Correlation between M30 immunochemistry and histological activity in steatohepatitis: One piece of a complex puzzle

AbstractChronic Hepatitis B virus (HBV) is still one of the major reasons for liver related mortality and morbidity all around the world. This study aimed to investigate the possible relationship between the immune system activation and presence, as well as progression, of hepatitis B infection by monitoring the tryptophan degradation and serum neopterin levels in patients with HBV. 110 patients with HBV and 23 healthy subjects were included in the study. The patients had significantly higher neopterin levels and increased kynurenine to tryptophan ratios, which were most probably due to enhanced indoleamine 2,3-dioxygenase (IDO) activity compared to healthy control. A strong positive correlation was found between neopterin levels and IDO activity in patient group. Neopterin levels and IDO activity were markedly increased in patients with histological activity index (HAI) ≥4 compared to HAI<4, and a significant correlation was found between neopterin and HAI. Moreover, there was a significant correlation between albumin levels and IDO activity in HBV patients. These findings suggest that tryptophan degradation results from IFN-γ-induced IDO activation, likewise depletion of albumin synthesis in HBV patients may result from diminished tryptophan availability. In conclusion, based on the study results, serum neopterin levels and IDO activity could provide additional immunological information for monitoring liver histological activity and can be used as prognostic markers in HBV disease.

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Sa1890 White Cell Apheresis (WCA) With Adacolumn is Effective in Selected Cases of Chronic Refractory Colitis With High Histological Activity

Gastroenterology ◽

10.1016/s0016-5085(12)61325-0 ◽

2012 ◽

Vol 142 (5) ◽

pp. S-351-S-352

Author(s):

Prem Premchand ◽

Charlotte Ford ◽

Dinesh Venkama

Keyword(s):

White Cell ◽

Histological Activity

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Can fecal calprotectin accurately identify histological activity of ulcerative colitis? A meta-analysis

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284821994741 ◽

2021 ◽

Vol 14 ◽

pp. 175628482199474

Author(s):

Xiaoqi Ye ◽

Ying Wang ◽

Harry H. X. Wang ◽

Rui Feng ◽

Ziyin Ye ◽

...

Keyword(s):

Ulcerative Colitis ◽

Meta Analysis ◽

Area Under The Curve ◽

Fecal Calprotectin ◽

Secondary Outcome ◽

Histological Response ◽

Summary Receiver Operating Characteristic ◽

Histological Activity ◽

Histological Remission ◽

Sensitivity Specificity

Background and Aims: Elevated fecal calprotectin (FC) levels have been reported to correlate with histological activity in patients with ulcerative colitis (UC). However, the accuracy of FC for evaluating histological activity of UC remains to be determined. The aim of this study was to determine the accuracy of FC for evaluating histological activity of UC, based on updated definitions. Methods: Related studies were retrieved from the PubMed, Web of Science, Embase, and Cochrane databases. Adult participants diagnosed with UC were included when sufficient data could be extracted to calculate the accuracy of FC for evaluating histological activity. The primary outcome was histological response, and the secondary outcome was histological remission, defined according to a recently updated position paper of European Crohn’s and Colitis Organization. Statistics were pooled using bivariate mixed-effects models. The area under the curve was estimated by summary receiver-operating characteristic curves. Results: Nine studies were included, from which 1039 patients were included for the analysis of histological response and 591 patients for histological remission. For the evaluation of histological response, the pooled sensitivity, specificity, and the area under the curve were 0.69 [95% confidence interval (CI): 0.52–0.82], 0.77 (95% CI: 0.63–0.87), and 0.80 (95% CI: 0.76–0.83), respectively. For the evaluation of histological remission, the corresponding estimates were 0.76 (95% CI: 0.71–0.81), 0.71 (95% CI: 0.62–0.78), and 0.79 (95% CI: 0.75–0.82), respectively. FC had a higher accuracy in studies using Nancy Index. For histological response, the cut-off values of FC ranged from 50 to 172 µg/g, and the sensitivity was higher in studies with FC cut-off values >100 µg/g (0.77 versus 0.65). Conclusion: FC is a valuable biomarker for assessing histological activity in patients with UC. A cut-off value of 100–200 µg/g is more appropriate to spare patients from an unnecessary endoscopy and biopsy.

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Serum Aspartate Aminotransferase Level and Previous Histopathological Findings Enable Reduction of Protocol Liver Biopsies after Liver Transplantation for Hepatitis C

Canadian Journal of Gastroenterology ◽

10.1155/2013/904636 ◽

2013 ◽

Vol 27 (3) ◽

pp. 131-136 ◽

Cited By ~ 1

Author(s):

Tomohiro Tanaka ◽

George Therapondos ◽

Nazia Selzner ◽

Eberhard L Renner ◽

Leslie B Lilly

Keyword(s):

Liver Transplantation ◽

Hepatitis C ◽

Antiviral Therapy ◽

Aspartate Aminotransferase ◽

Aminotransferase Level ◽

Fibrosis Stage ◽

Protocol Biopsy ◽

Serum Aspartate Aminotransferase ◽

Histological Activity ◽

Liver Biopsies

BACKGROUND: Hepatitis C virus (HCV) infection remains the leading indication for liver transplantation (LT) worldwide. Recurrent hepatitis C following LT is universal, and significant fibrosis (SF, Metavir fibrosis stage ≥2) apparent on protocol biopsy typically prompts antiviral therapy.OBJECTIVE: To determine the optimal timing of protocol liver biopsies in this setting.METHODS: A total of 151 patients who underwent LT related to HCV infection between July 2004 and December 2009 were analyzed retrospectively. Data regarding protocol liver biopsies at six, 12 and 24 months post-LT, conventional laboratory parameters and demographic information were obtained.RESULTS: The 151 patients included in the present study had significantly lower serum aspartate aminotransferase (AST) levels than the four patients who progressed to receive antiviral treatment for SF before six months post-LT (P<0.001). AST level, but not alanine aminotransferase level, histological activity or fibrosis stage at the six-month biopsy was independently associated with the progression to SF at 12 months (P<0.05). However, AST level, histological activity and fibrosis stage at the 12-month biopsy emerged as independent parameters associated with progression to SF at 24 months (P<0.05).CONCLUSION: The protocol liver biopsy at six months could be eliminated, especially in patients who consistently exhibit low AST levels. Histological activity, the presence or absence of fibrosis, and AST values at the 12-month biopsy may lead to the decision to defer the protocol biopsy at 24 months or result in earlier introduction of antiviral therapy.

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Cirrhosis in rats does not resolve in the long-term after induction by thioacetamide model

Journal of Morphological Sciences ◽

10.4322/jms.ao060313 ◽

2014 ◽

Vol 31 (01) ◽

pp. 033-041

Author(s):

L. Rui ◽

E. Silva ◽

T. Silva ◽

T. Portela ◽

A. Silva ◽

...

Keyword(s):

Biochemical Analysis ◽

Hepatic Cirrhosis ◽

Activity Index ◽

Experimental Period ◽

Female Wistar Rats ◽

Serum Biochemical ◽

Histological Activity ◽

Therapy Studies ◽

Future Therapy

Abstract Introductions: Hepatic cirrhosis is a final common pathway of all chronic liver diseases, characterized by deposit of fibrillar collagen and liver failure. Materials and Methods: In this experiment, hepatic cirrhosis was induced in 15 female Wistar rats by a 14-week period, with thioacetamide solution in a 200 mg/kg dosage, via intraperitoneal. Animals were submitted to liver biopsy, and euthanized after a 80-day post-induction period. Serum biochemical analysis was performed, in addition to histopathology by H.E., Picrosirius, Alcian Blue and P.A.S. stainings, following analysis of histological activity index and staging of fibrosis. Morphometric analysis of collagen on Picrosirius slides was also performed. Results: Mortality during experimental period was low (13.33%), and after 80-day period, liver function improved, cellular changes did not altered, and deposition of acidic mucopolysaccharides and glycogen were increased. Liver histological activity did not change significantly (7.25 ± 1.30 to 6.41 ± 1.32), but staging of fibrosis was altered (3.91 ± 0.76 to 4.70 ± 1.11). Interlobular collagen showed a significant decrease (5.14 ± 2.00 to 4.00 ± 1.20), while intralobular collagen was increased (0.23 ± 0.06 to 0.36 ± 0.08). Conclusions: These findings characterize thioacetamide as a safe experimental model for induction cirrhosis, which may be used for future therapy studies.

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592 Histological Normalization Is Associated With Superior Relapse Free Survival Compared to Histological Activity and Histological Quiescence in Ulcerative Colitis

Gastroenterology ◽

10.1016/s0016-5085(15)30395-4 ◽

2015 ◽

Vol 148 (4) ◽

pp. S-115 ◽

Cited By ~ 2

Author(s):

Britt Christensen ◽

Olufemi Kassim ◽

Jonathan Erlich ◽

Stephen B. Hanauer ◽

David T. Rubin

Keyword(s):

Ulcerative Colitis ◽

Relapse Free Survival ◽

Free Survival ◽

Histological Activity

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Serum Cytokeratin 18 M30 Levels in Chronic Hepatitis B Reflect Both Phase and Histological Activities of Disease

Mediators of Inflammation ◽

10.1155/2017/3480234 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Magdalena Świderska ◽

Jerzy Jaroszewicz ◽

Anna Parfieniuk-Kowerda ◽

Magdalena Rogalska-Płońska ◽

Agnieszka Stawicka ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Disease Activity ◽

Chronic Hepatitis B ◽

Hbv Infection ◽

Cytokeratin 18 ◽

Advanced Stages ◽

Histological Activity ◽

Normal Alt ◽

New Biomarkers

Chronic hepatitis B has highly a dynamic course with significant fluctuations of HBV-DNA and ALT impeding assessment of disease activity. New biomarkers of inflammatory versus noninflammatory stages of HBV infection are urgently needed. Cytokeratin 18 epitope M30 (M30 CK-18) is a sensitive marker of cell death. We aimed to investigate an association between serum M30 CK-18 and histological activity and phase of HBV infection. 150 Caucasian patients with HBV-infection were included in the study. Serum M30 CK-18 levels reflected phase of disease, being significantly higher in both HBeAg(+) and HBeAg(−) hepatitis B in comparison to HBsAg(+) carrier groups. The highest serum M30 CK-18 levels were observed in subjects with the most advanced stages of HBV. Moreover, its serum concentrations correlated with both inflammatory activity and fibrosis advancement (ANOVA P<0.001). Importantly, serum M30 CK-18 levels were able to discriminate patients with mild versus moderate-advanced fibrosis (AUC: 0.86) and mild versus active liver inflammation (AUC: 0.79). M30 CK-18 serum concentration has good sensitivity and specificity in discriminating mild versus moderate/severe fibrosis and inflammation even in patients with normal ALT activity. This study suggests M30 CK-18 as a potential noninvasive marker of disease activity and also a marker of phase of persistent HBV infection.

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