乙型肝炎病毒感染者病毒基因型和亚型分布及其临床意义

目的研究不同类型乙型肝炎病毒（HBV）感染者中HBV基因型和亚型分布情况及其临床意义。方法应用基因型和亚型特异性引物聚合酶链反应法（PCR），对北京、长春、汉川，深圳，清远和南京等6个城市445份HBV感染者血清进行基因型及亚型分型，其中急性肝炎7例，无症状携带者36例，慢性乙型肝炎352例，肝硬化28例，肝细胞癌22例。通过对PCR产物测序确定其基因型，以验证该法的准确性。结果445份血清中，239例（53．7％）为C型，其中13例（5．4％）为C1亚型，135例（56．5％）为C2亚型，91例（38．1％）为非C1／C2亚型；145例（32．6％）B型，其中100例（69．0％）为Ba亚型，25例（17．2％）为Bj亚型，20例（13．8％）为非Ba／Bj亚型；61例（13．7％）为B型与C型混合感染，其中6例（9．8％）为Ba与C1亚型混合感染，3例（4．9％）为Bj与C1亚型混合感染，15例（24．6％）为Ba与C2亚型混合感染，8例（13．1％）为Bj与C2型混合感染，11例（18．0％）为Ba与非C1／C2亚型混合感染，7例（11．5％）为Bj与非C1／C2亚型混合感染，2例（3．3％）为非Ba／Bj亚型与C1亚型混合感染，3例（4．9％）为非Ba／Bj亚型与C2亚型混合感染，6例（9．8％）为非Ba／BJ亚型与非C1／C2亚型混合感染。未检测到其他基因型及亚型。在不同类型乙型肝炎病毒感染者中，B型，C型、B与C型混合感染及亚型分布差异有统计学意义，在肝硬化和肝细胞癌患者中C型所占比例较高（分别为78．6％和86．4％），无症状携带者中B型所占比例较高（72．2％）。但不同性别患者中，HBV基因型和亚型分布无差异。在HBeAg阳性和阴性感染者中，HBV基因型和亚型分布差异也有统计学意义。结论该6个城市HBV感染者中，以B2和C2亚型占优势，C基因型可能与肝硬化和肝细胞癌的发生有关。     

贵州地区慢性乙型肝炎病毒感染者病毒基因亚型研究

目的调查贵州省B、C基因型慢性HBV感染者的病毒基因亚型。方法PCR扩增HBV P区长309 bp的基因片段,扩增产物分别经限制性内切酶NciⅠ、VspⅠ、BstEⅡ酶切,琼脂糖凝胶电泳,根据酶切图谱多态性,用限制性片段长度多态性分析（PCR-RFLP）检测HBV C基因亚型。直接测序确定B基因亚型、对178例用S基因限制性片段长度多态性鉴定为B、C基因型的不同临床类型慢性HBV感染者进行亚型分析。结果84例C基因型HBV感染者中,27例（32.14%）为C1亚型、56例（66.67%）为C2亚型,1例为C1、C2亚型混合感染。94例B基因型HBV感染者中,93例（98.94%）为Ba、1例为Bj亚型感染。从无症状乙型肝炎表面抗原携带者、CHB到肝硬化/肝癌,C1亚型在各组中的比例逐渐降低,分别为60.00%、30.65%和16.67%;而C2亚型在各对应组中的分布逐渐增高,分别为40.00%、67.74%和83.33%。结论贵州地区B、C基因型慢性HBV感染者中,以Ba、C2亚型为主。C1、C2亚型在疾病中的分布有一定差异。PCR-RFLP分析HBV C1、C2亚型,方法简便、特异性强,适合较大样本分析,可用于流行病学调查。     

Spatial and chronological differences in hepatitis B virus genotypes from patients with acute hepatitis B in Japan

Genotypes of hepatitis B virus (HBV) were determined in 485 patients with acute hepatitis B from all over Japan. They were A in 92 (19%), Ba in 26 (5%), Bj in 32 (7%), C in 330 (68%) and D in 5 (1%). Sexual contacts were the main route of transmission in them. Overall, HBV persisted in only 5 of the 464 (1%) followed patients. Genotypes C accounted for more than 68% in northern as well as southern areas, contrasting with genotype A accounting for 34% in and around the Metropolitan areas. During 24 years from 1982 to 2005, genotype A increased from 5% to 33%, while genotype B gradually decreased from 26% to 8%. Fulminant hepatitis was significantly more frequent in infection with genotype Bj (41%) than those with the other genotypes (p < 0.01). The core-promoter double mutation (T1762/A1764) and precore stop-codon mutation (A1896) were more frequent in patients with fulminant than acute self-limited hepatitis (57% versus 15% and 58% versus 10%, respectively, p < 0.01 for both). In conclusion, genotype A distributes unevenly over Japan, prevails in younger patients through sexual transmission and has increased with years. Furthermore, fulminant outcome was more frequent in patients with genotype Bj than those with the other genotypes.     

Infection with hepatitis B virus genotype A in Tokyo, Japan during 1976 through 2001

Background Because genotype A of hepatitis B virus (HBV) is not indigenous, there have been only few data on infection with it in Japan.Methods We examined clinical and virological features of the 66 Japanese patients who admitted Toranomon Hospital in Tokyo, Japan, between 1976 and 2001, who were found to have HBV/A infection. HBV genotype A was classified into subtype A (European type) and A (South African type) by phylogenetic analysis of the preS1 and preS2 regions, and the S gene sequences.Results Of the 66 patients infected with HBV/A, 14 (21%) were asymptomatic carriers, 26 (39%) presented with acute hepatitis, 22 (33%) with chronic hepatitis, and 4 (6%) with liver cirrhosis. HBV/A infection persisted for more than 6 months in 5 of the 26 (19%) patients with acute hepatitis. The frequency of acute hepatitis in patients infected with HBV/A was higher after than before 1991 (2/22 [9%] vs 24/44 [55%]; P < 0.0001). The frequency of nucleotide 1858 of T was higher in asymptomatic carriers than in patients with acute hepatitis in whom infection was resolved (5/14 [36%] vs 0/21 [0%]; P = 0.008). Of the 57 patients for whom subtypes of genotype A were determined, subtype A was identified in 53 (93%) and subtype A in only 4 (7%). All patients infected with subtype A were persistently infected with HBV.Conclusions HBV/A infection has become more frequent during recent years, predominantly presenting as acute hepatitis, and subtype A is uncommon in the Tokyo metropolitan area.     

135例乙型肝炎病毒感染者基因分型及其临床分布

目的研究乙型肝炎病毒（HBV）感染者中HBV基因分型及其临床分布情况。方法应用基因型和亚型特异性引物聚合酶链反应（PCR）法，对鲁西地区135例HBV感染者血清进行HBV基因型及亚型分型。结果未分型11例，已分型124例。其中C型111例（C2基因亚型87例、非C1／C2亚型24例）；B型11例，其中Ba型8例、Bj型3例；B／C混合型2例均为BaC2亚型混和感染。在肝硬化和重度慢性乙型肝炎中C型所占比例较高，分别为100％、88％；无症状携带者中B型所占比例较高为8．51％；HBV基因型分型与性别无关。结论鲁西地区HBV感染者以C基因型为主，其中C2亚型占优势。     

Distribution and characteristics of hepatitis B virus genotype C subgenotypes in China

Genetic diversity within the same hepatitis B virus (HBV) genotype indicates the presence of several subgenotypes. We have found that genotype C is the most common in China, and this study aimed to determine the geographical distribution and characteristics of HBV-C subgenotypes in the country. A cohort of 534 patients with chronic HBV genotype C infection, collected across China, was analysed by nucleotide sequencing or polymerase chain reaction-restriction fragment length polymorphism. HBV-C1/Cs (n = 112, 21%) and HBV-C2/Ce (n = 397, 74%) were the most common HBV-C subgenotypes and showed different geographical distribution in China. No significant differences were found between patients infected with HBV-C1 and HBV-C2 when comparing liver function tests, hepatitis B e antigen positive rate and clinical manifestations. We identified two other types of HBV-C provisionally designated as HBV-CD1 and HBV-CD2, which have particular virological features and clustered in one geographic area. These two types of C/D hybrids have emerged through recombination with genotype D and encode serotype ayw2 hepatitis B surface antigen. In conclusion, there are at least four subtypes of HBV genotype C: subgenotypes C1, C2 and two types of C/D recombinants CD1 and CD2 in China, which have a distinct geographic distribution. Whether HBV-C subgenotypes differ in their impact on liver disease progression requires prospective studies.     

Epidemiologic and virologic characteristics of hepatitis B virus genotype B having the recombination with genotype C

BACKGROUND & AIMS: Hepatitis B virus (HBV) isolates of genotype B (HBV/B) with or without the recombination with genotype C over the precore region plus core gene have been reported. METHODS: All the 41 HBV/B isolates having the recombination with genotype C (HBV/Ba) possessed the nucleotide 1838 of A in contrast to that of G in all 29 of those without the recombination (HBV/Bj). Taking advantage of this single nucleotide polymorphism, a restriction fragment length polymorphism method was developed that distinguished HBV/Ba from HBV/Bj. RESULTS: HBV/Bj was detected in 90 of the 97 (93%) carriers of HBV/B from Japan, whereas HBV/Ba occurred in all 177 carriers of HBV/B from other countries (China, 20; Hong Kong, 45; Taiwan, 32; Thailand, 30; Vietnam, 30; and the United States, 20 [all of an Asian ethnicity]). In a case-control study, hepatitis B e antigen (HBeAg) and the double mutation in the core promoter (T1762/A1764) were significantly more frequent in 80 carriers each of HBV/Ba than HBV/Bj (35% vs. 18%, P < 0.05 and 33% vs. 15%, P < 0.05, respectively). Differences in the prevalence of HBeAg were more conspicuous between the carriers of HBV/Bj and HBV/Ba older than 30 years (5 of 66 or 8% vs. 16 of 62 or 26%, P < 0.01). CONCLUSIONS: HBV/B having the recombination with genotype C is frequent in Asia, except in Japan, and HBeAg is more prevalent in carriers of HBV/Ba than HBV/Bj.     

Changes in levels of hepatitis B virus markers in patients positive for low-titer hepatitis B surface antigen

Aim: Recently, patients positive for the low-titer hepatitis B surface antigen (HBsAg) have been found occasionally owing to the increase in the accuracy of detection methods. The aim of this study is to clarify the clinical status of acute hepatitis B virus (HBV) infection in patients positive for low-titer HBsAg. Method: Eight patients, who were positive for HBsAg at low titers and diagnosed as having acute HBV infection, were enrolled in this study. Assays of HBsAg, hepatitis B core antibody (anti-HBc), hepatitis B e-antigen (HBeAg), hepatitis B e-antibody (anti-HBe), hepatitis B surface antibody (anti-HBs) and HBV DNA, and biochemical tests were basically conducted every 4 weeks for at least 24 weeks. Result: The average cut-off index of HBsAg was 8.7 ± 9.6 (range, 1.0–25.7). All the patients were negative for anti-HBc, HBeAg, anti-HBe and HBV DNA on their initial visit. The genotype of HBV could be determined in four patients: two were infected with genotype B/HBV, one was infected with genotype A/HBV, and the remaining patient was infected with genotype C/HBV. Although HBsAg clearance was observed within 4 months in all the patients, none of the other HBV markers seroconverted during the observation period. Conclusion: HBV infection terminating with seronegativity for HBV markers may occur in transient HBV infection.     

A case-control study of response to lamivudine therapy for 2 years in Japanese and Chinese patients chronically infected with hepatitis B virus of genotypes Bj, Ba and C.

BACKGROUND/AIMS: In eastern Asian countries, hepatitis B virus (HBV) genotype Ba (HBV/Ba), HBV/Bj and HBV/C are prevalent. The aim was to investigate the response or resistance to lamivudine therapy among patients with different HBV genotypes. METHODS: Of 67 Japanese and Chinese patients with chronic hepatitis B, 18 patients with HBV/Bj, 15 with HBV/Ba and 34 with HBV/C were selected for a case-control study matched according to gender and age. All the patients were treated with lamivudine for 2 years and evaluated the response or emergence of the YMDD mutation at year 2 during the treatment. HBV genotypes were detected by the restriction fragment length polymorphism. The YMDD mutation was detected by the direct sequencing after amplification by PCR. RESULTS: At year 2 during therapy, 44.8% of the patients showed normalization of ALT and undetectable HBV DNA (favorable response), 35.8% developed the YMDD mutation. There was no significant difference of response to the therapy among the three genotype groups. The emergence of the YMDD mutation was associated with HBV/C. By the multiple logistic regression analysis, however, the significant factor of a favorable response was a higher pretreatment ALT level and negative HBeAg status and the significant factor of the emergence of the YMDD mutation was HBV/C. CONCLUSIONS: Higher pretreatment ALT level, HBeAg status or HBV genotype may affect the response or resistance to lamivudine therapy.     

Differences of HBV genotypes and hepatocellular carcinoma in Asian countries

Hepatitis B virus (HBV) genotype B (HBV B) and genotype C (HBV C) are prevalent in Asia. Recently HBV B has been classified into two subtypes, HBV Ba, which is ubiquitous in Asia, and HBV Bj specific to Japan. However, little is known about etiological, virological and clinical differences among patients who have various genotypes and who developed hepatocellular carcinoma (HCC). We investigated the relation of HBV subgenotype with etiological and clinical differences of HCC patients between Taiwan and Okinawa in Japan. HBV Bj may be associated with lower incidence of HCC and older development of HCC while HBV Ba or HBV C may be associated withhigher incidence of HCC and younger development of HCC. In addition, we demonstrated the relationship of the specific mutation of HBV, T1653 mutation in the core promoter region, with development of HCC in Japanese patients with HBV C. These data suggest that great differences exist among patients with HCC who are infected with different HBV genotypes or genotype-specific mutations.     

Distribution of hepatitis B virus genotypes among patients with chronic infection.

Hepatitis B virus (HBV) can be classified into at least eight genotypes, A-H. We evaluated the distribution HBV genotypes among patients with chronic infection. METHODS: We consecutively evaluated adult patients with chronic HBV infection from Salvador, Brazil. Patients were classified according to HBV infection chronic phases based on HBV-DNA levels and presence of serum HBV markers. HBV-DNA was qualitatively and quantitatively detected in serum by polymerised chain reaction (PCR). Isolates were genotyped by comparison of amino acid mutations and phylogenetic analysis. RESULTS: One-hundred and fourteen patients were evaluated. HBV-DNA was positive in 96 samples. HBV genotype was done in 76. Mean age was 36 +/- 11.3. In 61 of 76 cases subjects were classified as inactive HBsAg carriers. Their mean HBV serum level was 1760 copies/ml and 53 of 61 were infected with HBV genotype A, seven with HBV genotype F and one with genotype B. Twelve of the 76 patients had detectable hepatitis B e-antigen (HBeAg) in serum. Ten were infected with HBV genotype A and two with genotype F; most had increased alanine aminotransferase and high HBV-DNA levels. Three patients were in the immunotolerant phase, two were infected with HBV genotype A and one with genotype F. HBV subtyping showed subtypes adw2 and adw4. CONCLUSIONS: HBV genotype A adw2 and genotype F adw4 were the most prevalent isolates found. We could not find differences in genotype distribution according to HBV clinical phases and DNA levels. We did not detect HBV genotype D in contrast to a previous study in our center with acute hepatitis B. All inactive HBsAg carriers had low HBV-DNA levels.     

Quantification of hepatitis B surface antigen and E antigen: correlation between Elecsys and Architect assays

Quantification of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) and their change model during treatment are emerging as a useful tool for assessing the outcome of hepatitis B virus (HBV) infection and predicting the efficacy of antiviral therapy. The aim of this study was to compare the performance of the Elecsys and Architect assays for HBsAg and HBeAg quantification. Quantification of HBsAg and HBeAg, determined by these two assays, were assessed in 1292 sera from patients with chronic hepatitis B(CHB). HBeAg quantification in serum was performed by calibrating the results through HBeAg Paul‐Ehrlich international (PEI) reference standard. The HBV genotype was determined by direct sequencing and phylogenetic analysis. Of 1292 samples, the distribution of genotype was 514 (39.78%) genotype B, 776 (60.06%) genotype C, 2 (0.16%) genotype D. The results of HBsAg and HBeAg quantification between the Architect and Elecsys assays were significantly correlated (HBsAg: r = 0.939; HBeAg: r = 0.987), independent of HBV genotype and treatment phase. The mean differences between the two methods (the log₁₀ [Elecsys] ‐ the log₁₀ [Architect]) were 0.075 log₁₀ IU/mL and ?0.149 log₁₀PE IU/mL in quantifying HBsAg and HBeAg, respectively. This study demonstrates a high correlation between the Elecsys and the Architect assays in quantifying HBsAg and HBeAg, regardless of HBV genotype. Both the two assays can be used to monitor the HBsAg and HBeAg levels in patients with chronic hepatitis B.     

Hepatitis B viral genotypes: clinical relevance and molecular characteristics

Hepatitis B virus (HBV) infection is a global health problem and the clinical outcome of chronic HBV infection depends on the frequency and severity of hepatitis flares in the immune clearance phase. Currently, four subtypes and seven genotypes of HBV are identified and most have specific geographic distributions. The impact of HBV genotypes on the clinical outcome of chronic HBV infection has been partially clarified. In Taiwan, genotype C is associated with more severe liver disease and genotype B is associated with the development of hepatocellular carcinoma (HCC) in young non-cirrhotic patients. In contrast, genotype B has a relatively good prognosis in Japan and China and is rarely associated with the development of HCC. Similarly, genotype D is associated with more severe liver disease than genotype A in India and may predict occurrence of HCC in young patients. Although superinfection of HBV on top of hepatitis B carriers occurs in Taiwan, it is rarely associated with acute exacerbations. As to the response to antiviral treatment, genotypes C and D are associated with a lower response rate to interferon therapy compared with genotypes B and A. In addition, the subtype adw is reported to be associated with a higher risk of lamivudine resistance than ayw. In HBV subtype adw-infected HCC patients, genotype B responds better to embolization therapy and has a lower rate of HCC recurrence than genotype C. In summary, pathogenic and therapeutic differences do exist among HBV genotypes and determining the genotype in patients with chronic HBV infection would help gain further information for etiologic, clinical, virologic and anthropologic investigations. Further studies to clarify the molecular virological factors that contribute to these differences are awaited.     

Case–control study for the identification of virological factors associated with fulminant hepatitis B

Background:  Host and viral factors can promote the development of fulminant hepatitis B (FHB), but there have been no case–control studies for figuring out virological parameters that can distinguish FHB.
Methods:  In a case–control study, virological factors associated with the development of FHB were sought in 50 patients with FH developed by transient hepatitis B virus (HBV) infection (FH-T) and 50 with acute self-limited hepatitis B (AHB) who were matched for sex and age. In addition, 12 patients with FH developed by acute exacerbation (AE) of asymptomatic HBV carrier (ASC) (FH-C) were also compared with 12 patients without FH by AE of chronic hepatitis B (AE-C).
Results:  Higher HBV DNA levels, subgenotype B1/Bj, A1762T/G1764A, G1896A, G1899A and A2339G mutation were significantly more frequent ( P  < 0.05), while hepatitis B e-antigen was less frequent in the FH-T patients than AHB. In multivariate analysis, G1896A mutation (odds ratio [OR], 13.53; 95% confidence interval [CI], 2.75–66.64), serum HBV DNA more than 5.23 log copies/mL (OR, 5.14; 95% CI, 1.10–24.15) and total bilirubin more than 10.35 mg/mL (OR, 7.81; 95% CI, 1.77–34.51) were independently associated with a fulminant outcome by transient HBV infection. On the other hand, in comparison with the patients between FH-C and AE-C groups, there was no significant difference of virological factors associated with the development of FHB.
Conclusion:  A number of virological factors have been defined that may distinguish FH-T from AHB in a case–control study. The pathogenic mechanism of FHB between transient HBV infection and AE of ASC would be different.     

中国广东地区乙型肝炎病毒基因亚型的分布

目的调查中国广东地区乙型肝炎病毒(HBV)基因型,主要是基因亚型的分布情况.方法应用聚合酶链反应-限制性片段长度多态性法以及序列测定法,对广东地区417例慢性HBV感染者血清进行研究.结果广东地区流行的HBV基因型主要为B型和C型,其中B型为Ba亚型,未发现Bj亚型的存在.C亚型有C1和C2两个亚型,其中C1占63%,C2占37%.结论广东地区流行的HBV基因型以Ba和C1亚型为主,C2亚型较少,Bj亚型极为罕见.     

Geographic distribution, virologic and clinical characteristics of hepatitis B virus genotypes in China

The significance of hepatitis B virus (HBV) genotypes for the heterogeneity of chronic HBV infection and severity of liver disease is not well understood. The aim of this study was to determine the distribution and virologic characteristics of HBV genotypes in China and possible association with the diversity of liver disease. The study includes 1096 chronic HBV carriers from nine provinces in China. We collected clinical and laboratory data and analysed the HBV strains in sera by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and nucleotide sequencing techniques. The most common HBV genotypes were B (41%) and C (53%), while genotypes A and D were also found. A North-South divide was identified in genotype B and C distribution - genotype C was predominant in northern China, while genotype B was more prevalent in southern provinces. Patients with genotype B were younger than those with genotype C, and had a lower prevalence of HBeAg - 65%vs 72%, respectively (P = 0.03). However, the severity of liver disease did not differ significantly between patients infected with genotype B or C - neither when comparing liver function tests (1024 patients), nor hepatic inflammation and fibrosis (264 patients). Amongst 47 patients with genotype D (by PCR-RFLP), 37 (79%) were infected with a new subtype (designated Dc), having a recombination fragment from genotype C precore/core region. This is the first large-scale HBV genotype study from China and convincing documentation of the North-to-South gradient of genotypes C vs B in this country. HBV DNA recombination over the surface and precore/core genes increases the diversity of HBV strains and may have diagnostic and clinical implications.     

Basal core-promoter mutant of hepatitis B virus and progression of liver disease in hepatitis B e antigen-negative chronic hepatitis B.

BACKGROUND/AIMS: The long-term outcomes in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B are distinct from those in HBeAg-positive chronic hepatitis. However, the molecular virological factors that contribute to the progression of liver disease in this special clinical setting remain largely unknown. We thus investigated the association of hepatitis B virus (HBV) genotypes as well as precore/basal core-promoter mutations with the clinical and virological characteristics of patients with HBeAg-negative chronic hepatitis B in Taiwan. METHODS: HBV genotypes and sequences of precore and basal core-promoter regions of the HBV genome were determined in 174 HBeAg-negative chronic HBV infection patients including 62 inactive carriers and 112 with different stages of liver disease. RESULTS: HBV carriers with older age (> 50 years) (odds ratio, 9.09; 95% confidence interval (CI), 3.22-25, P < 0.001) and basal core-promoter mutant of HBV (odds ratio, 4.12; 95% CI, 1.41-12.03, P = 0.01) were associated with the development of liver cirrhosis and hepatocellular carcinoma (HCC). The gender-related risk factors associated with the development of liver cirrhosis and HCC were further analyzed, and basal core-promoter mutant was only associated with the development of liver cirrhosis and HCC in male carriers (odds ratio, 4.35; 95% CI, 1.30-14.52, P = 0.02). CONCLUSIONS: The risk of development of liver cirrhosis and HCC is significantly increased in patients with advanced age as well as with basal core-promoter mutant of HBV. In addition, basal core-promoter mutant might contribute to the gender difference of the progression of liver disease in HBeAg-negative chronic hepatitis B in Taiwan.     

Difference in T helper responses during hepatitis flares in hepatitis B e antigen (HBeAg)-positive patients with genotypes B and C: implication for early HBeAg seroconversion

The underlying mechanisms for earlier hepatitis B e antigen (HBeAg) seroconversion in patients with chronic hepatitis B virus (HBV) genotype B when compared with genotype C are unknown. We aimed to determine whether there were any differences in the T helper (Th) responses during hepatitis flares in HBeAg-positive patients with genotypes B and C. Proliferative response measured by (3)H-thymidine uptake and Th responses measured by Enzyme-Linked Immunosorbent Spot assays for interleukin (IL)-2, interferon-gamma (IFN-gamma), IL-4, IL-5 and IL-10 were performed in 10 patients with genotype B and 10 with genotype C with hepatitis flares. HBV genotypes, core promoter, precore mutations, sequence of HBV core region and HBV DNA levels were determined. There was no difference in the HBV DNA levels during hepatitis flares between patients with genotypes B and C. Patients with genotype B had a significantly higher number of IFN-gamma producing cells [with hepatitis B core antigen (HBcAg) stimulation] and lower number of IL-10 producing cells (with HBcAg and HBeAg stimulation) compared with patients with genotype C (P = 0.011, =0.043, <0.001 respectively). There was a trend (P = 0.058) that patients with genotype B had a higher cumulative rate of HBeAg seroconversion. Patients with precore mutants also had a significantly higher number of IFN-gamma producing cells (with HBcAg stimulation) and lower number of IL-10 producing cells (with HBeAg stimulation) compared to patients without precore mutant (P = 0.038, =0.016 respectively). HBV genotype B induces a greater Th1 and lesser Th2 response than genotype C. This provides immunologic evidence for the higher chance of HBeAg seroconversion in patients with genotype B.     

A complete genomic analysis of hepatitis B virus genotypes and mutations in HBeAg-negative chronic hepatitis B in China

Summary.  We aimed to study the distribution of hepatitis B virus (HBV) genotypes/subgenotypes in different parts of China and their clinical impact on the severity of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. Residual serum samples from a cohort of HBeAg-negative chronic hepatitis B patients in Hong Kong, Shanghai and Beijing were studied. Complete HBV genomic sequencing was performed for phylogenetic tree analysis and determination of HBV mutations was carried out. Mutations associated with severe liver fibrosis (Ishak score 4 or more) were selected by computerized information gain criteria. Genotype B (all subgenotype Ba) HBV was present in 19 of 45 (42%), 12 of 31 (39%) and 5 of 25 (20%) patients in Hong Kong, Shanghai and Beijing, respectively ( P  = 0.16). Ninety-seven per cent of genotype C HBV in Shanghai and Beijing belonged to subgenotype Ce whereas 69% of genotype C patients in Hong Kong belonged to subgenotype Cs ( P  < 0.001). Patients infected by subgenotype Cs had the lowest serum albumin and highest alanine aminotransferase levels compared with subgenotype Ce and Ba. Patients infected by subgenotype Cs also had more severe histological necroinflammation than subgenotype Ce. Two HBV mutations were identified to associate with severe liver fibrosis (G2858C and C2289A) and one mutation was protective against severe liver fibrosis (T2201C). The T2201C mutation was found exclusively among patients (21 of 46 patients, 45%) infected by HBV subgenotype Ce. The clinical differences in HBeAg-negative chronic hepatitis B in China may be influenced by different distribution of subgenotype C HBV.     

Preliminary report of hepatitis B virus genotype prevalence in Iran

AIM: To determine the prevalence of hepatitis B virus (HBV) genotypes in Iranian hepatitis B surface antigen (HBsAg) carriers, chronic hepatitis B and cirrhotic patients. METHODS: A total of 109 HBsAg-positive patients were included in this study. HBV genotypes were determined by using INNO-LiPA methodology which is based on the reverse hybridization principle. RESULTS: The distribution of patients with different stages of liver disease was as follows: 95 (86.4%) chronic hepatitis, 11 (10%) liver cirrhosis, and 3 (2.7%) inactive carrier. Of the chronic hepatitis and liver cirrhosis patients, 26.4% were HBeAg-positive while 70% were HBeAg-negative. Genotype D was the only detected type found in all patients. CONCLUSION: Classifying HBV into genotypes has to be cost-effective and clinically relevant. Our study indicates that HBV genotype D prevails in the Mediterranean area, Near and Middle East, and South Asia. Continued efforts for understanding HBV genotype through international co-operation will reveal further virological differences of the genotypes and their clinical relevance.