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Summary: Background: Treatment of chronic drug‐induced liver injury (DILI) or herb‐induced liver injury(HILI) is an important and unresolved challenge. There is no consensus regarding the indications for corticosteroids for chronic DILI/HILI. Aims: To investigate the efficacy and safety of corticosteroid plus glycyrrhizin for patients with chronic DILI/HILI. Methods: This was a randomised open‐label trial. Eligible patients with causality assessment using the updated RUCAM were randomly assigned (1:1) either to the steroid treatment group (48‐week stepwise dose reduction of methylprednisolone plus glycyrrhizin) or control group (glycyrrhizin alone). Liver biopsies were performed at baseline and at the end of the 48‐week treatment period. The primary outcome was the proportion of patients with sustained biochemical response (SBR). The secondary outcomes were improvement in liver histology, time to biochemical normalisation and safety. Results: Of 80 participants, 70 (87.5%) completed the trial. The patients were predominantly female (77.5%), aged >40 years (77.5%) and had a hepatocellular injury pattern of DILI (71.2%). Compared to the control group, the treatment group showed a higher proportion of SBR (94.3% vs. 71.4%, p = 0.023), shorter biochemical normalisation time and histological improvements in both histological activity and fibrosis. The DILI and HILI subgroups, as well as the autoimmune hepatitis (AIH)‐like DILI and non‐AIH‐like subgroups, showed comparable responses. No severe adverse events were observed during the trial. Conclusion: This study provides the first clinical evidence that corticosteroid plus glycyrrhizin therapy for chronic DILI with or without AIH‐like features can achieve both biochemical response and histological improvements with good safety. (ClinicalTrials.gov, NCT 02651350). [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the differentiation potential of induced pluripotent stem cells (iPSCs) derived from human foreskin fibroblasts (HFFs) into hepatocyte-like cells (HLCs). The iPSCs were firstly induced by transduction of OCT4, SOX2, KLF4, and c-MYC into HFFs using retrovirus. Afterwards, expressions of pluripotency factors were identified by semiquantitative reverse transcription-polymerase chain reaction and immunofluorescence staining, and karyotype, embryoid, and teratoma were observed by microscope. Then, iPSCs were gradually differentiated into endoderm cells, hepatic progenitor cells, and mature HLCs by special culture medium. During this process, differentiation efficiency into each kind of cells was evaluated by detecting SOX17, HNF4a, and ALB using flow cytometry, respectively. Besides, enzyme-linked immunosorbent assay was conducted to detect the secretion of ALB in iPSC-induced HLCs and quantitative reverse transcription-polymerase chain reaction was performed to detect the expression levels of hepatocyte-specific genes. The iPSCs were successfully induced by HFFs, which exhibited typical embryonic stem cells morphology, positive alkaline phosphatase staining, normal diploid karyotype, and positive expression of various pluripotency factors. Meanwhile, spherical embryoid and teratoma with 3 germ layers were formed by iPSCs. The iPSCs were consecutively induced into endoderm cells, hepatic progenitor cells and mature HLCs, and the differentiation efficiency was 55.7 ± 2.9%, 45.7 ± 4.8%, and 35.0 ± 3.9%, respectively. Besides, the secretion of ALB and expression of various hepatocyte-specific genes was highly detected in iPSC-induced HLCs. The iPSCs were successfully derived from HFFs and then differentiated into HLCs, which proved a new source for hepatocyte transplantation. Highlights HFFs were successfully induced into iPSCs by transduction of OCT4, SOX2, KLF4, and c-MYC., Positive expressions of various pluripotency factors were exhibited in HFFs-induced iPSCs., The iPSCs were consecutively induced into endoderm cells, hepatic progenitor cells, and mature HLCs., Various hepatocyte-specific genes were highly expressed in iPSC-induced HLCs. [ABSTRACT FROM AUTHOR]

This study investigated features and clinical implications of HBV mutations in patients with different clinical manifestations. In total, 516 patients were enrolled in this study, including 131 patients with acute hepatitis B, 239 patients with chronic hepatitis B, and 146 patients with acute-on-chronic liver failure. HBV genotypes and mutations were analyzed by direct sequencing of complete viral genomes. Genotypes B2, C1, C2, and D1 accounted for 22.2%, 1.6%, 74.6%, and 1.6%, respectively. Genotype B was more frequently detected in patients with acute hepatitis B than those with chronic hepatitis B and acute-on-chronic liver failure. Deletion mutations were detected mostly in preS1 and preS2 regions and the detection rates were 3.8%, 19.7%, and 24.7% for acute hepatitis B, chronic hepatitis B and acute-on-chronic liver failure patients, respectively. Incidences of point mutation T53C (preS1F53L), G1613A (polR841K), G1775A and A1762T + G1764A in the basal core promoter region, G1896A and G1899A in precore region and A2189C (coreI97L) in core region increased along with acute hepatitis B, chronic hepatitis B, and acute-on-chronic liver failure. The mutation G1896A was independently associated with poor survival of patients with acute-on-chronic liver failure. The gradual increase of viral mutation incidences was also observed in three HLA-A2-restricted cytotoxic T lymphocyte epitopes from HLA-A2-positive patients, that is env188-196 (5.8%, 10.1%, 22.5%), core107-115 (4.3%, 4.6%, 19.7%), and x92-100 (1.4%, 20.2%, 33.8%). In conclusion, certain viral mutations in various regions of HBV genome are associated with disease progression of HBV infection. J Med. Virol. 85:1698-1704, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]