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Background & Aims: Nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB) patients reduces liver‐related mortality. However, long‐term outcomes after pegylated interferon (PEG‐IFN) therapy remain to be elucidated. Therefore, we aimed to investigate the long‐term effectiveness and clinical outcomes of PEG‐IFN therapy. Methods: A total of 190 patients treated with PEG‐IFN for CHB or compensated cirrhosis were consecutively enrolled between 2005 and 2014, and 122 patients who completed the treatment were analysed. The initial response was assessed at 6 months post‐treatment and defined as achieving both <2000 IU/mL HBV DNA and HBeAg loss or seroconversion in the HBeAg‐positive group, and <2000 IU/mL HBV DNA in the HBeAg‐negative group. The rates of HBsAg loss, disease progression to cirrhosis or HCC, and sustained off‐therapy response, defined as not requiring further NAs because of low viremia and liver enzymes, were analysed. Results: The median follow‐up period was 7.2 years. Forty‐three (35.2%) patients achieved an initial response and 53 patients (43.4%) achieved a sustained response. Initial responders displayed higher rates of sustained response than noninitial responders (69.6% vs 32.5%, P <.001). A higher rate of HBsAg loss was observed in patients who achieved a sustained response than in non‐sustained responders (16.2% vs 2.5%, P =.01). Disease progression to cirrhosis or HCC was observed in eight patients (6.6%) who were nonsustained responders. Conclusions: During long‐term follow‐up after PEG‐IFN treatment, nearly half of patients achieved sustained response without the need of further NA and these patients displayed favourable outcomes, including HBsAg loss and no disease progression. [ABSTRACT FROM AUTHOR]

Background & Aims We assessed predictors of response in HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a in routine clinical practice. Methods Ninety-five HBeAg-negative patients received peginterferonalfa-2a for 48 weeks and were followed-up for 48 weeks post-treatment. Serum HBsAg and HBV DNA levels were monitored during and after therapy with valid commercial assays. Sustained response (SR) was defined as HBV DNA <2000 IU/ml at study week 96. Results Twenty-two patients (23%) achieved SR and nine (9.5%) lost HBsAg. HBsAg decline was more profound in patients with SR. HBsAg decline ≥10% from baseline to week 24 was significantly associated with SR [81% (17/21) vs 37% (21/57); Odds ratio: 7.286 (2.162-24.552), P = 0.001]. The PARC rule (no decrease in HBsAg and <2 log drop in HBV DNA at week 12) was evaluated in a subset of 47 patients. Among eight patients who fulfilled the PARC rule, none achieved SR. Of the 39 patients who did not fulfil the PARC rule, 24 (62%) had HBsAg decline of ≥10% at week 24 (12 achieved SR) and 15 (38%) had HBsAg decline of <10% (1 achieved SR; negative predictive value: 93%). Conclusions In HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a, HBsAg decline >10% at 24 weeks is significantly associated with SR. The combination of the PARC rule and week 24 decline in HBsAg can identify almost two-thirds of patients who are unlikely to achieve SR. Clinicaltrials.gov identifier: NCT01283074. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B ( CHB) in serum HBeAg negative patients is a difficult to cure, progressive disease leading to end-stage liver disease and hepatocellular carcinoma. Currently, there are two different treatment strategies for such patients: a finite course of Pegylated interferon (PEG- IFN) or long-term administration of the more potent and less resistance-prone nucleot(s)ide analogues ( NUC), i.e. entecavir and tenofovir. Although NUC may ensure persistent viral suppression by preventing disease progression in most patients, they require lifelong administration with the hypothetical disadvantages of cost, lack of long-term safety data and, most important, the null rates of HBsAg seroclearance. On the other hand, 1 year of PEG- IFN has the advantage of providing an immune-mediated control of hepatitis B virus ( HBV) infection, with the possibility of achieving a sustained off-treatment response in 20% of the patients, ultimately leading to HBsAg loss in approximately 50% of these. However, these sustained response rates can be significantly increased by carefully selecting candidates for PEG- IFN therapy based upon baseline ALT and HBV DNA levels, viral genotype and IL28B polymorphisms, by extending PEG- IFN therapy beyond 48 weeks and, most importantly, by applying early on-treatment stopping rules based upon HBsAg kinetics. Overall, PEG- IFN is an ideal treatment strategy in selected patients with HBeAg-negative CHB, because of its well-recognized and predictable safety profile and a unique mechanism of antiviral activity leading to long-lasting immune control. Because of these features, new therapeutic trials based upon a combination of PEG- IFN and third generation NUC such as entecavir and tenofovir, in both naïve and NUC-exposed patients, are ongoing to further increase the rates of HBsAg seroclearance, which remains the 'ideal end-point' in all HBeAg-negative CHB subjects. [ABSTRACT FROM AUTHOR]

Hepatitis C virus contact and infection show three different phenotypes: spontaneous viral clearance (SVC), chronic hepatitis C (CHC) and sustained virological response (SVR) following antiviral treatment. Many factors, including genetics, influence the evolution of these three phenotypes. We performed a literature search (PubMed) up to 31 January 2010 without language restriction to identify relevant studies on genes and hepatitis C. Additional studies were sought by reviewing the reference lists of the identified articles. Meta-analysis (using Meta-disk 1.4) was conducted to evaluate the association of single nucleotide polymorphism (SNP) in the IL28B region and SVR. The candidate gene approach showed strong relationships between human leucocyte antigen class II (DQB10301 and DRB11101) and SVC. A cirrhosis risk score involving 7 SNPs has been validated recently. The set of odds ratios of studies demonstrated an association between SNP (rs12987960/rs8099917) in the IL28B and SVR in CHC treated with peginterferon plus ribavirin (OR: 4.6; 95% CI: 2.9-7.3). The overall distribution of protective allele correlated with ethnic differences in SVR (Asians, Europeans, Hispanic and Afro-Americans) together with SVC, but not with fibrosis stage or viral load. These polymorphisms did not influence SVR in very-easy-to-treat patients such as genotype 2/3, rapid virological responders or patients with acute hepatitis C. While the genetic fingerprint for fibrosis progression remains elusive, IL28b polymorphism predicts SVC and SVR. However, nearly half of patients achieving SVR did not show favourable genotype. Further genetic signals are warranted to complete the puzzle of factors influencing hepatitis C. [ABSTRACT FROM AUTHOR]