Immunotherapy vs Best Supportive Care for Patients With Hepatocellular Cancer With Child-Pugh B Dysfunction.

Importance: Whether patients with Child-Pugh class B (CP-B) cancer with unresectable hepatocellular carcinoma (uHCC) benefit from active anticancer treatment vs best supportive care (BSC) is debated. Objective: To evaluate the association of immune checkpoint inhibitor (ICI)-based therapies vs BSC with overall survival (OS) of patients with uHCC and CP-B liver dysfunction. Design, Setting, and Participants: This retrospective, multicenter, international clinical case series examined data of patients with CP-B with uHCC who were receiving first-line ICI-based regimens from September 2017 to December 2022 whose data were extracted from an international consortium and compared with a cohort of patients with CP-B receiving BSC. Patients were treated in tertiary care centers across Europe, US, and Asia in routine clinical practice. After applying the inclusion criteria, 187 and 156 patients were left in the ICI and BSC groups, respectively. The propensity score was calculated for the following variables: age, alpha-fetoprotein levels, Child-Pugh score, extrahepatic spread, portal vein tumor thrombosis, cirrhosis, ascites, and baseline Eastern Cooperative Oncology Group performance status. Exposures: Patients in the ICI group received first-line systemic therapy with either atezolizumab plus bevacizumab (A+B) (n = 141) or nivolumab (n = 46). Main Outcomes and Measures: OS in the inverse probability of treatment weighting (IPTW) populations was the main outcome, and it was estimated with Kaplan-Meier method; univariable Cox regression test was used to make comparisons between the 2 groups. Results: The median age was 66 (IQR, 61-72) and 73 (IQR, 66-81) years in the ICI (33 women [18%]) and BSC groups (41 women [26%]), respectively. In the IPTW populations, median OS was significantly longer in the ICI group (7.50 months; 95% CI, 5.62-11.15) compared with BSC (4.04 months; 95% CI, 3.03-5.03; hazard ratio, 0.59; 95% CI, 0.43-0.80; P < .001). Multivariable analysis confirmed that ICI exposure was associated with a reduction of approximately 50% in the risk of death (hazard ratio, 0.55; 95% CI, 0.35-0.86; P < .001), and the presence of portal vein tumor thrombosis, an Eastern Cooperative Oncology Group performance score of greater than 1, and alpha-fetoprotein levels of 400 ng/mL or greater were associated with increased risk of death. Conclusions and Relevance: The results of this case series provide comparative evidence of improved survival in association with ICI treatment compared with BSC in patients with uHCC with CP-B liver dysfunction.

Characteristics and outcome of anti-hepatitis D virus positive patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Chronic hepatitis D virus (HDV) often leads to end-stage liver disease and hepatocellular carcinoma (HCC). Comprehensive data pertaining to large populations with HDV and HCC are missing, therefore we sought to assess the characteristics, management, and outcome of these patients, comparing them to patients with hepatitis B virus (HBV) infection. METHODS: We analysed the Italian Liver Cancer database focusing on patients with positivity for HBV surface antigen and anti-HDV antibodies (HBV/HDV, n = 107) and patients with HBV infection alone (n = 588). Clinical and oncological characteristics, treatment, and survival were compared in the two groups. RESULTS: Patients with HBV/HDV had worse liver function [Model for End-stage Liver Disease score: 11 vs. 9, p < .0001; Child-Turcotte-Pugh score: 7 vs. 5, p < .0001] than patients with HBV. HCC was more frequently diagnosed during surveillance (72.9% vs. 52.4%, p = .0002), and the oncological stage was more frequently Milan-in (67.3% vs. 52.7%, p = .005) in patients with HBV/HDV. Liver transplantation was more frequently performed in HBV/HDV than in HBV patients (36.4% vs. 9.5%), while the opposite was observed for resection (8.4% vs. 20.1%, p < .0001), and in a competing risk analysis, HBV/HDV patients had a higher probability of receiving transplantation, independently of liver function and oncological stage. A trend towards longer survival was observed in patients with HBV/HDV (50.4 vs. 44.4 months, p = .106). CONCLUSIONS: In patients with HBV/HDV, HCC is diagnosed more frequently during surveillance, resulting in a less advanced cancer stage in patients with more deranged liver function than HBV alone. Patients with HBV/HDV have a heightened benefit from liver transplantation, positively influencing survival.

Sorafenib and Metronomic Capecitabine in Child-Pugh B patients with advanced HCC: A real-life comparison with best supportive care.

BACKGROUND AND AIMS: The efficacy of systemic therapy for unresectable advanced hepatocellular carcinoma (aHCC) has not been proven in patients with Child-Pugh (C-P) B cirrhosis. Nevertheless, in real-world these patients are treated both with tyrosine kinase inhibitors (TKIs) and with metronomic capecitabine (MC). This study aimed to compare sorafenib and MC outcomes versus best supportive care (BSC) in C-P B patients. METHOD: Between 2008 and 2020, among 774 C-P B patients with aHCC not amenable/responsive to locoregional treatments, 410 underwent sorafenib, 62 MC, and 302 BSC. The propensity score matching method was used to correct the baseline unbalanced prognostic factors. RESULTS: In the unmatched population, median OS was 9.7 months in patients treated with sorafenib, 8.0 with MC, and 3.9 months with BSC. In sorafenib vs. BSC-matched patients (135 couples), median OS was 7.3 (4.9-9.6) vs. 3.9 (2.6-5.2) months (p<0.001). ECOG-Performance Status, tumor size, macrovascular invasion, AFP, treatment-naive, and sorafenib were independent predictors of survival. In MC vs. BSC-matched patients (40 couples), median OS was 9.0 (0.2-17.8) vs.3.0 (2.2-3.8) months (p<0.001). Median OS did not differ (p = 0.283) in sorafenib vs. MC-matched patients (55 couples). CONCLUSION: C-P B patients with aHCC undergoing BSC have poor survival. Both Sorafenib and MC treatment improve their prognosis.

Landscape of alcohol-related hepatocellular carcinoma in the last 15 years highlights the need to expand surveillance programs.

Background & Aims: Alcohol abuse and metabolic disorders are leading causes of hepatocellular carcinoma (HCC) worldwide. Alcohol-related aetiology is associated with a worse prognosis compared with viral agents, because of the lower percentage of patients diagnosed with HCC under routine surveillance and a higher burden of comorbidity in alcohol abusers. This study aimed to describe the evolving clinical scenario of alcohol-related HCC over 15 years (2006-2020) in Italy. Methods: Data from the Italian Liver Cancer (ITA.LI.CA) registry were used: 1,391 patients were allocated to three groups based on the year of HCC diagnosis (2006-2010; 2011-2015; 2016-2020). Patient characteristics, HCC treatment, and overall survival were compared among groups. Survival predictors were also investigated. Results: Approximately 80% of alcohol-related HCCs were classified as cases of metabolic dysfunction-associated fatty liver disease. Throughout the quinquennia, <50% of HCCs were detected by surveillance programmes. The tumour burden at diagnosis was slightly reduced but not enough to change the distribution of the ITA.LI.CA cancer stages. Intra-arterial and targeted systemic therapies increased across quinquennia. A modest improvement in survival was observed in the last quinquennia, particularly after 12 months of patient observation. Cancer stage, HCC treatment, and presence of oesophageal varices were independent predictors of survival. Conclusions: In the past 15 years, modest improvements have been obtained in outcomes of alcohol-related HCC, attributed mainly to underuse of surveillance programmes and the consequent low amenability to curative treatments. Metabolic dysfunction-associated fatty liver disease is a widespread condition in alcohol abusers, but its presence did not show a pivotal prognostic role once HCC had developed. Instead, the presence of oesophageal varices, an independent poor prognosticator, should be considered in patient management and refining of prognostic systems. Impact and Implications: Alcohol abuse is a leading and growing cause of hepatocellular carcinoma (HCC) worldwide and is associated with a worse prognosis compared with other aetiologies. We assessed the evolutionary landscape of alcohol-related HCC over 15 years in Italy. A high cumulative prevalence (78%) of metabolic dysfunction-associated fatty liver disease, with signs of metabolic dysfunction, was observed in HCC patients with unhealthy excessive alcohol consumption. The alcohol + metabolic dysfunction-associated fatty liver disease condition tended to progressively increase over time. A modest improvement in survival occurred over the study period, likely because of the persistent underuse of surveillance programmes and, consequently, the lack of improvement in the cancer stage at diagnosis and the patients' eligibility for curative treatments. Alongside the known prognostic factors for HCC (cancer stage and treatment), the presence of oesophageal varices was an independent predictor of poor survival, suggesting that this clinical feature should be carefully considered in patient management and should be included in prognostic systems/scores for HCC to improve their performance.

Portal hypertensive gastropathy in cirrhotics without varices: a case-control study.

OBJECTIVE: Information is lacking on portal hypertensive gastropathy (PHG) in cirrhotics without varices; our aim it is to evaluate whether clinical and sonographic parameters are associated with PHG and may provide information suitable for the management of these patients. PATIENTS AND METHODS: After endoscopic selection of 145 cirrhotics without varices, 75 with PHG and 70 without PHG, clinical and sonographic characteristics were assessed. RESULTS: Forty portosystemic shunts were present in 27 patients. The mean Child-Pugh score was 6.3±1.4 and 5.6±0.5 in patients with severe and mild PHG, respectively (P=0.004). The mean portal vein diameter was 10.4±1.7 and 11.6±2.0 mm in cirrhotics without and with PHG, respectively (P=0.0002). CONCLUSION: A link between the presence of PHG and a more advanced phase of cirrhosis was found. Duplex Doppler sonography was confirmed to be a valuable diagnostic method in monitoring cirrhosis. Management of these patients cannot be performed on the basis of a single diagnostic method, and a multimodal diagnostic approach is required.

Radiofrequency ablation of pancreatic neuroendocrine tumors: a pilot study of feasibility, efficacy, and safety.

OBJECTIVE: This study aimed to assess the feasibility, safety, and efficacy of radiofrequency ablation (RFA) of pancreatic neuroendocrine tumors (PNETs). METHODS: We performed RFA on 10 patients (7 women) aged 38 to 75 years with histologically diagnosed PNETs (secreting in 3 cases) who could not or would not undergo surgical resection. Tumor nodules (diameter, 0.9-2.9 cm; mean [SD], 1.6 [0.5] cm) were located in the head (n = 7) or body (n = 3) of the pancreas. Ultrasound-guided RFA was performed percutaneously (n = 7), endoscopically (n = 1), or intraoperatively (n = 2) using commercially available equipment. Complete ablation was defined as absence of enhancing tissue at the tumor site on contrast-enhanced imaging studies and normalization of previously elevated serum hormone levels. RESULTS: Complete ablation was achieved with 1 (n = 9) or 2 (n = 1) RFA procedures. All neuroendocrine syndromes regressed within 24 hours of treatment. No recurrences were observed during follow-up (range, 12-60 months; median [SD], 34 [14] months). No deaths occurred. Major complications included acute pancreatitis in 3 patients, 2 of whom developed pancreatic fluid collections that were successfully managed with ultrasound-guided drainage and endoscopy. CONCLUSIONS: Radiofrequency ablation is a feasible, safe, and effective option for patients with small PNETs who cannot or do not want to undergo surgical resection.

Which clinical and sonographic parameters may be useful to discriminate NASH from steatosis?

BACKGROUND: The natural history of nonalcoholic steatohepatitis (NASH) includes the passage through steatosis. GOAL: To retrospectively evaluate the usefulness of sonographic parameters compared to histological diagnosis when differentiating steatosis from NASH. STUDY: This retrospective study reviewed records of patients with steatosis from databases of our Departments, selecting only those who had been diagnosed by sonography and liver biopsy [64 males (63.82%); 30 females (36.18%)]. RESULTS: Attenuation of the echo amplitude (P<0.05; odds ratio (OR): 3.43; confidence interval (CI): 1.02-11.57), focal fat sparing (P<0.05; OR: 3; CI: 1.02-11.88) and splenic diameter (P<0.05; OR: 1.66; CI: 1.04-3.26) were independent predictors of NASH. A significantly higher association of attenuation of the echo amplitude, enlarged splenic diameter, and presence of focal fat sparing was observed in NASH patients (P<0.01). CONCLUSIONS: It is very difficult to build a predictive system to distinguish NASH from steatosis based on sonographic scores. However, it is already possible to differentiate NASH from steatosis by combining 3 simple sonographic parameters: attenuation of the echo amplitude, enlarged splenic diameter, and presence of focal fat sparing.

Repeated radiofrequency ablation for management of patients with cirrhosis with small hepatocellular carcinomas: a long-term cohort study.

UNLABELLED: In most patients with cirrhosis, successful percutaneous ablation or surgical resection of hepatocellular carcinoma (HCC) is followed by recurrence. Radiofrequency ablation (RFA) has proven effective for treating HCC nodules, but its repeatability in managing recurrences and the impact of this approach on survival has not been evaluated. To this end, we retrospectively analyzed a prospective series of 706 patients with cirrhosis (Child-Pugh class ≤ B7) who underwent RFA for 859 HCC ≤ 35 mm in diameter (1-2 per patient). The results of RFA were classified as complete responses (CRs) or treatment failures. CRs were obtained in 849 nodules (98.8%) and 696 patients (98.5%). During follow-up (median, 29 months), 465 (66.8%) of the 696 patients with CRs experienced a first recurrence at an incidence rate of 41 per 100 person-years (local recurrence 6.2; nonlocal 35). Cumulative incidences of first recurrence at 3 and 5 years were 70.8% and 81.7%, respectively. RFA was repeated in 323 (69.4%) of the 465 patients with first recurrence, restoring disease-free status in 318 (98.4%) cases. Subsequently, RFA was repeated in 147 (65.9%) of the 223 patients who developed a second recurrence after CR of the first, restoring disease-free status in 145 (98.6%) cases. Overall, there were 877 episodes of recurrence (1-8 per patient); 577 (65.8%) of these underwent RFA that achieved CRs in 557 (96.5%) cases. No procedure-related deaths occurred in 1,921 RFA sessions. Estimated 3- and 5-year overall and disease-free (after repeated RFAs) survival rates were 67.0% and 40.1% and 68.0 and 38.0%, respectively. CONCLUSION: RFA is safe and effective for managing HCC in patients with cirrhosis, and its high repeatability makes it particularly valuable for controlling intrahepatic recurrences.

Intrabile duct metastasis from colonic adenocarcinoma without liver parenchyma involvement: contrast enhanced ultrasonography detection.

It is well-known that biliary duct invasion with intraluminal growth is one of the developmental patterns of primary liver tumors, and macroscopic intrabiliary growth of liver metastases in colorectal cancer is found with high frequency. Surgical treatment is the only potential curative therapy. However, many patients die of intrahepatic and/or extrahepatic recurrence after the resection. One of the causes of high recurrence rate after resective surgery, particularly surgical margin recurrences, is the invasion of biliary ducts mainly due to intraluminal tumor growth. We describe the first recorded case of a metastasis from colorectal cancer involving solely the common hepatic biliary duct, without invasion of contiguous liver parenchyma. A correct diagnosis was obtained by means of contrast enhanced ultrasound and ultrasound-guided fine needle aspiration biopsy.

Liver schistosomiasis: an unexpected finding in hepatitis B virus-related chronic hepatitis.

CASE REPORT: We report the unusual case of an African patient who underwent a liver biopsy for a chronic HBV-related hepatitis, whose histological sample also unexpectedly revealed elements diagnostic for schistosomiasis. The patient was only mildly symptomatic for the Schistosoma infestation; stool examination confirmed the presence of parasitic eggs. Hepatitis B virus (HBV)-schistosomiasis co-infection is particularly rare in Western countries. Only the identification of some pathological elements atypical for HBV infection by means of step sections in the liver biopsy sample allowed us to disclose the unsuspected diagnosis. CONCLUSIONS: Since migratory flows have increased, the number of foreign people being referred to our hospitals has increased. Patients coming from areas endemic for infectious diseases that are absent in Western countries must be carefully evaluated, taking into account possible unexpected co-infections, including in the setting of pathological studies of liver biopsies.

Contrast-enhanced ultrasonography and spiral computed tomography in the detection and characterization of portal vein thrombosis complicating hepatocellular carcinoma.

The aim was to compare the performances of contrast-enhanced (CE) ultrasonography (US) and spiral computed tomography (CT) in the detection and characterization of portal vein thrombosis complicating hepatocellular carcinoma (HCC). We studied 50 patients with HCC who had biopsy-proven portal vein thrombi that had been detected with US and color Doppler US. Thirteen of the thrombi involved the main portal trunk and 37 the segmental branches. CEUS and CT were performed within a week of thrombus biopsies. For each imaging technique, diagnoses of thrombosis (present/absent) and thrombus nature (malignancy/benignancy) were made by experienced readers under blinded conditions and compared with pathological findings to determine accuracy rates for thrombus detection and characterization. Forty-four of the 50 thrombi were pathologically diagnosed as malignant and the remaining six were benign. CEUS detected 50/50 (100%) thrombi and correctly characterized 49/50 (98%). CT detected 34/50 (68%) thrombi and correctly characterized 23 of these 34 (68%). CEUS outperformed CT in terms of both thrombus detection (P < 0.0001) and characterization (P = 0.0001). CEUS appears to be significantly superior to CT for detection and characterization of portal vein thrombosis complicating HCC, and it should be considered in the staging of these tumors.