For patients with normal or minimally diseased underlying liver parenchyma and HCC amenable to surgical resection, liver resection remains the treatment of choice. Most patients, however, develop HCC in the setting of some degree of underlying liver disease or dysfunction, making appropriate patient selection for resection essential. Most patients with well-compensated CTP Class A cirrhosis can typically tolerate hepatic resection, while patients with Class C cirrhosis and nearly all patients with Class B cirrhosis are not candidates for resection. The presence of significant portal hypertension, the sequelae of which are typically detectable on preoperative imaging in the form of parenchymal changes, splenomegaly, and/or varices, is a risk factor for postoperative liver failure following resection. Low preoperative platelet count, another hallmark of portal hypertension, has also been shown to be an important independent risk factor for increased complications, postoperative liver insufficiency, and mortality following hepatic resection for HCC [25]. Pathologically, the degree of hepatic fibrosis can be quantified by the METAVIR scoring system, which assigns a score on a five-point scale from 0 to 4, ranging from no liver scarring to cirrhosis or advanced scarring [26]. This score in turn is predictive of liver’s ability to regenerate following hepatic resection.

A key consideration is the extent of the indicated hepatic resection, which must be balanced against the need to preserve an adequate functional liver remnant (FLR) with hepatic portal and arterial inflow, venous outflow, and biliary drainage [27]. The volume of the FLR (ideally >30 % of the total liver volume for patients with normal liver parenchyma or >40 % for well-compensated patients with cirrhotic liver parenchyma) must be taken into account, particularly in the setting of underlying liver disease [27]. Hepatic resection in the setting of fibrosis or cirrhosis carries increased risk of hepatic insufficiency and perioperative complications; this risk increases with the extent of resection (Fig. 15.5a, b). Portal vein embolization is a potential option to induce hypertrophy and increase the size of the FLR in cases where preoperative volumetric calculations suggest an inadequate FLR will remain following partial hepatectomy.

Ideal candidates for resection are patients with minimal or well-compensated liver dysfunction and unifocal, small lesions < 5 cm [7]. While multifocality and larger tumor size are not absolute contraindications for surgical resection, both features are surrogate markers for microscopic vascular invasion and more aggressive tumor histology [28]. Other tumor features associated with increased recurrence and worse survival include vascular invasion, infiltrative growth pattern, positive margin status, and lymph node involvement [29, 30]. In the absence of other adverse features, however, solitary tumors larger than 5 cm can be considered for resection if they involve < 50 % of the liver, as resection may offer 5-year survival rates of 20–25 % (Fig. 15.6a, b) [29, 30]. Resection margins of ≥2 cm are advocated when possible, as long as the adequacy of the FLR size is not compromised, as they are associated with improved recurrence-free and overall survival outcomes versus resection margins of 1 cm [31]. Techniques of resection are beyond the scope of this review, and we refer our readers to the following excellent sources:

Patients with hepatitis B as the etiology of their cirrhosis and HCC often have comparatively well-preserved hepatic function versus patients with underlying hepatitis C, making resection a potentially more viable treatment for these patients. In Asia and Africa, where hepatitis B is endemic and where cadaveric organs are severely limited, resection is commonly employed for most patients with HCC amenable to surgical treatment. HCC arising secondary to NASH presents a new disease paradigm, and results to date suggest that these patients have a greater tendency to develop HCC within non-cirrhotic liver parenchyma. These patients may possess a theoretical lower risk of HCC recurrence in the liver remnant as compared with patients with underlying hepatitis B or C, and the benefit of resection may be greater in this patient population [32, 33].

One significant advantage of resection is the potential for immediate treatment, as opposed to the risk of disease progression while on the transplant wait list [34]. A trade-off for more expedited surgical therapy, however, is the significant risk of disease recurrence following partial hepatectomy. Recurrence rates following resection for HCC, whether from true recurrence or de novo tumor development in the cirrhotic liver remnant, have remained extremely high, reaching 50–75 % at 5 years in some series (Table 15.3) [35–47, 48]. Some groups have advocated a strategy of initial resection in patients with HCC within Milan Criteria and with relatively well-preserved liver function, followed by “salvage transplantation” or “secondary transplantation” for those who subsequently develop recurrent disease [49–52]. While primary resection of patients with early HCC and Child-Pugh Class A cirrhosis may be feasible, a significant portion of patients with recurrent disease following resection will not be candidates for transplantation, due to age, comorbidities, or recurrence outside of Milan Criteria [49, 51].

Liver transplant offers arguably the most effective cure for HCC, as it removes both the malignancy and the underlying diseased liver parenchyma in which HCC typically arises. Transplantation is limited, however, by access to donor organs and must be balanced against the need for lifelong immunosuppression. Across the globe, the most widely accepted transplant selection criteria are referred to as the Milan Criteria. First reported in 1996 by Mazzaferro et al [53], the Milan Criteria defined transplant criteria for patients as a single HCC lesion < 5 cm in maximum diameter or ≤ 3 lesions each < 3 cm in size, with no evidence of macrovascular invasion or extrahepatic disease on imaging. Numerous studies worldwide, many included in a comprehensive 2011 meta-analysis by the Milan group, have confirmed the favorable outcomes that can be achieved with transplantation for patients meeting these criteria [54]. Others have advocated broader transplantation guidelines, such as the expanded University of California, San Francisco (UCSF) criteria, which include patients with a single lesion < 6.5 cm or up to three tumors, each measuring less than 4.5 cm and a total tumor diameter < 8 cm [55, 56].

As a result of limited organ availability, the drawbacks of transplantation include the risk for disease progression and resulting patient dropout, while patients are on the transplant wait list. Particularly in parts of Asia where HCC is more prevalent, the number of patients with HCC on transplant wait lists far exceeds the supply of deceased donor livers available. In the United States, the UNOS (United Network for Organ Sharing) criteria dictate that patients with HCC meeting Milan Criteria radiographically receive a MELD “exception points” score of 22 when placed on the wait list. If patients remain on the wait list after 3 months, they typically receive an additional three exception points. Within this allocation scheme, wait times vary considerably across UNOS regions and globally, with median times to transplant of 6–12 months in many regions increasing patient dropout and affecting intention-to-treat outcomes [34, 57, 58]. As a result, many centers, particularly those with longer wait times, now offer locoregional neoadjuvant or “bridging” therapy to patients on the transplant wait list to attempt to minimize tumor progression while awaiting a donor organ [59]. Several non-randomized studies to date have reported decreased dropout rates, but none have demonstrated a correlation between pre-transplant bridging therapy with ablation or transarterial chemoembolization and improved posttransplant survival [60–64]. A cost-effective analysis of pretransplantation bridging ablation therapy, however, demonstrated benefit if projected wait time to transplant exceeded 6 months [65].