Korean J Intern Med > Volume 7(1); 1992 > Article
Kim, Lee, Min, Jeong, Hong, Lee, Cha, Yoo, and Park: Prevalence of Antibodies to Hepatitis C Virus in Patients with Various Types of Liver Diseases

Abstract

Background

Hepatitis C virus (HCV) is known to be a major cause of non-A, non-B hepatitis (NANBH) and is thought to be an important causative agent of serious liver disease. Recently the role of HCV in the development of various liver disease is suggested.

Methods

Sera from 222 patients with various liver diseases had been kept frozen at −20°C until the test. Anti-HCV was detected using the ABBOTT HCV EIA Test System (ABBOTT Co., America) following the manufacturer’s instructions. The assay uses a recombinant HCV antigen (C 100-3) synthesized in yeast.

Results

HCV antibodies (anti-HCV) were detected in 35 (31.5%) of 111 HBsAg-negative patients. The prevalence rate of anti-HCV was 61.9% (13 out of 21patients) in chronic hepatitis, 29.1% (14 out of 48) in liver cirrhosis, 26.3% (5 out of 19) in hepatocellular carcinoma and 13% (3 out of 23) in acute hepatitis was far less (3 out of 111 patients, 2.7%) than that of HBsAg-negative patients (p<0.01). In this group, anti-HCV was detected in 2 (5.1%) out of 39 liver cirrhosis, 1 (1.9%) out of 52 chronic hepatitis, among them 47 were biopsy-proven chronic active hepatitis, and none of 20 hepatocellular carcinoma.

Conclusions

These data suggest that, in Korea, 1) coinfection of HCV and HBV is infrequent, 2) HCV might be an important cause of HBsAg-negative chronic hepatitis, 3) HCV is seemed to be a less likely important factor associated with liver cirrhosis or hepatocellular carcinoma in HBsAg-negative patients, but further prospective study with a large population is necessary.

INTRODUCTION

Since the development of sensitive diagnostic tests for infection of hepatitis A virus (HAV) and hepatitis B virus (HBV) in 1975, it was well known that most cases of post-transfusion hepatitis are not caused by these agents or any other known hepatotropic virus such as cytomegalovirus (CMV) or Epstein-Barr virus (EBV)1). Although most acute infections are asymptomatic, at least half of these non-A, non-B (NANB) infections result in chronic hepatitis, which may result in cirrhosis in approximately 20% of cases2). A potential association with hepatocellular carcinoma has also been proposed3,4). In addition, NANB virus is a frequent cause of community-acquired (sporadic) hepatitis, a nonpercutaneously transmitted hepatitis that is also often chronic5). Despite intensive research over a decade, the causative agent (or agents) of these non-A, non-B hepatitis (NANBH) remained unidentified. However, in the late 1970s, transmission of the agent to chimpanzees was reported6,7). As in humans, about 50% of infected chimpanzees develop chronic NANB infections following innoculation with contaminated human serum or blood clotting concentrates8). These chimpanzee transmission studies have defined a NANB agent isolated form clotting factor VIII concentrates, which is chloroform sensitive, and induces ultrastructural cytoplasmic tubular changes in hepatocytes. A system for the detection of the non-A, non-B virus has been elusive, but such a system has been reported since the recent cloning of the genome of the previously uncharacterized NANB virus9), now tentatively designated the hepatitis C virus; both radioimmune and enzyme-linked assays have been developed to detect antibody (anti-HCV) to the protein expressed in the cloning experiments5). We tested anti-HCV, using the enzyme-immunoassay, in serum samples from patients with various liver diseases to assess the role of HCV infection in the development of liver diseases in Korea.

SUBJECTS AND METHODS

1. Patients

222 patients with various types of liver diseases diagnosed between 1987 and 1991, were studied. Sera from these patients had been kept frozen at −20°C until the test. Of these, serum HBsAg-negative patients were 111 and the remainder were positive for HBsAg. HBsAg-negative group consisted of 23 patients (M=14, F=9) with acute hepatitis who were negative for serum HBsAg, HBeAg and anti-HAV (IgM), 21 with chronic hepatitis, of whom 9 (M=6, F=3) were biopsy-proven chronic active hepatitis, 48 (M=37, F=11) with liver cirrhosis and 19 (M=15, F=4) with hepatocellular carcinoma. In HBsAg positive group, there were 52 patients (M=36, F=16) with chronic hepatitis consisting of 47 with biopsy-proven chronic active hepatitis, 39 (M=29, F=10) with liver cirrhosis and 20 (M=15, F=5) with hepatocellular carcinoma. Diagnosis of non-biopsy proven chronic hepatitis was made when the elevated serum alanine aminotransferase (sGPT) persisted at least 6 months. Liver cirrhosis was diagnosed based upon abnormal blood chemistry and physical findings and presence of any evidence of portal hypertension either on radiologic or endoscopic examinations. Diagnosis of hepatocellular carcinoma was confirmed either by histologically, radiologically (such as ultrasonography, computed tomography, radionuclide scanning or angiography of the liver) or significantly elevated serum alpha-fetoprotein (AFP) concentration.

2. Serologic Tests

1) Markers for Hepatitis A and Hepatitis B

Anti-HAV was tested with radio-immunoassay using HAVAB-M® (ABBOTT Co., America). HBsAg, HBeAg, anti-HBs, anti-HBe, and anti-HBc were tested with a commercially available enzyme immunoassay using AUSZYME®, HBe (rDNA) EIA, AUSAB®, CORZYME® tests, respectively (ABBOTT Co., America).

2) Antibody to Hepatitis C Virus (anti-HCV)

Anti-HCV was detected using the ABBOTT HCV EIA Test System (ABBOTT Co., America) following the manufacturer’s instructions. The assay uses a recombinant HCV antigen (C 100-3) synthesized in yeast. The presence or absence of antibody to HCV is determined by relating the absorbance of the specimen to the cutoff value. The cutoff value is the mean absorbance of the negative control plus 0.25 times the mean absorbance of the positive control. For the run to be valid, the difference between the mean absorbances of the positive and negative controls (P-N) should be 0.400 or greater. Specimens with absorbance values less than the cutoff value are considered negative and specimens with absorbance values greater than or equal to the cutoff value are considered initially reactive, but, before interpretation, the original sample should be retested in duplicate. If either duplicate retest is reactive, the specimen is interpreted to be repeatably reactive for antibodies, but initially reactive specimens which do not react in both of the duplicate tests are considered negative by the criteria of ABBOTT HCV EIA.

STATISTICAL ANALYSIS

Statistical significance was determined using the binomial test. A p value≤0.05 was considered significant.

RESULTS

1) Prevalence of anti-HCV in HBsAg-negative patients with various liver diseases.
Serum anti-HCV was detected in 7 (77.7%) among 9 biopsy-proven CAH patients, 13 (61.9%) among 21 patients with chronic hepatitis, 14 (29.1%) among 48 patients with liver cirrhosis, 5 (26.3%) among 19 patients with hepatocellular carcinoma and 3 (13%) among 23 patients with acute hepatitis (Table 1)
2) Prevalence of anti-HCV in HBsAg-positive patients with chronic liver diseases.
Serum anti-HCV was detected in 2 (5.1%) among 39 patients with liver cirrhosis, one (1.9%) among 52 patients with chronic hepatitis, none among 47 biopsy-proven CAH patients and none among 20 patients with hepatocellular carcinoma (Table 2).
3) Relationship between the appearance of other HBV markers and the prevalence of anti-HCV in the HBsAg-negative chronic liver diseases.
Serum anti-HCV was detected in 3 (60%) among 5 patients positive for anti-HBs only, 5 (41.6%) among 12 patients negative for anti-HBs and anti-HBc, 8 (38.0%) among 21 patients positive for anti-HBc only and 12 (29.2%) among 41 patients positive for anti-HBs and anti-HBc (Table 3).
4) Difference in the prevalence of anti-HCV between various HBsAg-negative chronic liver diseases.
The prevalence of anti-HCV in patients with chronic hepatitis was significantly higher than the prevalence in patients with liver cirrhosis (p<0.01) and primary liver cancer (p<0.05). There was no significant difference between liver cirrhosis and hepatocellular carcinoma.

DISCUSSION

We tested anti-HCV in sera from patients with various liver diseases to define the role of HCV infection in liver disease in Korea. The results indicate that HCV is a major cause of HBsAg-negative chronic liver disease, especially chronic hepatitis. The overall prevalence of anti-HCV in patients with HBsAg-negative chronic hepatitis was 61.9%. Similar results were reported in foreign countries (60–70%5,10), but the results in Korea ranged from 15% to 56.7%1113)). The prevalence of anti-HCV in HBsAg-negative patients with liver cirrhosis (29.1%) and primary liver cancer (26.3%) was markedly lower than the reports from foreign countries. Other reports from Korea also indicate the similar lower prevalences (15–40%) in patients with liver cirrhosis and primary liver cancer1115). The lower prevalence of anti-HCV in liver cirrhosis and hepatocellular carcinoma than in chronic hepatitis is difficult to explain at present. Although HCV infection is seemed to be the most frequent cause of non-B chronic hepatitis in Korea, progression to cirrhosis and cancer may be also associated with other etiologic agents, such as alcohol, drugs and aflatoxins. The low prevalence of anti-HCV in non-B acute hepatitis (13%) may be due to the lower titer and unstable structure of the antibodies formed during the acute phase17) and delayed appearance of the antibodies in the acute infection of HCV5,17).
We tested serum anti-HCV in HBsAg-positive patients with chronic liver diseases to evaluate the role of HCV coinfection in the progression of chronic liver diseases in HBV carriers. There was a report of increased prevalence of anti-HCV according to the severity of chronic liver diseases in HBV carriers in Italy4), suggesting that the concerted action of dual HBV and HCV infection may enhance the progression of chronic liver diseases and hepatic carcinogenesis. However, the prevalence of anti-HCV in HBsAg-positive patients with chronic liver diseases was low (2.7%) and not related to the severity of chronic liver diseases. The similar results of low prevalence of anti-HCV in HBsAg-positive patients were shown in other reports from Korea12,15,16). It may be partially due to the difference in the mode of transmission between HBV and HCV. In Korea, a majority of chronic persistent HBV infections appear to be caused by perinatal vertical transmission from HBV carrier mothers, whereas there is no definite evidence for vertical transmission of HCV.
In conclusion, coinfection of HBV and HCV is uncommon and HCV infection might be an important cause of non-B chronic hepatitis in Korea. The role of HCV infection in the development of liver cirrhosis and hepatocellular carcinoma in HBsAg-negative patients appears to be minor in Korea, but further studies are required to define it clearly.

Table 1.
Prevalence of Anti-HCV in HBsAg-negative Patients with Various Liver Diseases
Diagnosis No. patients No. positive % positive
Acute Hepatitis 23 3 13
Chronic Hepatitis 21 13 61.9
* (CAH) (9) (7) (77.7)
Liver Cirrhosis 48 14 29.1
Hepatocellular 19 5 26.3
Carcinoma

Total 111 35 31.5

* CAH = Biopsy-proven chronic active hepatits

Table 2.
Prevalence of Anti-HCV in HBsAg-positive Patients with Chronic Liver Diseases
Diagnosis No. patients No. positive % positive
Chronic Hepatitis 52 1 1.9
(CAH) (47) (0) (0)
Liver Cirrhosis 39 2 5.1
Hepatocellular Carcinoma 20 0 0

Total 111 3 2.7
Table 3.
Relationship between Anti-HCV Prevalence and the Appearance of Other Hepatitis B Viral Markers (anti-HBs and anti-HBc) in HBsAg-negative Chronic Liver Diseases
anti-HBc/anti-HBs No. patients No. positive (%)
+/+ 41 12(29.2)
+/− 21 8(39.0)
−/− 12 5(41.6)
−/+ 5 3(60.0)

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