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OBJECTIVE: The objective of this study was to determine the long-term clinical outcome and persistence of hepatitis B surface antigen (HBsAg) loss after discontinuation of treatment. BACKGROUND: The prognosis of patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs) who discontinue treatment after loss of HBsAg remains largely unknown, particularly in White patients. PATIENTS AND METHODS: We analysed a cohort of patients with CHB who discontinued NA treatment after loss of HBsAg. A total of 69 patients with hepatitis-B-e antigen-positive or hepatitis-B-e antigen-negative CHB with undetectable HBsAg during NA treatment were included after discontinuation of treatment, and followed up for a median period of 37.8 months (interquartile range: 23.8-54.6 months). RESULTS: At the end of follow-up, none of the patients showed spontaneous reappearance of HBsAg and only one patient had detectable hepatitis B virus DNA (22IU/ml). Another patient negative for HBsAg and anti-HBs developed hepatitis B virus reactivation without elevated transaminases after treatment with corticosteroids and vincristine for dendritic cell neoplasm, 38 months after withdrawal of the antiviral treatment. Regarding clinical outcome, a patient with cirrhosis developed hepatocellular carcinoma, 6.6 years after discontinuing treatment. None of the patients had hepatic decompensation or underwent liver transplantation. CONCLUSION: HBsAg clearance after discontinuing NAs in patients with CHB is persistent and associated with good prognosis. The risk for developing hepatocellular carcinoma persists among patients with cirrhosis.

[Abstract] A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) α-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions. Ministerio de Economía y Empresa; IDI-20151125 Ministerio de Ciencia, Innovación y Universidades; SAF SAF 2017-87846-R

SUMMARY Background Sustained virological response rates of up to 52% have been obtained with peginterferon α2a (40 kDa) plus ribavirin in patients suffering from chronic hepatitis C genotype 1 in randomized-controlled trials. Aim To assess early virological response and its clinical utility in predicting an sustained virological response in patients suffering from chronic hepatitis C genotype 1 in routine clinical practice in Spain. Methods Treatment-naive patients received pegylated interferon α2a (40 kDa) 180 µg/week plus ribavirin 1000/1200 mg/day for 48 weeks, and were followed for a further 24 weeks. Overall, 475 patients received at least one dose of medication and were included in the efficacy population. Results The overall sustained virological response rate was 48%. Of those with week 12 virological data, 83% had an early virological response. The negative predictive value of an early virological response was 93%. Conclusion If sustained virological response is the goal, a treatment-decision based on a 12-week evaluation during routine clinical practice is feasible.

This chapter will deal with the present role of Liver Biopsy in determining liver disease prognosis in hepatitis B and C patients on haemodialysis and its role in establishing treatment strategies and in the decision-making process prior to kidney transplant. In recent years, progress has been made in determining the natural history of this disease in renal patients (Espinosa et al., 2004; Jadoul et al., 2004). Chronic hepatitis due to HCV is frequent in renal transplant recipients and in dialysis patients and has a significant impact on their survival (Hanafusa et al., 1998; Orloff et al., 1995; Pouteil-Noble et al., 1995). Mathurin et al., (1999) demonstrated in a case-control study that anti-HCV and HBsAg positive were independently associated with patient and graft survival. This was the first time that a 10 year follow-up was carried out; previous publications are based on shorter follow-ups and fewer patients. It is known that the prevalence of chronic infection with the hepatitis C virus (HCV) in patients with chronic kidney disease is higher than in the general population (Lavanchy, 2009). The estimated prevalence of chronic infection in haemodialysis patients is 13%, ranging from 10 to 65 %, depending on the geographical zone (Hmaied et al., 2006; Huraib et al., 1995; Santos & Souto, 2007; Shamshiraz et al., 2004). When considering patients candidates to kidney transplantation we have to take into account that immunosuppressive therapy after renal transplantation predisposes a reactivation of chronic viral hepatitis B or C, which is usually a mild disease for patients remaining under haemodialysis. It should be noted that HBV and HCV may induce de novo glomerulonephritis and chronic allograft nephropathy which can lead to graft failure (Aouifi & Garcia, 2001). In such cases, patients have to undergo dialysis again and therefore it is beneficial to eradicate HCV RNA before transplantation and to control and maintain HBV DNA negative (Huskey & Wiseman, 2011). A routine liver histological analysis could improve a patient’s chance of being selected for renal transplantation. Liver biopsy has been considered the “gold standard” for many years, because it provides us with information that was otherwise unobtainable (Ghany et al., 2010). Nowadays however, due to progress in non-invasive methods, liver biopsy is only

Background & Aims : Liver transplantation for hepatitis C virus (HCV)-related liver disease is characterized by frequent graft infection by HCV The prognosis and risk factors for morbidity and mortality in this condition were determined. Methods A retrospective study of 652 consecutiveanti-HCV-positive patients undergoing liver transplantation between 1984 and 1995 in 15 European centers was conducted; 102 patients coinfected with hepatitis B virus (HBV) received immunoglobulin prophylaxis for antibody to hepatitis B surface antigen. Results Overall, 5-year survival was 72%. Five-year actuarial rates of hepatitis and cirrhosis were 80% and 10%. Genotypes 1b, 1a, and 2 were detected in 214 (80%), 24 (9%), and 24 (9%) of 268 patients analyzed. The only discriminant factor for patient or graft survival was hepatocellular carcinoma as primary indication. Independent risk factors for recurrent hepatitis included the absence of HBV coinfection before transplantation (relative risk [RR], 1.7; 95% confidence interval [CI], 1.2-2.6; P = 0.005), genotype 1b (RR, 2; 95% CI, 1.3–2.9; P = 0.01), and age > 49 years (RR, 1.4; 95% CI, 1.1–1.8; P = 0.01). Conclusions The results of transplantation for HCV related disease are compromised by a significant risk of cirrhosis, although 5-year survival is satisfactory. Genotype 16, age, and absence of pretransplantation coinfection by HBV are risk factors for recurrent HCV.

Sustained virological response rates of up to 52% have been obtained with peginterferon alpha2a (40 kDa) plus ribavirin in patients suffering from chronic hepatitis C genotype 1 in randomized-controlled trials.To assess early virological response and its clinical utility in predicting an sustained virological response in patients suffering from chronic hepatitis C genotype 1 in routine clinical practice in Spain.Treatment-naïve patients received pegylated interferon alpha2a (40 kDa) 180 microg/week plus ribavirin 1000/1200 mg/day for 48 weeks, and were followed for a further 24 weeks. Overall, 475 patients received at least one dose of medication and were included in the efficacy population.The overall sustained virological response rate was 48%. Of those with week 12 virological data, 83% had an early virological response. The negative predictive value of an early virological response was 93%.If sustained virological response is the goal, a treatment-decision based on a 12-week evaluation during routine clinical practice is feasible.

Liver transplantation for hepatitis C virus (HCV)-related liver disease is characterized by frequent graft infection by HCV. The prognosis and risk factors for morbidity and mortality in this condition were determined.A retrospective study of 652 consecutive anti-HCV-positive patients undergoing liver transplantation between 1984 and 1995 in 15 European centers was conducted; 102 patients coinfected with hepatitis B virus (HBV) received immunoglobulin prophylaxis for antibody to hepatitis B surface antigen.Overall, 5-year survival was 72%. Five-year actuarial rates of hepatitis and cirrhosis were 80% and 10%. Genotypes 1b, 1a, and 2 were detected in 214 (80%), 24 (9%), and 24 (9%) of 268 patients analyzed. The only discriminant factor for patient or graft survival was hepatocellular carcinoma as primary indication. Independent risk factors for recurrent hepatitis included the absence of HBV coinfection before transplantation (relative risk [RR], 1.7; 95% confidence interval [CI], 1.2-2.6; P = 0.005), genotype 1b (RR, 2; 95% CI, 1.3-2.9; P = 0.01), and age49 years (RR, 1.4; 95% CI, 1.1-1.8; P = 0.01).The results of transplantation for HCV-related disease are compromised by a significant risk of cirrhosis, although 5-year survival is satisfactory. Genotype 1b, age, and absence of pretransplantation coinfection by HBV are risk factors for recurrent HCV.