Treatment of Hepatocellular Carcinoma

Staging

In non-cirrhotic liver with HCC, resection is the treatment of choice provided an R0 resection can be carried out leaving an adequate liver remnant.
In cirrhotic patients with HCC of BCLC stage 0, resection is the first-line treatment option for solitary tumors <2 cm, very well-preserved liver function (defined as normal bilirubin with either HVPG <10 mmHg or a platelet count >100,000), no vascular invasion/satellites, and with good performance status.
In cirrhotic patients with HCC of BCLC stage A if liver transplantation is not feasible, resection may also be considered for:

Cirrhotic patients with multifocal tumors meeting Milan criteria (â‰¤3 nodules â‰¤3 cm) or
Cirrhotic patients who have mild portal hypertension.

However, these patients require prospective comparison of resection with loco-regional treatments.
Neo-adjuvant or adjuvant therapies have not proven to improve outcome of patients treated with resection.
Salvage transplantation can be done following liver resection in HCC.

Liver transplantation is indicated for patients of cirrhosis with early stage HCC (BCLC stage A), who are within the Milan criteria
Compared to other modalities primary liver transplant is a better cost effective strategy for small HCC with compensated cirrhosis as long as the 1-year survival rate after transplant exceeds 85% at that center
It is possible to go slightly beyond the Milan criteria (such as UCSF criteria) without markedly diminishing outcomes
Patients with 2-5 cm (T2) tumors waiting for DDLT should be offered bridging therapies
Patients beyond the conventional criteria may be offered LDLT with a guarded prognosis anticipating a 50% recurrence rate
Patients beyond the conventional criteria, if LDLT is not an option, should be offered downstaging followed by DDLT
Patients with an AFP level >400 ng/ml are at high risk for recurrence after liver transplantation and should be given a guarded prognosis

Local ablation with RFA or PEI is considered the standard of care for patients with BCLC 0-A tumors not suitable for surgery
The number and diameter of lesions treated by local ablation should not exceed 5 and 5 cm, respectively
RFA and PEI are having similar efficacy in lesions <2.0 cm and RFA provides better local control and overall survival in HCCs >2 cm
Percutaneous acetic acid injection could be a cost effective substitute for PEI

TACE is indicated in patients of HCC of BCLC stage B (i.e. multinodular tumor with Child-Pugh A or B, performance status 0, and with no vascular invasion or extra-hepatic spread) who have tumor burden <50% of liver volume and have adequate bone marrow function.
TACE may also be considered:

TAE is efficacious but the outcome with TACE is better. Hence bland TAE is not recommended currently
TACE using drug-eluting beads has comparable local response to lipiodol TACE and has less systemic side effects. Further evidence for long term survival and cost benefit is still emerging. TACE with DE beads may be preferred in select patients.
TART with Yttrium 90 may be considered in select patients of advanced HCC with portal vein thrombosis and good liver function (Child A)

Targeted molecular therapy with sorafenib is indicated in patients of HCC of BCLC stage C
The combination of Sorafenib with transplantation or resection, either sequential or concomitant, cannot be recommended outside clinical trials, however, Sorafenib can be given for residual / recurrent disease after surgery / transplant / TACE / RFA
There is no evidence that combination Sorafenib with other cytotoxic agents or targeted agents or hormonal therapy is superior to Sorafenib alone
In case of progression or intolerance to Sorafenib, best supportive care is preferred or patients should be included in clinical trials
Use of systemic cytotoxic chemotherapy, immunotherapy, or hormonal therapy (such as tamoxifen, anti-androgens, somatostatin analogues) are not recommended for the clinical management of HCC, either alone or in combination or as adjuvant or neoadjuvant therapies

Patients with BCLC-D have a poor survival and should receive palliative support including management of pain, nutrition and psychological support
Opioid analgesia should be used for pain management in terminal stage HCC
Radiotherapy can be used to alleviate pain in patients with bone metastasis and relieve of symptoms from pulmonary or lymph node metastases
Routine artificial nutrition is not justified in patients in the terminal stage HCC, however, in individual cases, dietary counseling and artificial nutrition can slow down nutritional deprivation, avoid dehydration and improve the quality of life
Management of psychosocial and spiritual issues should be a part of the care of terminal HCC patients
TAE is effective in controlling bleeding from ruptured HCC