Table of Contents  

Bhuyan, Pattnaik, Burma, Singh, Misra, and Mohanty: Profile of liver biopsies in a tertiary care centre in coastal eastern India

Introduction

Liver disorders are mostly chronic and asymptomatic and represent a major public health problem. Although viral hepatitis and alcoholic liver disease are critical to global health, they do not encompass all the conditions contributing to liver disease. Over the past couple of decades, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have become the leading causes of liver disease.1 Histological assessment of the liver is a cornerstone in the evaluation and management of patients with liver disease and has long been considered an integral component of the clinician’s diagnostic armamentarium.1,2 Clinical algorithms, advanced imaging technology and laboratory diagnostics have improved understanding of liver disease, but liver biopsy will remain a valuable diagnostic tool. The role of pretreatment liver biopsy still remains the gold standard. In liver disease, liver biopsy is now more often used selectively rather than routinely for diagnostic purposes.3

Studies on liver disease have been conducted in eastern India,4 but in view of the changing epidemiological profile more data are required to understand the burden of liver disease in this part of the country. The aim of the present study is to evaluate, histopathologically, the aetiological spectrum of liver disease in a tertiary referral centre in eastern India.

Materials and methods

All cases of liver biopsies over a period of 1 year, June 2013 to May 2014, were retrieved from the archives of our department. Records of serum assay for HbsAg (hepatitis B surface antigen), anti-HCV (hepatitis C virus), HbeAg (hepatitis B ‘e’ antigen), HBV (hepatitis B virus) DNA and HCV RNA were evaluated. Autoimmune markers, including antinuclear antibody (ANA), antismooth muscle antibody (ASMA) and antimitochondrial antibody (AMA-M2) reports, were correlated with biopsy findings. Formalin-fixed paraffin-embedded sections stained with haematoxylin and eosin (HE) were studied. Special stains, including Masson’s trichrome and reticulin stain, were carried out to assess the degree of fibrosis and variation in architecture. The Brunt1 scoring system was used for evaluation of NAFLD cases. The Modified Histological Activity Index, a grading and staging system devised by Ishak et al.,2 was used for the evaluation of chronic viral hepatitis cases.

Results

A total of 54 patients with chronic liver disease underwent liver biopsy. Of these patients, two were excluded for inadequate biopsy specimen. Of the remaining 52 patients, 42 (81%) were male and 10 (19%) were female, with a M:F ratio of 4:1. The age range was 21 to 70 years (mean age of 39.2 ± 10.8 years). Most patients were in their 40s or 50s (Figure 1).

FIGURE 1

Age distribution of total cases.

8-2-5-fig1.png

The details of the histological findings are shown in Table 1. Of the 52 patients who had a liver biopsy, NAFLD was present in 24 (46%), chronic viral hepatitis in 18 (34%) and other liver diseases in 10 (20%) patients.

TABLE 1

Histopathological profile of liver disease (n = 52)

Disease No of cases % of cases
NAFLD 24 46
Chronic hepatitis 18 34
Cholestatic liver disease 2 4
Cryptogenic cirrhosis 2 4
Bile duct obstruction 1 2
Drug-induced liver disease 1 2
Amoebic liver disease 1 2
Primary biliary cirrhosis 1 2
Amyloidosis 1 2
Cavernous haemangioma 1 2
Total 52 100

NAFLD cases were classified as per Brunt1 into three categories: not NASH, borderline NASH and definite NASH. In our study of 24 NAFLD cases, not NASH was reported in 10 (41.6%), borderline NASH in 8 (33.4%) and definite NASH in 6 (25%) of cases (Table 2). Most patients had either absent or minimal fibrosis. Of these patients, 13 (54.2%), 8 (33.3%) and 3 (12.5%) had stage 0, stage 1 and stage 2 fibrosis, respectively. Therefore, fibrosis of varying degrees was observed in 45.8% of NAFLD cases, which is noteworthy.

TABLE 2

Profile of NAFLD cases

Categories No of cases (%) Age Sex Fibrosis (staging)
< 40 years > 40 years M F 0 1 2
Not NASH 10 (41.6%) 3 7 8 2 8 2 0
Borderline NASH 8 (33.4%) 3 5 6 2 4 3 1
Definite NASH 6 (25%) 2 4 5 1 1 3 2

Out of the 18 cases of chronic viral hepatitis, two were infected with HCV and the remaining cases with HBV. Fibrosis was observed in 33% of cases (6/18).

The remaining 10 cases of chronic liver disease comprise two cases each of cirrhosis and cholestatic liver disease and single cases of primary biliary cirrhosis, drug-induced liver injury, bile duct obstruction, cavernous haemangioma, amoebic liver abscess and hepatic amyloidosis.

Discussion

Liver biopsy evaluation is the only means of diagnosis or exclusion of liver disease as, to date, neither laboratory tests nor imaging studies can provide complete data relating to parenchymal changes. Core biopsy of a length of 2 cm or more with at least 11 complete portal tracts is necessary in order to reliably grade and stage a case of liver disease.1,5 Although not representing the real picture of the population, data based on symptomatic patients are essential for understanding the spectrum of liver disease. Moreover, it is unethical and impractical to perform population screening with liver biopsies, so biopsies carried out in selected cases have been used to determine the prevalence of liver disease in eastern India.

In this study, NAFLD was the most common cause of liver disease (46%). There is wide variation in the reported prevalence of NAFLD in scientific literature. The prevalence is estimated to be 8–40% in Asian countries610 and 15–46% in western countries.1113 The frequency of NAFLD in our study was similar to that observed by Singh et al.,6 who reported steatosis in 40.6% of cases, borderline NASH in 34.4% of cases and definite NASH in 25% of cases from a total of 64 liver biopsies. The mean age of NAFLD in our study was 40.5 ± 6.4 years, compared with 44 ± 10.81 years reported by Singh et al.6 Male predominance is also observed in our study comprising 79.2% of cases of steatohepatitis versus 76.6% in Singh et al.6 Das et al.8 reported a prevalence of 8.7% NAFLD in a predominantly poor, non-obese, non-sedentary population in eastern India. Therefore, NAFLD has been reported in lean patients as well. Mohan et al.9 found that the prevalence of NAFLD in urban South Indians was 32%. This variation in prevalence could be caused by an inhomogeneous study population, but a significant increase in the prevalence of NAFLD has been observed and is a matter of concern. Although, earlier, NAFLD was considered relatively benign, it has now been observed to progress to cirrhosis, liver failure and hepatocellular carcinoma. Moreover, NAFLD is now strongly associated with metabolic syndrome and insulin resistance. In India, an increase in the incidence of obesity, type 2 diabetes mellitus and metabolic syndrome caused by physical inactivity, economic growth and environmental factors has been observed. NAFLD is now considered the hepatic manifestation of metabolic syndrome.6

Chronic viral hepatitis is the second most common cause of liver disease in our study, comprising 34% of liver biopsies. Infection with HBV predominates this group (89%) with only two cases of HCV. These results could be because the liver biopsies were carried out in selective cases in this referral centre. However, cases in published medical literature show variation in liver disease consistent with our study.14 Khokar15 reported chronic hepatitis (68.3%) as a major cause of liver disease in a study conducted in north Pakistan. Of these, 86% were infected with HCV, 10.7% with HBV and 3.1% were infected with both HBV and HCV. Of 41 cases of hepatocellular carcinoma, 29.3% were caused by HCV infection and 14% by HBV infection. In the study carried out by Nwokediuko et al.,16 cirrhosis and hepatocellular carcinoma (HCC) were the major causes of liver disease in a tertiary hospital in Nigeria.16 The aetiological factors were previous HBV infection in 49.4% of cases, HCV infection in 8.4% of cases, alcohol consumption in 52.1% of cases and use of herbal products in 45.5% of cases. The Dionysos study reported a HBV infection prevalence of 1.2% in the Italian population.17 A 9-year follow-up showed that 4.5% of those infected developed cirrhosis. No cases of HCC were detected. These findings suggest a slow progression of HBV-related liver disease. The prevalence of HCV was 3.2%, which was higher in subjects 60 years and older (10%). The prevalence of HCV observed in different populations shows a variation of 2% in United States of America to 50% in Egypt. Follow-up cases of HCV showed that 2.5% developed HCC. Liver cirrhosis due to HCV is more common than HBV, and has also been reported by Aziz et al.18 in two military hospital-based studies in Pakistan.

The other causes of morbidity caused by liver disease in our study were cholestatic liver disease (4%), cryptogenic cirrhosis (4%), primary biliary cirrhosis (2%), amoebic abscess (2%), cavernous haemangioma (2%), drug-induced liver injury (2%), amyloidosis (2%) and bile duct obstruction (2%).

Conclusion

Liver biopsy remains the gold standard for diagnosis and assessment of the degree of parenchymal damage in the form of grading and staging. NAFLD was the most common cause of liver disease in this study. HBV remains the most frequent cause of viral hepatitis. The study reflects the spectrum of chronic liver diseases in a tertiary centre in coastal eastern India.

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