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1.
Hepatitis delta is considered the most severe form of viral hepatitis, but variables associated with disease progression are poorly defined. This study aimed to identify risk factors associated with worse clinical outcome in patients with hepatitis delta and to develop a clinical score to determine their risk of experiencing liver‐related morbidity or mortality. We followed 75 HBsAg–anti‐HDV‐positive patients with hepatitis delta for up to 16 years (median 5 years). The baseline‐event‐anticipation score (BEA score) was developed based on variables associated with the development of liver‐related clinical complications. Age, region of origin, presence of cirrhosis, albumin, INR, hyperbilirubinemia and thrombocytopenia were all associated with the development of an event in the training cohort. The BEA score included age, sex, region of origin, bilirubin, platelets and INR. Points were allocated according to hazard ratios, and three risk groups were defined: BEA‐A mild risk, BEA‐B moderate risk and BEA‐C high risk. Hazard ratios of BEA‐B and BEA‐C patients for liver‐related clinical endpoints were 9.01 and 25.27 vs BEA‐A with an area under curve of the receiving operating characteristic curve of 0.88. The accuracy of the BEA score was confirmed in two independent validation cohorts followed in Barcelona (= 77) and Düsseldorf (= 62). Delta hepatitis is associated with a very severe long‐term outcome. The BEA score is easy to apply and predicts with a very high accuracy the development of liver‐related complications in patients with hepatitis delta.  相似文献   

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Summary. Long‐term changes in the frequency and outcome of hepatitis delta virus (HDV) infection have seldom been analysed. This retrospective, longitudinal study includes 398 consecutive hepatitis B surface antigen (HBsAg)‐positive patients with anti‐HDV antibodies who attended our institution between 1983 and 2008. At enrolment, 182 patients had acute and 216 chronic hepatitis. Patients were grouped into two periods. Those who attended between 1983 and 1995 and those between 1996 and 2008. The former group was significantly younger, mainly intravenous drugs users, and had a greater incidence of acute HDV and HIV and HCV coinfection. Patients with acute HBV/HDV coinfection cleared both infections in 90% of cases, while all patients with HDV superinfection evolved to chronic disease. One hundred and fifty‐eight patients with chronic HDV were followed for a median period of 158 months. Seventy‐two per cent of the patients remained stable, 18% had hepatic decompensation, 3% developed hepatocellular carcinoma, and 8% cleared HBsAg. Liver‐related death was observed in 13% of patients and mainly occurred in patients from the first period (P = 0.012). These results indicate an outbreak of HDV at the end of the 1980s and the beginning of the 1990s, with a large number of acute HDV cases affecting predominately young, male intravenous drug users. Currently, patients with chronic HDV disease are older, and factors associated with worse prognosis include the presence of cirrhosis and age at the time of diagnosis.  相似文献   

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The impact of IFNL3 (IL28B) polymorphism on response to interferon (IFN) treatment in patients infected with hepatitis B virus (HBV) is controversial. We aimed to investigate whether IFNL3 polymorphism (rs12979860) influences the long‐term response of chronic hepatitis B (CHB) treatment to conventional IFN. Design: Ninety‐seven HBeAg‐positive patients treated with IFN were evaluated in this study. Associations were investigated between IFNL3 genotypes and (i) HBeAg seroconversion at the end of treatment (EOT), (ii) sustained virological response (SVR) and (iii) HBsAg seroconversion through long‐term follow‐up (LTFU). Patients were followed for a median of 14 years. The majority of patients were infected with HBV genotype A (69.6%) and were Caucasian (77.9%). Ninety‐five patients were genotyped at rs12979860. Similar IFNL3 distribution was observed among the different ethnicities (P = 0.62) or across HBV genotypes A through G (P = 0.70). Thirty‐six patients experienced HBeAg seroconversion at EOT; HBeAg seroconversion rates were 37.0 and 35.5% in patients with CC and CT/TT genotypes, respectively (P = 0.82). Among the 44 patients (45%) who achieved a SVR, SVR rates were 48.9 and 39.6% in patients with CC and CT/TT IL28B genotypes, respectively (P = 0.80). HBsAg seroconversion occurred through LTFU in 28 patients. HBsAg seroconversion rates were 25.5 and 31.2% in patients with CC and CT/TT genotypes, respectively (P = 0.51). No significant relationship between IFNL3 rs12979860 and fibrosis stage was observed (P = 0.85). IFNL3 genotype was neither associated with SVR, nor with HBeAg seroconversion and long‐term HBsAg seroconversion in HBeAg‐positive CHB patients responding to IFN therapy.  相似文献   

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Background/aims: To evaluate the association between demographical features, serum ALT and HBV DNA and the prevalence of significant fibrosis and inflammation on liver biopsy in patients with chronic hepatitis B. Methods: In this cross‐sectional study of patients on St Vincent's Hospital HBV database, patients were classified into three groups on the basis of HBeAg status and HBV DNA level and the prevalence of significant (F2/3/4) fibrosis and (A2/3) inflammation in each group was established. Patients were also divided into HBeAg‐positive and ‐negative groups and examined for the prevalence of significant fibrosis/inflammation in the strata of HBV DNA and ALT. Predictors of significant fibrosis and inflammation in HBeAg‐positive and ‐negative patients were examined by logistic regression. Results: Three hundred and ninety four patients (HBeAg positive=198; HBeAg negative=196) with liver biopsy were identified. Fifty‐eight percent of HBeAg‐negative patients with HBV DNA >25 000 IU/ml had F2/3/4 fibrosis. HBV DNA and F2/3/4 were positively correlated in HBeAg‐negative patients [odds ratio (OR) 1.42, P=0.001] but inversely correlated in HBeAg‐positive patients (OR 0.71, P=0.03). HBV DNA was an independent predictor of significant fibrosis in HBeAg negative (P=0.03) but not HBeAg‐positive patients. In HBeAg‐positive patients, age was the only predictor of significant fibrosis (P=0.001) and ALT the only predictor of significant inflammation (P=0.003). In the whole cohort there was a close positive association between inflammation and fibrosis. Conclusion: Increasing levels of HBV DNA are associated with increasing prevalence of significant fibrosis only in patients with HBeAg‐negative CHB.  相似文献   

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The role of quantitative hepatitis B surface antigen (HBsAg) levels in patients receiving highly potent oral antiviral therapy is controversial, and here, we determined the HBsAg response in 121 chronic hepatitis B patients treated with tenofovir 300 mg daily. During tenofovir treatment, HBsAg decline of ≥1.0 log from baseline was seen in 16.1%, 16.3%, 18.4%, 34.6%, 36.4% and 11.8%, 15.2%, 14.8%, 28.6%, 20% at years 1, 2, 3, 4, 5 for HBeAg‐positive and HBeAg‐negative patients, respectively. Early decline in HBsAg levels at week 4 was predictive of subsequent significant HBsAg level decline. HBeAg seroconversion occurred in 29.9% of HBeAg‐positive patients. On multinomial logistic regression, HBsAg level decline from baseline at week 4 and week 12 or any time subsequently did not correlate with HBeAg seroconversion and HBV DNA level decline from baseline at week 4 and week 12 (OR = 3.704; 95% CI = 1.511–9.076; P = 0.006 and OR = 1.732; 95% CI = 1.032–2.867; P = 0.037, respectively) was significantly predictive of seroconversion. A small proportion of chronic HBV‐infected patients treated with tenofovir exhibit a significant (≥1.0 log) decline in HBsAg levels. Early decline in HBsAg levels at week 4 was predictive of subsequent and significant HBsAg level decline. The HBsAg decline did not correlate with HBeAg seroconversion in HBeAg‐positive patients. Reduction in HBV DNA levels at week 4 and 12 correlated with seroconversion.  相似文献   

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Hepatitis B virus (HBV) is a very complex and intricate DNA structure associated with a particular genomic organization and replication cycle. However, many years of investigations allowed clarification of the real HBV natural history, through a deeper knowledge of the behavior of HBV antigens and viral structures. Several of the old diagnostic tools, such as HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) determinations, gained prominence now, since the variation of both HBsAg and HBeAg plasma levels was shown to predict treatment response. In addition, the availability of more sensitive methods, such as HBV DNA detection by real‐time PCR, has improved the current knowledge of the relationships between HBV replication levels and the natural history of the disease. It is now well established that some HBV genotypes are associated with a better response to treatment with pegylated interferon. Despite the widely accepted value of liver biopsy as a staging tool, transient elastography is being increasingly acknowledged as a non‐invasive method to assess liver stiffness, chiefly for detection of advanced fibrosis. Current international guidelines for the management of chronic hepatitis B have provided several accurate biochemical and serological criteria for selecting patients for treatment, allowing a higher number of cases to be enrolled into antiviral therapy. This review describes the different serological markers used for the study of HBV and their clinical significance. It also deals with methods used for detection of genotypes and HBV DNA, emphasizing the effectiveness of such determinations for both patient selection and chronic hepatitis B therapy/monitoring.  相似文献   

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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.  相似文献   

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Little is known about the risk factors associated with hepatitis B virus (HBV) intrauterine transmission among HBsAg‐positive mothers. We conducted a study in Taiyuan, China, including 1133 HBsAg‐positive mothers and their babies. A total of 101 neonates had HBsAg and/or HBV DNA positive with an intrauterine transmission rate of 8.9%. Maternal menstrual irregularity (OR = 4.95, 95% CI: 1.71, 14.33) and severe nausea during the first trimester (OR = 1.86, 95% CI: 1.11, 3.09) were associated with an increased risk of intrauterine transmission, while caesarean delivery (OR = 0.32, 95% CI: 0.20, 0.51) was associated with a decreased risk after adjusting for potential confounders. Maternal HBeAg positive was a strong independent predictor for intrauterine transmission (OR = 2.56, 95% CI: 1.54, 4.27). A positive association between maternal HBV DNA levels and intrauterine transmission was suggested. Maternal HBIG administration during pregnancy, family history of HBV infection and premature rupture of membranes was not associated with the risk of intrauterine transmission. The study confirmed that maternal HBeAg positive was a risk factor and caesarean delivery was a protective factor for intrauterine transmission. The new findings associated with menstrual irregularity and severe nausea during the first trimester warrant further investigation.  相似文献   

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Addition of peginterferon alpha (PEG‐IFN add‐on) to entecavir (ETV) treatment after a short lead‐in phase results in more response than ETV monotherapy in HBeAg‐positive chronic hepatitis B infection (CHB). This study is the first to assess long‐term efficacy of this treatment strategy. Patients who received ETV ± 24 weeks of PEG‐IFN add‐on in a global trial (ARES study) and completed follow‐up were eligible to participate in this observational LTFU study if they had at least one combined HBeAg and HBV DNA measurement beyond week 96 of the ARES study. The primary endpoint was combined response (HBeAg loss and HBV DNA <200 IU/mL) at LTFU. In total, 48 patients treated with PEG‐IFN add‐on and 48 patients treated with ETV monotherapy were included. The median follow‐up duration was 226 (IQR 51) weeks, and 86/96 (90%) patients were initial non‐responders. At LTFU, combined response was present in 13 (27%) vs 11 (23%) patients (P = 0.81), and 1 log10 HBsAg decline in 59% vs 28% (P = 0.02) for PEG‐IFN add‐on and ETV monotherapy, respectively. In 41 initial non‐responders who continued ETV therapy, combined response at LTFU was present in 9 patients (PEG‐IFN add‐on: 5/22 [23%]; ETV monotherapy: 4/19 [21%]). Beyond week 96 of follow‐up, rates of serological response became comparable between PEG‐IFN add‐on and ETV monotherapy. Although in this LTFU study initial non‐responders were overrepresented in the add‐on arm, PEG‐IFN add‐on possibly leads rather to accelerated HBeAg loss than to increased long‐term HBeAg loss rates.  相似文献   

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Hepatitis B virus (HBV) infection is a major cause of cirrhosis and hepatocellular carcinoma worldwide. On the basis of virus–host interactions, the natural history of HBV carriers can be divided into four chronological phases. In the first immune tolerance phase, HBV carriers are positive for hepatitis B e antigen (HBeAg) and have high HBV replication activity, normal ALT levels as well as minimal liver disease. Ample evidence has shown that patients in the immune tolerance phase have very low viral evolution and minimal risk of fibrosis progression. However, recent immunological studies argued that HBV‐specific immune responses already exist in a proportion of immune‐tolerant patients and the immune activities are comparable to those in the immune clearance phase. Regarding antiviral therapy, whether these immune‐tolerant patients are indicated for treatment remains debated. Previous studies showed that HBeAg‐positive patients with normal or near‐normal ALT levels, who are assumed to be in the immune tolerance phase, have a lower HBeAg seroconversion rate receiving either pegylated interferon or nucleos(t)ide analogue treatment. The latest clinical trial focusing on‐treatment response of immune‐tolerant patients with tenofovir disoproxil fumarate‐based therapy also confirmed the results. The HBeAg seroconversion rates are <5% at 4 years of treatment. Considering the minimal risk of disease progression and low treatment response rates in immune‐tolerant patients, current antiviral therapy should not be recommended unless the patients have advanced liver fibrosis. In addition, novel agents targeting the HBV template known as covalently closed circular DNA and aiming to reduce or eliminate it are urgently required.  相似文献   

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Achieving ‘clinical cure’ in children with chronic hepatitis B (CHB) with safe and effective antiviral treatment is an unmet medical need. Peginterferon (PegIFN) has higher hepatitis B s antigen (HBsAg) clearance than nucleoside analogs (NUC). Currently, studies on interferon (IFN) in the treatment of Chinese children with CHB are relatively rare. This study aimed to further explore the efficacy of PegIFNα‐2a as an antiviral treatment in Chinese children and analyse the long‐term follow‐up after drug discontinuation. We enrolled 118 patients with CHB (2‐16 years old, 79 cases are males) treated with PegIFNα‐2a by the author in the Third People's Hospital of Kunming City from February 2009 to February 2015. The course of treatment was 52 weeks, with a follow‐up period of 104 weeks. All the patients completed at least 1 dose, of which 104 completed at least 36 weeks of treatment and 104 weeks of follow‐up. During treatment and follow‐up, indicators such as alanine aminotransferase (ALT), hepatitis B virus (HBV) DNA and HBV serological markers were monitored, and the efficacy and safety of PegIFNα‐2a in the treatment of CHB patients were observed. Hepatitis B e antigen (HBeAg) clearance and seroconversion rates were 53.8% and 49%, respectively, when the drug was discontinued; 72.1% and 72.1%, respectively, at the end of the follow‐up; and 98.2% and 98%, respectively, for sustained response. HBsAg clearance and seroconversion rates were 48.1% and 47.1%, respectively, when the drug was discontinued; 53.8% and 52.9%, respectively, at the end of the follow‐up; and 94% and 95.9%, respectively, for sustained response. The HBV DNA suppression rate was 89.4% when the drug was discontinued, 90.4% at the end of the follow‐up and 97.8% for sustained response. Two patients had virological relapse (2.3%) during follow‐up; however, no clinical relapse occurred. Multivariate regression analysis showed that genotype B, weight < 25 kg or between 25 and 45 kg, and reduction of HBsAg by more than 1 log following 24 weeks of treatment were independent predictors of HBsAg clearance at the end of follow‐up. Adverse events that occurred during treatment were similar to those reported in previous clinical studies on PegIFN. The results of this study showed that PegIFN was safe and effective in the treatment of children with CHB, and sustained response could be achieved after treatment. PegIFN treatment of children with CHB helps more achieve ‘clinical cure’.  相似文献   

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Background: It is unclear whether clinical indication for antiviral treatment is in agreement with histological indication in HBeAg‐negative chronic hepatitis B (CHB). This study aimed to clarify this relationship and identify factors associated with liver histology. Patients and methods: We investigated 152 consecutive, treatment‐naïve, HBeAg‐negative CHB patients who had undergone liver biopsies at a tertiary medical centre in Taiwan. Clinical indications for treatment included a serum alanine aminotransferase level more than twice the upper limit of normal and an hepatitis B virus DNA level >2000 IU/ml. Factors associated with the histological indication (Ishak's grade ≥7 and/or stage ≥2) were analysed. Results: The association between the clinical and the histological indications was significant (P=0.011). However, the agreement was poor (κ value=0.197). In patients satisfying the clinical indication, age >52 years [odds ratio (OR)=2.669, P=0.042], serum α‐fetoprotein (AFP) level >7 ng/ml (OR=7.070, P<0.001) and platelet count <130 × 109/L (OR=11.720, P=0.025) were identified to be independent factors associated with histological indication. In patients who did not satisfy the clinical indication, multivariate analysis revealed that only an AFP level >7 ng/ml (OR=10.345, P=0.021) was independently associated with histological indication. Combining the clinical indication and/or AFP level >7 ng/ml to predict liver histology, the sensitivity and the negative predictive value could improve from 86 to 94.4% and 66.7 to 81% respectively. Conclusion: AFP level is associated with liver histology in HBeAg‐negative CHB. Serum AFP level can serve as a surrogate indicator to identify patients who need antiviral treatment.  相似文献   

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