Summary: Background: A few cases of hepatitis B virus (HBV) reactivation during anti‐viral therapy against hepatitis C (HCV) have been reported. However, the information regarding the real impact of this phenomenon is scarce.Aim: To evaluate the risk ofHBVreactivation during anti‐viral therapy againstHCVwith an interferon‐free regimen with direct‐acting anti‐virals (DAAs).Methods: Observational and prospective study of 352 patients receivingDAAs therapy between September 2015 and May 2016.HBV‐DNAandALTlevels were monitored at baseline, at week 4 of anti‐viral therapy, at end of treatment and 12 weeks after treatment discontinuation in patients withHBVsurface antigen (HBsAg) positive orHBVcore antibody (anti‐HBc) positive before starting anti‐viral therapy.Results: Ten (2.8%) and 64 (18%) patients wereHBsAg and anti‐HBc positive at baseline, respectively. Five (50%) of 10HBsAg positive and one (1.6%) of 64 anti‐HBc positive patients presentedHBVvirological reactivation (>1log increase inHBV‐DNAlevels). None of these patients presented clinical reactivation (increase inALTlevels).Conclusions: HBVvirological reactivation is frequent inHBsAg+ patients receiving anti‐viral therapy againstHCV. However,HBV‐DNAelevations were modest (<20 000IU/mL) and without clinical impact (noALTelevation).

The hepatitis B virus (HBV) infection remains a global public health problem. This review presents updated recommendations for the optimal current treatment of choice with nucleos(t)ide analogues (NA). Current clinical practice guidelines on the management of chronic hepatitis B (CHB) by the Asian Pacific Association for the Study of the Liver, the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases have been considered. Patients with chronic HBV infection are at increased risk of liver disease progression to cirrhosis and hepatocellular carcinoma (HCC) development. The main goal of therapy is to improve survival preventing disease progression and HCC. The induction of long-term suppression of HBV replication represents the main endpoint of current treatment strategies, while hepatitis B surface antigen (HBsAg) loss is the optimal endpoint. The typical indication for treatment requires elevated HBV desoxyribonucleic acid (DNA), elevated alanine aminotransferase and/or at least moderate histological lesions, while all cirrhotic patients with detectable HBV DNA should be treated. The long-term administration of a potent NA with high barrier to resistance, ie, entecavir, tenofovir disoproxil fumarate or tenofovir alafenamide, represents the treatment of choice. However, HBsAg seroclearance is anecdotal with NA. Treated patients should be monitored for therapy response, adherence, risk of disease progression, and risk of HCC development. This review aims to assess the evolving trends on the potent NA and the new perspectives on finite therapy.

Background: Liver fibrosis and transient elastography (TE) correlation in hepatitis C virus (HCV)‐infected patients with compensated advanced chronic liver disease (cACLD) after the sustained virological response (SVR) is unknown.Aims: To evaluate TE accuracy at identifying cirrhosis 3 years after HCV‐eradication.Methods: Prospective, multi‐centric study including HCV‐cACLD patients before direct‐acting antivirals (DAA). Diagnostic accuracy of TE (area under ROC, AUROC) to identify cirrhosis 3 years after SVR was evaluated.Results: Among 746 HCV‐infected patients (95.4% with TE ≥10 kPa), 76 (10.2%) underwent a liver biopsy 3 years after SVR. Before treatment, 46 (63%) showed a TE>15 kPa. The TE before DAA was the best variable for predicting cirrhosis (METAVIR, F4) after SVR (AUROC = 0.79). Liver function parameters, serological non‐invasive tests (APRI and FIB‐4), and TE values improved after SVR. However, liver biopsy 3 years after HCV elimination (median time = 38.4 months) showed cirrhosis in 41 (53.9%). Multivariate analysis (OR (95% CI), P) showed that HCV‐genotype 3 (20.81 (2.12‐201.47), .009), and TE before treatment (1.21 (1.09‐1.34), <.001) were the only variables associated with cirrhosis after SVR. However, the accuracy of TE after SVR was poor (AUROC = 0.75) and 6 (27.3%) out of 22 patients with a TE <8 kPa had cirrhosis. Similar results were found with APRI and FIB‐4 scores.Conclusions: Cirrhosis is present, 3 years after SVR, in more than half of HCV‐cACLD patients even with the normalisation of liver function parameters, serological non‐invasive tests and TE values. The low diagnostic accuracy of non‐invasive methods after SVR reinforces the need for long‐term surveillance.

Cryopreservation of serum samples is a standard procedure for biomedical research in tertiary centers. However, studies evaluating the long-term biological stability of direct liver fibrosis markers using cryopreserved samples are scarce. We compared the stability of hyaluronic acid (HA), tissue inhibitor of metalloproteinases (TIMP-1) and amino-terminal propeptide of type III procollagen (PIIINP) in 225 frozen serum samples of HCV-infected patients with a paired liver biopsy for up to 25 years (1990–2014). Moreover, we assessed the diagnostic accuracy (AUROC) of the Enhanced Liver Fibrosis (ELF^®) score to identify significant fibrosis (F2-4) and its predictive capacity to identify clinical events during follow-up. Seventy-six patients (39,8%) had mild fibrosis (F0-1) and 115 (60,2%) significant fibrosis (F2-4). HA, PIIINP and TIMP-1 values remained stable during the period from 1995 to 2014 while those of 1990–94 were slightly higher. We did not find significant differences in the median ELF^® values during the 20-year period from 1995–2014 in patients with mild (from 8,4 to 8,7) and significant fibrosis (from 9,9 to 10,9) (p = ns between periods and fibrosis stages). The AUROCs of ELF^® to identify significant fibrosis were high in all the periods (from 0,85 to 0,91). The ELF^® score showed a good predictive capability to identify clinical events during follow-up. The biological stability of direct serum markers (HA, PIIINP and TIMP-1) using HCV-infected samples cryopreserved for 20 years is good. Therefore, the diagnostic accuracy of the ELF^® score to identify significant fibrosis and clinical events during follow-up is very high.

HBeAg-negative chronic hepatitis B patients require long-term nucleos(t)ide analogues(NAs) because loss of surface antigen (HBsAg) is unusual. Low quantitative HBsAg (qHBsAg) levels can identify patients with higher probability of seroclearance. The aim of our study was to evaluate qHBsAg in HBeAg-negative patients receiving NAs to predict a reduction of HBsAg levels and seroclearance. Retrospective analysis of qHBsAg in HBeAg-negative patients before and at years 1, 3, 5, 8 and over of NAs treatment. From 1999 to 2015, HBsAg was quantified in 358 serum samples from 95 HBeAg-negative patients. Low qHBsAg (<120 IU/mL) was identified at baseline or during follow-up in 14% of patients and HBsAg loss in 4%. No baseline variables predicted seroclearance and only treatment duration predicted low qHBsAg. The annual decline of qHBsAg was -0.102 log IU/mL and the median time to HBsAg loss was 6.04 years. The decline was greater in patients achieving low HBsAg levels (-0.257) than in those who did not (-0.057)(p0.3 log IU/mL showing a positive and negative predictive value of 42% and 100% to identify patients achieving low levels of HBsAg. Reduction of qHBsAg is slow in HBeAg-negative patients receiving NAs, although low levels or faster qHBsAg decline may occur in 14%. A qHBsAg reduction >0.3 log IU/mL at year 3 can identify patients with a higher probability of achieving low levels and HBsAg seroclearance.