Hepatocellular Carcinoma (HCC)

Recommendations  

Strength of recommendations  

Vaccination against hepatitis B reduces the risk of HCC and is recommended for all newborns and high-risk groups .

Strong  

Governmental health agencies should implement policies to prevent HCV/HBV transmission, counteract chronic alcohol abuse, and encourage life styles that prevent obesity and metabolic syndrome.  

Strong  

In general, chronic liver disease should be treated to avoid progression of liver disease.  

Strong  

In patients with chronic hepatitis, antiviral therapies leading to maintained HBV suppression in chronic hepatitis B and sustained viral response in hepatitis C are recommended, since they have been shown to prevent progression to cirrhosis and HCC development.  

Strong  

Once cirrhosis is established, antiviral therapy is beneficial in preventing cirrhosis progression and decompensation. Furthermore, successful antiviral therapy reduces but does not eliminate the risk of HCC development .

Strong  

Patients with HCV-associated cirrhosis and HCC treated with curative intent, maintain a high rate of HCC recurrence even after subsequent DAA therapy resulting in sustained viral response. close surveillance is advised in these patients.  

Strong  

Coffee consumption has been shown to decrease the risk of HCC in patients with chronic liver disease. In these patients, coffee consumption should be encouraged.  

Strong  

Implementation of screening programs to identify at- risk candidate populations should be improved. Such programs are a public health goal, aiming to decrease HCC-related and overall liver-related deaths.  

Strong  

Screening for HCC is warranted in all patients with cirrhosis irrespective of aetiology as long as liver function and co-morbidities allow curative or palliative treatment.  

Strong  

Screening for HCC is warranted for all patients with chronic HBV, regardless of the fibrosis stage.  

Strong

Screening for HCC is warranted in all patients with advanced fibrosis (F3 or F4) with HCV or NAFLD .  

Strong  

Screening of patients at risk of HCC should be carried out by abdominal Us with AFP every 4 months.  

Good practice statement

Patients with  liver nodule(s) < 1cm or 1-2 cm [LI-RADS 1or 2]on abdominal ultrasound should  repeat short-interval ultrasound and AFP  after 3 months.

Strong

In at-risk patients with any suspicious lesion ≥ 1 cm  on ultrasound should undergo diagnostic evaluation with multi-phasic contrast- enhanced CT or contrast-enhanced multi-phasic MRI. 

Strong

All patients with HCC should be carefully discussed and managed by an experienced multidisciplinary team(MDT) with the involvement of hepatologists, diagnostic radiologists, interventional radiologists, surgeons, transplant surgeons ,medical oncologists ,radiation oncologists, pathologists with hepatobiliary cancer expertise ,clinical pharmacists ,nutritionists and palliative care specialists.

Strong

The noninvasive diagnosis of HCC should be based on either multi-phasic contrast- enhanced CT or dynamic contrast enhanced MRI for diagnosis and evaluation of tumor extent(number and size of nodules,vascular invasion,extra-hepatic spread),they should could be performed,interpreted, and reported through the CT/MRI Liver Imaging Reporting and Data System(CT/MRI LI-RADS).

Strong

The diagnosis of HCC can be established if the typical vascular hallmarks of HCC (hypervascularity in the arterial phase with washout in the portal venous or delayed phase) are identified in a nodule of >1 cm diameter using one of the two contrast enhancing imaging techniques, either CT or MRI, in a cirrhotic patient.

strong

The optimal diagnostic method is core biopsy.Indicators for consideration of core needle biopsy include:                                                                                                                                            

     •    lesion> 1cm in cirrhotic patients  but does not meet imaging criteria for HCC in multi-phasic CT and MRI.

    •    lesion meets imaging criteria for HCC but patients is not considered at high risk for HCC development(In non-cirrhotic patients).

    •     lesion meets imaging criteria for HCC but patient has elevated CA19-9 or CEA with   suspicion of iCCA or cHCC-CCA.

Conditional

Repeated bioptic sampling is recommended in cases of inconclusive histological or discordant findings, or in cases of growth or change in enhancement pattern identified during follow-up, but with imaging still not diagnostic for HCC.

Conditional

Staging of HCC is important to determine outcome and planning of optimal therapy and includes assessment of tumor extent,AFP, liver function,portal pressure and clinical performance status.

strong

The Barcelona Clinic Liver Cancer (BCLC) is the commonly accepted staging system for prognostic prediction and treatment allocation.

strong

Multi-phasic contrast-enhanced CT or MRI of the abdomen, CT of the chest, and CT/MRI of the pelvis are also used in the evaluation of the HCC tumor burden to detect the presence of metastatic disease.

Conditional

Initial workup for patients with suspected HCC is a multidisciplinary evaluation including careful review of medical history to identify any potential chronic liver diseases, investigations of the etiologic origin of liver disease, an assessment of the presence of comorbidity, imaging studies to detect the presence of metastatic disease, and an evaluation of hepatic function, including a determination of whether portal hypertension is present.

Conditional

Laboratory evaluation of patients with newly diagnosed HCC include testing to detect  Aetiology of liver disease: HBV (at least HBsAg and anti-HBc), HCV (at least anti-HCV), iron status, autoimmune profile,HbAIc,others as indicated.

Good practice statement

Initial Workup for patient with HCC include an initial assessment of hepatic function involves liver function testing including measurement of serum levels of bilirubin, AST, ALT, ALP, measurement of  PT expressed as INR, albumin, and platelet count (surrogate for portal hypertension). Other recommended tests include CBC, BUN, and creatinine to assess kidney function.

Strong

Endoscopic assessment of any HCC patient: Upper GIT endoscopy is advised before receiving  systemic therapy or surgery.

Conditional

FDG PET-scan is not recommended for early diagnosis of HCC because of the high rate of false negative cases  and  may be considered when there is an  equivocal extrahepatic finding  before liver transplant.

Strong

Partial hepatectomy should be offered to HCC patients without advanced fibrosis and is the treatment of choice as long as an R0-resection can be carried out.  

Strong  

In the case of cirrhosis, surgical treatment is recommended for localized HCC with a single lesion and intact liver function (Child-Pugh A), and in the absence of clinically  significant portal hypertension with the evaluation of the extent of hepatectomy,future liver revenant and patient performance status.

strong  

For patients with chronic liver disease being considered for major resection, preoperative portal vein embolization should be considered.  

strong  

Patients meeting the UNOS criteria [AFP level ≤1000 ng/mL and single lesion ≥2 cm and ≤5 cm, or 2 or 3 lesions ≥1 cm and ≤3 cm and no evidence of macro vascular involvement or extra-hepatic  disease] should be considered for liver transplantation.

strong  

Thermal ablation by RFA or MWA are recommended as an alternative for resection for a single nodule ≤ 3 cm, BCLC stage 0, and those early stages that are not candidates for resection.  

Strong

The number and diameter of lesions treated by RFA in one session should not exceed three lesions, 3 cm each.  

Conditional

Unresectable lesions measuring up to 4 cm are recommended to be subject to local ablative therapy by radiofrequency ablation (RFA) or microwave ablation.  

Strong

Percutaneous ethanol injection is considered an option in some cases of very early HCC with tumor size up to 2 cm when thermal ablation is not technically feasible.  

Strong

EBRT (i.e. IMRT, SRS/SBRT) is recommended as a potential first line single option for patients with liver-confined HCC who are not candidates for curative options (surgery or thermal ablation) and for whom TACE is being considered.  

Strong

Single lesions (4–6 cm) that are beyond local ablative therapy and are ineligible for surgical resection and transplantation could benefit from a combination of heat ablation and chemoembolization and/or radiotherapy.  

Strong

TACE may be considered as an eligible option in intermediate HCC for bridging and down staging before liver transplantation and in case of non-feasibility or failure of other curative options in single lesions up to 8 cm.      

Conditional

TACE is recommended for BCLC-B patients with Child score up to B7 and tumor burden less than 50 % of liver volume  

Strong  

TACE should not be recommended for patients with decompensated liver disease (Child-Pugh score > 7), advanced liver and/or kidney dysfunction, main portal vein or its main branches invasion, extrahepatic spread, or tumor occupying>50 % of the liver size.  

Strong  

TACE should not be repeated after two consecutive sessions, with at least one month interval, and there is no response or there is tumor progression or decompensation of liver beyond Child-Pugh score B7.  

Conditional

Transarterial bland embolization may be used in same indications of TACE as A second choice if TACE is not feasible.  

Conditional

Radiotherapy in HCC is recommended to be integrated in the treatment plan through expert MDT and should be carried out in well trained and equipped centers with image guided, stereotactic radiotherapy, and radiosurgery facilities.  

Strong  

Radiotherapy could be implemented for unresectable or medically inoperable disease irrespective of the location (3D conformal RT, intensity-modulated RT [IMRT], or stereotactic body RT [SBRT]).  

Strong  

To give radiotherapy, there should be no extrahepatic disease or it should be minimal and addressed in a comprehensive management plan. Those with Child-Pugh B (max 7) cirrhosis can be safely treated, but they may require dose modifications and strict dose constraint adherence.  

Strong  

Image-guided RT is strongly recommended to improve treatment accuracy and reduce treatment related toxicity.  

Strong  

SBRT or SRS can be considered after ablation/ embolization techniques have failed or are contraindicated.  

Strong  

SBRT (typically 3–5 fractions) is recommended for patients with 1 to 3 tumors. And could be considered for larger lesions or more extensive disease, if there is sufficient uninvolved liver and liver radiation tolerance can be respected.  

Conditional

SBRT or SRS are recommended for compensated cirrhotic patients with HCC and portal vein thrombosis and when patients are ineligible for other modalities with building-up results.  

Conditional

Palliative RT is indicated for symptomatic control and/or prevention of complications from metastatic lesions as bone or brain, and extensive liver tumor burden.  

Strong  

The recommended doses of radiotherapy should be based on meeting normal organ constraints and underlying liver function as follows: 

           ▪️ SBRT, SRS: 30–50 Gy (typically in 3–5 fractions)

          ▪️ Hypofractionation: 37.5–72 Gy in 10–15 fractions 

          ▪️ Conventional fractionation by IMRT: 50–66 Gy in 25–33 fractions  

Strong

Systemic therapy should be offered to patients with preserved liver function (Child-Turcotte

Pugh A or well-selected Child-Turcotte-Pugh B cirrhosis),ECOG PS0-1,who have BCLC Stage C  HCC,or BCLC Stage B HCC not amenable to or progressing after locoregional therapy.  

Strong  

Sorafenib is the standard of care as first line for patients with advanced HCC and those with intermediate-stage (BCLC B) disease not eligible for, or progressing despite, locoregional therapies. It is recommended in patients with well-preserved liver function and ECOG PS 0-2.  

Strong  

Regorafenib is the standard of care for patients with advanced HCC who have tolerated sorafenib but progressed. It is recommended in patients with well- preserved liver function and ECOG PS 0-1.  

Strong  

Patients with BCLC-Stage-D HCC  should receive the best supportive care (BSC), including pain management, palliative radiotherapy for painful bone metastasis, nutrition optimization, and psychological support  

Conditional  

Follow-up of patients who underwent radical treatments should consist of clinical evaluation with, multi-phasic, high-quality, cross-sectional imaging of the chest, abdomen, and pelvis(ie,CT or MRI) every 3 to 6 months for 2 years, then every 6 months and AFP should be measured every 3 to 6 months for 2 years, then every 6 months. Surveillance imaging and AFP should continue for at least 5 years and thereafter screening is dependent on HCC risk factors.

Conditional

Follow-up of patients with advanced stages of HCC treated with systemic therapies or locoregional treatment , periodic response assessment with cross-sectional imaging including chest, multiphase abdomen, pelvis and serum level of  AFP (every 3 months)

Good practice statement

Using the mRECIST Criteria in the assessment of progression and radiological response after HCC management is recommended.

Conditional