Background and Objectives: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer with a highly unfavorable prognosis. Aims: Retrospective statistical analysis of patients with HCC in the field of liver cirrhosis treated at our center from the perspective of demography, and the effects of key changes in diagnostic and therapeutic procedures in the last 10 years on overall survival (OS) and earlier diagnosis. Materials and Methods: This study included 170 cirrhotic patients with HCC (136 men, 80%). Demographic and etiological factors and OS were analyzed based on distribution into three groups according to the period and key changes in diagnostic and therapeutic approaches (BCLC classification staging; standardization of protocol for transarterial chemoembolization (TACE) and the introduction of direct-acting antivirals (DAA) for the treatment of chronic viral hepatitis C (HCV); expansion of systemic oncological therapy). Results: The mean age at the time of diagnosis was 69.3 years (SD = 8.1), and etiology was as follows: non-alcoholic steatohepatitis (NASH) 39%, alcoholic liver disease (ALD) 36%, HCV 18%, cryptogenic liver cirrhosis 3%, chronic hepatitis B infection (HBV) 2%, and other etiology 2%. Distribution of stages according to the BCLC: 0 + A 36%, B 31%, C 22%, and D 11%. However, the distribution in the first studied period was as follows: 0 + A 15%, B 34%, C 36%, and D 15%; and in the last period: 0 + A 45%, B 27%, C 17%, and D 11%, and difference was statistically significant (p < 0.05). The median OS for stages 0 + A, B, C, and D was 58, 19, 6, and 2 months, respectively. During the monitored period, there was a visible increase in the etiology of ALD from 30% to 47% and a decrease in HCV from 22% to 11%. In patients treated with TACE (stage B), the median OS grew from 10 to 24 months (p < 0.0001) between the marginal monitored periods. Conclusions: We described a decreasing number of patients with HCV-related HCC during follow-up possibly linked with the introduction of DAA. In our cohort, an improvement in early-stage diagnosis was found, which we mainly concluded as a result of proper ultrasound surveillance, the institution of a HCV treatment center, and increased experience of our sonographers with an examination of cirrhotic patients. Lastly, we described significantly improved overall survival in patients with intermediate HCC treated by TACE, due to the increased experience of interventional radiologists with the method at our facility and an earlier switch to systemic therapy in case of non-response to TACE.
SouhrnHepatocelulární karcinom (HCC) je nejčastější primární zhoubný nádor jater, který se ve většině případů rozvíjí v terénu jaterní cirhózy různé etiologie. Jen časná stadia onemocnění jsou indikována k chirurgické, potenciálně kurativní léčbě. Jen přibližně třetina HCC je zachycena v časných stadiích. Screeningovým vyšetřením rizikových skupin pacientů je ultrasonografie jater (USG) v 6měsíčních intervalech. USG má vedle svých známých výhod i značné limitace. Senzitivita USG pro časná stadia HCC se pohybuje pouze okolo 60 %. Vzhledem k tomu a i proto, že se jedná o expert dependentní metodu, existuje naléhává potřeba objektivního biomarkeru HCC. Alfa-fetoprotein je obecně vnímán jako biomarker HCC, nicméně jeho senzitivita a specificita pro účely diagnostiky či dokonce screeningu je nedostatečná. Byly zkoumány i jiné další biomarkery s různými výsledky, ale žádný nedosáhl efektivity USG. Poměrně novým přístupem k této problematice je spektroskopie krevní plazmy, která prokázala svoji účinnost u různých onemocnění. Z pohledu HCC se spektroskopii krevní plazmy věnovalo jen málo studií. Autoři prezentují v přehledu i vlastní práci, kdy spektroskopie krevní plazmy dosáhla senzitivity a specificity v odlišení nemocných s jaterní cirhózou bez HCC a s ním 88 %, respektive 90 %. Přes veškeré snahy nebyl dosud dostatečně spolehlivý a validovaný biomarker HCC použitelný pro účely časné diagnostiky a screeningu identifikován.
Summary: None of the biomarkers studied so far in the HCC area has yielded higher sensitivity and specificity in the early-stage diagnosis than the liver ultrasonography examination. There is an urgent clinical need for establishing a laboratory marker for HCC that meets the requirements for high sensitivity and specificity for the screening and early diagnosis of at-risk patients. As a variety of pathological processes, including carcinogenesis, may cause changes in both the concentration and the structure and spatial arrangement of body biomolecules, the spectroscopic analysis of blood-based derivatives appears to be an appropriate tool for the early detection thereof. In our research, the focus is on the identification of novel biomarkers in blood plasma, which would exhibit sufficient sensitivity and specificity to detect early and potentially curable HCC stages, and which would be potentially useful for routine screening of this disease in well-defined at-risk groups. For this purpose, we utilised a unique combination of two chiroptical methods – electronic circular dichroism (ECD) and Raman optical activity (ROA) – supplemented by non-polarised variants – infrared (IR) absorption and Raman spectroscopy. Methods: Blood plasma of 18 selected patients with liver cirrhosis, 8 of which also suffered from HCC, was analysed by a combination of ECD, ROA, IR and Raman spectroscopy. Results: The obtained spectral data were processed by a multivariate statistical evaluation using principal component analysis (PCA) and linear discriminant analysis (LDA). The visualisation of the LDA results showed the separation of the two monitored groups with only a slight overlap. Based on the spectral analysis within this preliminary study, sensitivity and specificity for the discrimination between cirrhotic individuals with and without HCC reached 88% and 90% after leave-one-out cross validation, respectively. The area under the ROC curve of 0.975 proved high reliability of the established model. Conclusion: Based on our findings, the combination of advanced spectroscopic methods for the analysis of blood plasma might be a promising tool in HCC diagnosis and potentially in the screening thereof. Key words: hepatocellular carcinoma – blood plasma – spectroscopy – cirrhosis
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