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Hepatitis B virus (HBV) surface antigen (HBsAg) seroconversion to anti-HBs antibody is the best final objective for all available chronic hepatitis B (CHB) treatments. Unfortunately, this goal is rarely achieved with the currently applied therapeutic approaches. Here we describe the case of an anti-HBe-positive CHB patient who was successfully treated with a particular therapeutic schedule. The patient was initially treated with lamivudine (LAM) for nine years. Breakthrough was observed after eight years of LAM therapy. HBV-DNA was 3x10E4 IU/mL and LAM resistance mutations were present. Subcutaneous pegylated interferon (PEG-IFN) alfa 2a, 180 mcg/week, was added to LAM and after 4 weeks LAM was discontinued and PEG-IFN alone was continued up to week 52. HBV-DNA became undetectable at week 4 of therapy; serum HBsAg started to decline from week 4 and became undetectable at week 36, with the subsequent appearance of anti-HBs antibodies. IL28-B was genotyped at the polymorphic site rs12979860 and the CC allele was detected. Rescue therapy with Peg-IFN may be an option for selected patients with resistance to nucleos(t)ide analogues.

The inosine triphosphatase (ITPA) gene and interleukin 28B (IL28-B) gene variants have been associated to protection of anemia and sustained virological response, respectively, in patients with chronic hepatitis C (CHC) during antiviral therapy. Aim of this study was to evaluate the single and combined role of both polymorphisms in the management of peg-interferon-ribavirin treatment in CHC patients. We studied 79 Italian patients with histology proven CHC treated with pegylated interferon plus ribavirin for 6-12 months on the base of HCV genotype. Patients were carefully followed-up for anemia development which was classified as mild, moderate or severe in relation to levels of haemoglobin decreasing; ribavirin dosage reduction and/or epoietin administration were carried out, where needed. Sustained virological response (SVR) was considered for HCV-RNA clearance after 6 months of treatment stop. Decay of haemoglobin at month 1 of treatment significantly correlated with ITPA activity (p 0.0004) and at multivariate analysis ITPA activity was the only parameter associate with anemia (R - 0.4; p 0.0004). SVR was obtained in 47% of patients. IL28B CC variant was associated with SVR (p 0.01), but IL28B polymorphisms had no influence on the ITPA polymorphism. This study confirms the role of ITPA variants in the prediction of development of severe anemia during antiviral treatment for CHC and demonstrates the absence of influence of IL28B variant on ITPA polymorphisms. These two polymorphisms can be useful in the management of patients that need antiviral therapy for HCV chronic infection.

Here it is reported the virological dynamic of HBV and HCV, identified in the plasma, peripheral blood mononuclear cells and tissue liver, in a patient with chronic HBV-HCV coinfection. A treatment with pegylated Interferon plus Ribavirin determined a sustained virological response for HCV in all the three studied compartments, but a reactivation of chronic HBV infection was observed. In fact, while at the first observation HBV-DNA was detectable only in the liver tissue, after antiviral therapy it was detectable in all the three compartments; moreover this HBV reactivation was associated with a hepatic flare. Then, the patient was treated with Entecavir, which has been determining the clearance of HBV from the peripheral compartments (plasma and PBMC) until today.

A durable suppression of viral replication in chronic HBV infection decreases the risk of liver disease progression. Treatment is recommended for patients in the immune-active phases of chronic HBV infection (HBeAg positive or HBeAg negative patients with serum HBV-DNA and elevated ALT). Licensed HBV therapies include interferon (sIFN, pegylated-IFN alfa-2a) and nucleoside/nucleotide analogues (lamivudine, adefovir, entecavir) allowing for two different treatment strategies: a finite treatment course of IFN that provides sustained off-treatment response in about one third of patients, or an indefinite treatment with nucleoside/nucleotide analogues that provides a therapy maintained response. IFN has the advantage of a defined treatment duration and of lacking resistance selection; disadvantages are the subcutaneous route of administration and poor tolerability. Nucleoside/nucleotide analogues are orally administered and well tolerated; their drawback is the risk of developing antiviral resistance which increases with duration of treatment. A finite course of IFN should be tried as first-line therapy; a long-term treatment with nucleoside/nucleotide analogues should be used for patients not responding or intolerant to interferon.