Clinical Case Summary

A 68-year-old male patient was referred to the Hepatology clinic following incidental findings on a computed tomography scan performed to reassess an abdominal aortic aneurysm. Three nodular lesions were identified, measuring 24, 42, and 72mm, in liver parenchyma without signs of chronic liver disease. These lesions had hypodense central areas on the non-contrast study, heterogeneous and mosaic enhancement on the arterial phase, and washout on the venous phase, with a capturing pseudocapsule. In the absence of a context of liver cirrhosis, a percutaneous biopsy was performed, and the morphological characteristics and the immunohistochemical profile were compatible with the diagnosis of hepatocellular carcinoma. After multidisciplinary discussion, transarterial chemoembolization (TACE) was proposed. Due to the inability to catheterize one of the nodules and the persistence of viable tumor in another, TACE was repeated after three months. Due to mild but persistent pain and an increase in inflammatory parameters seven days after the procedure, a CT scan was performed, which revealed two necrotic collections with apparent over-infection (47 and 87mm), the latter perforated into the duodenal bulb. Considering the presence of contained peritonitis and the risk-benefit ratio, conservative therapy (antibiotics + percutaneous drainage + total parenteral nutrition) was decided, with close clinical monitoring, and analytical and imaging surveillance, as a bridge to surgical intervention. The patient had a good clinical evolution and underwent antrectomy, segmental duodenoectomy, and gastrojejunal anastomosis 46 days after TACE. TACE is an effective treatment with a low rate of complications. However, rarely, gastrointestinal ischemia can occur due to the embolization of visceral arteries. Most often, symptoms appear within two weeks post-TACE; however, these are nonspecific, being essential to keep a low threshold of suspicion to identify this serious complication.

Introduction

The literature regarding the risk of progression to extrahepatic disease and clinical factors associated with the development of metastases in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) is sparse.

Aims & Methods

We aimed to assess the incidence of extrahepatic recurrence and to identify clinically relevant risk factors for the development of metastases in patients with HCC treated with TACE as first-line treatment.
From the Italian Liver Cancer (ITA.LI.CA) database, data of 981 HCC patients undergoing TACE as first-line treatment were retrieved and retrospectively analyzed. Incidence of extrahepatic recurrence was compared between two groups according to the diameter of the largest liver lesion at the time of TACE (HCC ≤ 3 cm vs. HCC > 3 cm). Multivariate Cox regression was used to identify predictor of extrahepatic recurrence.

Results

During a median follow-up of 27.0 months (IQR, 13.2-49.0) the overall recurrence rate was 75.4%. Only 78/981 patients (8.0%) had an extrahepatic tumor localization at first recurrence (5.4% in the ≤3 cm group and 10.7% in the >3 group; p=0.002), while the overall extrahepatic recurrence rate was 26.0% (21.2% and 31.0% patients in the ≤3 cm and >3 cm groups, respectively; p=0.0006) (Figure 1). Compared to those with larger tumors, patients with HCC ≤ 3 cm had a significantly longer recurrence-free survival (12.0 [95% CI 10.7-13.3] vs. 9.7 [95% CI 8.2-11.2] months; p=0.02) and overall survival (52.5 [95% CI 45.5-59.4] vs. 34.7 [95% CI 30.7-38.7] months; p<0.0001). HCC size ≥ 3 cm, multifocality and AFP levels were independent predictors of extrahepatic recurrence.

Conclusion

Although the majority of patients treated with TACE do not develop metastases during their lifespan, knowledge of risk factors for extrahepatic recurrence (HCC size, multifocality, AFP levels) may help to assess patient prognosis and to identify patients deserving closer follow-up in order to start early systemic therapy.

Introduction

Hepatocellular carcinoma (HCC) is the most common primary malignant liver cancer globally and ranks as the third leading cause of cancer-related mortality. Treatment with immune checkpoint inhibitors (most commonly atezolizumab in combination with bevacizumab) is the most effective first-line systemic therapy for patients with advanced HCC. Since it is a new method of treatment, there is little clinical data on the use of this combination of drugs in practice (outside of prospective studies). This study aims to present the clinical outcomes of patients with HCC who underwent immunotherapy at our center over the past three years.

Aims & Methods

In this retrospective observational study, we included patients treated with the atezolizumab and bevacizumab combination between March 2020 and September 2023. Demographic information, general physical assesments, disease etiology, disease staging, liver cirrhosis status, portal hypertension and laboratory values (aminotransferases and total bilirubin) were collected. Adverse events were analyzed according to the Common Terminology Criteria (CTCAE). Descriptive statistics and survival analysis were performed using Statistical Package for the Social Sciences (SPSS) version 22.

Results

53 HCC patients received atezolizumab and bevacizumab in studied time period, 8 (15.1%) females and 45 (84.9%) males. The median age at the initiation of immunotherapy was 68 years (range 41 – 84 years). Thirteen patients (24.5%) had esophageal varices prior to immunotherapy, with three (5.6%) requiring ligation. The majority of patients had liver cirrhosis A 27 (50.9%) according to Child Pugh criteria, a minority B (9.4%), and 21 patients (39.6%) were without cirrhosis. The primary causes of the disease were alcohol (51.6%), metabolic dysfunction-associated steatotic liver disease (MASLD) (16.1%), hepatitis C virus (12.9%), hepatitis B virus (6.5%), and hemochromatosis (3.2%). Stage C HCC, according to The Barcelona Clinic Liver Cancer, World Health Organization (WHO) performance status 0, and absence of macrovascular invasion and extrahepatic spread were predominant at treatment initiation. Grade I or II adverse events occurred in almost all patients (98.1%). Severe adverse events were present in 36 patients (67.9%). Due to severe side effects, 8 (15.1%) patients discontinued treatment, 2 (3.8%) died due to treatment related complications (encephalitis and bleeding from esophageal varices). Treatment was modified in 21 (39.6%) patients due to adverse events. The estimated median survival was 15.7 months.

Conclusion

The majority of patients with unresectable HCC, treated with a combination of atezolizumab and bevacizumab immunotherapy, experienced adverse events, primarily grades I-II. The immunotherapy combination proved to be more effective in patients with viral etiology of liver cirrhosis. The estimated median survival was 15.7 months. This combination of immunotherapy has been demonstrated to be a safe and effective treatment method. Currently, there is limited data regarding the utilization of this treatment in standard clinical practice and our data aligns reasonably well with the findings of the registration study.

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