Clinical, biochemical, immunological and virological profiles of, and differential diagnosis between, patients with acute hepatitis B and chronic hepatitis B with acute flare

Background and Aim: In areas with high or intermediate endemicity for chronic hepatitis B virus (HBV) infection, it is difficult to distinguish acute hepatitis B (AHB) from chronic hepatitis B with an acute flare (CHB‐AF) in patients whose prior history of HBV infection has been unknown. The present study aimed to screen laboratory parameters other than immunoglobulin M antibody to hepatitis B core antigen (IgM anti‐HBc) to discriminate between the two conditions. Methods: A retrospective and prospective study was conducted in patients first presenting clinically as HBV‐related acute hepatitis to sort out acute self‐limited hepatitis B (ASL‐HB). Then, clinical and laboratory profiles were compared between patients with ASL‐HB and CHB‐AF. Parameters closely associated with ASL‐HB were chosen to evaluate sensitivity, specificity, accuracy, positive predictive values and negative predictive values for diagnosing AHB. Results: There were significant differences between patients with ASL‐HB and CHB‐AF in relation to clinical and laboratory aspects, with many outstanding differences in levels of serum HBV‐DNA, hepatitis B e antigen (HBeAg) and alpha‐fetoprotein (AFP) as well as IgM anti‐HBc. In particular, there was a greater difference between the two groups in low levels of HBeAg (ratio of the optical density of the sample to the cut‐off value [S/CO] <20) than in negativity for HBeAg (42.7% and 13.5% vs 49.3% and 45.9%). 1:10 000 IgM anti‐HBc had a sensitivity and specificity of 96.2% and 93.1%, respectively, for predicting ASL‐HB. Combining it with AFP, HBeAg or HBV‐DNA could improve diagnostic power. A combination of IgM anti‐HBc, HBV‐DNA and HBeAg had a predictive value of 98.9% and a negative predictive value of 100.0%, similar to that of a combination of IgM anti‐HBc and HBV‐DNA. Adding AFP to the combinations of IgM anti‐HBc and HBV‐DNA or HBeAg could further heighten the positive predictive value. The positive predictive value and negative predictive value of the combination of IgM anti‐HBc, HBV‐DNA and AFP were both 100.0%. Conclusions: (i) There are significant differences with respect to clinical, biochemical, immunological and virological aspects between ASL‐HB and CHB‐AF. (ii) Of several diagnostic combinations, IgM anti‐HBc jointing HBV‐DNA is most effective and most practicable in distinguishing ASL‐HB from CHB‐AF. (iii) A low HBeAg level is more useful than negative HBeAg in differential diagnosis between ASL‐HB and CHB‐AF. (iv) In those patients with a high level of IgM anti‐HBc, serum AFP level >10× upper reference limit could rule out a probability of ASL‐HB.     

Chinese medicinal herbs for chronic hepatitis B: a systematic review

Abstract: Aims/Background: Chronic hepatitis B is a serious health problem worldwide. Chinese medicinal herbs are widely used for treatment of chronic hepatitis B in China and many clinical trials have been conducted. This systematic review is to assess the efficacy and safety of Chinese medicinal herbs for chronic hepatitis B. Methods: Randomised clinical trials comparing Chinese medicinal herbs versus placebo, no intervention, nonspecific treatment, or interferon treatment for chronic hepatitis B with ≥3 months follow‐up were included. No language and blinding limitations were applied. The electronic databases were searched, combined with handsearches on Chinese literature. Data were extracted independently by two reviewers. The methodological quality of trials was assessed by the Jadad‐scale plus allocation concealment. Results: Nine randomised trials (n=936) were included, with only one being of high quality. There was a funnel plot asymmetry (intercept 3.37, p=0.047). Compared to nonspecific treatment or placebo, the herbal compound Fuzheng Jiedu Tang showed an effect on clearance of serum HBsAg (relative risk 5.19, 95% CI 1.24–21.79), HBeAg (10.85, 3.56–33.06), and HBV DNA (8.50, 1.23–58.85). Polyporus umbellatus polysaccharide showed an effect on serum HBeAg (3.06, 1.13–8.29) and HBV DNA (4.14, 1.0–17.19); Phyllanthus amarus showed an effect on serum HBeAg (3.35, 1.49–7.56). Phyllanthus compound and kurorinone showed no significant difference on clearance of serum HBeAg and HBV DNA and on alanine aminotransferase normalisation compared to interferon. No serious adverse event was observed. Conclusions: Chinese medicinal herbs are not recommended for chronic hepatitis B because of the publication bias and low quality of the trials. Rigorously designed, randomised, double‐blind, placebo‐controlled trials are needed.     

Factors associated with isolated anti‐hepatitis B core antibody in HIV‐positive patients: impact of compromised immunity

Summary. In regions that are hyperendemic for chronic hepatitis B virus (HBV) infection, prevalence of and risk factors associated with isolated anti‐hepatitis B core antibody (anti‐HBc) in HIV‐positive patients are less well described. HIV‐positive patients who were tested for hepatitis B surface antigen (HBsAg), anti‐hepatitis B surface antibody (anti‐HBs) and anti‐HBc at designated hospitals for HIV care in Taiwan were included for analysis. HBV DNA was detected by real‐time polymerase chain reaction in patients with and without isolated anti‐HBc. Of 2351 HIV‐positive patients, 450 (19.1%) were HBsAg positive, 411 (17.5%) were anti‐HBc positive alone and 963 (41.0%) for both anti‐HBs and anti‐HBc. Compared with patients who were positive for both anti‐HBs and anti‐HBc, patients with isolated anti‐HBc were older, less likely to have anti‐hepatitis C virus antibody (anti‐HCV), had lower CD4 lymphocyte counts and higher plasma HIV RNA loads. Older age (adjusted odds ratio, 1.029; 95% confidence interval, 1.015–1.043) and CD4 <100 cells/μL (adjusted odds ratio, 1.524; 95% confidence interval, 1.025–2.265) were independently associated with isolated anti‐HBc by logistic regression, while presence of anti‐HCV and injecting drug use were not. HBV DNA was detectable in 8.3% of 277 patients with isolated anti‐HBc and 14.3% of 56 patients with both anti‐HBs and anti‐HBc (P = 0.160). In a country hyperendemic for HBV infection, HIV‐positive patients at older age and with CD4 <100 cells/μL were more likely to have isolated anti‐HBc, suggesting that compromised immunity plays a role in the presence of this marker.     

KIR2DL3 and the KIR ligand groups HLA‐A‐Bw4 and HLA‐C2 predict the outcome of hepatitis B virus infection

Killer immunoglobulin‐like receptors (KIRs) regulate the activation of natural killer cells through their interaction with human leucocyte antigens (HLA). KIR and HLA loci are highly polymorphic, and certain HLA‐KIR combinations have been found to protect against viral infections. In this study, we analysed whether the KIR/HLA repertoire may influence the course of hepatitis B virus (HBV) infection. Fifty‐seven subjects with chronic hepatitis B (CHB), 44 subjects with resolved HBV infection and 60 healthy uninfected controls (HC) were genotyped for KIR and their HLA ligands. The frequency of the HLA‐A‐Bw4 ligand group was higher in CHB (58%) than subjects with resolved infection (23%) (crude OR, 4.67; P<.001) and HC (10%) (crude OR, 12.38; P<.001). Similar results were obtained for the HLA‐C2 ligand group, more frequent in CHB (84%), than subjects with resolved infection (70%) (crude OR, 2.24; P<.10) and HC (60%) (crude OR, 3.56; P<.01). Conversely, the frequency of KIR2DL3 was lower in CHB (81%) than in subjects with resolved infection (98%) (crude OR, 0.10; P<.05). These results suggest a detrimental role of HLA‐A‐Bw4 and HLA‐C2 groups, which are associated with the development of CHB, and a protective role of KIR2DL3. A stepwise variable selection procedure, based on multiple logistic regression analysis, identified these three predictive variables as the most relevant, featuring high specificity (90.9%) and positive predictive value (87.5%) for the development of CHB. Our results suggest that a combination of KIR/HLA gene/alleles is able to predict the outcome of HBV infection.     

Role of Functional IFNL4, IFNLR1, IFNA,IFNAR2 Polymorphisms in Hepatitis B virus‐related liver disease in Han Chinese population

Recent studies show that variants in some interferon genes together with interferon receptor genes are associated with the outcome of infectious diseases. We examined the association between the risk of hepatitis B virus (HBV)‐related liver disease and the functional polymorphisms within IFNL4, IFNLR1, IFNA1, IFNA2, IFNA5 and IFNAR2 genes (14 loci in all) in a Han Chinese population. A total of 3128 people participated and were divided into 5 groups: healthy controls, natural clearance, chronic hepatitis B(CHB), liver cirrhosis and hepatocellular carcinoma (HCC). Significant associations were observed for 4 variants in IFNAR2, IFNLR1 with HBV infection, and IFNLR1‐rs4649203 was associated with HBV recovery. Moreover, we demonstrated the clear relevance of 5 polymorphisms in IFNA1, IFNA2, IFNL4 with HCC. Three SNPs in IFNL4 gene may be important susceptible factors for the progression of HBV‐related liver disease by trend chi‐square test. The IFNL4 haplotype conformed by rs12971396_G, rs8113007_T and rs7248668A was more frequent in HCC than CHB and LC group. Three polymorphisms in the 5′ region of the IFNL4 gene are associated with the progression of HBV‐related liver disease. IFNA1‐ rs1831583 and IFNA2‐ rs649053 are associated with the development of HCC. IFNLR1‐ rs4649203, rs7525481 are predictors for HBV infection, and rs4649203 is a predictor of spontaneous clearance. IFNAR2 ‐rs1051393, rs12233338 may be predictive markers of HBV infection in the Chinese population.     

In vivo infectivity of liver extracts after resolution of hepadnaviral infection following therapy associating DNA vaccine and cytokine genes

DNA‐based vaccination appears of promise for chronic hepatitis B immunotherapy, although there is an urgent need to increase its efficacy. In this preclinical study, we evaluated the therapeutic benefit of cytokine (IL‐2, IFN‐γ) genes co‐delivery with DNA vaccine targeting hepadnaviral proteins in the chronic duck hepatitis B virus (DHBV) infection model. Then, we investigated the persistence of replication‐competent virus in the livers of apparently resolved animals. DHBV carriers received four injections of plasmids encoding DHBV envelope and core alone or co‐delivered with duck IL‐2 (DuIL‐2) or duck IFN‐γ (DuIFN‐γ) plasmids. After long‐term (8 months) follow‐up, viral covalently closed circular (ccc) DNA was analysed in duck necropsy liver samples. Liver homogenates were also tested for in vivo infectivity in neonatal ducklings. Co‐delivery of DuIFN‐γ resulted in significantly lower mean viremia starting from week 21. Viral cccDNA was undetectable by conventional methods in the livers of 25% and 57% of animals co‐immunized with DuIL‐2 and DuIFN‐γ, respectively. Interestingly, inoculation of liver homogenates from 7 such apparently resolved animals, exhibiting cccDNA undetectable in Southern blotting and DHBV expression undetectable or restricted to few hepatocytes, revealed that three liver homogenates transmitted high‐titre viremia (3–5×10¹⁰ vge/mL) to naïve animals. In conclusion, our results indicate that IFN‐γ gene co‐delivery considerably enhances immunotherapeutic efficacy of DNA vaccine targeting hepadnaviral proteins. Importantly, we also showed that livers exhibiting only minute amounts of hepadnaviral cccDNA could induce extremely high‐titre infection, highlighting the caution that should be taken in occult hepatitis B patients to prevent HBV transmission in liver transplantation context.     

Serum protein expression patterns in detecting a new viral protein in HBeAg‐negative chronic hepatitis B

We analysed the changes in viral protein expression in HBeAg‐negative chronic hepatitis B (CHB). In total, 160 samples were obtained from individuals infected by hepatitis B virus (HBV) and divided into four groups. Group A included 71 cases of hepatitis B e antigen (HBeAg)‐negative CHB, Group B included 58 cases of inactive seroconverters and Group C included 31 cases of HBeAg‐positive CHB. Group D included 22 normal healthy individuals as a control. All serum samples were examined using surface enhance laser desorption/ionization time of flight‐mass spectrometry (SELDI‐TOF‐MS). The results indicated that a peak with 4140 m/z increased markedly in Group A at 1295.55 ± 745.87, which was significantly different from that in Group B at 896.99 ± 534.86 (P = 0.013). This peak indicated a close relationship with HBV DNA replication and may contribute to pathogenesis of HBeAg‐negative chronic hepatitis.     

Interferon‐α treatment in children and young adults with chronic hepatitis B: a long‐term follow‐up study in Taiwan

Background/Aims: The short‐ and long‐term benefits of interferon (IFN)‐α therapy in young patients with chronic hepatitis B (CHB) acquiring infection perinatally or during early childhood have been questioned. Methods: Twenty‐one Taiwanese hepatitis B envelope antigen (HBeAg)‐positive CHB patients aged 1.8–21.8 years (median 14.0 years) with alanine aminotransferase (ALT)>80 IU/L at entry were enrolled for IFN‐α therapy. They received IFN‐α therapy with a dose of 3 MU/m²/day three times a week for 24 weeks. A control group included untreated 21 CHB patients closely matched for gender, age, duration of ALT >80 IU/L and HBeAg status. All 42 patients were prospectively followed for 6.5–12.5 years after the end of therapy. Results: The cumulative rate of virological response [anti‐HBe seroconversion and serum hepatitis B virus (HBV)‐DNA <10⁵ copies/ml] was not different between the IFN‐treated patients and control patients at 1 year (41 vs 44%) and at 6 years (88 vs 89%) after stopping treatment. Serum hepatitis B surface antigen loss occurred in two (9.5%) treated patients and in one (4.8%) control patient. Patients with a successful treatment response (anti‐HBe seroconversion, HBV‐DNA <10² copies/ml and ALT normalization at 1 year after stopping treatment) were younger than those without a successful response (P=0.03). A lower pretreatment serum HBV‐DNA level (<2 × 10⁸ copies/ml) is not only a significant factor to predict successful treatment response (P=0.008) but also has a beneficial effect on the long‐term cumulative rate of virological response in IFN‐treated patients (P=0.021), but not in control patients. Genotype difference or emergence of a precore stop codon mutant before treatment was not predictive for HBeAg clearance. Conclusion: For young CHB patients in Taiwan with infection occurring perinatally or in early childhood, the real advantage of IFN‐α therapy was not observed. IFN‐α therapy showed a beneficial effect on short‐ and long‐term virological outcomes only in those with a lower pretreatment serum HBV‐DNA level.     

Demonstration of an association between detection of IgG antibody reactivity towards the C-terminal region of the preS1 protein of hepatitis B virus and the capacity to respond to interferon therapy in chronic hepatitis B

Background and Aim: The treatment of hepatitis B virus (HBV) remains complex, with somewhat unpredictable responses. The aim of this study was to determine the predictive value of the pretreatment presence of circulatory antibodies towards a synthetic peptide mimicking the amino acids 94–117 of the preS1 protein of HBV and the capacity to respond to alpha‐inteferon (IFN‐alpha) treatment. Methods: The anti preS1(94–117) antibodies were measured by a peptide‐based enzyme‐linked immunosorbent assay (ELISA) and the response to INF‐alpha therapy was judged by the effect on the viral kinetics as measured by an assay based on quantitative polymerase chain reaction during the treatment and follow up. Results: We found a significant (P < 0.001) correlation between the pretreatment presence of anti preS1(94–117) antibodies and a decrease in viral levels on follow up after the end of IFN‐alpha therapy. The combined response of HBV DNA suppression (P < 0.001), hepatitis B e antigen (HBeAg) loss (P < 0.0001), anti‐HBe seroconversion (P < 0.005) and AST aminotransferase normalization (P < 0.01) was also highly associated with the pretreatment presence of anti preS1(94–117) antibodies. Conclusion: The positive predictive value (PPV) of anti preS1(94–117) in determining a virological response was 83% and the negative predictive value (NPV) was 100%, indicating that in the absence of pretreatment anti preS1 reactivity virtually no patient has the capacity to respond to IFN‐alpha therapy. Our findings may help to improve the efficacy of INF‐alpha therapy for chronic hepatitis B (CHB) by guiding the selection of patients for treatment and optimizing the clinical management of the individual patient.     

Treatment of chronic liver diseases with traditional Chinese medicine

Traditional Chinese medicine is still being extensively used for treatment of liver disease in China. The anti‐viral herbs, Phyllanthus amarus, P. niruri and P. urninaria, and Oxymatrine extracted from Sophora flavecientis and S. subprostratae, have been shown to have a remarkable HBV suppressing effect with a serum conversion rate for HBeAg and HBV DNA around 45%, similar to that of IFN‐α. The anti‐inflammatory compound, Stronger NeoMinophagen C (SNMC), is a Japanese preparation of glycerrhizin, extracted from Glyceriza glabra, which has shown an effective rate of ALT and AST normalization and reduction to < 60 U/L in 65.6% and 73.5% of patients. Compound 861, made of 10 herbs with Salvia miltiorrhiza as its chief component, has been shown experimentally to be effective in suppressing fibrogenesis, enhancing collagen degradation, and inhibiting TIMP expression. Clinically, an open trial of 2000 patients showed improvement of symptoms in 83% and normalization of serum ALT in 82%. In a controlled study of 107 patients with HBV‐related diseases, double liver biopsies showed that the fibrosis reversal rate after 6 months treatment with Cpd 861 was 78% in S2, 82% in S3 (precirrhotic stage) and 75% in S4 (early cirrhosis), as assessed by Scheuer’s and Chevallier’s criterion. In conclusion, traditional Chinese medicine has great potential in the treatment of chronic hepatitis B.     

Demographic and serological characteristics of Asian Americans with hepatitis B infection diagnosed at community screenings

There is limited information regarding follow‐up and hepatitis B serological status of Asian Americans diagnosed with chronic hepatitis B (CHB) through community screening. The aims of this study were to evaluate the prevalence and characterize CHB among Asians living in Los Angeles, assess follow‐up of individuals with CHB diagnosed at screening and compare with patients with CHB followed by community gastroenterologists. Between October 2007 and May 2010, 7387 Asians were tested for HBV. HBsAg positive individuals (CHB) underwent additional testing for ALT, HBeAg/anti‐HBe and HBV DNA. Patients with CHB were contacted 6 months later to determine whether they received follow‐up care. We compared serological patterns of these individuals with CHB to patients with CHB who were seen for the first time (treatment naïve) by community gastroenterologists during the study period. Prevalence of CHB was 5.2%. About 99% patients with CHB were foreign‐born, and only 27% could read/write English. 297 (77%) patients with CHB could be reached 6 months after diagnosis; 43% did not receive follow‐up care, mostly because of lack of medical insurance. Patients with CHB followed by gastroenterologists were more likely to have insurance (69% vs 26%, P < 0.0001). 90% patients with CHB at screening were HBeAg negative/anti‐HBe positive with 62% having inactive disease compared to only 30% of patients seen by gastroenterologists (P < 0.0001). Among CHB participants, 13% met criteria for treatment compared to 51% of patients with CHB (P < 0.0001). Only a small number of CHB screening participants require antiviral therapy. Lack of medical insurance is the main reason for most patients with CHB not seeking follow‐up care after screening.     

HLA‐C and KIR combined genotype as new response marker for HBeAg‐positive chronic hepatitis B patients treated with interferon‐based combination therapy

Current treatment for chronic hepatitis B infection (CHB) consists of interferon‐based therapy. However, for unknown reasons, a large proportion of patients with CHB do not respond to this treatment. Hence, there is a pressing need to establish response markers to select patients who will benefit from therapy and to spare potential nonresponders from unnecessary side effects of antiviral therapy. Here, we assessed whether HLA‐C and KIR genotypes were associated with treatment outcome for CHB. Twelve SNPs in or near the HLA‐C gene were genotyped in 86 CHB patients (41 HBeAg positive; 45 HBeAg negative) treated with peginterferon alfa‐2a + adefovir. Genotyping of killer immunoglobin‐like receptors (KIRs) was performed by SSP‐PCR. One SNP in HLA‐C (rs2308557) was significantly associated with combined response in HBeAg‐positive CHB patients (P = 0.003). This SNP is linked to the HLA‐C group C1 or C2 classification, which controls KIR binding. The combination of KIR2DL1 with its ligand HLA‐C2 was observed significantly more often in HBeAg‐positive patients with a combined response (13/14) than in nonresponders (11/27, P = 0.001). Patients with the KIR2DL1/C2 genotype had significantly higher baseline ALT levels (136 vs 50 U/L, P = 0.002) than patients without this combination. Furthermore, KIR2DL1‐C2 predicted response independent of HBV genotype and ALT at baseline. HLA‐C and KIR genotype is strongly associated with response in HBeAg‐positive CHB patients treated with interferon‐based therapy. In combination with other known response markers, HLA‐C/KIR genotype could enable the selection of patients more likely to respond to interferon‐based therapy.     

Hepatitis B surface antigen loss and sustained viral suppression in Asian chronic hepatitis B patients: A community‐based real‐world study

Community‐based real‐world outcomes on effectiveness of antiviral therapies for chronic hepatitis B virus (CHB) in Asians are limited. Whether hepatitis B surface antigen (HBsAg) loss correlates with undetectable virus and alanine aminotransferase (ALT) normalization on treatment or what predicts risk of seroreversion or detectable virus after stopping therapy is unclear. We aim to evaluate rates and predictors of HBsAg loss, seroconversion, ALT normalization and undetectable HBV DNA, including HBsAg seroreversion or re‐emergence of HBV DNA among Asian CHB patients. We retrospectively evaluated 1072 CHB adults on antiviral therapy at two community gastroenterology clinics from 1997 to 2015. Rates of HBsAg loss, ALT normalization, achieving undetectable HBV DNA and developing surface antibody (anti‐HBs) were stratified by HBeAg status. Following HBsAg loss, HBsAg seroreversion or re‐emergence of detectable HBV DNA was analysed. With median treatment of 76.7 months, the overall rate of HBsAg loss was 4.58%, with similar HBsAg loss rates between HBeAg‐positive and HBeAg‐negative patients (4.44% vs 4.71%, P=.85) in a predominantly Asian population (98.1%). Among HBsAg loss patients, 33.3% developed anti‐HBs, 95.8% achieved undetectable virus and 66.0% normalized ALT. No significant baseline or on‐treatment predictors of HBsAg loss were observed. While six patients who achieved HBsAg loss had seroreversion with re‐emergence of HBsAg positivity, viral load remained undetectable, demonstrating the sustainability of viral suppression. Among a large community‐based real‐world cohort of Asian CHB patients treated with antiviral therapy, rate of HBsAg loss was 4.58%. Despite only 33.3% of HBsAg loss patients achieving anti‐HBs, nearly all patients achieved sustained undetectable virus.     

Occult Hepatitis B Virus Infection in Japanese Chronic Hemodialysis Patients

We investigated the prevalence of occult hepatitis B virus (HBV) infection in Japanese chronic hemodialysis patients. Hemodialysis patients (n = 1041) were screened for occult HBV. The presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody, and hepatitis B core antibody (anti‐HBc) was determined by various chemiluminescent immunoassays. HBV‐DNA was quantified in patients positive for anti‐HBc using quantitative real‐time polymerase chain reaction. Among the 1041 patients, six (0.6%) were HBsAg‐positive and 218 (20.9%) were anti‐HBc‐positive. All HBsAg‐positive patients also tested positive for the presence of HBV DNA. Of 212 HBsAg‐negative and anti‐HBc‐positive patients, three were positive for HBV DNA. Our study showed that the prevalence of occult HBV infection in chronic hemodialysis patients from eastern Japan was 0.3%.     

Tumour necrosis factor‐alpha,interleukin‐10, interferon‐gamma and vitamin D receptor gene polymorphisms in patients with chronic hepatitis delta

No data exist to assess certain polymorphisms that have a potential effect on the immune response in patients with chronic hepatitis delta (CHD). The aim of this study was to investigate polymorphisms in 6 polymorphic sites: IL‐10 ‐1082 (rs1800896), IL‐10 ‐627 (rs1800872), IFN‐γ +874 (rs62559044), TNF‐α ‐308 (rs1800629), vitamin D receptor (VDR) FokI (rs2228570) and VDR TaqI (rs731236). The genotypes of 67 patients with CHD and 119 patients with chronic hepatitis B (CHB) were compared. In addition, 56 individuals with resolved hepatitis B virus (HBV) infection were used as a control group for patients with CHB. Polymorphisms in TNF‐α, IL‐10, and VDR genes were analysed using polymerase chain reaction/restriction fragment length polymorphism methods. The IFN‐γ gene polymorphism was detected by allele‐specific polymerase chain reaction (PCR). Patients with CDH were more likely to have advanced liver disease compared with patients with CHB (P < 0.0001). IL‐10 ‐1082 and VDR TaqI polymorphisms showed significant differences between patients with CHD and CHB. The high secretory IL‐10 ‐1082 genotype GG was less frequent in CHD compared with patients with CHB and resolved HBV (17.7%, 37.4% and 47.1%, respectively (P < 0.05 for CHD vs CHB and resolved HBV). The frequency of the high secretory VDR TaqI TT genotype was 86.6% in patients with CHD, 62.7% in patients with CHB and 62.5% in resolved HBV individuals (CHD vs CHB: P < 0.05). None of the polymorphisms analysed had an effect on HBV persistence. IL‐10 ‐1082 and VDR TaqI polymorphisms may contribute to the more severe liver disease associated with CHD compared with CHB.     

Association of human leukocyte antigen polymorphism with outcomes of hepatitis B virus infection

Background and Aim: Host genetic and environmental factors are viewed as a common basis of the different outcomes of hepatitis B virus (HBV) infection. Human leukocyte antigen (HLA) plays an important role in immunological reaction to HBV infection. In this study, we aimed to determine the association between HBV infection and HLA‐A, B, and DRB1 alleles in northern Iran. Methods: HLA‐A, B, and DRB1 alleles in 33 patients with chronic hepatitis B (CHB) and 31 healthy carriers as the persistent group, and 30 subjects who had spontaneously recovered from HBV infection were analyzed by using the polymerase chain reaction (PCR)–sequence‐specific primer (PCR‐SSP) technique. Results: The frequency of the HLA‐A*33 allele was higher in the persistent group than in the recovered group (10.16% vs 0%, P < 0.008); the frequency of the DRB1*13 allele was lower in the persistent group than in the recovered group (3.13% vs 11.67%, P < 0.03). The frequency of the B*52 allele was higher in CHB patients than healthy carriers (7.58% vs 0%, P < 0.05). The logistic regression model showed that the presence of the HLA‐DRB1*13 allele was the significant factor associated with protection against the persistency of HBV. There were significant differences between the HBV recovered group, CHB patients, and healthy carriers regarding age, hepatitis B e antigen, and anti‐hepatitis B e positivity. Conclusion: HLA‐A*33 was closely related with susceptibility to persisting hepatitis B infection, and HLA‐DRB1*13 was closely related with protection against persisting hepatitis B in an Iranian population. These findings emphasized that the host HLA polymorphism is an important factor in determining the outcome of HBV infection.     

Sequential therapy with entecavir and PEG‐INF in patients affected by chronic hepatitis B and high levels of HBV‐DNA with non‐D genotypes

Complete eradication of hepatitis B virus (HBV) is rarely achieved. Treatment options include currently available nucleos(t)ide analogues and pegylated interferon. The aim of our exploratory study was to assess the effectiveness of sequential therapy for chronic hepatitis B (CHB) vs the current standard of care. We evaluated an association with entecavir and pegylated interferon alfa‐2a (PEG‐IFN) in 20 patients with hepatitis B, high HBV viremia and genotypes A, B, C and E. Patients received entecavir alone for 12 weeks, then entecavir and PEG‐IFN for 12 weeks, lastly PEG‐IFN alone for 36 weeks. The results were compared with 20 patients (control group) treated in the past with 48 weeks of PEG‐IFN monotherapy. Our results show that complete sustained virological response (SVR) and partial SVR were, respectively, 60% and 80% in the study group and 10% and 30% in the control group; anti‐HBe seroconversion rate were 76.9% vs 15%, and anti‐HBs seroconversion were 20% vs 0%, respectively. We found a correlation among different genotypes and virological and serological outcomes – genotype C has a better virological response, while genotype A had a better serological response, and E genotype had a poor response. These results show that a sequential approach is a promising strategy of treatment in patients with CHB and high viremia in comparison with PEG‐IFN monotherapy. The E genotype seems to have the worse rate of response and requires other treatment strategies.