Hepatitis delta virus: From infection to new therapeutic strategies

The hepatitis delta virus(HDV)is a small RNA virus that encodes a single protein and which requires the hepatitis B virus(HBV)-encoded hepatitis B surface antigen(HBsAg)for its assembly and transmission.HBV/HDV co-infections exist worldwide and show a higher prevalence among selected groups of HBV-infected populations,specifically intravenous drug users,practitioners of high-risk sexual behaviours,and patients with cirrhosis and hepatocellular carcinoma.The chronic form of HDV-related hepatitis is usually severe and rapidly progressive.Patterns of the viral infection itself,including the status of co-infection or super-infection,virus genotypes(both for HBV and HDV),and persistence of the virus’replication,influence the outcome of the accompanying and manifested liver disease.Unfortunately,disease severity is burdened by the lack of an effective cure for either virus type.For decades,the main treatment option has been interferon,administered as mono-therapy or in combination with nucleos(t)ide analogues.While its efficacy has been reported for different doses,durations and courses,only a minority of patients achieve a sustained response,which is the foundation of eventual improvement in related liver fibrosis.The need for an efficient therapeutic alternative remains.Research efforts towards this end have led to new treatment options that target specific steps in the HDV life cycle;the most promising among these are myrcludex B,which inhibits virus entry into hepatocytes,lonafarnib,which inhibits farnesylation of the viral-encoded LHDAg large hepatitis D antigen,and REP-2139,which interferes with HBsAg release and assembly.

Autoimmune hepatitis treatment in the elderly: A systematic review

BACKGROUND Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease with a high risk of progression to liver cirrhosis. The initial treatment for AIH usually includes a steroid, with or without azathioprine. AIH can present at any age;however, the most effective and safe induction treatment for AIH in the elderly remains unclear. AIM To systematically review available data on both effectiveness and safety of AIH treatments in elderly subjects. METHODS To identify studies on AIH induction treatment in elderly patients (≥ 60 years of age), an electronic research was performed (PubMed, EMBASE and Cochrane Library databases) until February 2019. Eligible studies were selected through screening of titles and abstracts, followed by full-text critical evaluation. After risk of bias assessment, data on study designs, interventions, and outcomes were extracted and reviewed. RESULTS Among the 1736 retrieved papers, 15 studies were selected. Out of them, eight studies were excluded because of a critical risk of bias. The remaining seven studies included 789 patients and out of them 239 subjects were elders. First-line treatment was a steroid either alone or in combination with azathioprine in most patients (87.6%) and only one study investigated the effect of combined steroid and mycophenolate mofetil therapy. Standard therapy was effective in inducing remission in the elderly. Moreover, treatment failure and relapses occurred less often in the elderly compared to younger people.CONCLUSION Treatment of AIH is challenging in elderly patients. This systematic review confirms the efficacy and safety of standard induction treatment for AIH in the elderly. Available evidence is insufficient to draw any conclusion on the effect of novel AIH treatments in elderly subjects.