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

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 antrbody 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. (Received Oct. 13, 1997; accepted June 26, 1998)     

Anticardiolipin antibodies in chronic hepatitis B and chronic hepatitis D infection,and hepatitis B-related hepatocellular carcinoma. Relationship with portal vein thrombosis

OBJECTIVE: To assess the presence of anticardiolipin antibodies (ACAs) in patients with chronic hepatitis B virus (HBV) infection, chronic hepatitis D virus (HDV) infection and HBV-related hepatocellular carcinoma (HCC) and to associate this with the incidence of portal vein thrombosis (PVT) in HCC patients. PATIENTS AND METHODS: Sixty-five cirrhotic patients with HBV-related HCC, 28 naive patients with chronic HBV infection and 14 naive patients with chronic HDV infection were enrolled prospectively in the study. Thirty-two healthy blood donors were used as controls. The ACAs (immunoglobulin G and immunoglobulin M) were measured using an enzyme-linked immunosorbent assay system. Statistical analysis used non-parametric methodology (chi-squared test, Student t-test and Fisher exact test, P value<0.05). RESULTS: Eleven of the 65 patients with HCC (16.9%) showed a positive ACA titre and 22 of the patients (34%) had PVT. Of these patients, eight (36%) had a positive ACA titre. In contrast, from the 43 patients without PVT, only three (11%) showed a positive titre. From the 28 HBV patients, six (21.5%) had a positive ACA titre, and six out of 14 (42.8%) HDV patients also showed a positive ACA titre. Three of the six ACA positive HBV patients presented an extrahepatic manifestation of the disease. One out of 32 control patients (3%) had positive ACAs. CONCLUSION: Both chronic HBV and chronic HDV infections are potent stimulants for the production of ACAs. The presence of ACAs in a great proportion of HBV-cirrhosis-related HCC patients with PVT suggests their possible participation in thrombotic mechanisms and in the hypercoagulable state that occurs in advanced liver disease and HCC.     

HDV重叠感染可增加慢性乙型肝炎患者的肝细胞癌风险

HDV的重叠感染可加速慢性乙型肝炎患者的肝病进程,尤其肝细胞癌(HCC)的发生风险明显增高。但HDV的致癌机制有待进一步探索,治疗方式及效果也亟待突破。综述了HDV相关HCC流行病学新特点、致病机制的新认识和诊疗进展等,对推进研发更精准的HDV检测手段、更有效的治疗药物及减少HDV相关HCC具有重要意义。     

Study of reactivation of chronic hepatitis delta infection

Five patients with chronic hepatitis delta virus (HDV) infection suffered spontaneous episodes of liver enzyme elevation on a background of otherwise biochemically stable liver disease. In all five patients these episodes were accompanied by a rise in serum levels of anti-HDV IgM, HDV antigen and HDV RNA. These episodes of increased HDV replication accompanied by biochemical evidence of liver injury are reminiscent of reactivation in chronic hepatitis B. Surges of increased HDV replication may be important in the progression of liver disease in chronic HDV infection.     

Hepatitis D virus RNA in serum from patients with hepatitis B

To clarify the correlation of hepatitis D virus (HDV) infection and viral replication in liver diseases, the authors detected HDV RNA and serological HDV markers in serum from 285 patients with hepatitis B and 45 asymptomatic carriers of HBsAg. With dot blot hybridization, serum HDV RNA was detected in 8.8% (29/330) of the patients with HBV infection. The positive rate of HDV RNA in fulminant hepatitis was higher than that in benign hepatitis (15/74 vs 3/47, P less than 0.05). 10 of the 139 patients with chronic active hepatitis and 1 of the 6 cases with cirrhosis were positive for HDV RNA. However, all of the 19 cases with chronic persistent hepatitis and 45 asymptomatic carriers of HBsAg were negative fo, HDV RNA. Serological HDV markers, HDAgr anti-HD and IgM-anti-HD, were determined with ELISA. HDV RNA was detected in all of the serum samples with positive HDAg and/or IgM-anti-HD, in 15 of the 26 cases with positive-anti-HD and in 8 cases without HDV markers. Our results showed that 40 of the 330 patients with HBsAg were infected by HDV. This investigation suggests that HDV is one of the etiological factors for fulminant hepatitis and chronic active hepatitis.     

Relationship between hepatocyte proliferation and hepatitis delta virus replication in neoplastic and non-neoplastic liver tissues

SUMMARY. We studied the relationship between hepatocyte proliferation and hepatitis delta virus (HDV) replication at the single cell level. The proliferating cell nuclear antigen (PCNA) (by immunohistochemistry) and the HDV RNA (by in situ hybridization) were stained in neoplastic and non-neoplastic liver tissues of 19 patients with chronic HDV infection, including four cases of cirrhosis with superimposed hepatocellular carcinoma (HCC). As controls, we assessed the hepatocyte proliferation of liver tissues from 16 patients with chronic hepatitis B and on three normal livers. The hepatocyte PCNA labelling index of HDV-infected tissues was comparable with that seen in chronic hepatitis B-infected livers but was significantly higher than that observed in normal livers. Although cirrhotic tissues had lower hepatocyte proliferating fractions than non-cirrhotic tissues, the difference was not statistically significant. The hepatocyte proliferation rate did not correlate with the level of intrahepatic HDV replication or with the histological activity. In double-labelling experiments, PCNA and HDV RNA staining did not co-localize, with the exception of two of three cirrhotic tissues associated with HCC, where the association between the two markers was statistically significant. This co-localization was not observed, however, in the adjacent tumorous tissues. In patients with chronic HDV infection the hepatocyte proliferation was increased with respect to normal liver tissue, but was comparable with that observed in patients with chronic hepatitis B virus infection and did not correlate with the level of HDV replication or the histological activity. In the cirrhotic tissue of patients with HCC (but not in the tumour counterpart), HDV RNA may occasionally co-localize with the marker of hepatocyte proliferation. Whether this association between viral replication and cell division is related to liver carcinogenesis remains to be established.     

Different outcomes of chronic hepatitis delta virus infection in woodchucks

Hepatitis delta virus (HDV) superinfection of woodchuck chronic carriers of woodchuck hepatitis virus (WHV) results in acute and chronic disease. The different courses of disease mimicked the outcome of human HDV superinfection, making woodchucks valuable models for clinical studies of HDV. Ten of 11 woodchuck chronic carriers of WHV superinfected with HDV developed acute HDV infection with markers of viral replication in the serum and liver. One animal (DW128) had no serological markers of acute HDV infection. Nine of 11 (82%) superinfected animals developed chronic HDV infection. An unusual course of chronic HDV infection occurred in one woodchuck (DW128): no serum markers of acute or chronic HDV infection appeared but HDV RNA was detected in the liver, indicating that chronic HDV infection can occur without serological markers.     

Influence of human immunodeficiency virus infection on cell-mediated immunity in chronic D hepatitis.

To determine whether the abnormalities of cell-mediated immunity described in chronic D hepatitis are associated with hepatitis D virus (HDV) infection or concomitant human immunodeficiency virus (HIV) infection, serologic and tissue hepatitis B virus (HBV) and HDV markers and T lymphocyte subsets were studied in serum samples from 38 patients with chronic D hepatitis, 26 of whom had HIV infection. Patients with chronic D hepatitis and HIV infection had significantly lower peripheral blood T4:T8 ratios resulting from a significant increase in T8+ (suppressor/cytotoxic) cells, while numbers of T lymphocyte subsets were normal in cases with chronic D hepatitis only. HIV+ patients showed an increase in HBV replication (identified by hepatitis B core antigen in liver and hepatitis B e antigen and HBV DNA in serum) and in HDV replication (tissue D antigen and HDV RNA) without evidence of more active liver disease. Probably the immunologic disturbances detected in chronic D hepatitis are secondary to HIV infection, do not contribute to the pathogenesis of liver injury, and are associated with increased viral B and D replication.     

Prevalence of hepatitis C antibody in patients with chronic liver disease and hepatocellular carcinoma in Korea

Summary. To investigate the contribution of hepatitis C virus (HCV) to chronic liver disease and hepatocellular carcinoma (HCC) in Korea, antibodies to HCV (anti-HCV) were tested by enzyme immunoassay in 1759 patients with chronic liver disease and HCC, and in 808 healthy adults. The prevalence of anti-HCV was 1.6% in 808 controls. Anti-HCV was present in 32 (7.7%) of 418 hepatitis B surface antigen (HBsAg)-positive and 128 (53.1%) of 241 HBsAg-negative patients with chronic hepatitis, 16 (6.0%) of 265 HBsAg-positive and 90 (30.5%) of 295 HBsAg-negative patients with liver cirrhosis, and 16 (4.8%) of 330 HBsAg-positive and 61 (29.0%) of 210 HBsAg-negative patients with HCC. Antibodies to hepatitis B core antigen (anti-HBc) were present in 80–88% of patients who were seropositive for anti-HCV and seronegative for HBsAg. Among the sera from 114 patients with HBsAg-negative and anti-HCV-positive chronic liver diseases, HBV DNA and HCV RNA were detected by polymerase chain reaction (PCR) in 54 (47.4%) and 61 (53.3%), respectively. Both HBV DNA and HCV RNA were detected in 4 (4.4%) samples. The mean age of the patients with both HBsAg and anti-HCV was not different from that of patients who were seropositive for HBsAg alone. These findings indicate that current and/or past HBV infection is still the main cause of chronic liver disease in Korea. Although multivariate analysis showed that anti-HCV is a risk factor for chronic hepatitis, cirrhosis of the liver and HCC, PCR data for HBV DNA and HCV RNA indicate that HCV infection plays only a minor role in HBsAg-positive as well as in HBsAg-negative liver disease and does not accelerate the development of HCC in HBV carriers.     

Prevalence of hepatitis delta virus (HDV) infection in chronic hepatitis B patients in eastern Turkey: still a serious problem to consider

Summary. Hepatitis delta virus (HDV) is a serious cause of liver‐related morbidity and mortality. Coexistent infection with HDV tends to aggravate the course of hepatitis B virus (HBV)‐associated liver disease. The aim of this study was to determine the prevalence of HDV infection among patients chronically infected with HBV in the Elazig region, which is in eastern Turkey. A group of 282 patients infected with chronic HBV were investigated for the study. Anti‐HDV seropositivity was evaluated in all patients. The anti‐HDV‐positive patients were further tested for HDV RNA. Severity of liver disease was assessed by liver biopsy. Regression analysis was used to determine the relationship between independent variables and HDV positivity. Of 282 chronic HBV patients, 192 were men (68.1%) and 90 were women (31.9%). The mean age was 43.8 ± 12.7 (between 18 and 73 years). Anti‐HDV was positive in 45.5% of the patients (128/282). Among the 128 anti‐HDV‐positive patients, 116 were checked for HDV RNA and 56.9% were found positive (66/116). Chronic HDV infection rate was therefore present in at least 23.4% of the whole study group (66/282). There were 83 patients with cirrhosis (29.4%) in the study group. Anti‐HDV seroprevalence and HDV RNA presence were higher in those with cirrhosis (61.4% and 42.2%, respectively). No significant relationship was found between anti‐HDV seropositivity and demographic factors such as age, sex and operation or transfusion history except family history. HDV‐RNA‐positive patients had significantly higher ALT and lower albumin levels when compared to HDV‐RNA‐negative patients. HDV‐RNA‐positive patients also had a significantly higher fibrosis stage. In conclusion, these findings demonstrated that HDV infection is endemic and still a serious problem in the Elazig region of eastern Turkey. HDV infection is significantly related to the family exposure and increases the risk of severe liver fibrosis in this region.     

Circulating microRNA,miR-122 and miR-221 signature in Egyptian patients with chronic hepatitis C related hepatocellular carcinoma

AIM: To explore the potential usefulness of serum miR-122 and miR-221 as non-invasive diagnostic markers of hepatitis C virus(HCV)-related hepatocellular carcinoma(HCC).METHODS: This prospective study was conducted on 90 adult patients of both sex with HCV-related chronic liver disease and chronic hepatitis C related HCC. In addition to the 10 healthy control individuals, patients were stratified into; interferon-na?ve chronic hepatitis C(CH)(n = 30), post-hepatitis C compensated cirrhosis(LC)(n = 30) and treatment-naive HCC(n = 30). All patients and controls underwent full clinical assessment and laboratory investigations in addition to the evaluation of the level of serum miR NA expression by RT-PCR.RESULTS: There was a significant fold change in serum mi RNA expression in the different patient groups when compared to normal controls; mi R-122 showed significant fold increasing in both CH and HCC and significant fold decrease in LC. On the other hand, mi R-221 showed significant fold elevation in both CH and LC groups and significant fold decrease in HCC group(P = 0.01). Comparing fold changes in miR NAs in HCC group vs non HCC group(CH and Cirrhosis), there was non-significant fold elevation in miR-122(P = 0.21) and significant fold decreasing in miR-221 in HCC vs non-HCC(P = 0.03). ROC curve analysis for miR-221 yielded 87% sensitivity and 40% specificity for the differentiation of HCC patients from non-HCC at a cutoff 1.82. CONCLUSION: Serum miR-221 has a strong potential to serve as one of the novel non-invasive biomarkers of HCC.     

Quantitative HBsAg and HDV‐RNA levels in chronic delta hepatitis

Background: Hepatitis delta virus (HDV) causes severe liver disease. Aims: To investigate the quantitative HDV‐RNA, HBsAg and hepatitis B virus (HBV)DNA levels in correlation to histological, biochemical and demographical parameters in patients with chronic HDV infection as similar data in a large series of HDV patients are missing. Methods: Eighty HDV patients were recruited in Germany, Turkey and Greece; quantitative determination of HDV‐RNA, HBsAg and HBV‐DNA was performed by real‐time polymerase chain reaction, the Architect HBsAg assay and Cobas TaqMan HBV test respectively. Results: All patients were infected with HDV‐genotype 1. Thirty‐five patients (48%) had significant fibrosis (Ishak 3–4) and 15 (20.5%) had cirrhosis. HDV viraemia ranged from 1.1 × 10³ to 8.4 × 10⁷ copies/ml with 60% of patients showing HDV‐RNA levels above 10⁵ copies/ml accompanied by low HBV viraemia (<10⁵ copies/ml). However, HDV‐RNA and HBV‐DNA levels showed no direct inverse correlation. HDV‐RNA correlated positively with HBsAg and negatively with age. HBsAg correlated negatively with age and positively with histological grading. Only γ‐glutamyltranspeptidase was independently associated with cirrhosis (P=0.032), while no biochemical parameter was associated with grading. Conclusions: (i) HBsAg levels correlated with HDV viraemia in chronic HDV. (ii) Biochemical parameters did not accurately indicate the stage and grade of liver disease in chronic HDV and thus liver biopsy seems to remain the major tool for the evaluation of delta hepatitis patients.     

Epidemiology and clinical aspects on hepatitis C

Hepatitis C virus (HCV) infects an estimated 170 million persons worldwide, and 2 million persons in Japan. HCV is a major cause of chronic liver diseases, especially hepatocarcinogenesis, and the number of patients with HCV-related hepatocellular carcinoma (HCC) is increasing worldwide as well as in Japan. Most patients with acute hepatitis C develop chronic hepatitis. Spontaneous disappearance of HCV in patients with type C chronic liver disease is uncommon, and it tends to progress to further advanced and more severe liver disease, ultimately to HCC over a period of 30 years in most cases. Chronic liver disease due to HCV infection is commonly associated with extrahepatic manifestation, for example cryoglobulinemia. Antiviral treatment for HCV infection with interferon alone during 24 weeks was associated with a low rate (less than 10%) of sustained virologic response (SVR), especially in patients infected with HCV genotype 1b and high HCV RNA concentration. However, combination therapy of interferon and ribavirin raises the SVR rate. More recently, pegylated interferon used for treatment of chronic hepatitis C resulted in a high SVR rate. These modalities of antiviral treatment will reduce HCC occurrence. So far, there is no HCV vaccine in spite of many efforts.     

Serum hepatitis delta virus RNA in patients with delta hepatitis and in liver graft recipients

We have investigated the usefulness of serum hepatitis delta virus (HDV) RNA detection using a slot hybridization analysis of serum samples from ten patients with acute hepatitis and delta markers (group I), from 28 patients with chronic delta hepatitis (group II) and from seven liver graft recipients with hepatitis B virus (HBV) and HDV related cirrhosis or fulminant hepatitis (group III). The slot-blots were hybridized with both HDV-complementary DNA and single-stranded RNA probes. With the single-stranded RNA probe, HDV RNA was detected in the first serum sample available in 9/10 of the patients with acute hepatitis (group I). In addition, HDV RNA was detected in 8/9 and 7/8 of the samples obtained within and after 1 month of the onset of hepatitis. Five of the ten patients scored positive for HDV RNA and negative for hepatitis delta antigen (HDAg) while one was negative for HDV RNA and positive for HDAg. The same RNA probe enabled the detection of serum HDV RNA in 21/28 chronic hepatitis patients (liver HDAg and/or IgM anti-HD positive) (group II). Among the liver graft recipients (group III), 7/7 had a recurrent delta infection. Serum HDAg, liver HDAg and anti-HD IgM were identified in 3/7, 6/7 and 5/7 of the patients, respectively. HDV RNA was detected in the seven patients with either persistent (4/7) or transient (3/7) positivity. In addition, HBsAg and HBV RNA were persistently shown in 4/7 patients with continuous HDV replication. In the remaining three patients, HDV RNA was detectable despite the absence of HBsAg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of human immunodeficiency virus infection on hepatitis δ virus superinfection in chronic HBsAg carriers

SUMMARY. It is generally agreed that hepatitis B virus (HBV) replication is reduced by hepatitis δ virus infection (HDV) and augmented by human immunodeficiency virus (HIV) infection. However, the precise nature of the interactions between HBV. HDV and HIV is controversial. The aim of this study was to evaluate the impact of HIV infection on HBV and HDV replication, and on histological scores during δ virus super-infection in HDV-positive. chronic carriers of hepatitis B surface antigen (HBsAg). We studied 38 men and six women, 15 of whom were HIV-positive and all of whom had at least one marker of HDV infection. Serum hepatitis B e antigen (HBeAg), HBV DNA, HDV RNA, anti-δ antigen antibodies (anti-HD) IgM, anti-HD IgG and hepatitis δ antigen (HDAg) were tested for in the serum and liver, respectively; anti-hepatitis C virus (HCV) antibodies were detected using a second-generation recombinant immunoblot assay. Histological specimens were scored blindly according to Knodell's classification for periportal and intralobular necrosis, portal inflammation and fibrosis. HBV DNA was detected more frequently in the HIV-positive patients than in those who were HIV-negative (25 vs 0% P = 0.01), while markers of HDV replication (serum anti-HD IgM. serum HDV RNA and liver HDAg) were as frequent in the HIV-positive patients (69%, 40% and 50% respectively) as in those who were HIV-negative (75%, 52% and 30%. respectively; P>0.05). By contrast, 31% of the HIV-positive patients were serum HDAg-positive compared to only 6% of the HIV-negative patients (P = 0.001). HDV antigenaemia and anti-HD antibodies usually fluctuated in the HIV-positive patients during follow-up. The mean Knodell score was similar in the HIV-positive (11.5 ± 3.2) and HIV-negative (10.7 ± 2) subgroups, as was the mean semi-quantitative index of hepatic necrosis, inflammation and fibrosis. Our results provide evidence that in HDV-positive patients: (1) HIV infection counters the inhibitory effect of HDV superinfection on HBV replication; (2) serum anti-HD IgM, HDV RNA and liver HDAg are not more frequent in HIV-positive than in HIV-negative patients, suggesting that HIV infection has no effect on HDV replication (although the significance of the increased frequency of HD antigenaemia remains unclear): (3) the histological severity of liver disease is not influenced by HIV status.     

Natural course of patients with chronic type B hepatitis following acute hepatitis delta virus superinfection

A 6-96-month prospective follow-up study on the natural course of chronic type B hepatitis after contracting acute hepatitis delta virus (HDV) superinfection was conducted in 30 patients with clear-cut onset of acute HDV superinfection (HDV group). Thirty patients with acute exacerbation without evidence of HDV infection, and well matched in terms of age, sex and hepatitis B e antigen/antibody status, served as the control group. The clinical and biochemical presentations tended to be more severe in the HDV group. More patients in the HDV group had persistent abnormal liver biochemical tests (69% vs 47%) and progressed to chronic active hepatitis (46% vs 20%) or cirrhosis (9.4%/year vs 5.2%/year), but the differences were not significant statistically. The results suggest that HDV superinfection induces slow progression of liver disease. However, in the early stage, the impact of HDV superinfection is not particularly different from that of the acute exacerbation unrelated to HDV in patients with chronic type B hepatitis.     

Detection of hepatitis delta virus RNA in chronic liver disease

A series of 120 patients with chronic delta hepatitis virus (HDV) were investigated using a newly developed assay for the detection of serum delta RNA and this marker was correlated with other markers of HDV infection. The assay was shown to be both specific and sensitive and provides a direct non-invasive measurement of HDV infectivity. Serum HDV RNA was detected in 51.2% of all patients and in about 64% of those who were liver HDV antigen positive. Its presence was particularly associated with the early stages of the disease where it was found in 83% of cases with chronic active hepatitis (CAH) and progressively less common in CAH associated with cirrhosis and in inactive cirrhosis. The presence of both HBeAg (and HBV DNA) and high levels of HDV RNA in the sera of 5 of the patients analysed, clearly demonstrates simultaneous replication of both HBV and HDV. The serum HDV RNA 'slot blot' assay described in this study should prove invaluable in elucidating further the natural history of delta hepatitis and in monitoring antiviral therapy.     

Seroprevalence and epidemiological characteristics of HDV infection among HBV patients in the Nile Delta,Egypt

The epidemiology of HDV infection worldwide is obscure. Mapping the epidemiology of the infection is highly required, so, we aimed to estimate the prevalence of hepatitis D virus infection among chronic hepatitis B patients and the epidemiological characteristics in the Nile delta in Egypt. This was a prospective observational cross-sectional study including consecutive chronic hepatitis B patients in the out-patient clinics at the Egyptian Liver Research Institute and Hospital (ELRIAH) and its satellites in the Nile Delta from January 2016 until August 2018. They were recruited from patients enrolled in Educate, Test and Treat program, which was implemented in 73 Egyptian Villages. Subjects were tested by using HBsAg serological rapid diagnostic tests (RDTs), and then HBV DNA by PCR was done in HBsAg-positive cases. HDV IgG antibody testing and confirmatory HDV RNA PCR were done. Complete liver functions, abdominal ultrasonography and FibroScan were also performed. The prevalence of HDV was 3.4% using anti-delta antibody (22/631), and only 8 were positive for HDV RNA (8/22, 36.4%). Overall HDV prevalence using PCR was 8/631(1.27%). HDV-positive cases were mainly males (68.2%). Eight cases were cirrhotic (36.4%), 3 (13.6%) had HCC and 7 (31.8%) were HBeAg positive. HDV prevalence is low among chronic hepatitis B patients in the Nile delta, Egypt. Screening for HDV IgG is recommended in CHB patients who had cirrhosis, HCC or HBeAg positive.     

Hepatitis delta virus RNA in serum of patients with chronic delta hepatitis

We studied 28 patients with chronic delta hepatitis for the presence of hepatitis delta virus (HDV) RNA in serum. The hot start polymerase chain reaction (PCR) method, in which the reaction begins at 60–80° C, showed a higher sensitivity than conventional PCR reaction. Additionally, the presence of hepatitis B (HBV) and C virus (HCV) infections were determined by PCR. HDV RNA was detected in 26 patients (93%), HBV DNA in 22 (79%), and HCV RNA in only one. Detection of HDV RNA correlated very well with detection of hepatitis delta antigen by immunostaining in the liver. In six patients HDV RNA was detectable despite the absence of HBV DNA in serum, suggesting that high levels of HBV are not required for HDV replication. Of 29 control patients with chronic hepatitis B without antibody to HDV, none had detectable HDV RNA, while all had HBV DNA in serum. Detection of HDV RNA with PCR proved highly sensitive and specific, demonstrating that virtually all patients with chronic HDV infection had ongoing viral replication.     

Famciclovir treatment of chronic delta hepatitis

BACKGROUND/AIMS: Interferon is the only established therapy for chronic delta hepatitis and alternative treatment options are an urgent need. Since successful treatment of a case of post-transplant delta hepatitis with the nucleoside analogue famciclovir had been reported, a pilot study was undertaken to evaluate the use of famciclovir in the treatment of chronic delta hepatitis.METHODS: A total of 15 adult patients, 13 men, two women, ages 20-52 years, with chronic delta hepatitis were treated with famciclovir, 500 mg, three times a day for 6 months and were then followed-up for 6 months posttreatment. All patients had compensated chronic liver disease, elevated liver enzymes and were hepatitis delta virus (HDV) RNA positive by polymerase chain reaction at baseline. Patients were monitored and tested for HBsAg, hepatitis B virus (HBV) DNA and HDV RNA levels. Liver biopsies were obtained before starting famciclovir and within 1 month of completion of treatment.RESULTS: HBV DNA levels decreased in nine of the 15 patients and levels rose again after treatment (P<0.05). Famciclovir had no effect on alanine aminotransferase (ALT) and HBsAg levels or on serum HDV RNA and overall, there was no improvement in liver histology.CONCLUSIONS: Treatment of chronic delta hepatitis with famciclovir has no effect on disease activity and HDV RNA levels.