Prevalence and clinical features of hepatitis delta virus infection in the Miyako Islands, Okinawa, Japan

Abstract

The aims of this study were twofold: (1) to determine the prevalence and clinical features of hepatitis delta virus (HDV) infection among subjects positive for hepatitis B surface antigen (HBsAg) living in the Miyako Islands, Okinawa Prefecture, Japan, and (2) to clarify the relationship between HDV-RNA level and severity of HDV-related liver disease. One hundred and ninety-nine HBsAg-positive subjects (123 asymptomatic carriers [ASCs], 3 patients with acute hepatitis [AH], 50 patients with chronic hepatitis [CH], 15 patients with liver cirrhosis [LC], and 8 patients with hepatocellular carcinoma [HCC], were tested for antibody to HDV (anti-HDV) by radioimmunoassay. Anti-HDV-positive individuals were examined to determine semi-quantified HDV-RNA level by polymerase chain reaction (PCR). The overall prevalence of anti-HDV among the 199 subjects was 21.1%. The positivity rate tended to increase with age or the severity of the underlying liver disease: anti-HDV-positive rates were 10.6% (13/123) in ASCs, 32.0% (16/50) in patients with CH, 40.0% (6/15) in patients with LC, and 87.5% (7/8) in patients with HCC. None of the patients with AH were positive for anti-HDV. There was no correlation between semi-quantified serum HDV-RNA levels and the severity of chronic liver disease in patients positive for anti-HDV. The present study showed the local spread of HDV infection in the Miyako Islands, Okinawa, Japan. Although the anti-HDV positivity rate tended to increase with the severity of the underlying liver disease, the severity of HDV-related liver disease did not correlate with the semi-quantified serum HDV-RNA level.

Quantitation of the Level of Hepatitis Delta Virus RNA in Serum, by Real‐Time Polymerase Chain Reaction—and Its Possible Correlation with the Clinical Stage of Liver Disease

“…We found that the levels of HDV RNA in the serum of subjects with CH and of subjects with LC were significantly higher than those in the serum of ASC subjects, thereby extending our previous finding that, for RT-PCR, the rate of detection of HDV RNA in ASC subjects positive for anti-HD is low, compared with that in subjects with either CH or LC [2]. The levels of HDV RNA in serum were below the threshold of detection (!1 kC/mL) in 9 of the 14 ASC subjects and also seemed to be low (!10 2 kC/mL) in the remaining 5 subjects.…”

“…In the present study, we used real-time PCR to develop a new, sensitive method for the quantitation of the level of HDV RNA in serum and determined these levels in 48 subjects positive for anti-HD who were living in the Miyako Islands (Okinawa, Japan) [2][3][4][5]; subsequently, we assessed the relationship between these levels and the extent of liver damage. The levels of HDV RNA in serum of subjects with either CH or LC were significantly higher than those in ASC subjects, but the levels of HBV DNA in serum did not differ among the 3 groups.…”

“…Previously, in the Miyako Islands (Okinawa, Japan), where HDV infection is endemic [2][3][4][5], we studied subjects positive for both HBsAg and anti-HD. The levels of HBV DNA in serum were generally low in these subjects, regardless of the severity of liver disease, raising the possibility that the level of HDV replication plays a major role in liver damage.…”

“…Therefore, the use of a simple method to measure the level of HDV RNA in clinical samples was important in the analysis of the pathophysiology of HDV infection, because many laboratory tests for the detection of HDV RNA are rather complicated [7,8]. By introducing the use of reverse-transcription polymerase chain reaction (RT-PCR) [9] for the measurement of the level of HDV RNA in serum, we showed that half of the patients in the Miyako Islands who were positive for anti-HD were negative for HDV [2]; most were clinically asymptomatic carrier (ASC) patients, which suggests that a low level of HDV replication is associated with an indolent clinical course, despite the presence of chronic HBV infection.…”

Delta Hepatitis

“…The prevalence of HDV infection was low (0.5% to 13.3%) in Japan except in some islands of Okinawa, Russia except in Yakutia (18-20%), Korea, Indonesia (< 0.05%), Malaysia, Thailand (0.7%), Philippines and Vietnam (1.3%), and Lebanon (1.2%) [22]. In Japan, the prevalence of antibodies against HDV (anti-HDV) ranges from 21.3% to 63.3% in Okinawa: these high figures are due to older HBV carriers, and reflect previous acquirement of HDV infection in that cohort [23]. Taiwan was endemic for hepatitis B before vaccination [22].…”