INTRODUCTION — Hepatocellular carcinoma (HCC) is a tumor with highly variable biology that often occurs in the setting of chronic liver disease and cirrhosis. When not detected through screening, it is typically diagnosed late in its course, and the median survival following diagnosis is approximately 6 to 20 months [1]. The mainstay of potentially curative treatment for HCC is surgical resection, but several other treatment modalities may also have a role.
Surgical resection of HCC will be reviewed here. The clinical manifestations and diagnosis of HCC, an overview of the treatment approach to HCC, nonsurgical local ablative options, liver transplantation, and adjuvant and neoadjuvant therapy are reviewed elsewhere.
●(See "Epidemiology and risk factors for hepatocellular carcinoma".)
●(See "Overview of treatment approaches for hepatocellular carcinoma".)
●(See "Liver transplantation for hepatocellular carcinoma".)
TREATMENT ALGORITHMS FOR HCC — A general approach to treatment of HCC is shown in the algorithm (algorithm 1). The suggested approach is useful for conceptualizing the various treatment options that are available for individual patients but may not be applicable in all settings. An alternative approach, the Barcelona Clinic Liver Cancer (BCLC) staging system, has been a dominant approach to HCC internationally. There are five stages based on the extent of the primary lesion, performance status, vascular invasion, and extrahepatic spread; this classification was updated in 2022 (figure 1) [2]. Yet another alternative approach is widely used in the Asia-Pacific region where HCC is prevalent [3]. An overview of available therapies for HCC are summarized elsewhere. (See "Overview of treatment approaches for hepatocellular carcinoma", section on 'Treatment algorithms'.)
Treatment options for surgical candidates — Surgery (liver resection and transplantation) offers long-term survival with good quality of life and is the only potential cure for large HCCs.
Patients ideally suited for liver resection have localized HCC confined to the liver without radiographic evidence of invasion of the vasculature of the liver (image 1), preserved hepatic function, and no evidence of portal hypertension (although a minor resection could be considered in some patients with portal hypertension) [4-6]. Resection can provide benefits for some patients with multifocal disease or those with major vascular invasion, although outcomes are less favorable [7,8]. (See "Staging and prognostic factors in hepatocellular carcinoma", section on 'Clinical implications'.)
Despite even aggressive surgical approaches, most patients have disease (either HCC or underlying chronic liver disease) that is too extensive to permit treatment with "curative" intent. In high-incidence regions of the world, only 10 to 15 percent of newly diagnosed patients are candidates for standard resection, whereas in low-incidence areas, between 15 and 30 percent of patients have potentially resectable disease [9-11]. (See "Epidemiology and risk factors for hepatocellular carcinoma".)
Surgical candidates who have early HCC and underlying liver disease are increasingly being considered for transplantation because of potential for better disease-free survival and resolution of underlying liver disease, though this approach is limited by organ availability, especially in resectable patients. (See "Liver transplantation for hepatocellular carcinoma".)
Treatment options for nonsurgical candidates — For patients with liver-confined HCC who are not candidates for standard resection, alternative treatment modalities include interstitial therapies; transarterial chemoembolization; transarterial radioembolization (embolization with particles emitting radiation); localized ablative techniques involving either cryoablation, chemical desiccation (eg, ethanol or acetic acid ablation), or heating with laser; microwave, or radiofrequency ablation. These nonsurgical local ablative treatments are discussed elsewhere. These approaches are used as definitive therapies as well as bridging or downstaging therapy to liver transplantation. (See "Localized hepatocellular carcinoma: Liver-directed therapies for nonsurgical candidates who are eligible for local ablation" and "Localized hepatocellular carcinoma: Liver-directed therapies for nonsurgical candidates not eligible for local thermal ablation".)
IMPORTANCE OF COMPREHENSIVE MULTIDISCIPLINARY CARE — A majority of patients with HCC have an underlying liver disease, such as hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection (more common in the United States), or metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver diseases (NAFLD) [12]. Management of MASLD is particularly challenging because many patients have concomitant viral hepatitis in addition to obesity [13-16].
Furthermore, patients with chronic liver disease who undergo any form of therapy for HCC are at high risk for recurrent disease and progression to liver failure. It is important that patients with more advanced liver disease have proper monitoring and assessment of their underlying liver disease, which may have a major impact on longer-term survival.
The wide variety of treatments for HCC are offered by different specialties: surgery, transplant hepatology, interventional radiology, radiation oncology, and medical oncology. Multidisciplinary evaluation, planning, and management are frequently coordinated by hepatologists and improves patient outcomes [17].
PREOPERATIVE ASSESSMENT FOR RESECTABILITY — Only one-half of patients initially thought to be resectable and referred for surgery actually have resectable tumors. Among the reasons for unresectability are the extent of intrahepatic disease, extrahepatic extension, inadequate functional hepatic reserve, and involvement of the confluence of the portal or hepatic veins [9,18]. The assessment of potential resectability of HCC focuses on two main issues:
●The likelihood of the disease being confined to the liver (except fibrolamellar subtype of HCC). (See "Epidemiology, clinical manifestations, diagnosis, and treatment of fibrolamellar carcinoma".)
●Whether the size and location of the tumor/extent of liver resection required relative to the patient's underlying liver function will permit resection without excess morbidity and mortality.
There is no general rule regarding tumor location, size, or number in selecting patients with HCC for resection; however, most consider stage IIIB, IVA, and IVB disease to be incurable by resection (table 1). These stages are defined by invasion of a major portal or hepatic vein, direct invasion of organs other than the gallbladder, perforation of the visceral peritoneum (IIIB), and nodal (IVA) or distant metastases (IVB). However, hepatic resection for stage IIIB and IVA disease may be considered in a center of excellence because clinical benefits and long-term survival can be achieved in a properly selected, though admittedly small, minority of patients. Such resections are often considered only after neoadjuvant therapy.
Exclude extrahepatic metastasis — The recognized sites of metastatic spread of HCC are lung, bone, peritoneum, and adrenals [19]. For patients being evaluated for surgical resection, we suggest excluding pulmonary metastasis with a chest computed tomography (CT) with contrast if liver transplant is considered, excluding bone metastasis with a bone scan in patients with skeletal symptoms, and excluding peritoneal metastasis with a diagnostic laparoscopy if there are high risk features.
In patients who have localized HCC, the rate of extrahepatic disease spread at diagnosis is overall low, and staging chest CT and bone scans do not provide additional information on metastases. The utility of 18-fluorodeoxyglucose positive emission tomography scanning for detection of otherwise occult distant metastatic disease is uncertain and not recommended in guidelines from the National Comprehensive Cancer Network (NCCN) [20]. (See "Clinical features and diagnosis of hepatocellular carcinoma", section on 'Postdiagnostic evaluation'.)
However, the risk of extrahepatic metastatic disease is higher in patients with a tumor that is large (>5 cm), is located at a subdiaphragmatic location, demonstrates vascular invasion, or is associated with markedly elevated alpha-fetoprotein. Patients who have such tumors warrant additional imaging studies or diagnostic laparoscopy prior to resection, particularly if they have worrisome symptoms such as bone pain. (See "Diagnostic staging laparoscopy for digestive system cancers", section on 'Hepatocellular carcinoma'.)
Although other sites of disease may be demonstrated by standard imaging techniques, peritoneal disease is frequently missed. Laparoscopy and intraoperative ultrasound (IOUS) may improve the selection of patients for potentially curative resection [21]. IOUS can accurately determine the size of the primary tumor and detect lymph node or portal or hepatic vein involvement, which precludes curative resection [22,23]. Another benefit of IOUS is the identification of major intrahepatic vascular structures, which can be used to guide segmental or nonanatomic resections [24]. However, IOUS can be difficult to interpret, and findings may be nonspecific in patients with regenerative nodules in more advanced cirrhosis. (See "Diagnostic staging laparoscopy for digestive system cancers", section on 'Laparoscopic ultrasound'.)
Exclude portal lymph node metastasis — Although practice is variable [25-28], we consider that documented regional (portal) nodal involvement precludes potentially curative resection for HCC. However, lymph node involvement is not a contraindication to resection for patients with fibrolamellar HCC; these patients undergo a formal lymph node dissection. (See "Epidemiology, clinical manifestations, diagnosis, and treatment of fibrolamellar carcinoma", section on 'Potentially resectable disease'.)
Lymph node metastases are uncommon overall (between 1 and 8 percent), but their presence portends a worse outcome [29,30]. Preoperative detection of nodal metastases is limited by the frequent presence of benign nodal enlargement, most often involving the porta hepatis and portacaval space, in patients with cirrhosis [31]. Highly suspicious nodes based on enhancement similar to the intrahepatic HCC lesions indicate the need for biopsy in a patient being considered for resection [32]. Outcomes are worse in patients who have regional nodal involvement.
Delineate tumor extent — For patients being evaluated for surgical resection, we suggest assessing tumor extent with either a multiphase CT (including arterial phase) or an MRI of the abdomen and pelvis.
●CT – Anatomic delineation of tumor extent is best achieved with dynamic multiphase CT, for which the nonenhanced, hepatic arterial phase is assessed separately from the portal venous phase and a late "wash-out" phase. Small HCCs are often isodense to the liver in the portal venous phase and may be missed on a conventional "screening" CT [33]. In contrast, arterial phase imaging detects 30 to 40 percent more tumor nodules than conventional CT and may be the only phase needed to demonstrate the tumor in 7 to 10 percent of cases [34,35].
●MRI – Magnetic resonance imaging (MRI) appears to be as accurate, or more accurate, than CT in liver staging for HCC using both multiphasic and multiparametric imaging (combining T1, T2, and diffusion-weighted imaging with dynamic multiphasic imaging). Several studies have shown MRI to be superior to CT for detection of HCC, particularly in cirrhotic livers and particularly for correct diagnosis of smaller nodules [36-38]. MRI with hepatocyte-specific contrast agents (eg, gadolinium-based agents such as Gd-BOPTA and Gd-EOB-DTPA) may increase lesion detection, improve lesion characterization, and may be useful in the detection of recurrence as well [39-41].
●Others – The role of other imaging studies in the evaluation of primary HCC, including positron emission tomography with conventional and novel agents and CT arteriography, is discussed in detail elsewhere. In general, these studies add little to thin-slice, multiphasic imaging except in highly selected cases or for detecting metastatic diseases (eg, to lymph nodes or bone). (See "Clinical features and diagnosis of hepatocellular carcinoma", section on 'Postdiagnostic evaluation'.)
Determine resectability based on tumor extent — Advances in the surgical management of HCC have expanded the indications for curative hepatectomy, including more extensive liver resections [42]. The impact of size, multifocality, and tumor rupture on resectability is debated; there is no general internationally accepted consensus regarding tumor location, size, or number in selecting patients with HCC for resection. (See "Overview of treatment approaches for hepatocellular carcinoma", section on 'Potentially resectable disease'.)
●Tumor size – Although some surgeons restrict eligibility for resection to patients with tumors that are ≤5 cm in diameter, most centers do not use size alone to select patients for resection [7,43,44].
•The likelihood of microvascular invasion increases with increasing tumor size. Patients with small tumors are less likely to harbor occult vascular invasion and have a better outcome after surgery. Patients with a solitary HCC without vascular invasion have a similar survival regardless of tumor size (figure 2) [5,7,45-54]. In the latest iteration of the American Joint Committee on Cancer (AJCC) staging system, T1 classification includes not only solitary tumors of any size without vascular invasion but also tumors ≤2 cm with or without microvascular invasion (table 1) [55]. Although the presence and degree of vascular invasion portends increased risk for recurrence and is a powerful predictor of survival postresection, microvascular invasion in small tumors has a lesser impact on outcome and may be predicted from preoperative parameters [56].
•In a multicenter retrospective review of 1115 patients with HCC, major hepatectomy was performed in 539 patients, for which the mean tumor size was 10 cm (range 1 to 27 cm) [42]. The tumor, node, metastasis (TNM) stage distribution was 29 percent stage I, 31 percent stage II, 38 percent stage III, and 2 percent stage IV. Five-year survival rates improved for each successive cohort at 30 percent for 1981 to 1989, 40 percent for 1990 to 1999, and 51 percent for 2000 to 2008. Perioperative mortality also improved. In multivariate analysis, factors significantly associated with worse outcomes included earlier time period, AFP level >1000 ng/mL, tumor size >5 cm, presence of major vascular invasion, presence of extrahepatic metastases, and positive surgical margins.
•In a prospective study of over 11,000 patients undergoing hepatectomy for HCC from 2002 to 2010 in Taiwan, patients with small (<3 cm), medium (3 to 4.9 cm), large (5 to 10 cm), and huge (>10 cm) tumors had five-year overall survival rates of 72, 62, 51, and 35 percent, and 10 year overall survival rates of 53, 42, 36, and <20 percent, respectively [57]. Known factors that are predictive of poor outcomes, such as inadequate margins of resection, poor differentiation, multiple tumors, vascular invasion, and cirrhosis, also applied to patients with huge HCC.
•In a meta-analysis of 24 retrospective studies involving 3326 patients with HCC ≥10 cm and 20421 patients with smaller HCCs who underwent hepatectomy, HCC ≥10 cm was associate with both worse overall survival (hazard ratio [HR] 0.53, 95% CI 0.50-0.55) and disease-free survival (HR 0.62, 95% CI 0.58-0.84), although no significant difference was found for 30-day mortality rate (odds ratio [OR] 0.73, 95% CI 0.50-1.08), postoperative complications (OR 0.81, 95% CI 0.62-1.06), and posthepatectomy liver failure (OR 0.81, 95% CI 0.62-1.06) [58].
●Multiple tumors – Multifocality increases the T classification (table 1) and is associated with lower survival but does not exclude a good outcome in selected patients [59]. In a systematic review, resection of multifocal HCC was associated with a median five-year survival of 49 percent (range 30 to 64) when up to three nodules were present, and 23 percent (range 0 to 54) in patients with more than three nodules [60].
Patients with multinodular HCC who appeared to benefit from resection were those with sufficient liver reserve to tolerate resection, without extrahepatic disease, and without major vascular invasion. Size alone is not a contraindication for resection of multinodular HCC. Unfortunately, many patients have multifocal disease that is underestimated even by high-quality CT and MRI.
●Tumor rupture – Approximately 10 percent of HCCs spontaneously rupture. The clinical picture is that of acute abdominal pain and distension, hypotension, and a drop in the hematocrit. Initially, these patients should be stabilized hemodynamically, followed by transarterial embolization for control of bleeding. If unsuccessful, emergency surgery may be required [61]. (See "Clinical features and diagnosis of hepatocellular carcinoma", section on 'Clinical features'.)
Although the presence of a tumor rupture suggests a high likelihood of peritoneal seeding and usually a poor outcome from resection, this is not inevitable [62,63]. If bleeding can be controlled with embolization, a formal staging evaluation should be undertaken, followed by laparoscopic exploration and a subsequent attempt at resection, if feasible [64]. Several retrospective series suggest a low but defined long-term survival rate following resection in such situations [64-70].
In a large retrospective study comparing ruptured versus nonruptured HCC that were resected, spontaneous rupture of HCC is not a risk factor for survival by multivariate analysis, and propensity-score matched patients with ruptured HCC (n = 156) had comparable five-year survival with those with unruptured HCC (n = 312, 44 versus 46 percent, p = 0.600) [71].
Response of disease to neoadjuvant therapy is often used to help determine suitability for resection in these patients.
Assessment of hepatic reserve — Operative mortality for HCC is related to the severity of the underlying liver disease, being twice as high in cirrhotic as in noncirrhotic patients (10 versus 5 percent, respectively) [72]. As a general rule, patients who have complications of cirrhosis, such as bleeding, ascites, or marked portal hypertension, have insufficient hepatic reserve to withstand a partial hepatectomy, although there are exceptions [73].
With proper patient selection, operative mortality, even in cirrhotic patients, should be low [74-76]. However, only approximately 20 to 30 percent of patients presenting with HCC will have adequate hepatic reserve to undergo resection [77,78].
Hepatic reserve can be assessed by clinical tools, radiographic volumetry, functional test, or a combination of methods (eg, combined volumetric-functional assessment). The choice of methods is largely determined by their availability and locoregional preference, as some assessment is mandated by algorithms and guidelines [79,80].
Clinical scores — Various clinical tools have been used to predict outcomes of liver resection based on baseline biochemical profiles of the patients. (See "Staging and prognostic factors in hepatocellular carcinoma", section on 'Staging and prognostic scoring systems'.)
●Child-Pugh class – In patients with cirrhosis, surgical resection is most safely performed in those with Child-Pugh class A disease (table 2) who have a normal bilirubin level and well-preserved liver function. However, the Child-Pugh classification was not developed or validated in patients with HCC, and it provides too rough an estimate to allow accurate quantitative evaluation of the liver functional reserve or accurate prediction of the surgical risk in patients with liver dysfunction [3]. As an example, in one study of 29 such patients with HCC who underwent resection, 11 (38 percent) developed liver failure that was unresolved three months postoperatively due to increased portal pressure [6].
●MELD score – Another tool for assessing underlying liver disease, the Model for End-stage Liver Disease (MELD) score (calculator 1), was really intended for the transplant population. However, it is not useful to decide indication of resection, because it assesses only the degree of synthetic dysfunction but not the severity of portal hypertension. (See "Assessing surgical risk in patients with liver disease", section on 'MELD score and Mayo risk score'.)
●ALBI score – By contrast, the albumin-bilirubin (ALBI) score (calculator 2) may provide a simple, evidence-based, objective, and discriminatory method of assessing liver function in patients with HCC, and the use of the ALBI score may allow better refinement of prognostic estimates in patients with HCC across a wide spectrum of treatments, particularly among those with better liver function [81-83].
Hepatic volumetry — The volume and function of residual liver remnant can be determined using hepatic volumetry, which can be performed prior to and following portal vein embolization, which can be used in selected patients to increase the volume of the liver remnant prior to major hepatic resection [84,85]. (See 'Portal vein embolization' below.)
Increasingly, functional analyses in conjunction with CT volumetry are gaining acceptance when major resection is considered. As examples, combined volumetric-functional assessment using technetium hepatobiliary scintigraphy may be more accurate than volumetry alone in assessing risk for liver insufficiency/failure and mortality after major liver resection [86,87].
Other assessment tools — Alternatively, many groups (especially in Asia) use clearance of indocyanine green at 15 minutes (ICG-15) as a defining criterion for selection of resection type [88]. Absence of portal hypertension as measured by the wedged hepatic venous pressure gradient may also be helpful [6,89]. However, these techniques have been widely adopted and are not yet considered the current standard of care in North America.
Portal vein embolization — Preoperative portal vein embolization (PVE) is a valuable adjunct to major liver resection, particularly for right-sided tumors [84,90-93]. PVE can initiate hypertrophy of the anticipated future liver remnant and allow a more extensive resection. (See "Overview of hepatic resection", section on 'Preoperative PVE and other alternatives' and "Preoperative portal vein embolization", section on 'Introduction'.)
Transarterial chemoembolization (TACE) has been proposed as a complementary procedure prior to PVE in patients with HCC [94-103]. TACE eliminates the arterial blood supply to the tumor and also embolizes potential arterioportal shunts that attenuate the effects of PVE in cirrhotic livers [95,104]. Complementary improvements in safety and disease-free and overall survival using combined TACE/PVE prior to resection have sparked further interest in this therapeutic sequence prior to right hepatectomy for HCC in cirrhosis [94,95,104].
In a systematic review and meta-analysis of 40 studies of primary hepatobiliary cancers, PVE was typically performed in patients with HCC and presence of liver fibrosis or cirrhosis when either functional liver reserve (FLR) <40 percent and liver function was good (ICG-15 <10 percent) or when FLR <50 percent and liver function was affected (ICG-15 10 to 20 percent) [105]. The median excision rate was 90 percent for HCCs. The combination of TACE and PVE increased hypertrophy rate and was associated with better disease-free and overall survival and should be considered in advanced HCC tumors with inadequate FLR.
PVE may have oncologic benefits beyond facilitating liver resection. Five-year disease-free survival and five-year overall survival were 17 to 49 percent and 12 to 53 percent in non-PVE patients, and 21 to 78 percent and 44 to 72 percent in PVE patients, respectively [106].
Liver venous deprivation performed at the time of PVE may enhance speed of hypertrophy of the future liver remnant, although the experience with this approach remains early [107].
HEPATIC RESECTION — The type of hepatic resection depends upon the location of the lesion(s) and presence, severity of cirrhosis, and surgeon preference.
Anatomic versus nonanatomic resection — Until further data are available, most surgeons recommend anatomic resection in noncirrhotic patients when feasible and safe based on analysis of liver function. But data are not conclusive in showing an oncologic benefit of anatomic resection for HCC in the setting of cirrhosis.
●Anatomic resection – Anatomic resection of the liver follows the planes of the liver segments as delineated by Couinaud (figure 3). It is accomplished by selective ligation of the inflow portal triad and ligation of dominant outflow hepatic veins to the segment(s) that will be resected [108]. If subsegmental resection is planned, intraoperative ultrasonography facilitates localization of the intrahepatic vessels [109-111]. Anatomic resection is largely used for resecting HCC in noncirrhotic patients, in whom up to two-thirds of functional parenchyma can be removed safely depending upon the age of the patient [112].
●Nonanatomic resection – For cirrhotic patients, the resection needs to remove the least amount of nonmalignant parenchyma possible to preserve postoperative liver function (picture 1). Because the capacity for liver regeneration is impaired in cirrhotics, resection is generally limited to <25 percent of the functional parenchyma [112]. Thus, nonanatomic resection may be necessary to minimize the loss of functioning parenchyma in patients with cirrhosis [113]. (See 'Portal vein embolization' above and "Open hepatic resection techniques", section on 'Specific resections'.)
In theory, the systematic removal of the hepatic segment supplied by tumor-bearing portal tributaries (ie, the entire functional unit) through an anatomic resection could eradicate tumors and metastases more effectively. Indeed, a meta-analysis of 43 studies associated anatomic resection with a disease-free survival (DFS) benefit at one (hazard ratio [HR] 0.79, 95% CI 0.68-0.92), three (HR 0.87, 95% CI 0.78-0.95) and five years (HR 0.87, 95% CI 0.82-0.93), as well as a decreased risk of death at five years (HR: 0.88, 95% CI 0.79-0.97); there was no difference in perioperative morbidity or mortality rates [114]. However, other studies found no significant difference in outcomes between anatomic and nonanatomic resections [115-117]. The extreme heterogeneity of the patient populations and tumor biology no doubt contributed to the discrepancy. As such, the benefit of anatomic resection is unknown, and future randomized trials are needed to directly compare the two strategies.
Anterior versus conventional approach — The absence of a downside and significant technical advantage provided by the anterior approach (particularly with the liver-hanging maneuver) have led to widespread use of this technique in both open and minimally invasive liver surgery.
●The conventional technique of hepatectomy fully mobilizes the portion of the liver to be resected before initiating parenchymal division. (See "Open hepatic resection techniques", section on 'General techniques'.)
●For HCC, some surgeons have advocated an anterior or "no touch" technique for the resection of HCC. The anterior approach technique involves initial vascular inflow control, completion of parenchymal transection, and complete venous outflow control before the hemiliver was mobilized [118]. The advocates for this technique hypothesize that separation of the hemiliver and tumor from the IVC before mobilization reduces the risk of vessel rupture and theoretically minimizes the potential for tumor cell dissemination.
A meta-analysis of three trials and 13 other studies found that for right hepatectomy, the anterior approach was associated with less intraoperative blood loss and transfusion, morbidity (odds ratio [OR] 0.77, 95% CI 0.62-0.95), recurrence rate (OR 0.62, 95% CI 0.47-0.83), overall survival (HR 0.71, 95% CI 0.50-1.00), and disease-free survival (HR 0.67, 95% CI 0.58-0.79) compared with conventional hepatectomy [119].
Additionally, with the additional modification to the anterior approach technique, the liver can be lifted with a tape, providing a tremendous technical advantage when addressing large tumors [120], and many authors have found the technical advantage alone a reason to use the anterior approach (with hanging maneuver). Although originally described for right hepatectomy, variations of the hanging maneuver may be used for other types of resections, including left lateral sectionectomy and left hepatectomy.
Centrally located HCCs — Surgical management of centrally located HCCs (ie, those in segments IV, V, and VIII) is more problematic than peripherally located tumors (figure 3).
●Extended right or left hemihepatectomy is indicated if potentially curative surgery can be undertaken safely. However, these resections can be associated with high morbidity and mortality rates due to insufficient residual functional liver parenchyma [121-123]. (See "Open hepatic resection techniques", section on 'Right extended hemihepatectomy' and "Open hepatic resection techniques", section on 'Left extended hemihepatectomy'.)
●An alternative approach, mesohepatectomy (also called central hepatectomy), is used in which the central liver segments IV and/or V, and VIII (with or without segment I), are removed, leaving the lateral sectors intact [124,125].
Although randomized trials have not been conducted, the available data suggest that mesohepatectomy is a reasonable alternative to extended hepatic resection for centrally located tumors, giving comparable oncologic outcomes with less liver parenchymal loss [126,127].
Central hepatectomy has the advantage of not requiring a preoperative portal vein embolization and increased chances of a repeat hepatectomy in case of recurrence [128]. However, in some centers, it is seldom used, partly because it is a complex and technically demanding procedure that requires two hepatic resection planes and potentially bilateral biliary reconstruction. This could result in a higher risk of bleeding and postoperative bile leak as well as long-term biliary stricture and biliary dysfunction [129].
Minimally invasive hepatic resection — The available data support the view that, in experienced hands, laparoscopic or robotic resection is feasible and safe, but it is also highly technically demanding and should be undertaken only in high-volume centers with a program of graduated procedural complexity. (See "Minimally invasive liver resection (MILR)".)
The following represents the range of findings in patients undergoing minimally invasive liver resection for HCC, although none of the included studies were randomized trials [130]:
●In a 2018 systematic review of 17 studies published in the preceding 10 years, over 1500 patients underwent laparoscopic liver resection for HCC, most with good liver function and a single HCC; 33 to 100 percent had cirrhosis as determined by pathology. Overall perioperative mortality and morbidity ranged from 0 to 2.4 percent and 4.9 to 44 percent, respectively. The overall survival rates ranged from 73 to 100 percent at one year, 61 to 94 percent at two years, and 38 to 90 percent at three years. Compared with open surgery, laparoscopic resection was associated with shorter operative time, lower complication rate, reduced blood loss and transfusion requirement, and a shorter hospital stay [131].
●A 2019 systematic review and meta-analysis of 24 studies comparing laparoscopic with open liver resection for HCC associated laparoscopic surgery with favorable short-term outcomes and comparable long-term outcomes [132]. Both minor and major liver resections, and both noncirrhotic and noncirrhotic patients were included in the studies.
●A 2014 systematic review and meta-analysis of four studies specifically compared laparoscopic with open liver resection of HCC in cirrhotic patients [133]. Laparoscopic surgery was associated with less blood loss, wider margin, fewer complications, and shorter hospital study than open resection. Long-term and oncologic outcomes were not reported.
●A 2020 systematic review and meta-analysis of 14 studies comparing robotic with laparoscopic liver resection for HCC found comparable short-term outcomes between the two techniques [134]. Despite that the tumor sizes were significantly larger in the robotic surgery group, the margin status was comparable.
●A 2021 systematic review and meta-analysis of 26 studies comparing robotic with laparoscopic liver resection also found comparable short-term outcomes between the two techniques [135]. Robotic surgery took longer operative time but incurred less blood loss.
One advantage of a minimally invasive approach may be simplification of subsequent liver transplantation, if ultimately needed, due to fewer abdominal adhesions after the initial resection of HCC [136]. A second advantage may be the avoidance of division of abdominal wall collaterals associated with some abdominal incisions.
POSTOPERATIVE MORBIDITY AND MORTALITY — Postoperative morbidity and mortality is related to the extent of operative resection as well as the underlying liver condition (cirrhosis versus noncirrhosis) [137-140]. There is increasing evidence that the surgical morbidities may be reduced by using minimally invasive liver resection techniques. (See 'Minimally invasive hepatic resection' above.)
Mortality — The 30-day perioperative mortality rate in modern series of HCC resection is very low and ranges from 0 to 2 percent [59,141-144]. Consensus is growing that 30-day operative mortality is an inadequate indicator of risk, particularly of postoperative hepatic insufficiency and failure. Using an approach similar to liver transplantation reporting, 90-day mortality rates appear to be a more valuable indicator of outcome of liver resection, especially in the cases of extended resection and resection in patients with diseased livers [145,146]. This relates to the late development of slowly progressive jaundice, ascites, and eventual death, which typically occurs outside the hospital and well after 30 postoperative days in patients with marginal or inadequate liver remnants. The reported 90-day mortality rate in contemporary series ranges from 1.9 to 4.5 percent for noncirrhotic or Child-Pugh class A patients [147,148], and from 1.7 to 22 percent for Child-Pugh class B patients [149-151].
Most deaths are due to postoperative liver failure, and fewer than 10 percent are due to complications from bleeding. Mortality can be reduced by appropriate selection of patients with the inclusion of preoperative volumetry and portal vein embolization when appropriate, and meticulous surgical technique, including techniques to minimize blood loss and the need for transfusion.
●The presence of cirrhosis is the most important predictor of postresection liver failure and death. Major resection in cirrhotic patients without careful selection and/or portal vein embolization (PVE) continues to be a major challenge. Series assessing major resection in patients with cirrhosis without PVE continue to report mortality rates up to 18 percent compared with <3 percent for those undergoing PVE [94].
●Two additional factors influence the development of postoperative liver failure in cirrhotic patients: intraoperative blood loss of >1500 mL and postoperative infection of any type [152]. Massive intraoperative blood loss (defined as >800 mL) has also been independently associated with early postoperative mortality [153,154]. Postoperative infective complications have also been independently associated with decreased overall and disease-free survival [155].
Morbidities — About half of the patients develop a complication after liver resection for HCC, and 7 to 11 percent develop a major complication [156-158]. Major complications include ascites, hepatic insufficiency, biliary fistula, hepatic abscess, hemoperitoneum, and pleural effusion [158].
POSTTREATMENT SURVEILLANCE AND LONG-TERM OUTCOMES — Models are being developed to predict the risk of recurrence after liver resection for HCC [159,160]. The long-term outcomes, benefit of adjuvant therapy, and recommendations for posttreatment surveillance after potentially curative resection are discussed in detail elsewhere. (See "Management of potentially resectable hepatocellular carcinoma: Prognosis, role of neoadjuvant and adjuvant therapy, and posttreatment surveillance" and "Staging and prognostic factors in hepatocellular carcinoma".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hepatocellular carcinoma".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Liver cancer (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Management of hepatocellular carcinoma – Hepatocellular carcinoma (HCC) is a tumor with highly variable biology that often occurs in the setting of chronic liver disease and cirrhosis. The treatment algorithms for HCC vary widely by geography, but all require comprehensive multidisciplinary care. (See 'Introduction' above and 'Treatment algorithms for HCC' above and 'Importance of comprehensive multidisciplinary care' above.)
●Preoperative assessment – The preoperative evaluation for resection of HCC focuses on the likelihood of disease being confined to the liver and whether the size and location of the tumor and the patient's underlying liver function will permit resection. (See 'Preoperative assessment for resectability' above and 'Assessment of hepatic reserve' above.)
•Exclude extrahepatic or portal metastasis – Most consider stage IIIB, IVA, and IVB disease to be incurable by resection (table 1). These stages are defined by invasion of a major portal or hepatic vein, direct invasion of organs other than the gallbladder, perforation of the visceral peritoneum (IIIB), and nodal (IVA) or distant metastases (IVB). (See 'Exclude extrahepatic metastasis' above and 'Exclude portal lymph node metastasis' above.)
•Delineate tumor extent – Anatomic delineation of tumor extent is best achieved with dynamic multiphase CT, in which the nonenhanced, hepatic arterial, and portal venous phases are assessed separately, or with MRI scanning. Tumor size, multiple tumors, or tumor rupture are not universally considered contraindications to resection. (See 'Delineate tumor extent' above and 'Determine resectability based on tumor extent' above.)
•Assess hepatic reserve – The volume and function of residual liver remnant can be assessed by clinical scores, hepatic volumetry, or other functional studies (eg, ICG-15) prior to major resection to minimize posthepatectomy liver failure. (See 'Assessment of hepatic reserve' above.)
•Portal vein embolization – Preoperative portal vein embolization (PVE) or liver hepatic deprivation can initiate hypertrophy of the anticipated future liver remnant to enable an extended resection that would otherwise leave a remnant liver insufficient to support life following partial hepatectomy. Transarterial chemoembolization (TACE) may be combined with PVE. (See 'Portal vein embolization' above.)
●Hepatic resection for HCC
•For noncirrhotic patients undergoing curative hepatectomy for HCC, we suggest anatomic resection (Grade 2C). However, nonanatomic resection may be necessary to minimize the loss of functioning parenchyma in patients with cirrhosis. (See 'Anatomic versus nonanatomic resection' above.)
•The anterior approach with a liver-hanging maneuver is preferred to the conventional approach by many surgeons for resecting large tumors. (See 'Anterior versus conventional approach' above.)
•Central hepatectomy may better preserve liver parenchyma in patients with HCC in central lobes of the liver but can be technically challenging compared with extended hepatectomy. (See 'Centrally located HCCs' above.)
•Minimally invasive liver resection for HCC in the hands of experienced surgeons is safe and may reduce surgical morbidities (See 'Minimally invasive hepatic resection' above and "Minimally invasive liver resection (MILR)".)
●Outcomes – In contemporary series, surgical mortality after liver resection for HCC is very rare (0 to 2 percent at 30 days and 2 to 5 percent at 90 days). Most deaths are due to postoperative liver failure; 10 percent are from massive blood loss or infection. Major surgical morbidity rates are also low at 7 to 11 percent. (See 'Postoperative morbidity and mortality' above.)
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