Liver cancer remains a global health challenge, with an estimated incidence of >1 million cases by 2025 Hepatocellular carcinoma (HCC) is the most common form of liver cancer and accounts for ~90% of cases Infection by hepatitis B virus and hepatitis C virus are the main risk factors for HCC development, although non-alcoholic steatohepatitis associated with metabolic syndrome or diabetes mellitus is becoming a more frequent risk factor in the West Moreover, non-alcoholic steatohepatitis-associated HCC has a unique molecular pathogenesis Approximately 25% of all HCCs present with potentially actionable mutations, which are yet to be translated into the clinical practice Diagnosis based upon non-invasive criteria is currently challenged by the need for molecular information that requires tissue or liquid biopsies The current major advancements have impacted the management of patients with advanced HCC Six systemic therapies have been approved based on phase III trials (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab) and three additional therapies have obtained accelerated FDA approval owing to evidence of efficacy New trials are exploring combination therapies, including checkpoint inhibitors and tyrosine kinase inhibitors or anti-VEGF therapies, or even combinations of two immunotherapy regimens The outcomes of these trials are expected to change the landscape of HCC management at all evolutionary stages

Hepatocellular carcinoma.

Objectives To evaluate the effectiveness, cost-effectiveness and cost-utility of surveillance of patients with cirrhosis [alcoholic liver disease (ALD)-, hepatitis B (HBV)- and C virus (HCV)-related], using periodic serum alpha-fetoprotein (AFP) testing and/or liver ultrasound examination, to detect hepatocellular carcinoma (HCC), followed by treatment with liver transplantation or resection, where appropriate. Data sources Electronic databases were searched up to March 2006. Review methods A systematic review was carried out using standard methodological guidelines. A computerised decision-analytic model was then developed to compare various surveillance strategies. Results No studies were identified that met the criteria of the systematic review. Based on the assumptions used in the model, the most effective surveillance strategy uses a combination of AFP testing and ultrasound at 6-monthly intervals. Compared with no surveillance, this strategy is estimated to more than triple the number of people with operable HCC tumours at time of diagnosis, and almost halves the number of deaths from HCC. On all effectiveness measures and at both testing frequencies, AFP- and ultrasound-led surveillance strategies are very similar. This may be because test sensitivity was varied according to tumour size, which means that AFP testing is capable of identifying many more small tumours than ultrasound. The best available evidence suggests that AFP tests will detect approximately six times as many small tumours as ultrasound. Increasing the frequency of either test to 6-monthly intervals is more effective than performing combined testing on an annual basis. The undiscounted lifetime cost of the surveillance strategies, including all care and treatment costs, ranges from 40,300 pounds (annual AFP triage) to 42,900 pounds (6-monthly AFP and ultrasound). The equivalent discounted costs are 28,400 pounds and 30,400 pounds. Only a small proportion of these total costs results from the cost of the screening tests. However, screening test costs, and the cost of liver transplants and caring for people post-transplant, accounted for most of the incremental cost differences between alternative surveillance strategies. The results suggest that different surveillance strategies may provide the best value for money in patient groups of different cirrhosis aetiologies. The surveillance of people with HBV-related cirrhosis for HCC provides the best value for money, while surveillance in people with ALD-related cirrhosis provides the poorest value for money. In people with HBV-related cirrhosis, at an assumed maximum willingness to pay (WTP) for a quality-adjusted life-year (QALY) of 30,000 pounds, both the deterministic and probabilistic cost-utility analyses suggest the optimal surveillance strategy would be 6-monthly surveillance with the combination of AFP testing and ultrasound. In contrast, for those with ALD-related cirrhosis, annual screening with AFP as a triage test is the only surveillance strategy that is likely to be considered cost-effective at this WTP. The probabilistic analysis implies that the estimated benefits of a 6-monthly AFP triage strategy will only be worth the cost in those with ALD when society's WTP for a QALY exceeds around 40,000 pounds. For people with HCV-related cirrhosis, the model suggests that the most cost-effective surveillance strategy at a WTP threshold of 30,000 pounds/QALY would be surveillance with a 6-monthly AFP triage strategy. Conclusions In a mixed-aetiology cohort, the most effective surveillance strategy is to screen each patient with AFP assay and ultrasound imaging on a 6-monthly basis. However, when costs are taken into account it is doubtful whether ultrasound should be routinely offered to those with blood AFP of less than 20 ng/ml, unless policy-makers are prepared to pay over 60,000 pounds per QALY for the benefits achieved. Furthermore, the cost-effectiveness of surveillance for HCC varies considerably depending on the aetiology of cirrhosis; it is much more likely to be cost-effective in those with HBV-related cirrhosis, and much less likely to be cost-effective in those with ALD-related cirrhosis. Further development of the model would help to enable refinement of an optimal screening strategy. Research into the use of contrast-enhanced ultrasound technology for HCC detection would also be valuable, as would research into the epidemiology and natural history of ALD-related cirrhosis. Studies are also needed to investigate the influence of cirrhosis aetiology on tumour AFP expression.

Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis

https://www.siemc.it/images/download/afp-smallhcc.pdf

Alpha-fetoprotein has no prognostic role in small hepatocellular carcinoma identified during surveillance in compensated cirrhosis†

Elevated alpha-fetoprotein: differential diagnosis - hepatocellular carcinoma and other disorders.

Hepatocellular dysplastic nodules

Purpose: To determine the frequencies of various echogenicity patterns in 153 consecutive unifocal hepatocellular carcinomas (HCCs) <2 cm detected in cirrhotic livers and to identify their relationships with clinical, laboratory, and microscopic features.



Patients and methods: The tumors were classified as hypoechoic, hyperechoic, isoechoic, or nodule-in-nodule. Correlation was evaluated between hypoechoic and hyperechoic patterns and the following variables: age, gender, serum alphafetoprotein (AFP), tumor size, ultrasound features of liver parenchyma, cirrhosis etiology, and cyto/histological tumor grading.



Results: One hundred and seventeen tumors (76.4%) were hypoechoic, 26 (17.0%) were hyperechoic, 5 (3.3%) were isoechoic, and 5 (3.3%) had nodule-in-nodule patterns. The hyperechoic pattern was more common in patients under 69 years (25.0% vs. 11.3% in those under 69 years or older, P=0.033). Patients with a hyperechoic pattern displayed a trend towards lower AFP levels and higher prevalence of hepatitis C-related cirrhosis. The prevalence of well-differentiated tumors was identical (56.6% and 56.5%) in the hypoechoic and hyperechoic subgroups. AFP was higher than 400 ng/ml in only 11/153 cases (7.2%).



Conclusions: The hyperechoic pattern of HCC is by no means uncommon, particularly in patients under 70. Hyperechogenicity is not related to an increased frequency of well-differentiated tumors. AFP shows limited value as a confirmatory test of small HCC.

Hepatocellular carcinomas <2 cm in diameter complicating cirrhosis: ultrasound and clinical features in 153 consecutive patients.

The Italian experience on paediatric liver transplantation: 1988–1999 report

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Hepatocellular carcinomas <2 cm in diameter complicating cirrhosis: ultrasound and clinical features in 153 consecutive patients.

The Italian experience on paediatric liver transplantation: 1988–1999 report