Hepatocellular carcinoma: Primary and secondary prophylaxis as well as medical therapy

Hepatocellular carcinoma (HCC) as one of the five most common malignancies worldwide arises most commonly in a cirrhotic liver. Since diagnosis is generally made at an advanced stage no longer amenable to curative approaches, both prevention and palliation are important. HCC is effectively prevented by avoiding the underlying liver diseases often caused by alcohol abuse, chronic viral infection or environmental factors through e.g. expositional prophylaxis or immunization. If this has failed or, in the case of genetic diseases, is impossible, existing acute (hepatitis C) or chronic diseases should be treated effectively by eliminating viral infection, abstaining from alcohol, or in case of hereditary hemochromatosis performing venesection in order to prevent the development of a chronic course and cirrhosis. Up to date, there is no effective treatment such as antifibrogenic drugs which could prevent the development of HCC by mechanisms other than specifically approaching the underlying disease. The systemic use of the acyclic retinoid polyprenoic acid or the intraarterial application of iodine-131 lipiodol has been demonstrated in one controlled trial each to effectively prevent secondary tumors arising in liver remnants after curative resection or local ablation of a primary HCC. Confirmation is warranted before such treatment may be recommended for clinical practice. To date, there is no systemic medical therapy of proven efficacy for locally advanced or metastatic HCC. Mono- or polychemotherapy is weakly effective and poorly tolerated by patients with reduced liver function. Tamoxifen is of no help in unselected cases with advanced HCC. The value of megestrol for HCC with aberrant estrogen receptors awaits approval by larger phase III trials. Data on the efficacy of octreotide are controversial; thus such treatment is also unwarranted outside of clinical trials. This holds also true for the HMG-CoA-reductase inhibitor pravastatin. Immune modulation with low-dose interferon-alpha has been shown to be poorly tolerated and ineffective. Thymostimulin is currently being evaluated in a placebo-controlled phase III trial.