Hepatocellular carcinoma hcc is one of the most common malignancies, with an increasing incidence. With advances in surgical techniques and instrumentation and the development of molecular target drugs, a number of potentially curative treatments have become available. Liver resection remains the first choice for very early stage hcc, but it is being challenged by local ablative therapy. For early stage hcc that meet the milan criteria, liver transplantation still offers a better outcome however, local ablative therapy can be a substitute when transplantation is not feasible.

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Hcc recurrence is the main obstacle to successful treatment, and there is currently no effective means of preventing or treating hcc recurrence. Transarterial therapy is considered suitable for intermediate stage hcc, while sorafenib is recommended for advanced stage hcc. This stage based approach to therapy not only provides acceptable outcomes but also improves the quality of life of hcc patients. Because of the complexity of hcc, therapeutic approaches must be adapted according to the characteristics of each individual patient. keywords: chemotherapy, hepatocellular carcinoma, liver resection, liver transplantation, intervention therapy hepatocellular carcinoma hcc is the fifth most common form of cancer and the third leading cause of cancer related death worldwide 1 . The number of cases diagnosed with hcc is expected to increase in western countries 2 .

Therapeutic approaches for the treatment of hcc can be classified into three categories: potentially curative, palliative, and symptomatic. Potentially curative treatments, including liver resection, transplantation, and local ablation, are associated with promising 5 year survival rates of up to 75% 3 . However, because of a shortage of donor livers, advanced tumor stage, or liver dysfunction, less than 20% hcc patients are eligible for such treatments 4.

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The majority of hcc patients are subjected to palliative or symptomatic treatment. The 3 year survival rate for palliative treatment is 10 x02013 40%, and the duration of survival for patients who receive symptomatic treatment is x03c 3 months 6 . The choice of therapy is mainly based on by the stage of hcc, severity of the underlying liver disease, availability of treatment resources, and clinical expertise 7 . Selection criteria for these treatments have been recommended by bruix and sherman et al. Stage evaluation is essential to assess the resectability of the tumor mass, choose an appropriate therapy, and predict the prognosis of hcc patients. Numerous staging evaluation systems have been proposed and applied in clinical practice, including the cancer of the liver italian program clip score, barcelona clinic liver cancer bclc staging, groupe d'etude et de traitement du carcinome h x0e9 patocellulaire getch classification, chinese university prognostic index cupi grade, japan integrated staging jis score, modified jis mjis score, okuda staging, and the tokyo score.

Comparisons of the different staging systems are mainly based on retrospective analyses. We collected data from the past five years, and these are summarized in table x200b table1. Although these data do not suggest any consensus, the bclc staging system has been proposed as a standard for the assessment of prognosis in europe and the united states 7. The exclusion of risk factors in the current staging systems may potentially decrease prognostic accuracy. This special web collection from nature reviews clinical oncology and nature reviews gastroenterology amp hepatology comprises a selection of articles covering key aspects of the pathogenesis and treatment of hcc, including insights into disease pathways and possible future therapeutic targets.

This collection has been produced with educational support from onyx pharmaceuticals, inc and bayer healthcare llc. All content has been chosen by the editors of nature reviews clinical oncology and nature reviews gastroenterology amp hepatology. Doi: 10.1/j.1365 2036.2009.04200.x

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section of hepatobiliary diseases, division of gastroenterology, hepatology and nutrition, university of florida, gainesville, fl, usa dr r. Cabrera, section of hepatobiliary diseases, division of gastroenterology, hepatology and nutrition, department of medicine, university of florida, po box 100277, gainesville, fl 32610 0277, usa. E mail: [email protected] hellen chiao, chao hsiung edward yang, catherine t.

Frenette department of organ and cell transplantation, scripps green hospital, 106 n. Torrey pines road, la jolla, ca 92037, usa abstract: orthotopic liver transplant olt is a curative treatment for patients with hepatocellular carcinoma hcc. It is widely practiced around the world, but there is no specific set of recommendations to guide physicians. Milan criteria mc is a starting point in selecting optimal candidates for olt, but no consensus exists for patients whose tumors exceed beyond mc.

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This article will review current literature and discuss controversial topics within hcc and olt. keywords: organ procurement and transplantation network optn united network for organ sharing unos hepatocellular carcinoma hcc orthotopic liver transplant olt milan criteria mc locoregional therapy lrt end stage liver disease esld submitted oct 10, 2013. Doi: 10.3978/j.issn.2218 676x.2013.10.04 the first solid organ transplant in the modern era was performed in 1883 by dr. Theodor kocher, who successfully implanted thyroid tissues in post thyroidectomy patients 1 . The concept of replacing a failed organ through transplant was widely acknowledged soon thereafter.

Olt became the standard of care for end stage liver disease esld in the 1980s, especially with the invention of various immunosuppressants. Today, the success of olt is marked by a 1 and 5 yr survival of 85% and 70% 2 , in an otherwise terminal condition. In some parts of southeast asia, it is the most common malignancy, in part due to the endemic spread of hepatitis b and c viruses. Other common risk factors for developing hcc include cirrhosis, alcohol, and non alcoholic fatty liver disease. Overall, hcc has become more prevalent globally, causing 250,0 to 1 million deaths annually worldwide 3 .

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Without treatment, hcc has a high mortality rate, with a 5 year survival of 10% 4 . Olt offers a potential cure for hcc, especially if the cancer is found in early stages t1 or t2. Unfortunately, the worldwide shortage of deceased liver donors presents a challenge to justifiably distribute liver grafts among patients in need of olt. In the years prior to 2002, the overall 5 year survival for hcc was merely 11.7% 5 . However, it drastically improved over the last decade, due to earlier diagnosis from better cancer screening, and new treatment options, from locoregional therapy lrt to olt.

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In the 1980’s, distribution of this scarce resource used to be ad hoc basis, solely determined by medical providers. In the 1990’s, icu patients and hospital patients had priority over clinic patients, considering that inpatients are likely to have a higher mortality without immediate intervention. In 1998, minimal listing criteria were instituted using the child turcotte pugh ctp score 6 . This scoring system takes into account encephalopathy, ascites, bilirubin, albumin, and pro thrombin time.

A numeric score was then converted to class a, b, or c, with c being on the more severe end of the spectrum. Despite its seemingly comprehensive determinants, this score became quite subjective, requiring physicians to accurately stage hepatic encephalopathy and ascites. Finally, in 2002, the model of end stage liver disease meld score was adopted in prioritizing patients for liver transplant 7 . This score was initially developed to predict mortality in patients with complications of portal hypertension undergoing transjugular intrahepatic portosystemic shunt placement tips 8 . It is calculated based on three objective variables: international normalized ratio inr , bilirubin, and serum creatinine.

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This score was subsequently found to be also useful in predicting three months mortality in patients with liver disease, and thus is currently used to prioritize deceased donor liver allocation. Disadvantage of this scoring system is that it does not take into account quality of life issues, such as when hepatic encephalopathy or ascites can be detrimental to patients’ lives. Other than the meld score along, there are several other factors that go into candidacy for a liver transplant, including bmi, social support, cardiac/pulmonary status, portal vein patency, and other malignancy or co morbidities. In regards to allocation, the united states is divided into 11 different regions. Deceased donor livers that become available in a certain region can be shared amongst those living within the region 9 unos.org. However, every region has a different meld average for receiving a liver, thus making certain regions more favorable in receiving a liver than others.