The current study was conducted on a prospective database and reviewed retrospectively. All consecutive patients with hepatocellular carcinoma treated by liver resection from January 2013 to March 2019 at the Luigi Sacco University Hospital in Milan were enrolled. We included patients older than 18 years of age with HCV-related HCC, and in this set of patients, we identified two groups based on the presence of HIV infection. Our analysis focused on the study of the HIV+/HCV+ co-infected group; we therefore excluded patients with HCC related to other etiologies and prior operated.
The diagnosis of HCC was reached according to the European Association for the Study of the Liver (EASL) guidelines . All patients were preoperatively investigated by both quadriphasic-computed tomography (CT) and magnetic resonance imaging (MRI) with liver-specific contrast agents, notably after the finding of a focal lesion > 1 cm on abdominal ultrasonography. Percutaneous liver biopsy was limited to doubtful cases with atypical nodules at imaging.
Patients were evaluated in a multidisciplinary board with hepatologists, oncologists, interventional radiologists, and general surgeons. The combination of CT and MRI was used to enhance sensitivity and specificity and to identify patients with multifocal disease, portal thrombosis, and extrahepatic dissemination. Radiological parameters of the number, site, and size of nodules were evaluated and used to define BCLC stage and potential inclusion in Milan criteria [16,17,18,19,20]. We analyzed liver global function and the presence of cirrhosis or steatosis through liver elastography, Child-Pugh score, and model for end-stage liver disease score (MELD) [21,22,23,24]. We assessed the presence of main comorbidities, and we used parametric scores to evaluate general clinical conditions like ECOG-PS , anesthesiologic risk like ASA score [26, 27], and the Charlson comorbidity index (CCI)  as overall comorbidity indicator.
Each patient was screened for the presence of hepatitis viruses and HIV. We considered a sustained virologic response (SVR) in HCV patients if viral RNA was undetectable in the blood for 6 months after completing antiviral treatment, and we assessed lymphocytes CD4 levels, adherence to HAART, and the presence of active viral replication specifically in HIV patients.
Before surgery, patients were controlled with serial laboratory tests: leucocytes, hemoglobin, platelets, liver transaminases, total bilirubin, serum albumin, sodium, creatinine, and prothrombin time. We routinely analyzed alpha-fetoprotein as an oncological marker.
Surgical technique and follow-up
Surgical resection was performed with laparoscopic or laparotomic approach, and the type of resection (anatomical or nonanatomical) was chosen preoperatively considering liver function, tumor location, drainage tumor area, and technical difficulty of LR. The resections were carried out using a mixture of monopolar cautery, bipolar forceps, and ultrasonic dissection devices. Intraoperative ultrasonography (IOUS) was routinely performed for planning and for guiding the liver dissection. Intermittent Pringle maneuver was used with cycles of 15 min of inflow occlusion followed by 5 min of reperfusion when necessary. We evaluated surgical duration, the need for blood or plasma transfusion, and intraoperative complications.
In the postoperative course, patients were evaluated clinically and with blood tests to assess general and specific complication, like biliary complications (bile leaks), postoperative liver failure, and ascites. Postoperative complications were classified according to the Clavien-Dindo classification , and the assessment of patients’ overall morbidity was based on comprehensive complication index (CCI) [30, 31]. In addition, we considered the length of hospital stay, the need of reintervention, and 30-day mortality.
Histological examination of the surgical specimens and parenchymal biopsy of an uninvolved site were performed to evaluate the general liver status. We analyzed pathologic parameters like Edmondson grading, numbers of lesions, dimension of major nodule, satellitosis, microvascular invasion, and resection margin distance and status.
After hospital discharge, a follow-up program was planned for all patients including clinical, laboratory, and imaging evaluation with periodic infectious and oncological follow-up. We focused on the eventual occurrence of recurrence, its characteristics, and its management. In patients deceased during the follow-up, we distinguished the causes of death based on the progression of the underlying liver disease, cancer progression, or other causes.
Categorical variables are reported as number of cases and percentages. Continuous variables are expressed as mean ± standard deviation (SD) or by median and range. Overall survival (OS) and recurrence-free survival (RFS) were evaluated using the Kaplan-Meier method and the compared with the log-rank test. Differences between HCV+/HIV+ and HCV+/HIV− groups have been assessed by Fisher exact test and the Freeman-Halton extension for categorical variables, by Student’s t-test and Wilcoxon-Mann-Whitney test for continuous variables when appropriate. Statistical significance was set at p < 0.05. Statistical analysis was performed with IBM SPSS Statistics 25.0.