The diagnosis is based on the combination of biochemical, autoimmune, and histological parameters, and exclusion of other liver diseases. Standard therapy consists of a combination of corticosteroids and azathioprine, which is efficacious in 80% of patients. Alternative therapies
are increasingly being explored in patients who do not respond to the standard treatment and/or have unacceptable adverse effects. This review examines the role of alternative drugs (second-line agents) available for AIH treatment non-responders. These agents include budesonide, mycophenolate mofetil, cyclosporin, tacrolimus, 6-mercaptopurine, 6-thioguanine, rituximab, ursodeoxycholic acid, rapamycin, and methotrexate. In addition, the risk of opportunistic infections MK1775 and malignancies are discussed. A treatment algorithm selleck chemicals is proposed for the management of patients with AIH treatment non-responders. “
“Liver tumor-initiating cells (T-ICs) are capable of self-renewal and tumor initiation and are more chemoresistant to chemotherapeutic drugs. The current therapeutic strategies for targeting stem cell self-renewal pathways therefore represent rational approaches for cancer prevention
and treatment. In the present study, we found that Lup-20(29)-en-3β-ol (lupeol), a triterpene found in fruits and vegetables, inhibited the self-renewal ability of liver T-ICs present in both hepatocellular carcinoma (HCC) cell lines and clinical HCC samples, as reflected by hepatosphere formation. Furthermore, lupeol inhibited in vivo tumorigenicity in nude mice and down-regulated CD133 expression, which was previously shown to be a T-IC marker for HCC. In addition, lupeol sensitized HCC cells to chemotherapeutic agents through the phosphatase and tensin homolog (PTEN)–Akt–ABCG2 pathway. PTEN plays a crucial role in the self-renewal and chemoresistance of liver T-ICs; down-regulation of PTEN by a lentiviral-based approach reversed the effect of lupeol on liver T-ICs. Using an in vivo chemoresistant
HCC tumor model, lupeol dramatically decreased the tumor volumes of MHCC-LM3 HCC cell line-derived xenografts, and the effect was equivalent to that Amylase of combined cisplatin and doxorubicin treatment. Lupeol exerted a synergistic effect without any adverse effects on body weight when combined with chemotherapeutic drugs. Conclusion: Our results suggest that lupeol may be an effective dietary phytochemical that targets liver T-ICs. (HEPATOLOGY 2011.) Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world.1 The curative treatment for HCC is liver transplantation or surgical resection.2, 3 However, 80% of HCC cases are presented at advanced stages and are no longer operable. Even after surgical resection, the long-term prognosis of HCC remains unsatisfactory due to high recurrence rates. For HCC patients in advanced stages, chemotherapy by way of either transarterial chemoembolization or systemically is the second-line treatment.