BACKGROUND: Patients with advanced chronic liver disease (ACLD) are at high risk of developing hepatocellular carcinoma (HCC). Therefore, biannual surveillance is recommended. This large-scale multicenter study aimed to stratify the risk of HCC development in ACLD. METHODS: From 3016 patients with ACLD screened in 17 European and Chinese centers, 2340 patients with liver stiffness measurement (LSM) determined using different techniques (two-dimensional shear-wave elastography [2D-SWE], transient elastography, and point shear-wave elastography) and with different disease severities were included. Cox regression was used to explore risk factors for HCC. We used these data to create an algorithm, named PLEASE, but referred to in this manuscript as "the algorithm"; the algorithm was validated in internal and two external cohorts across elastography techniques. RESULTS: HCC developed in 127 (5.4%) patients during follow-up. LSM by 2D-SWE (hazard ratio: 2.28) was found to be associated with developing HCC, alongside age, sex, etiology, and platelet count (C-index: 0.8428). We thus established the algorithm with applicable cutoffs, assigning a maximum of six points: platelet count less than 150×109/l, LSM greater than or equal to 15 kPa, age greater than or equal to 50 years, male sex, controlled/uncontrolled viral hepatitis, or presence of steatotic liver diseases. Within 2 years, with a median follow-up of 13.7 months, patients in the high-risk group (≥4 points) had an HCC incidence of 15.6% (95% confidence interval [CI], 12.1% to 18.7%) compared with the low-risk group, at 1.7% (95% CI, 0.9% to 2.5%). CONCLUSIONS: Our algorithm stratified patients into two groups: those at higher risk of developing HCC and those at lower risk. Our data provide equipoise to test the prospective utility of the algorithm with respect to clinical decisions about screening patients with ACLD for incident HCC. (Funded by the German Research Foundation and others; ClinicalTrials.gov number, NCT03389152.).
- MeSH
- algoritmy MeSH
- chronická nemoc MeSH
- dospělí MeSH
- elastografie * MeSH
- hepatocelulární karcinom * epidemiologie diagnostické zobrazování diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory jater * epidemiologie diagnostické zobrazování diagnóza MeSH
- nemoci jater epidemiologie diagnostické zobrazování diagnóza MeSH
- rizikové faktory MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
We analyzed long-term incidence trends in liver cancer (including hepatocellular carcinoma and intrahepatic cholangiocarcinoma) with an aim to interpret the changes in terms of known risk factors and hypothesize that historical exposure to Thorotrast, a radiographic contrast medium emitting alpha particles, has changed population rates. The NORDCAN database was used to collect cancer registry data from Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE), which we used from 1953 (DK, FI and NO) and 1960 (SE) through 2019. Thorotrast, which caused a 100-fold risk of liver cancer was used in DK and SE, and probably also in FI between 1930 and 1950, but not in NO. The incidence trend for liver cancer showed a broad maximum at around 1980, most prominent and statistically significant in SE and DK men and women, and in all countries, a steadily increasing trend towards the end of follow-up. Incidence for NO was lower than for the other countries and the rates showed no peaking at around 1980. Birth cohort analysis identified a transient risk which could be dated to a period between 1930 and 1950 in countries other than NO. Considering a lag time between Thorotrast use and liver cancer appearance, the large incidence peak around 1980 in DK and DE was probably contributed by Thorotrast but considering the ecological nature of the findings, the association should be considered cautiously as hypothesis generating. The late increase in liver cancer risk is most likely lifestyle related and largely preventable.
- MeSH
- hepatocelulární karcinom * chemicky indukované epidemiologie MeSH
- incidence MeSH
- lidé MeSH
- nádory jater * chemicky indukované epidemiologie MeSH
- nádory žlučových cest * epidemiologie MeSH
- oxid thoričitý * škodlivé účinky MeSH
- žlučové cesty intrahepatální MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Dánsko MeSH
- Finsko MeSH
- Norsko MeSH
- Švédsko MeSH
- MeSH
- hepatocelulární karcinom * epidemiologie MeSH
- inhibitory zpětného vychytávání serotoninu a noradrenalinu * MeSH
- kohortové studie MeSH
- lidé MeSH
- nádory jater * chemicky indukované epidemiologie MeSH
- selektivní inhibitory zpětného vychytávání serotoninu škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- komentáře MeSH
- systematický přehled MeSH
PURPOSE: Recent studies have suggested a lower risk of hepatocellular carcinoma (HCC) in patients receiving selective serotonin reuptake inhibitors (SSRIs). The current study aimed to provide an updated and comprehensive assessment of the association between SSRI use and development of HCC. METHODS: This is a systematic review and meta-analysis of all observational studies published until June 2021. We comprehensively searched PubMed/Medline, Web of Science, and Embase to identify studies comparing SSRIs use with control in relation to the risk of HCC. We calculated pooled relative risks (RRs) and 95% confidence intervals (CIs) for the association between SSRI use and incident HCC risk using random-effects meta-analysis. A dose-response analysis was conducted to evaluate the HCC risk according to the defined daily dose (DDD) of SSRI use. RESULTS: Eight observational studies, comprising 1,051,096 participants and 22,316 incidences of HCC, examining the association between SSRIs use and HCC risk, were included in the systematic review (adjusted RR: 0.66; 95% CI: 0.56-0.79; P ≤ 0.001). In subgroup analysis, the magnitude of benefit associated with SSRIs was significantly higher in patients with hepatitis infection (RR: 0.70, 95% CI: 0.51-0.95) than the general population (Pheterogeneity = 0.700). The dose-response analysis indicated strong inverse association between cumulative DDD of SSRI and risk of HCC (coefficient: - 0.0030; P = 0.002; R2 = 0.78). CONCLUSIONS: The results of this review show that SSRI use was associated with a 34% lower risk of HCC, which tend to be dose dependent. Further prospective studies are warranted to confirm these observations across the spectrum of chronic liver disease and hepatitis infection.
- MeSH
- hepatocelulární karcinom * epidemiologie MeSH
- kohortové studie MeSH
- lidé MeSH
- nádory jater * chemicky indukované epidemiologie MeSH
- pozorovací studie jako téma MeSH
- riziko MeSH
- selektivní inhibitory zpětného vychytávání serotoninu škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
- MeSH
- hepatocelulární karcinom * epidemiologie MeSH
- inhibitory protonové pumpy škodlivé účinky MeSH
- lidé MeSH
- nádory jater * epidemiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- systematický přehled MeSH
- MeSH
- hepatocelulární karcinom * epidemiologie terapie MeSH
- lidé MeSH
- vztahy mezi lékařem a pacientem MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodníky MeSH
OBJECTIVE: Chronic HCV infection is associated with cirrhosis of the liver, hepatocellular carcinoma (HCC), and liver transplantation. HCV disease burden and the impact of new potent direct acting antivirals (DAAs) in the Czech Republic are unknown. METHODS: Using a modelling framework, HCV disease progression in the Czech Republic was predicted to 2030 under the current standard of care treatment structure. In addition, two strategies to reduce the future burden of HCV infection were modelled: an incremental increase in treatment annually and WHO targets. RESULTS: The number of viremic infected individuals in the Czech Republic is estimated to peak in 2026 (n = 55,130) and to decline by 0.5% by 2030 (n = 54,840). The number of individuals with compensated cirrhosis (n = 1,400), decompensated cirrhosis (n = 80), HCC (n = 70), and liver-related deaths (n = 60) is estimated to more than double by 2030. Through aggressive increases in diagnosis and treatment, HCV related mortality may decrease by 70% by 2030. CONCLUSIONS: Disease burden associated with chronic HCV infection is projected to peak in the Czech Republic in 30-40 years. Assuming that the current portion of DAAs used remains constant, a significant reduction in HCV disease burden is possible through increased diagnosis and treatment through 2030. This analysis provides evidence in order to facilitate the development of national strategies for HCV care and management in the Czech Republic.
- MeSH
- antivirové látky ekonomika terapeutické užití MeSH
- chronická hepatitida C farmakoterapie ekonomika epidemiologie MeSH
- dospělí MeSH
- hepatocelulární karcinom epidemiologie MeSH
- jaterní cirhóza epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- nádory jater epidemiologie MeSH
- osobní újma zaviněná nemocí * MeSH
- prevalence MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- surveillance populace MeSH
- transplantace jater MeSH
- věkové rozložení MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND & AIMS: Robust data on hepatocellular carcinoma (HCC) incidence among HIV/hepatitis B virus (HBV)-coinfected individuals on antiretroviral therapy (ART) are needed to inform HCC screening strategies. We aimed to evaluate the incidence and risk factors of HCC among HIV/HBV-coinfected individuals on tenofovir disoproxil fumarate (TDF)-containing ART in a large multi-cohort study. METHODS: We included all HIV-infected adults with a positive hepatitis B surface antigen test followed in 4 prospective European cohorts. The primary outcome was the occurrence of HCC. Demographic and clinical information was retrieved from routinely collected data, and liver cirrhosis was defined according to results from liver biopsy or non-invasive measurements. Multivariable Poisson regression was used to assess HCC risk factors. RESULTS: A total of 3,625 HIV/HBV-coinfected patients were included, of whom 72% had started TDF-containing ART. Over 32,673 patient-years (py), 60 individuals (1.7%) developed an HCC. The incidence of HCC remained stable over time among individuals on TDF, whereas it increased steadily among those not on TDF. Among individuals on TDF, the incidence of HCC was 5.9 per 1,000 py (95% CI 3.60-9.10) in cirrhotics and 1.17 per 1,000 py (0.56-2.14) among non-cirrhotics. Age at initiation of TDF (adjusted incidence rate ratio per 10-year increase: 2.2, 95% CI 1.6-3.0) and the presence of liver cirrhosis (4.5, 2.3-8.9) were predictors of HCC. Among non-cirrhotic individuals, the incidence of HCC was only above the commonly used screening threshold of 2 cases per 1,000 py in patients aged >45 years old at TDF initiation. CONCLUSIONS: Whereas the incidence of HCC was high in cirrhotic HIV/HBV-coinfected individuals, it remained below the HCC screening threshold in patients without cirrhosis who started TDF aged <46 years old. LAY SUMMARY: We investigated the incidence of hepatocellular carcinoma in HIV/hepatitis B virus-coinfected individuals from a large multi-cohort study in Europe. Over 32,673 patient-years, 60 individuals (1.7%) developed hepatocellular carcinoma. The incidence of hepatocellular carcinoma remained low in patients without cirrhosis, who started on tenofovir disoproxil fumarate when aged <46 years old.
- MeSH
- dospělí MeSH
- hepatitida B - antigeny povrchové analýza MeSH
- hepatitida B farmakoterapie virologie MeSH
- hepatocelulární karcinom epidemiologie MeSH
- HIV * MeSH
- incidence MeSH
- koinfekce farmakoterapie virologie MeSH
- látky proti HIV terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory jater epidemiologie MeSH
- následné studie MeSH
- oportunní infekce doprovázející AIDS farmakoterapie virologie MeSH
- prospektivní studie MeSH
- tenofovir terapeutické užití MeSH
- virus hepatitidy B imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- lenvatinib, cabozantinib,
- MeSH
- analýza přežití MeSH
- hepatocelulární karcinom * epidemiologie farmakoterapie imunologie mortalita MeSH
- imunoterapie metody MeSH
- inhibitory proteinkinas farmakologie škodlivé účinky terapeutické užití MeSH
- ipilimumab aplikace a dávkování MeSH
- kombinovaná farmakoterapie MeSH
- lidé MeSH
- nivolumab aplikace a dávkování MeSH
- protinádorové látky farmakologie škodlivé účinky terapeutické užití MeSH
- sorafenib terapeutické užití MeSH
- tyrosinkinasy antagonisté a inhibitory MeSH
- Check Tag
- lidé MeSH
Úvod: Vlastnosti hepatocelulárneho karcinómu (HCC) z rôznych geografických oblastí sú odlišné. Cieľ: Analyzovať kohortu pacientov v nemocnici 3. stupňa. Metodológia: Retrospektívna analýza za sebou idúcich pacientov. Vstupné kritériá: HCC; vylučovacie kritériá: nedostatok dát; interval: roky 2007–2016. Výsledky: Súbor 207 pacientov, 95 % s cirhózou, 76 % mužov; vek 62 rokov. Etiológia hepatálneho ochorenia: Alkohol (ALD) 106 (48 %), hepatitída C 17 %, hepatitída B 13 %, nealkoholová steatohepatitída 10 %, kryptogénna 7 %, necirhotická 4 %, iná 1 %. Diagnóza prostredníctvom surveillance 24 %, bez surveillance 67 %, neznámy spôsob diagnózy 9 %. Priemer ložiska pri diagnóze SUR-HCC 5 cm, bez SUR-HCC 8,6 cm (p = 0,001). BCLC štádium: A – 30 pacientov (15 %), B – 29 %, C – 36 %, D – 20 %; BCLC podľa diagnózy (SUR-HCC vs. non-SUR-HCC): A – 15/49 (31 %) vs. 12/140 (9 %), B 43 vs. 27 %, C – 16 vs. 39 %, D – 10 vs. 25 %. Terapia: Chirurgická resekcia 17 pacientov (7 %), transplantácia pečene 14 (6 %), rádiofrekvenčná ablácia 20 (8 %), transarteriálna chemoembolizácia 60 (24 %), sorafenib 88 (35 %), suportívna starostlivosť 46 (19 %), 3 pacienti sú čakateľmi na transplantaci pečene. Priemerné prežívanie 17 (0,06–112) mesiacov, prežívanie podľa BCLC: A – 37 (2–112), B – 21 (0,6–86), C – 14 (0,06–92), D – 3 (0,06–24) mesiacov. Záver: Demografické údaje v našej kohorte sú porovnateľné s krajinami západnej Európy a Severnej Ameriky. ALD bola najčastejšou etiológiou základného ochorenia pečene, 95 % pacientov malo cirhózu. Len 24 % pacientov bolo zachytených prostredníctvom SUR-HCC, preto bol zaznamenaný výrazný posun doprava v BCLC štádiách, čo viedlo k suboptimálnej alokácii radikálnej liečby a následne aj k horšiemu prežívaniu. Súhrnne sú tieto výsledky porovnateľné s údajmi z Európy a Severnej Ameriky.
Introduction: The features of hepatocellular carcinoma (HCC) differ between geographical regions. Aim: To analyze a cohort from a tertiary referral centre. Methodology: The study employed a retrospective analysis of consecutive outpatients. The inclusion criterion was patients with HCC and the exclusion criterion was insufficient data. The study interval was 2007–2016. Results: Cohort 207 patients, 95% with cirrhosis, 76% men; age 62 years. Etiology of liver disease: Alcoholic 106 (48%), hepatitis C 17%, hepatitis B 13%, non-alcoholic steatohepatitis 10%, cryptogenic 7%, non-cirrhotic 4%, other 1%. Diagnosis by surveillance 24%, otherwise 67%, unknown 9%. Diameter if diagnosis by SUR-HCC 5 cm, otherwise 8.6 cm (p = 0,001). BCLC stages: A – 30 patients (15%), B – 29%, C – 36%, D – 20%; BCLC according to diagnosis (SUR-HCC vs. otherwise): A – 15/49 (31%) vs. 12/140 (9%), B – 43 vs. 27%, C – 16 vs. 39%, D – 10 vs. 25%. Treatment: Surgical resection in 17 patients (7%); liver transplantation 14 (6%); radiofrequency ablation 20 (8%); transarterial chemoembolization 60 (24%); sorafenib 88 (35%); best of supportive care 46 (19%), 3 patients were awaiting liver transplantation. Mean survival 17 (0.06–112) months; survival according to BCLC: A – 37 (2–112), B – 21 (0.6–86), C – 14 (0.06–92), D – 3 (0.06–24). Conclusion: The demographics in our cohort resembled those of Western Europe and North America. Alcoholic liver disease was the most common etiology for underlying liver disease; 95% of patients had cirrhosis. Only 24% of cases were detected by SUR-HCC; therefore, a marked shift to the right in the BCLC stage distribution was seen, what resulted in a suboptimal allocation of curative treatments and subsequently to worse survival. The treatment results and the management of HCC in our region are comparable with standard of care in West Europe and North America.
