchymal areas and bile duct epithelium. The correlations of CK-7 expression grade with copper deposition, bile duct/portal tract ratio, bilirubin concentration, and activity of alkaline phosphatase and gamma-glutamyl transpeptidase were studied. CK-7 expression was evaluated as a marker of cholestasis (cholestatic pattern) and inflammation (hepatitic pattern). RESULTS: A positive correlation of CK-7 expression grade with copper-binding protein grade (r=0.698, P<0.0001; OR=6.199, P<0.0001), serum bilirubin level (r=0.375, P=0.001), and alkaline phosphatase activity (r=0.276, p=0.014) was found. CK-7 expression grades correlated positively with histological stages of primary biliary cirrhosis (r=0.639, P<0.000) and negatively with granulomas (r=-0.432, P<0.0001; OR=0.173, P=0.0011). CONCLUSIONS: CK-7 expression is a sensitive marker of bile duct injury, which correlated well with histological stages of primary biliary cirrhosis, copper deposits, and biochemical markers of cholestasis: serum bilirubin level and alkaline phosphatase activity. Evaluation of CK-7 expression may improve the diagnosis of this serious and progressive disease. It is recommended to evaluate copper staining together with cytokeratin 7 expression in liver biopsy specimens for more precise diagnostic evaluation of asymptomatic primary biliary cirrhosis.

Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis.

We genotyped individuals with primary biliary cirrhosis and unaffected controls for suggestive risk loci (genome-wide association P < 1 x 10(-4)) identified in a previous genome-wide association study. Combined analysis of the genome-wide association and replication datasets identified IRF5-TNPO3 (combined P = 8.66 x 10(-13)), 17q12-21 (combined P = 3.50 x 10(-13)) and MMEL1 (combined P = 3.15 x 10(-8)) as new primary biliary cirrhosis susceptibility loci. Fine-mapping studies showed that a single variant accounts for the IRF5-TNPO3 association. As these loci are implicated in other autoimmune conditions, these findings confirm genetic overlap among such diseases.

Changes in hepatitis C virus infection routes and genotype distribution in a Lithuanian cohort with chronic hepatitis C.

BACKGROUND: We evaluated the distribution of hepatitis C virus genotypes and determined their association with routes of infection according to the sex and age of the study subjects. MATERIAL/METHODS: We studied 1158 patients with chronic hepatitis C. Hepatitis C virus antibodies were detected with a microparticle enzyme immunoassay, hepatitis C virus ribonucleic acid was identified via polymerase chain reaction, and hepatitis C virus genotypes were determined with a line probe assay. An anonymous questionnaire completed by all subjects included the date of chronic hepatitis C diagnosis, the age and sex of the patient, the hepatitis C virus genotype and subtype, and possible routes of infection. RESULTS: Of the patients studied, 50.9% had more than 1 possible route of infection, 41.2% had a single route of infection, and 7.9% had an unknown route of infection. The most common hepatitis C transmission routes were intravenous drug use and tattoos in younger patients and surgery or long or multiple hospitalizations in older patients. The genotype distribution was as follows: genotype 1, 65.0% of patients; genotype 2, 26.3%; and genotype 3, 8.7%. The transmission of genotype 1 was associated primarily with surgery and that of genotype 3 was linked with intravenous drug use. CONCLUSIONS: Today, the main routes of hepatitis C virus transmission are intravenous drug use and tattoos. Some hepatitis C infections are associated with surgery or are acquired from a family member. The shift in transmission pathways predetermined the shift in hepatitis C virus genotypes from 1 to 3.

Primary biliary cirrhosis in Lithuania: diagnosis and clinical picture.

BACKGROUND: The rising detection and considerable geographical variation of primary biliary cirrhosis (PBC) in some regions demand increased awareness of the disease. The aim was to analyze the clinical, biochemical, immunological, and histological criteria of PBC patients in Lithuania and evaluate the patterns of disease presentation and histological features. MATERIAL/METHODS: One hundred thirty-one PBC patients were examined and followed in the Center of Hepatology, Gastroenterology, and Dietetics, Vilnius University Hospital. Their case records were evaluated in this retrospective record-review study. RESULTS: Most of the patients were women (94.6%) older than 50 years with late stages of PBC. Men were significantly older and had a threefold shorter duration from disease presentation to diagnosis (4.0+/-0.4 vs. 1.4+/-0.4 years). 29.8% of patients had asymptomatic disease at presentation and at diagnosis, were older than the symptomatic ones, and presented with significantly lower prevalence of jaundice, skin signs, and lower alkaline phosphatase (ALP) activity, but higher frequency of sicca syndrome. Antimitochondrial antibody (AMA) positivity was found in 91.7%, bile duct lesions in all patients, while the frequency of histological signs of cholestasis (except copper accumulation) was lower. No significant differences in these parameters in asymptomatic and symptomatic patients were found. CONCLUSIONS: Most PBC patients in Lithuania were at late histological stages, with a predominance of females older than 50 years and long duration from disease presentation to diagnosis. One third of these PBC patients initially had asymptomatic course, with some differences in clinical signs and their prevalence compared with initially symptomatic patients.

Prevalence of cryoglobulinemia in patients with chronic HCV infection.

BACKGROUND: The purpose of our research was to determine the prevalence of cryoglobulins in patients with chronic hepatitis C (CHC) at different levels of activity and stage of fibrosis and to identify their association with the extrahepatic clinical manifestations. MATERIAL/METHODS: 87 patients with CHC were investigated for the presence of cryoglobulins. Cryocrit was measured by the Weiner method. AntiHCV, HCV RNR, conventional biochemical tests and liver biopsy were also performed. RESULTS: Cryoglobulins were found in a total of 44 patients: 16 from Group I, 11 from Group II, and 17 from Group III. A low level of cryoglobulinemia (Cg) (cryocritL2%) was detected in 16 patients: 9 from Group I, 3 from Group II, and 4 from Group III. Moreover, a high Cg (cryocrit >5-10%) or very high Cg (cryocrit >10%) was found in a total of 13 patients: 1 patient from Group I, 3 from Group II, and 9 from Group III. Cryo positivity was found in 5 patients with F 1-2, in 13 with F 2-3, in 4 with F 3-4, and in 17 with F 4. CONCLUSIONS: Our findings confirmed the high prevalence of Cg in CHC patients in Lithuania, a clear association between Cg and the stage of fibrosis, the higher prevalence of Cg in cirrhotic patients, and the occurrence of several typical extrahepatic manifestations. The impact of Cg on the course of chronic hepatitis C is not clearly understood; therefore, further studies are needed to clarify this issue.