LIVER BIOPSY: IMPORTANCE OF SPECIMEN SIZE IN THE DIAGNOSIS AND STAGING OF CHRONIC VIRAL HEPATITIS

Liver biopsy is the gold standard method for the grading and staging of chronic viral hepatitis, but optimal biopsy specimen size remains controversial. The aim of this study was to evaluate the quality of liver specimen (number of portal tracts) and to evaluate the impact of the number of portal tracts in the staging of chronic hepatitis. Material and Methods: 468 liver biopsies from consecutive patients with hepatitis C virus and hepatitis B virus infection from 2009 to 2010 were evaluated. Results: The length of fragment was less than 10 mm in 43 cases (9.3%), between 10 and 14 mm in 114 (24.3%), and ≥ 15 mm in 311 (64.4%); of these, in 39 (8.3%) cases were ≥ 20 mm. The mean representation of portal tracts was 17.6 ± 2.1 (5-40); in specimens ≥ 15 mm the mean portal tract was 13.5 ± 4.7 and in cases ≤ 15 mm was 11.4 ± 5.0 (p = 0.002). Cases with less than 11 portal tracts were associated with F3, and cases with 11 or more portal tracts with F2 (p = 0.001). Conclusion: this study demonstrated the good quality of liver biopsy and a relationship between the macroscopic size of the fragment and the number of portal tracts.

Histopathological study of chronic hepatitis B: a comparative study of Ishak and METAVIR scoring systems

Ishak and METAVIR scoring systems are among the most commonly used histopathological systems to evaluate chronic hepatitis. To assess the level of agreement between these two scoring systems in patients with chronic hepatitis B. Liver biopsy samples taken from 92 patients with chronic hepatitis B were considered as the training set; 57 more biopsy specimens were used as the validation set. In the training set, grade of necroinflammation and stage of fibrosis for each liver biopsy specimen were determined by two expert liver pathologists using both Ishak and METAVIR systems. Inter-observer variability between the two pathologists was evaluated. Biopsy specimens of the validation set were seen and scored by a third expert pathologist. In the training set, criteria were developed to categorize Ishak grading and staging systems separately to best fit with the METAVIR scoring system. The criteria found in the training set, was then tested in the validation set. The level of agreement between the two scoring systems was assessed by weighted kappa statistics. For the training set, agreement between the two pathologists was excellent. Using our proposed criteria in the training set, there was excellent level of agreement in grading [Kappa = 0.89] and staging [Kappa = 0.99] between Ishak and METAVIR systems. In the validation set, the criteria led to substantial correlation [Kappa = 0.61] in grading, and excellent correlation [Kappa = 0.94] in staging between the two systems. Using our proposed criteria, excellent or at least substantial concordance between Ishak and METAVIR scoring systems can be achieved for the degree of both necro-inflammatory changes and fibrosis

Hepatoprotective activity of Psidium guajava Linn. leaf extract.

The study was designed to evaluate the hepatoprotective activity of P. guajava in acute experimental liver injury induced by carbon tetrachloride, paracetamol or thioacetamide and chronic liver damage induced by carbon tetrachloride. The effects observed were compared with a known hepatoprotective agent, silymarin. In the acute liver damage induced by different hepatotoxins, P. guajava leaf extracts (250 and 500mg/kg, po) significantly reduced the elevated serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bilirubin. The higher dose of the extract (500 mg/kg, po) prevented the increase in liver weight when compared to hepatoxin treated control, while the lower dose was ineffective except in the paracetamol induced liver damage. In the chronic liver injury induced by carbon tetrachloride, the higher dose (500 mg/kg, po) of P. guajava leaf extract was found to be more effective than the lower dose (250 mg/kg, po). Histological examination of the liver tissues supported the hepatoprotection. It is concluded that the aqueous extract of leaves of guava plant possesses good hepatoprotective activity.

Caraterización histológica de los diagnósticos en enfermedades hepáticas crónicas en el municipio de Matanzas: estudio de 5 años / Histologic characterizatio from diagnoses in chronic hepatitic diseases in Matanzas municipality: a five year study

Se realizó un estudio prospectivo-descriptivo de 107 pacientes a quienes se les practicó punción biópsica hepática en los hospitales HCQD “José R. López Tabrane”, Universitario “Cmdte. Faustino Pérez” y Militar “Mario Muñoz Monroy” de Matanzas entre enero de 1998 y diciembre de 2003, por diagnóstico clínico de Enfermedad Hepática Crónica y que histológicamente se concluyeron como hepatitis crónica, aplicándose el índice semicuantitativo de Knodell. Se hizo una reevaluación aplicando el índice de Scheuer. Los cambios histológicos reflejaron que las alteraciones histológicas más frecuente vistas fueron la inflamación portal, la inflamación y necrosis lobulillar y la fibrosis portal. Al aplicar el índice de Scheuer los diagnósticos más emitidos resultaron los de hepatitis crónica B y C leves con fibrosis portal y la hepatitis y cirrosis criptogenéticas. Se describieron alteraciones no comprendidas en el índice de Scheuer, pero de importancia etiológica: esteatosis, cuerpos de Mallory y folículos linfoides, fundamentalmente. Los principales diagnósticos clínicos de enfermedades hepáticas crónicas, histológicamente comprobadas fueron: hepatitis crónica viral B y C, hepatitis crónica alcohólica y esteatohepatitis no alcohólica. El índice de Scheuer resultó más efectivo al evaluar los casos por brindarnos diagnósticos más completos y evolutivamente sugerentes...

Nonalcoholic steatohepatitis [NASH]

Nonalcoholic steatohepatitis [NASH] is a chronic liver disease that is attracting increasing significance characterized by diffuse fatty infiltration and inflammation.The exact prevalence of NASH is unclear, but it is becoming more evident that the disease is much more common than previously thought, although originally believed to be a benign clinical entity, NASH is now recognized as a cause of progressive fibrotic liver disease with adverse clinical sequelae. Clinical characteristics associated with NASH include obesity, hyperlipidemia, and diabetes mellitus, all of which have been associated with underlying insulin resistance. Typically, this disease becomes evident in the fourth or fifth decade of life with an equal sex predilection. NASH is thought to be caused, in part, by impaired insulin signaling, leading to elevated circulating insulin levels and subsequent altered lipid homeostasis. This process is likely multifactorial and includes both genetic and environmental factors. Treatment options to date are limited and are based on very small clinical trials. Current investigations are focusing on improving the underlying insulin resistance that has been associated with NASH as well as other therapies that decrease oxidative stress or improve hepatocyte survival

Electron Microscopic Mesenchymal Response in Chronic Viral Hepatitis / 대한간학회지

BACKGROUND/AIMS: This study was designed to clarify the fine structures of the hepatocytes and mesencymal tissues in chronic hepatitis according to severity. METHOD: For the purpose of elucidating the ultrastructural characteristics of mesenchymal tissues, liver biopsy specimens were studied by light and electron microscopy in 20 patients with chronic hepatitis. RESULTS: 1) Hepatocytes in mesenchymal tissues were thought to be in the stage of regenerated or degenerated process. 2) Regenerating nodules were surrounded by a basement membrane-like materials in the space of Disse. 3) In the widened Disse space the deposition of collagen fiber bundles and increased numbers of hepatic stellate cells in necrotic area were observed. 4) In necrotic areas, hepatic mesenchymal cell response including an increase of collagen fibers and fibroblast, angiogenesis, and a proliferation of bile ductules were also observed. CONCLUSIONS: These observations suggest that the fibrosis in severe chronic hepatitis was accompanied by the mesenchymal response including the proliferation of hepatic stellate cells, fibroblasts, capillarization of Disse space, and mesenchymal proliferation. Finally, this fibrosis observed electron microscopically may be a cause of functional hepatic failure.

Acute exacerbation in chronic hepatitis B virus infection

A case of an acute exacerbation of liver injury in a chronic HBV infected young male is reported. The correlation between the severe symptomatic hepatitis is done with the histopathologic findings of extense areas of bridging necrosis on the liver biopsy. The serological pattern for markers of HBV (Bhs Ag +, anti Hbs -, HBeAg -,antiHBe +, anti Hbc IgG + and IgM -) confirm a chronic infection, and the authors propose that the episode of severe hepatitis relates to the recent spontaneous seroconvertion of HbeAg to anti Hbe. Other causes of hepatitis were excluded, and the control liver biopsy (6 months later) showed normalization of hepatic architecture and absence of markers of viral replication in tissue and serum. A review of literature is done in an attempt do elucidate the diagnostic possibilities in this cases, with emphasis on new immunoassays useful in differentiating between acute hepatitis B and acute exacerbation of a chronic hepatitis by the same virus.

Clinico-pathological predictive factors of response to interferon therapy in chronic hepatitis C.

We performed a clinico-pathological study to determine which pre-treatment factors could predict the response to interferon (IFN) therapy in 55 Japanese patients with chronic hepatitis C. Responses to the IFN therapy were evaluated as sustained response, relapse and non-response by the presence or absence of serum hepatitis C virus (HCV) RNA during the course of treatment and at least 6-months post-treatment. The numbers of sustained response, relapse and non-response were 16 (29.0%), 25 (45.5%) and 14 (25.5%), respectively. Eight out of 16 sustained response cases (50%) showed HCV genotype III. Eight among 10 patients with HCV genotype III (80%) were sustained responders. HCV genotypes were found to be correlated with the response to the IFN therapy (p < 0.0001). None of the histological features, the types of the IFN therapy and other clinical factors showed significant differences. These findings suggest that outcome of the IFN therapy in chronic hepatitis C can be predicted by a virological factor, and that HCV genotype III is a useful predictor of a favorable outcome.

A clinico-pathological study of 163 untreated cases of chronic hepatitis C

We performed a clinico-pathological study of 163 untreated cases of chronic hepatitis C. Eighty five percent of the patients were clinically asymptomatic and their physical examinations showed unremarkable or minimal changes at the time of the liver biopsy. Liver function tests tended to present slight abnormalities, involving mild elevations of the activity of the aminotransferases and gamma-glutamil transferase levels. In spite of these mild abnormalities, advanced chronic liver disease was histologically detected in eighty nine percent of the patients, mainly showing chronic active hepatitis. The most characteristic histological finding was an interlobular bile duct damage, which correlated with the presence of lymphoid aggregates in the portal tracts and with the development of fibrosis.

Seguimiento prolongado de pacientes con enfermedad hepática crónica por VHC / Long term follow up of patients with chronic hepatitis by CHV

Thirty two patients (18 males whose ages ranged from 32 to 68 years old) with hepatitis C virus chronic hepatitis (positive anti-HCV by ELISA, conformed by RIBA II) that were followed by the authors during 2 to 25 years, were retrospectively analyzed. 13 subjects had a history of blood transfusions, one had an accidental pinprick and other sexual contact with a HCV positive individual; the transmission source was not identified in the resting 19 subjects. Only 5 individuals had an acute onset. The rest of the patients had a few symptoms with moderate and fluctuating transaminase elevations. Liver biopsy at the onset showed a chronic hepatitis with moderate activity, even in 15 individuals with cirrhosis (47 percent). During follow up, six subjects deteriorated clinically, appearing liver failure and 3 of these died 4, 5 and 14 years after the disease appearance. No subject developed a hepatocarcinoma

Hepatitis crónica activa: correlación clínica, bioquímica e histopatológica / Chronic hepatitis active: clinical, biochemical and histopathological correlation

Se realizó un estudio retrospectivo de 26 pacientes mujeres con hepatis crónica activa. La edad promedio fue de 39 años y el tiempo de enfermedad de 8 meses; 5 pacientes tuvieron marcadores virales positivos. Los casos se seleccionaron de acuerso al grado de actividad histopatológica: 8 pacientes con formas leves (2A) y 16 pacientes con formas severas (2B). En la casuística predominó el grupo 2B, en este grupo la alteración más frecuente fue el infiltrado inflamatorio severo; solo en éste grupo se observó: necrosis multilobulillar o colapso, necrosis en puente, eosinófilos y marcada hiperplasia de las células de Kupffer. Desde el punto de vista clínico existen casos con manifestaciones puramente hepóticas, existiendo otros con manifestaciones sistémicas variadas. La hepatitis crónica activa puede presentar colestasis, sin que esto necesariamente se vincule con el grado de actividad. El grupo 2B cursó cifras elevadas de transaminasas y disminución de la concentración de protrombina

Estudio a largo plazo de pacientes con hepatitis cronica activa tratados con interferon leucocitario

Siete pacientes con hepatitis crónica activa tratados con Interferón Alfa mostraron una notable mejoría humoral e histológica un año después de finalizado el tratamiento, en 3 de ellos la histología hepática era prácticamente normal, 2 evolucionaron a una Hepatitis Crónica persistente y sólo se apreció un empeoramiento en uno de ellos. Estos resultados difirieron de los obtenidos inmediatamente al final del tratamiento (p < 0,05). El Interferón Alfa resulta de gran utilidad en esta afección, debiendo continuarse el estudio de los pacientes hasta un año después de finalizado el tratamiento