What are the guideline sources, guidelines and references for Hepatocellular carcinoma ?
Guideline sources The following summarized guidelines for the evaluation and management of hepatocellular carcinoma are prepared by our editorial team based on guidelines from the Enhanced Recovery After Surgery Society (ERASS 2023), the American Association for the Study of Liver Diseases (AASLD 2023), the Asian Pacific Association for the Study of the Liver (APASL 2023), the American Gastroenterological Association (AGA 2022), the American Society for Radiation Oncology (ASTRO 2022), the European Association for the Study of the Liver (EASL 2022; 2020; 2018), the American Society of Clinical Oncology (ASCO 2020), the European Federation of Societies for Ultrasound (EFSU 2020), and the European Society of Medical Oncology (ESMO 2018). 1 2 3 4 5 6 7 8 9 10 11 12 12 12 13 14 15 16 Definition HCC is a disease occurring due to malignant transformation of normal hepatocytes within the liver parenchyma. 12 https://web.pathway.md/diseases/recURgzrLYpU9qco8 1/17 6/24/23, 12:42 PM Hepatocellular carcinoma Pathway Epidemiology The risk factors that induce malignant transformation of normal hepatocytes include chronic infections of HBV and/or HCV, aflatoxin toxin, cirrhosis, or consumption of large amounts of alcohol. Underlying liver cirrhosis is present in about 80-90% of patients. 14 Pathophysiology HCC accounts for 75-85% of all liver malignancies. In the United States, the incidence of HCC is estimated at 7.7 cases per 100,000 person-years. 12 13 Disease course Clinical manifestations relate to local mass effect (abdominal pain, distension, loss of appetite, palpable masses), hepatic dysfunction (jaundice, ascites, gastrointestinal bleeding, splenomegaly, and encephalopathy), and constitutional effects of malignancy. 15 Prognosis and risk of recurrence Multiple treatment modalities exist; however, only orthotopic liver transplantation or surgical resection is curative. The overall prognosis for HCC in the United States is poor with a 2-year survival < 50% and a 5-year survival of only 10%. 12 16 CalculatorEastern Cooperative Oncology G CalculatorKarnofsky performance status s CalculatorLiver deco Guidelines 1. Screening and diagnosis Epidemiology: the prevalence of hapatocellular carcinoma is increasing both in Europe and worldwide; it is amongst the leading causes of cancer death globally. A Indications for screening, liver cirrhosis: As per AASLD 2023 guidelines, obtain surveillance for HCC in patients with Child-Pugh A-B cirrhosis of any etiology or Child-Pugh C cirrhosis eligible for liver transplantation. B Do not obtain surveillance in patients with Child-Pugh C cirrhosis ineligible for liver transplantation. B As per EASL 2022 guidelines, consider obtaining screening for hepatobiliary malignancy every 6 months in patients with PSC in the presence of cirrhosis. C As per EASL 2018 guidelines, obtain surveillance for HCC in high-risk patients, B including patients with cirrhosis, Child-Pugh stages A-B, B or Child-Pugh stage C, awaiting liver https://web.pathway.md/diseases/recURgzrLYpU9qco8 2/17 6/24/23, 12:42 PM Hepatocellular carcinoma Pathway transplantation. B Show 2 more As per ESMO 2018 guidelines: Obtain surveillance for HCC in all patients with cirrhosis, irrespective of the etiology, as long as liver function and comorbidities allow curative or palliative treatments. B Obtain surveillance for HCC in patients at risk for HCC with abdominal ultrasound every 6 months with or without AFP. A Indications for screening (hemochromatosis): obtain surveillance for HCC with 6-monthly ultrasound, with or without AFP testing, in patients with cirrhosis due to hemochromatosis. Obtain surveillance only if a diagnosis of HCC will alter management. A Indications for screening, viral hepatitis: As per AASLD 2023 guidelines: Obtain surveillance for HCC in patients with chronic HBV infection without cirrhosis. B Do not obtain routine surveillance for HCC in patients with HCV infection post-sustained virological response with advanced fibrosis but without cirrhosis. D As per EASL 2018 guidelines, obtain surveillance for HCC in patients with HBV infection (without cirrhosis) at intermediate or high risk of HCC (according to PAGE-B classes for Caucasian subjects, respectively 10-17 and 18 score points). B As per ESMO 2018 guidelines, obtain surveillance for HCC in hepatitis virus-infected patients without cirrhosis, especially in HBV carriers with serum viral load > 10,000 copies/mL or HCV- infected patients with bridging fibrosis (F3). B Indications for screening (occupational liver disease): consider obtaining ultrasound surveillance for the development of liver neoplasms in workers exposed to high levels of vinyl chloride monomer in the past, that is until the mid-1970s, as defined by their job title (reactor cleaners). C Indications for screening, NAFLD: As per AASLD 2023 guidelines, do not obtain routine surveillance for HCC in patients with nonalcoholic fatty liver disease with advanced fibrosis but without cirrhosis. D As per EASL 2018 guidelines, insufficient evidence regarding the role of HCC surveillance in patients with nonalcoholic fatty liver disease without cirrhosis. I Indications for screening, liver transplant candidates: As per AASLD 2023 guidelines: Obtain semiannual surveillance for HCC in all patients listed for liver transplantation because identifying early-stage HCC changes the priority for transplantation. B Do not obtain surveillance for HCC in patients with life-limiting comorbid conditions not treatable by liver transplantation or other directed therapies. D As per EASL 2018 guidelines, implement surveillance programs for HCC in patients on the waiting list for liver transplantation to detect and manage tumor occurrence or tumor response and to help define priority policies for transplantation. B https://web.pathway.md/diseases/recURgzrLYpU9qco8 3/17 6/24/23, 12:42 PM Hepatocellular carcinoma Pathway Choice of screening tests: As per AASLD 2023 guidelines, obtain liver ultrasound and AFP measurement approximately every 6 months for HCC surveillance. B Assess and report ultrasound visualization, given its impact on recommended recall procedures. B Show 3 more As per EFSU 2020 guidelines, do not obtain contrast-enhanced ultrasound routinely for HCC surveillance in at-risk patients. D As per EASL 2018 guidelines, do not use tumor biomarkers alone (including AFP, lectin-reactive fraction of AFP, and des-gamma-carboxy prothrombin) for routine surveillance for early HCC. D Diagnostic criteria: As per AASLD 2023 guidelines, diagnose HCC based on noninvasive imaging criteria and/or pathology in at-risk patients with cirrhosis or chronic HBV infection. A Show 3 more As per EASL 2018 guidelines: Diagnose HCC based on noninvasive criteria and/or pathology in patients with cirrhosis. A Diagnose HCC based on pathology in patients without cirrhosis. B As per ESMO 2018 guidelines, diagnose HCC based on histological analysis and/or contrast- enhanced imaging findings. B Show 2 more 2. Classification and risk stratification Staging: As per AASLD 2023 guidelines: Assess and document tumor staging, including tumor burden, degree of liver dysfunction, and ECOG performance status, at the time of initial treatment evaluation in patients with HCC. B Use the Barcelona Liver Clinic Cancer system for HCC staging. B As per EASL 2018 guidelines, use the Barcelona Liver Clinic Cancer staging system for treatment allocation and prognostication in patients with HCC. A As per ESMO 2018 guidelines, assess tumor extent, AFP level, liver function, portal pressure, and clinical performance status for the staging of HCC to determine outcome and planning of optimal therapy. B Show 3 more 3. Diagnostic investigations Diagnostic imaging, CT/MRI: As per AASLD 2023 guidelines, obtain either dynamic contrast-enhanced MRI or multiphasic CT for noninvasive diagnosis of HCC. A https://web.pathway.md/diseases/recURgzrLYpU9qco8 4/17 6/24/23, 12:42 PM Hepatocellular carcinoma Pathway Show 2 more As per EASL 2018 guidelines, obtain CT or MRI as first-line imaging evaluation for HCC due to their higher sensitivity and ability to visualize the entire liver. A As per ESMO 2018 guidelines: Consider obtaining MRI (based on techniques such as DWI and the use of hepatobiliary contrast agents) to identify and stratify nodules as high-risk nodules (either HCC not displaying the typical imaging hallmarks features or high-grade dysplastic nodules). C Consider obtaining contrast-enhanced ultrasound as a suitable noninvasive technique for diagnosing hepatocellular in patients with liver cirrhosis. C Diagnostic imaging (CEUS): Consider obtaining contrast-enhanced ultrasound as first-line imaging for characterizing focal liver lesions to establish a diagnosis of malignancy (contrast-enhanced ultrasound LR-M) or, specifically, HCC (contrast-enhanced ultrasound LR-5) in patients with liver cirrhosis. C Consider obtaining contrast-enhanced ultrasound to assess the probability of HCC when CT or MRI is inconclusive, especially in focal liver lesions in the cirrhotic liver unsuitable for biopsy. C Tumor biomarkers: avoid obtaining biomarkers, including AFP alone, to diagnose HCC. D Evaluation for portal hypertension: assess for portal hypertension by the presence of esophageal varices and/or splenomegaly with blood platelet counts of 100 10 cells/L suggesting clinically important portal hypertension (or based on invasive measured by the transjugular route: hepatic venous pressure gradient > 10 mmHg). B Imaging for staging, CT/MRI: As per AASLD 2023 guidelines: Obtain multiphase CT or contrast-enhanced MRI of the abdomen for staging in all patients with HCC. B Obtain non-contrast CT of the chest to evaluate for metastatic disease in patients with HCC beyond Barcelona Liver Clinic Cancer stage 0. B As per EFSU 2020 guidelines, obtain CT or MRI for accurate staging unless contraindicated. B Imaging for staging (CEUS): do not obtain contrast-enhanced ultrasound routinely for staging HCC. D Imaging for staging, PET: As per AASLD 2023 guidelines, avoid obtaining routine positron emission tomography and bone scan for staging, given low sensitivity for HCC. D As per ESMO 2018 guidelines, insufficient evidence to recommend obtaining FDG-positron emission tomography for staging. I 4. Diagnostic procedures Liver biopsy: https://web.pathway.md/diseases/recURgzrLYpU9qco8 5/17 6/24/23, 12:42 PM Hepatocellular carcinoma Pathway As per AASLD 2023 guidelines, consider performing biopsy over repeat imaging in patients with an LR-4 observation if an immediate diagnosis would impact management decisions. B Show 3 more As per EASL 2018 guidelines: Perform a tissue biopsy to confirm the diagnosis of HCC in patients without cirrhosis. B Repeat tissue biopsy in patients with 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. B As per ESMO 2018 guidelines, use standard (H&E) and special stains (such as reticulin), and immunohistochemistry if required, for histopathological diagnosis of tumor biopsies. E Show 2 more Ancillary testing: obtain immunohistochemistry in unclear cases. Obtain CD34 immunohistochemistry to assess capillarization of sinusoids. B Show 2 more 5. Medical management General principles: As per AASLD 2023 guidelines, discuss and manage cases of HCC in a multidisciplinary care setting. B As per EASL 2018 guidelines, discuss cases of HCC in multidisciplinary teams to fully capture and tailor individualized treatment options. B Expectant management: Consider monitoring patients with decompensated cirrhosis developing T1 HCC eligible for liver transplantation with cross-sectional imaging at least every 3 months until criteria are met for Model for End-Stage Liver Disease exception before pursuing locoregional therapy. C Consider offering immediate locoregional therapy in patients with decompensated cirrhosis developing T1 HCC with significantly elevated AFP levels or if the patient is not otherwise eligible for liver transplantation. C Neoadjuvant therapy: As per AASLD 2023 guidelines, avoid offering neoadjuvant systemic therapies in patients undergoing liver resection outside a clinical trial setting. D As per EASL 2018 guidelines, do not offer neoadjuvant therapy in patients with HCC because it has not been proven to improve the outcome of patients treated with resection. D Adjuvant therapy: As per AASLD 2023 guidelines, offer adjuvant immune checkpoint inhibitor-based systemic therapy in patients at high risk of recurrence after liver resection or local ablation. B As per AGA 2022 guidelines: https://web.pathway.md/diseases/recURgzrLYpU9qco8 6/17 6/24/23, 12:42 PM Hepatocellular carcinoma Pathway Avoid offering adjuvant sorafenib therapy in patients with HCC undergoing curative surgical resection, curative local ablation, D or transarterial chemoembolization locoregional therapy. D Avoid offering adjuvant bevacizumab therapy in patients with HCC undergoing transarterial chemoembolization locoregional therapy. D As per EASL 2018 guidelines, do not offer adjuvant therapy in patients with HCC because it has not been proven to improve the outcome of patients treated with resection. D As per ESMO 2018 guidelines, do not offer adjuvant therapy in patients with HCC after orthotopic liver transplantation, liver resection, or local ablation. D Landmark trials: STORM In patients with HCC with a complete radiological response after surgical resection or local ablation, sorafenib was not superior to placebo with respect to median recurrence-free survival. Jordi Bruix et al. Lancet Oncol. 2015 Oct. Primary systemic therapy, first-line therapy: As per AASLD 2023 guidelines, consider offering systemic therapy in patients with intermediate HCC unsuitable for or refractory to locoregional therapies due to contraindications, worsening hepatic dysfunction, progression of HCC, or lack of objective response. B Show 4 more Landmark trials: HIMALAYA (STRIDE) In patients with unresectable HCC and no previous systemic treatment, STRIDE was superior to sorafenib with respect to median overall survival. Ghassan K. Abou-Alfa et al. NEJM Evid. 2022. As per AGA 2022 guidelines, consider offering sorafenib in patients with HCC with preserved liver function ineligible for locoregional therapy/resection or with metastatic disease. C Show 3 more As per ASCO 2020 guidelines, consider offering atezolizumab plus bevacizumab as first-line therapy in most patients with advanced HCC, Child-Pugh class A, ECOG performance status 0- 1, and following management of esophageal varices, when present, according to institutional guidelines. B Show 2 more Landmark trials: IMbrave 150 https://web.pathway.md/diseases/recURgzrLYpU9qco8 7/17 6/24/23, 12:42 PM Hepatocellular carcinoma Pathway In patients with unresectable HCC who had not previously received systemic treatment, atezolizumab-bevacizumab was superior to sorafenib with respect to overall survival at 12 months. Richard S Finn et al. N Engl J Med. 2020 May 14. As per EASL 2018 guidelines: Offer sorafenib as the standard first-line systemic therapy for HCC in patients with well- preserved liver function (Child-Pugh A) and advanced tumors (BCLC stage C), or earlier stage tumors progressing despite or unsuitable for locoregional therapies. A Offer lenvatinib as another first-line option in patients with well-preserved liver function (Child- Pugh A class), good performance status, and with advanced tumors (BCLC-C without main portal vein invasion), or tumors progressing despite or unsuitable for locoregional therapies. A As per ESMO 2018 guidelines, do not offer chemotherapy as the standard of care in patients with advanced HCC. D Show 3 more Primary systemic therapy, second-line therapy: As per AASLD 2023 guidelines, consider offering second-line therapy in patients with preserved liver function (Child-Pugh A or well-selected Child-Pugh B cirrhosis), ECOG performance status 0-1 developing HCC progression or intolerance with first-line systemic therapy. B Show 3 more As per AGA 2022 guidelines, consider offering regorafenib in patients with HCC with preserved liver function ineligible for locoregional therapy or with metastatic disease with progressive disease on sorafenib. C Show 3 more As per ASCO 2020 guidelines: Consider offering second-line therapy with a TKI (sorafenib, lenvatinib, cabozantinib, or regorafenib) following first-line therapy with atezolizumab plus bevacizumab. C Consider offering second-line therapy with another TKI (cabozantinib or regorafenib), ramucirumab (AFP 400 ng/mL), or atezolizumab plus bevacizumab in appropriate candidates following first-line therapy with sorafenib or lenvatinib. C As per EASL 2018 guidelines, offer regorafenib as second-line therapy in patients tolerating and progressing on sorafenib and with well-preserved liver function (Child-Pugh A class) and good performance status. A As per ESMO 2018 guidelines, consider offering cabozantinib in patients with progressive disease on 1-2 systemic therapies with well-preserved liver function and ECOG performance status. B Show 2 more Management of pain: consider using acetaminophen (maximum dose: 3 g per day, PO) to manage pain of mild intensity in patients with HCC in the context of cirrhosis. C https://web.pathway.md/diseases/recURgzrLYpU9qco8 8/17 6/24/23, 12:42 PM Hepatocellular carcinoma Pathway Show 2 more Palliative care: As per AASLD 2023 guidelines, offer advance care planning in all patients receiving palliative- intent therapy or best supportive care for HCC, regardless of transplant eligibility. B As per EASL 2018 guidelines: Provide supportive care (including pain management, nutritional and psychological support) to patients with BCLC stage D HCC ineligible for liver transplantation. B Consider offering palliative radiotherapy for bone metastases causing pain or at significant risk of spontaneous secondary fracture. C 6. Nonpharmacologic interventions Psychosocial and nutritional support: provide psycho-oncological support and counseling on adequate nutrition according to the patients' condition. B 7. Therapeutic procedures Local ablation: As per AASLD 2023 guidelines: Perform local ablative therapies with curative intent in patients with solitary tumors 5 cm ineligible for or declining surgical therapy. A Consider performing thermal ablation (radiofrequency or microwave ablation) in patients with early-stage HCC 3 cm ineligible for or declining surgery. B As per EASL 2018 guidelines, perform thermal ablation with radiofrequency in patients with Barcelona Liver Clinic Cancer stage 0-A tumors ineligible for surgery. A Show 4 more As per ESMO 2018 guidelines: Consider performing local ablation in cases of a long-anticipated waiting time (> 3 months) for liver transplantation to minimize the risk of tumor progression and to offer a bridge to transplant. C Consider performing radiofrequency ablation or microwave ablation as first-line therapy in very early-stage disease (Barcelona Liver Clinic Cancer stage 0). B Transarterial therapies: As per AASLD 2023 guidelines, perform transarterial chemoembolization in patients with Barcelona Liver Clinic Cancer stage B HCC. A Consider performing radioembolization as an alternative therapy to chemoembolization. B Show 2 more As per EASL 2018 guidelines, perform transarterial chemoembolization in suitable patients with BCLC stage B HCC. A https://web.pathway.md/diseases/recURgzrLYpU9qco8 9/17 6/24/23, 12:42 PM Hepatocellular carcinoma Pathway Show 3 more As per ESMO 2018 guidelines, consider performing transarterial chemoembolization in cases of a long-anticipated waiting time (> 3 months) for liver transplantation to minimize the risk of tumor progression and to offer a bridge to transplant. C Show 2 more External beam radiation therapy, indications: As per AASLD 2023 guidelines, consider offering targeted radioembolization (radiation segmentectomy) or EBRT as alternative therapies to thermal ablation in patients with Barcelona Liver Clinic Cancer stage A HCC ineligible for surgical resection, including tumors > 3 cm in size. B As per ASTRO 2022 guidelines, offer EBRT as a potential first-line single therapy option in patients with liver-confined HCC ineligible for curative options (surgery or thermal ablation) and being considered for catheter-based therapies. B Show 7 more As per ESMO 2018 guidelines: Consider offering high conformal high-dose-rate radioablation or stereotactic body radiotherapy as alternatives for the ablation of tumors with a high risk of local failure after thermal ablation due to location. C Do not offer stereotactic body radiotherapy as first-line therapy in patients in intermediate or advanced stages. D External beam radiation therapy (technical considerations): administer dose-escalated ultra- or moderately hypofractionated external beam radiation therapy with choice of regimen based on tumor location, underlying liver function, and available technology in patients with liver-confined HCC, if external beam radiation therapy is recommended. B Show 4 more 8. Perioperative care Preoperative care (counseling): Provide preoperative information and counseling regarding the upcoming liver surgery. Consider using brochures and multimedia support to improve verbal counseling. B Advise preoperative smoking cessation at least 4 weeks before hepatectomy. Advise alcohol cessation in heavy drinkers (> 24 g/day for females or > 36 g/day for males) 4-8 weeks before surgery. A Preoperative care (nutrition): obtain a nutritional assessment before liver surgery. Administer enteral supplementation at least 7-14 days before surgery to optimize nutritional status in malnourished patients (weight loss > 10% or > 5% over 3 months and reduced BMI or a low fat- free mass index). A Show 2 more https://web.pathway.md/diseases/recURgzrLYpU9qco8 10/17 6/24/23, 12:42 PM Hepatocellular carcinoma Pathway Preoperative care (rehabilitation): offer prehabilitation in high-risk patients (elderly, malnourished or overweight patients, smokers, or patients with psychological disorders) before liver surgery. Initiate prehabilitation 4-6 weeks before the operation depending upon the urgency of surgery. Insufficient evidence to recommend the content (physical exercises, dietary interventions, or anxiety reduction exercises) and duration of the prehabilitation program for liver surgery. B Preoperative care (biliary drainage): perform biliary drainage in the cholestatic liver (> 50 mmol/L). Prefer percutaneous over endoscopic biliary drainage in perihilar cholangiocarcinoma. Avoid performing surgery until the bilirubin level drops < 50 mmol/L. B Preoperative care (antibiotic prophylaxis): administer antibiotic prophylaxis (such as cefazolin) within 60 minutes before surgical incision with no extension into the postoperative period. Consider administering a targeted antibiotic preemptive regimen based on preoperative bile culture in case of complex liver surgery with biliary reconstruction. B Preoperative care (corticosteroids): administer a preoperative dose of corticosteroids (methylprednisolone 500 mg). Insufficient evidence for its use in diabetic patients undergoing liver surgery. B Preoperative care (preanesthetic medication): avoid administering long-acting anxiolytic drugs, particularly in the elderly. D Show 3 more Intraoperative care (anesthesia and analgesia): Administer multimodal analgesia, including the potential use of intrathecal opioids, both for open A and laparoscopic surgery. B Recognize that thoracic epidural analgesia can provide excellent analgesia for open liver surgery but has significant disadvantages. Do not use regional anesthesia techniques in laparoscopic surgery as multimodal analgesia combined with judicious IV opioids provide functional analgesia. Perform continuous local anesthetic wound infiltration to provide lower complication rates and overall equivalent analgesia to thoracic epidural analgesia. Perform local anesthetic transversus abdominis plane blockade as a supplement to standard analgesia to improve pain control and reduce opioid usage. A Intraoperative care (fluid management): Maintain low central venous pressure (< 5 cmH O) with close monitoring during hepatic transection. A Prefer balanced crystalloids over 0.9% saline or colloids for fluid maintenance. Provide goal- directed fluid therapy to optimize cardiac output and end-organ perfusion, recognizing that this may be particularly beneficial after the intraoperative liver resection during a low central venous pressure state to restore tissue perfusion, with patients having comorbidities and reduced cardiac function benefiting the most. A Intraoperative care (temperature management): maintain perioperative normothermia with multimodal temperature management (including circulating water garments or forced warm air) during open and minimally invasive liver surgery. B https://web.pathway.md/diseases/recURgzrLYpU9qco8 11/17 6/24/23, 12:42 PM Hepatocellular carcinoma Pathway Postoperative care (thromboprophylaxis): administer routine postoperative LMWH or UFH to reduce the risk of thromboembolic events unless exceptional circumstances make this unsafe. Use intermittent pneumatic compression devices to reduce this risk further. B Postoperative care (early mobilization): initiate early mobilization (out of bed) after liver surgery from the operative day until hospital discharge. Insufficient evidence regarding the optimal duration of mobilization. B Postoperative care (nutrition): implement early oral intake with a normal diet after hepatectomy. Assess the individualized needs for artificial nutrition in malnourished patients, patients with complications causing several days of fasting, and patients with liver cirrhosis. Prefer enteral administration for artificial nutrition. A Show 2 more Postoperative care (antiemetics): use a multimodal approach to postoperative nausea and vomiting. Administer postoperative nausea and vomiting prophylaxis with at least 2 antiemetic drugs, such as dexamethasone and ondansetron. A Postoperative care (laxatives): insufficient evidence to support the routine use of postoperative laxatives, gum chewing, herbal medicine, or decoction to stimulate bowel movement after liver surgery. I 9. Surgical interventions Surgical resection, indications: As per AASLD 2023 guidelines, perform surgical resection in patients with localized HCC without underlying cirrhosis. B Consider performing surgical resection in patients with cirrhosis with limited tumor burden, well-compensated cirrhosis without clinically significant portal hypertension, and an adequate future liver remnant. B As per EASL 2018 guidelines, perform surgical resection in patients with HCC arising on a non- cirrhotic liver. B Show 4 more As per ESMO 2018 guidelines, perform minor/major liver resection in patients with Child-Pugh A without immanent portal hypertension. B Show 2 more Surgical resection, technical considerations: As per AASLD 2023 guidelines, consider performing minimally invasive liver resection (laparoscopic or robotic) to enhance recovery and lower the risk of perioperative morbidity in selected patients. C As per ERASS 2023 guidelines, perform liver resection laparoscopically, in trained teams and when clinically appropriate, to reduce the postoperative length of stay and complication rates. B Show 3 more https://web.pathway.md/diseases/recURgzrLYpU9qco8 12/17 6/24/23, 12:42 PM Hepatocellular carcinoma Pathway As per EASL 2018 guidelines, consider performing liver resection via laparoscopic/minimally invasive approaches in properly trained centers, especially for tumors in anterolateral and superficial locations. C As per ESMO 2018 guidelines, prefer a laparoscopic approach for liver resection in patients with cirrhosis. B Liver transplantation, indications: As per AASLD 2023 guidelines, offer liver transplantation in transplant-eligible patients with early-stage HCC occurring in the setting of clinically significant portal hypertension and/or decompensated cirrhosis. B Show 2 more As per EASL 2018 guidelines, offer liver transplantation as a first-line treatment option in patients with HCC meeting Milan criteria but unsuitable for resection. A Show 2 more As per ESMO 2018 guidelines, use the Milan criteria (1 lesion < 5 cm; alternatively, up to 3 lesions, each < 3 cm; no extrahepatic manifestations; no evidence of macrovascular invasion) for the selection of patients with HCC for orthotopic liver transplantation. B Show 2 more Liver transplantation, bridging therapy: As per AASLD 2023 guidelines, consider offering pre-transplant locoregional bridging therapy in patients with adequate hepatic reserve being evaluated or listed for liver transplantation to reduce the risk of waitlist dropout in the context of anticipated prolonged wait times for transplant. B Show 2 more As per ASTRO 2022 guidelines, consider offering ultra- or moderately hypofractionated EBRT as a bridge to transplant in patients with HCC being potential candidates for orthotopic liver transplantation. C As per ESMO 2018 guidelines, consider offering resection, local ablation, or transarterial chemoembolization in cases of a long-anticipated waiting time (> 3 months) for liver transplantation to minimize the risk of tumor progression and to offer a bridge to transplant. C 10. Preventative measures Public health measures: As per AASLD 2023 guidelines: Implement interventions such as best practice alerts or outreach programs to increase HCC surveillance adherence, given the underuse of surveillance in clinical practice. B Implement public health policies and interventions to address the significant mortality of HCC. B As per EASL 2018 guidelines, implement public health policies to decrease HBV and HCV transmission, counteract chronic alcohol abuse, and encourage healthy lifestyles preventing https://web.pathway.md/diseases/recURgzrLYpU9qco8 13/17 6/24/23, 12:42 PM Hepatocellular carcinoma Pathway obesity and metabolic syndrome. B Hepatitis B immunization: As per AASLD 2023 guidelines, administer vaccination for HBV infection in all newborns and high-risk adults failed to receive vaccination at birth to reduce the risk of HCC. B As per EASL 2018 guidelines, immunize newborns and high-risk patients against hepatitis B to decrease the risk of HCC. A As per ESMO 2018 guidelines, implement universal vaccination at birth against HBV to prevent chronic liver disease and HCC. A Management of viral hepatitis: As per AASLD 2023 guidelines, initiate antiviral treatment for HBV and HCV infections according to current evidence-based clinical practice guidelines. Suppress HBV and eradicate HCV infection to decrease the risk of HCC development in patients with chronic viral hepatitis. B As per EASL 2018 guidelines: Initiate antiviral therapy to maintain HBV suppression in patients with chronic HBV infection or to sustain the viral response in patients with HCV infection to prevent progression to cirrhosis and HCC. A Initiate antiviral therapy in patients with cirrhosis and chronic HBV infection or HCV infection to prevent cirrhosis progression and decompensation. B As per ESMO 2018 guidelines, initiate early antiviral treatment of viral HBV and HCV infections to prevent chronic liver disease and HCC. B Chemoprevention: do not use chemoprevention therapies, such as statins, aspirin, and metformin, solely to reduce the risk of HCC. D Lifestyle modifications: counsel patients with chronic liver disease to maintain a healthy weight, adopt a balanced diet, avoid tobacco and alcohol use, and achieve adequate control of comorbid conditions, including components of the metabolic syndrome, as a healthy lifestyle has multiple benefits and may decrease the risk of HCC. B Coffee: consider advising coffee consumption in patients with chronic liver disease as it has been associated with decreased risk of HCC development. C 11. Follow-up and surveillance Surveillance for hepatic nodules: As per AASLD 2023 guidelines, consider obtaining repeat short-interval ultrasound and AFP measurement in approximately 3-6 months in patients with a < 1 cm lesion on ultrasound. B Consider returning to semiannual surveillance with ultrasound and AFP if the lesion is stable for 2 follow-up ultrasounds. C Show 4 more As per EASL 2018 guidelines, obtain surveillance ultrasound at 4-month intervals in the first year in high-risk patients with hepatic nodules measuring < 1 cm in diameter. Consider returning https://web.pathway.md/diseases/recURgzrLYpU9qco8 14/17 6/24/23, 12:42 PM Hepatocellular carcinoma Pathway surveillance to the usual 6-month interval if there is no increase in the size or number of nodules. B Assessment of treatment response: As per EASL 2018 guidelines: Use mRECIST criteria to assess the response to loco-regional therapies for HCC. B Use mRECIST and RECIST1.1 criteria to assess the response to systemic therapies for HCC. B As per ESMO 2018 guidelines: Obtain dynamic CT or MRI for the assessment of viable tumor, defined as uptake of contrast agent in the arterial phase. B Consider using the mRECIST to include not only tumor diameters but also lesion viability in therapy decision-making. Use the mRECIST for the assessment of response to locoregional therapies. C Post-treatment follow-up: As per AASLD 2023 guidelines: Obtain routine postoperative surveillance with contrast-enhanced multiphasic CT or MRI every 3-6 months to detect recurrence in all patients with HCC following liver resection. B Consider obtaining post-transplant surveillance with multiphasic contrast-enhanced abdominal CT or MRI and chest CT to detect recurrence in patients with HCC following liver transplantation. B As per EASL 2018 guidelines, obtain follow-up (every 3-4 months for the first year) in patients after curative-intent liver resection because of high rates of treatable recurrence. A As per ESMO 2018 guidelines: Obtain clinical evaluation of liver decompensation and dynamic CT or MRI every 3 months during the first 2 years and every 6 months thereafter for early detection of recurrence in patients treated with radical treatments (resection or radiofrequency ablation). B Obtain clinical evaluation for signs of liver decompensation and dynamic CT or MRI every 3 months for tumor progression to guide therapy decisions in patients with more advanced stages of HCC treated with transarterial chemoembolization or systemic therapy. B Management of recurrence: As per AASLD 2023 guidelines: Consider offering post-progression treatment after adjuvant therapy based on the recurrence pattern. C Avoid using immune checkpoint inhibitors in patients with recurrent HCC after liver transplantation, given the increased risk of graft loss and death. D Consider offering sorafenib or lenvatinib as first-line therapy in these patients. As per ASTRO 2022 guidelines, consider offering palliative hypofractionated EBRT directed to the liver and/or macrovascular tumor thrombus, alone or sequenced with systemic therapy or catheter-based therapies, in patients with symptomatic locally advanced HCC. 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