Histopathological study of chronic hepatitis B and C: a comparison of two scoring systems

doi:10.1016/S0168-8278(02)00357-4

Journal of Hepatology

Volume 38, Issue 2, February 2003, Pages 223-229

https://doi.org/10.1016/S0168-8278(02)00357-4 Get rights and content

Abstract

Background/Aims: Several histological scoring systems are used to evaluate chronic viral hepatitis. This study was undertaken to determine the correlation between the Ishak system (modified histological activity index, HAI) and the METAVIR system, in Indian patients with chronic viral hepatitis.

Methods: Liver biopsies from 127 patients with chronic viral hepatitis B or C were examined, and scored using the Ishak and METAVIR systems, and weighted kappa analysis of correlation was done. Correlation of necroinflammatory activity with serum transaminase levels was analyzed, and prevalence of specific histological features compared in hepatitis B virus (HBV) and HCV biopsies.

Results: HBV infection accounted for 64.6% of cases, and HCV for 35.4%; 91.3% of patients had minimal or mild hepatitis. The necroinflammatory scores of the Ishak and METAVIR systems correlated moderately well (weighted kappa 0.627), while there was excellent correlation with regard to fibrosis (weighted kappa 0.998). Similar concordance was found when HBV and HCV cases were analyzed separately. HAI showed poor correlation with serum transaminases (weighted kappa 0.21). Micronodular cirrhosis, lymphoid aggregates, bile duct damage, bile ductular proliferation and steatosis were significantly more common in HCV biopsies compared to HBV.

Conclusions: Concordance between Ishak and METAVIR scoring systems is good for necroinflammatory change, and excellent for fibrotic change.

Introduction

In developed countries, hepatitis C virus (HCV) infection is the commonest cause of chronic liver disease with prevalence as high as 60–90% in affected patients [1], while HBV infection is more important than HCV as a cause of chronic hepatitis in developing countries such as India [2], [3].

Although serological and virological parameters are useful to confirm the clinical diagnosis of chronic hepatitis, the liver biopsy remains the gold standard for evaluating hepatitis in terms of assessing histological activity and stage of disease. It is also important in excluding other coexistent disease processes. A number of systems have evolved to score liver biopsies [4], [5], [6], [7], [8], [9]. The use of such scoring systems on paired liver biopsies, obtained from patients before and after therapy, is particularly useful in the objective documentation of reduction in inflammation or fibrosis brought about by antiviral therapy or interferon [10], [11], [12], [13], [14], [15], [16]. Two scoring systems have been introduced in recent years: the modified histological activity index (HAI) of Ishak et al., and the METAVIR system [7], [9]. The Ishak system is comprehensive and shows good inter-observer agreement [17], [18]. The METAVIR scoring system has been implemented in Western countries, and has been particularly useful in scoring of biopsies from patients with HCV infection [19], [20]. Each of these scoring systems individually generates reliable scores, with relatively little intra- and interobserver variations within each system, when carried out by hepatopathologists [18], [19], [21], [22]. There is no study comparing these two scoring systems.

The present study was undertaken to compare the grade and stage obtained using the Ishak system with that obtained using the METAVIR system, and to determine the degree of correlation between these two scoring systems using biopsies obtained from patients with chronic hepatitis B or C. A secondary aim of the study was to determine whether there was any correlation between necroinflammatory score (HAI grade) and serum transaminase levels, and to compare the prevalence of specific histological findings in HBV and HCV biopsies.

Section snippets

Materials and methods

All liver biopsies received in the Department of Pathology between March 1998 and July 2000 were prospectively evaluated for inclusion in the study. Of these, 133 biopsies from 133 patients with chronic hepatitis B (HBV) and, or C (HCV) were found adequate for study. Six biopsies were from patients who had both HBV and HCV coinfection, and these were excluded from the study, leaving 127 biopsies that were examined. All biopsy specimens were fixed in 10% formalin, embedded in paraffin and 4-μm

Results

Of the 127 patients, 82 (64.6%) had chronic HBV infection, and 45 (35.4%) had chronic HCV infection. One hundred and two of the patients were male and 25 were female. The mean age of HCV patients was 43.9 years compared to 32.5 years for HBV patients. Of the patients with HBV infection, all 82 tested positive for HBsAg and 67 tested positive for HBeAg. HBV DNA was measured in 28 patients, of whom 25 tested positive. Forty-four of the 45 HCV patients were HCV antibody positive, while in one

Discussion

Chronic viral hepatitis is a significant problem worldwide. Presently available therapies lead to sustained resolution of inflammation in only a minority of treated patients, and newer therapies are constantly being introduced. Such therapies need to be evaluated particularly to determine whether they halt inflammation and result in regression of fibrosis. Histological scoring systems to evaluate inflammation and fibrosis offer objective measures of improvement in either of these parameters [4]

Acknowledgements

We would like to thank Dr. Selvaraj, Department of Biostatistics, CMC Hospital, for his invaluable assistance in statistical analysis, and Mr. T. Ebinezer for typing the manuscript.

References (33)

P.J Scheuer
Classification of chronic viral hepatitis: a need for reassessment
J Hepatol
(1991)
K Ishak et al.
Histological grading and staging of chronic hepatitis
J Hepatol
(1995)
P Bedossa et al.
An algorithm for the grading of activity in chronic hepatitis C
Hepatology
(1996)
Y Suzuki et al.
Histological changes in liver biopsies after one year of lamivudine treatment in patients with chronic hepatitis B infection
J Hepatol
(1999)
R.D Goldin et al.
Intraobserver and interobserver variation in the histopathological assessment of chronic viral hepatitis
J Hepatol
(1996)
L.E Adinolfi et al.
Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity
Hepatology
(2001)
H Ikawa et al.
Various scoring systems evaluating histologic features of chronic hepatitis C treated with interferon
Hum Pathol
(2001)
A.M Wesley et al.
Epidemiology of hepatitis C: geographic differences and temporal trends
Semin Liver Dis
(2000)
S.K Issar et al.
Prevalence and presentation of hepatitis C related chronic liver disease in southern India
J Trop Med Hyg
(1995)
G Ray et al.
Aetiological spectrum of chronic liver disease in Eastern India
Trop Gastroenterol
(2000)

B.G Knodell et al.

Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis

Hepatology

(1981)

V.J Desmet et al.

Classification of chronic hepatitis: diagnosis, grading and staging

Hepatology

(1994)

E.M Brunt

Grading and staging the histopathological lesion of chronic hepatitis. The Knodell histological activity index and beyond

Hepatology

(2000)

E.J Heathcote et al.

Peginterferon alpha-2a in patients with chronic hepatitis C and cirrhosis

N Engl J Med

(2000)

N Leung

Liver disease – significant improvement with lamivudine

J Med Virol

(2000)

Y Shiratori et al.

Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy

Ann Intern Med

(2000)

Cited by (111)

EASL Clinical Practice Guidelines on haemochromatosis
2022, Journal of Hepatology
Citation Excerpt :
This recommendation is based on the fact that patients with chronic hepatitis C and bridging fibrosis have been shown to be at risk of HCC,112 possibly related to under-staging of liver biopsy, rapid worsening of liver disease stage, and difficulties defining the transition from advanced fibrosis to cirrhosis. Stages 4 and 5 of the Ishak system, representing advanced bridging fibrosis and/or early nodule formation, have shown excellent correlation with F3 in the METAVIR system.113 Based on the above premises, although information about the HCC incidence in patients with non-viral liver disease without cirrhosis is limited,73 it seems reasonable to recommend HCC surveillance for patients with haemochromatosis and bridging fibrosis, especially in the presence of adjunctive risk factors for cancer.
Haemochromatosis is characterised by elevated transferrin saturation (TSAT) and progressive iron loading that mainly affects the liver. Early diagnosis and treatment by phlebotomy can prevent cirrhosis, hepatocellular carcinoma, diabetes, arthropathy and other complications. In patients homozygous for p.Cys282Tyr in HFE, provisional iron overload based on serum iron parameters (TSAT >45% and ferritin >200 μg/L in females and TSAT >50% and ferritin >300 μg/L in males and postmenopausal women) is sufficient to diagnose haemochromatosis. In patients with high TSAT and elevated ferritin but other HFE genotypes, diagnosis requires the presence of hepatic iron overload on MRI or liver biopsy. The stage of liver fibrosis and other end-organ damage should be carefully assessed at diagnosis because they determine disease management. Patients with advanced fibrosis should be included in a screening programme for hepatocellular carcinoma. Treatment targets for phlebotomy are ferritin <50 μg/L during the induction phase and <100 μg/L during the maintenance phase.
A novel nomogram to predict evident histological liver injury in patients with HBeAg-positive chronic hepatitis B virus infection
2021, EBioMedicine
HBeAg-positive chronic infection is a unique phase of chronic hepatitis B virus (HBV) infection. Current guidelines advise against starting antiviral treatment for HBeAg-positive chronic hepatitis B virus (HBV) infection patients, some data suggest treating such patients may reduce the risk of hepatocellular carcinoma. We aimed to explore whether these patients can have evident histological liver injury (EHLI), and develop a non-invasive model for identifying EHLI in such patients.
We assessed whether HBeAg-positive chronic HBV infection patients can have EHLI defined by Ishak fibrosis stage ≥3 and/or histologic activity index ≥ 9 in a prospective multicenter study. Logistic and Lasso regression was used to select the optimal predictors. We used Akaike information criterion, discrimination improvement, net reclassification improvement to develop and validate models predicting EHLI risk in training cohort and two external validation cohorts.
Of these 336 patients met the inclusion criteria, 181(54%) were HBeAg-positive chronic HBV infection, of whom 60 patients (33%) had EHLI, the proportion of significant fibrosis was higher than that of significant inflammation (33% vs. 8%, P < 0.001). Age, liver stiffness measurement, ALT, alkaline phosphatase, and albumin were identified as independent predictors for EHLI and used to develop a nomogram that have been demonstrated having a good performance in predicting EHLI with AUROCs of 0.92(95%CI: 0.86–0.99) in the training cohort (n = 233) and 0.90(95%CI: 0.84–0.95) in validation cohort 1(n = 103), significant correcting current guidelines recommendations overestimating insignificant or significant histological disease. After 72-weeks entecavir treatment for HBeAg-positive chronic HBV infection patients with EHLI identified by nomogram, histological improvement occurred in 40 of 49(82%), 38(78%) had fibrosis reversal, and 35(73%) no longer had EHLI.
In HBeAg-positive chronic HBV infection patients, 33% has EHLI. The nomogram developed in this study can accurately identify HBeAg-positive chronic HBV infection patients with EHLI, and that responded very well to antiviral therapy.
This study was funded by the State Key Projects Specialized on Infectious Disease, Chinese Ministry of science and technology (2013ZX10005002; 2018ZX10725506), National Natural Science Foundation of China (81970525) and Beijing Key Research Project of Special Clinical Application (Z151100004015221).
Targeted delivery of celastrol to renal interstitial myofibroblasts using fibronectin-binding liposomes attenuates renal fibrosis and reduces systemic toxicity
2020, Journal of Controlled Release
Renal fibrosis often occurs in chronic kidney disease, and effective treatment is needed. Celastrol (CEL) may attenuate renal fibrosis, but it distributes throughout the body, leading to severe systemic toxicities. Here we designed a system to deliver CEL specifically to interstitial myofibroblasts, which is a key driver of renal fibrogenesis. Fibronectin is highly expressed in fibrotic kidney. The pentapeptide CREKA, which specifically binds fibronectin, was conjugated to PEGylated liposomes (CREKA-Lip). CREKA-coupled liposomes significantly increased the uptake of unmodified liposomes by activated NRK-49F renal fibroblasts. Systemic administration of CREKA-Lip to mice led to their accumulation in fibrotic kidney, where they were specifically internalized by interstitial myofibroblasts. Loading CEL into CREKA-Lip effectively inhibited the activation and proliferation of NRK-49F cells in vitro, and they markedly alleviated renal fibrosis, injury and inflammation induced by unilateral ureteral obstruction in mice. Besides, CEL-loaded CREKA-Lip was associated with significantly lower toxicity to major organs than free CEL. These results suggest that encapsulating CEL in CREKA-Lip can increase its therapeutic efficacy and reduce its systemic toxicity as a potential treatment for renal fibrosis.
Association between non-hypervascular hypointense nodules on gadoxetic acid-enhanced MRI and liver stiffness or hepatocellular carcinoma
2017, European Journal of Radiology
Citation Excerpt :
Although the precise reason for this is unclear, it can be explained in part as follows: cirrhosis can be classified into a micronodular or macronodular type based on the size of cirrhosis-related nodules in the pathologic specimen [23]. In contrast to hepatitis C virus infection or alcohol abuse, hepatitis B virus infection tends to induce macronodular cirrhosis, which could promote the frequent development of NHHNs on gadoxetic acid-enhanced MRI in patients with the hepatitis B virus [24]. In terms of the natural history of NHHNs on gadoxetic acid-enhanced MRI, many longitudinal observation studies have reported that a considerable number of these nodules have become hypervascular HCCs during the follow-up [3,5,8].
To assess the association between non-hypervascular hypointense nodules (NHHNs) on gadoxetic acid-enhanced magnetic resonance imaging (MRI) and liver stiffness (LS) in patients with chronic liver disease, and analyzed their progression to overt hepatocellular carcinoma (HCC).
Between August 2012 and March 2016, a total of 714 consecutive patients who had undergone transient elastography for LS measurement and gadoxetic acid-enhanced MRI were investigated. The association between the presence of NHHNs on the hepatobiliary phase and LS, and the patient’s HCC status [none, presence of treatment-naïve HCC, or a history of previous HCC treatment] was assessed. In patients with these nodules, cumulative progression rates of nodules to overt HCC were compared with rates of new HCC development in other parts of the liver.
The prevalence of NHHNs was 16.8% (120/714). The presence of these nodules was significantly associated with the log LS (Odds ratio [OR], 1.48, p = 0.002) and hepatitis B virus infection (OR, 3.14, p = 0.017), regardless of the patient’s HCC status. The two year cumulative progression rate of overt HCC from corresponding nodules and rate of progression to HCC in other parts of the liver were 34.1% and 18.3%, respectively (p = 0.071).
The presence of NHHNs on gadoxetic acid-enhanced MRI was associated with higher LS and hepatitis B virus infection. Furthermore, these lesions frequently progressed to overt HCC.
Alcohol and HBV synergistically promote hepatic steatosis
2019, Annals of Hepatology
Hepatitis virus and alcohol are the main factors leading to liver damage. Synergy between hepatitis B virus (HBV) and alcohol in promoting liver cell damage and disease progression has been reported. However, the interaction of HBV and ethanol in hepatic steatosis development has not been fully elucidated.
Eight-week-old male C57BL/6 mice were treated with or without HBV, ethanol, or the combination of HBV and ethanol (HBV + EtOH), followed by a three-week high-fat diet (HFD) regimen. Liver histology, serum biomarkers, and liver triglyceride levels were analysed. Furthermore, a meta-analysis of the effects of alcohol and HBV on hepatic steatosis in populations was performed.
Hepatic steatosis was significantly more severe in the HBV + EtOH group than in the other groups. The serum alanine aminotransferase, aspartate aminotransferase and liver triglyceride levels in the HBV + EtOH group were also significantly higher than those in the other groups. The HBeAg and HBsAg levels in the HBV + EtOH group were significantly higher than those in the pair-fed HBV-infected mice. In addition, the meta-analysis showed that alcohol consumption increased the risk of hepatic steatosis by 43% in HBV-infected patients (pooled risk ratio (RR) = 1.43, P < 0.01).
Alcohol and HBV synergistically promote high-fat diet-induced hepatic steatosis in mice. In addition, alcohol consumption increases the risk of hepatic steatosis in HBV-infected patients.
Letter: Use of liver stiffness measurement to identify liver cirrhosis in patients with chronic hepatitis D
2024, Alimentary Pharmacology and Therapeutics

View all citing articles on Scopus

View full text

Histopathological study of chronic hepatitis B and C: a comparison of two scoring systems

Abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Acknowledgements

J Hepatol

J Hepatol

Hepatology

J Hepatol

J Hepatol

Hepatology

Hum Pathol

Epidemiology of hepatitis C: geographic differences and temporal trends

Semin Liver Dis

Prevalence and presentation of hepatitis C related chronic liver disease in southern India

J Trop Med Hyg

Aetiological spectrum of chronic liver disease in Eastern India

Trop Gastroenterol

Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis

Hepatology

Classification of chronic hepatitis: diagnosis, grading and staging

Hepatology

Grading and staging the histopathological lesion of chronic hepatitis. The Knodell histological activity index and beyond

Hepatology

Peginterferon alpha-2a in patients with chronic hepatitis C and cirrhosis

N Engl J Med

Liver disease – significant improvement with lamivudine

J Med Virol

Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy

Ann Intern Med