Last updated March 15, 2022

Diagnosis, Staging, and Management of Hepatocellular Carcinoma

Surveillance

Guidance Statements

  • Adult patients with cirrhosis are at the highest risk for developing HCC and should undergo surveillance.
  • The risk of HCC for patients with HCV-related cirrhosis who develop SVR after DAA treatment is lowered, but not eliminated, and therefore patients with cirrhosis and treated HCV should continue to undergo surveillance.
  • The risk of HCC is significantly lower in those with HCV or NAFLD and no cirrhosis compared to those with cirrhosis, and surveillance is not recommended for these patients.
  • Novel biomarkers, outside of AFP, have shown promising results in case-control studies, but require further evaluation in phase III and IV biomarker studies before routine use.
  • CT and MRI are not recommended as the primary modality for the surveillance of HCC in patients with cirrhosis. However, in select patients with a high likelihood of having an inadequate US or if US is attempted but inadequate, CT or MRI may be utilized.
(, )
611

The AASLD recommends surveillance of adults with cirrhosis because it improves overall survival (OS). (ModerateStrong)
611

The AASLD recommends surveillance using US, with or without AFP, every 6 months. (LowConditional (weak))
611

The AASLD recommends not performing surveillance of patients with cirrhosis with Child’s class C unless they are on the transplant waiting list, given the low anticipated survival for patients with Child's C cirrhosis. (LowConditional (weak))
611

Diagnosis

The AASLD recommends diagnostic evaluation for HCC with either multiphase CT or multiphase MRI because of similar diagnostic performance characteristics.
(Low for CT versus MRI)
611

AASLD suggests several options in patients with cirrhosis and an indeterminate nodule, including follow-up imaging, imaging with an alternative modality or alternative contrast agent, or biopsy, but cannot recommend one option over the other. (Very LowConditional (weak))
611

The AASLD suggests against routine biopsy of every indeterminate nodule. (Very LowConditional (weak))
611

PATHOLOGY

Guidance Statements

  • A lesion of >1 cm on US should trigger recall procedures for the diagnosis of HCC. If using AFP with US, then an AFP >20 ng/mL should trigger recall procedures for diagnosis of HCC.
  • Stringent criteria on multiphase imaging should be applied to enable noninvasive diagnosis of HCC in high-risk patients. For multiphase CT and MRI, key imaging features include size ≥1 cm, arterial phase hyperenhancement, and, depending on exact size, a combination of washout, threshold growth, and capsule appearance. If these criteria are not present but HCC or other malignancy is considered probable, then a liver biopsy should be considered for diagnosis.
  • Diagnosis of HCC cannot be made by imaging in patients without cirrhosis, even if enhancement and washout are present, and biopsy is required in these cases.
  • Histological markers GPC3, HSP70, and GS can be assessed to distinguish high-grade dysplasia from HCC on histology if HCC cannot be diagnosed based on routine histology.
(, )
611

Staging

Guidance Statement

  • The BCLC staging should be utilized in the evaluation of patients with HCC.
(, )
611

Treatment

CURATIVE THERAPIES

The AASLD suggests that adults with Child's A cirrhosis and resectable T1 or T2 HCC undergo resection over radiofrequency ablation (RFA). (ModerateConditional (weak))
611
The AASLD suggests against the routine use of adjuvant therapy for patients with HCC following successful resection or ablation. (LowConditional (weak))
611

LIVER TRANSPLANT

The AASLD suggests observation with follow-up imaging over treatment for patients with cirrhosis awaiting LT who develop T1 HCC. (Very LowConditional (weak))
611
The AASLD suggests bridging to transplant in patients listed for LT within OPTN T2 (Milan) criteria to decrease progression of disease and subsequent dropout from the waiting list. (Very LowConditional (weak))
611
The AASLD does not recommend one form of liver-directed therapy over another for the purposes of bridging to LT for patients within OPTN T2 (Milan) criteria. (Very LowConditional (weak))
611
The AASLD suggests that patients beyond the Milan criteria (T3) should be considered for LT after successful downstaging into the Milan criteria. (Very LowConditional (weak))
611

Guidance Statements

  • Resection is the treatment of choice for localized HCC occurring in the absence of cirrhosis, or resectable HCC occurring in the setting of cirrhosis with intact liver function and absence of CSPH.
  • Transplantation is the treatment of choice for patients with early-stage HCC occurring in the setting of CSPH and/or decompensated cirrhosis, though access is limited by the extreme organ shortage.
  • Surveillance for HCC recurrence in posttransplant patients should include abdominal and chest CT scan for better evaluation of the soft tissue, though optimal timing and duration, as well as the impact of surveillance, is not certain.
611

ABLATION

Guidance Statements

  • Thermal ablation is superior to ethanol injection.
  • Thermal ablative techniques have the best efficacy in tumors with maximum diameter less than 3 cm, although microwave ablation potentially provides better tumoral response than RFA.
  • SBRT is an alternative to thermal ablation, with prospective comparative randomized studies needed.
  • Patients postablation are at high risk for recurrence and surveillance should be performed with contrast-enhanced CT or MRI every 3-6 months
  • Thermal ablation is superior to ethanol injection.
  • Thermal ablative techniques have the best efficacy in tumors with maximum diameter less than 3 cm, although microwave ablation potentially provides better tumoral response than RFA.
  • SBRT is an alternative to thermal ablation, with prospective comparative randomized studies needed.
  • Patients postablation are at high risk for recurrence and surveillance should be performed with contrast-enhanced CT or MRI every 3-6 months.
(, )
611

Noncurative Therapy

The AASLD recommends LRT over no treatment in adults with cirrhosis and HCC (T2 or T3, no vascular involvement) who are not candidates for resection or transplantation.
  • TACE
(ModerateStrong)
611
  • Transarterial bland embolization
(Very LowStrong)
611
  • TARE
(Very LowStrong)
611
  • External radiation
(Very LowStrong)
611
The AASLD does not recommend one form of LRT over another. (Very LowConditional (weak))
611

PATIENTS WITH BCLC STAGE B

Guidance Statements

  • LRT should be considered for patients with intermediate-stage HCC who are not eligible for curative treatments. Studies comparing TACE with TARE are needed.
  • Patients who are ineligible for or progress after TACE/TARE should be considered for systemic therapy.
611

PATIENTS WITH BCLC STAGE C

Guidance Statements

  • Sorafenib is the first-line therapy for patients with advanced HCC
  • Current data do not demonstrate benefit of TARE compared to sorafenib in patients with advanced HCC. Further trials are needed to establish whether microsphere-based TARE can be considered as an option for patients with advanced HCC.
611

SYSTEMIC THERAPY

The AASLD recommends the use of systemic therapy over no therapy for patients with ChildPugh A cirrhosis or well-selected patients with Child-Pugh B cirrhosis plus advanced HCC with macrovascular invasion and/or metastatic disease. (ModerateStrong)
611

Guidance Statements

  • Patients with BCLC stage B HCC progressing after TACE should be considered for systemic therapy with either sorafenib, or lenvatinib upon approval, as first-line options for these patients.
  • Patients with BCLC stage CHCC should be treated with sorafenib, or lenvatinib upon approval, as first-line options for these patients.
  • Upon radiological progression to sorafenib, regorafenib and nivolumab should be considered as second-line options. There are no specific data in HCC to support the use of regorafenib or nivolumab after progression on lenvatinib, but the sequential use of multikinase tyrosine kinase inhibitors with similar mechanisms of action may be considered.
611

Recommendation Grading

Overview

Title

Diagnosis, Staging, and Management of Hepatocellular Carcinoma

Authoring Organization

Publication Month/Year

March 1, 2018

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

This guidance is meant to supplement the recently published HCC Guidelines in order to provide updated information on the aspects of clinical care for patients with HCC.

Target Patient Population

Patients with hepatocellular carcinoma

Inclusion Criteria

Female, Male, Adolescent, Adult, Child, Older adult

Health Care Settings

Ambulatory, Hospital, Long term care, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening, Diagnosis, Management

Diseases/Conditions (MeSH)

D008107 - Liver Diseases, D006528 - Carcinoma, Hepatocellular

Keywords

cancer, liver disease, hepatocellular carcinoma

Source Citation

Hepatology, VOL. 68, NO. 2, 2018