Risk of Treatment Failure and Death after Ablation in Hepatocellular Carcinoma Patients-A Multiparametric Prediction.

BACKGROUND: Ablation is a first-line treatment for Barcelona Clinic Liver Cancer (BCLC)-0/A hepatocellular carcinoma (HCC). However, there are scarce data about patients' outcomes after recurrence. The present study evaluates the impact of patient and tumor characteristics at baseline and at recurrence on the Clinical Decision-Making process. METHODS: We evaluated BCLC-0/A patients treated with percutaneous ablation from January 2010 to November 2018. Clinical and radiological data such as age, tumor location at ablation, pattern of recurrence/progression, and comorbidities during follow-up were registered. Tumor location was divided into 'suboptimal' vs. 'optimal' locations for ablation. The Clinical Decision-Making was based on tumor burden, liver dysfunction, or comorbidities. The statistical analysis included the time-to-recurrence/progression, censoring at time of death, date of last follow-up or liver transplantation, and time-to-event was estimated by the Kaplan-Meier method and Cox regression models to evaluate the risk of an event of death and change of treatment strategy. RESULTS: A total of 225 patients [39.1% BCLC-0 and 60.9% BCLC-A] were included, 190 had unifocal HCC and 82.6% were ≤3 cm. The complete response rate and median overall survival were 96% and 60.7 months. The HCC nodules number (Hazard Ratio-HR 3.1), Child-Pugh (HR 2.4), and Albumin-Bilirubin score (HR 3.2) were associated with increased risk of death during follow-up. HCC in 'suboptimal location' presented a shorter time to recurrence. When comorbidities prevented further loco-regional or systemic treatment, the risk of death was significantly increased (HR 2.0, p = 0.0369) in comparison to those who received treatment. CONCLUSIONS: These results expose the impact of non-liver comorbidities when considering treatment for recurrence after ablation in the real-world setting and in research trials. Ultimately, we identified an orphan population for which effective interventions are needed.

Documento de posicionamiento de la Societat Catalana de Digestologia y la Societat Catalana de Radiologia: ecografía para especialistas en enfermedad digestiva en Catalunya / Joint position statement of the Societat Catalana de Digestologia and the Societat Catalana de Radiologia on gastroenterologist-led ultrasound in Catalonia

Desde hace años y de manera progresiva, la ecografía se ha incorporado en las diferentes especialidades médicas como una herramienta necesaria e indispensable. En patología digestiva la ecografía abdominal a pie de cama o inmediata permite el diagnóstico rápido y/o el seguimiento de distintas patologías intraabdominales. Por otro lado, la ecografía es muy útil como guía en determinados procedimientos intervencionistas dado que comporta una mayor seguridad.A pesar de ser una técnica no invasiva, la ecografía tiene el inconveniente de ser muy operador dependiente, por lo que es necesario garantizar que aquellos profesionales que realicen ecografías dispongan del suficiente nivel de capacitación técnica.En Catalunya, tradicionalmente la ecografía digestiva es una técnica que es llevada a cabo por el servicio de radiología y, todavía no se ha incorporado como herramienta en la especialidad en Ap. Digestivo. En este contexto, la Societat Catalana de Radiologia y la Societat Catalana de Digestologia han considerado necesaria la redacción de un documento marco, consensuado, sobre la utilización y aprendizaje de la ecografía por especialistas en el aparato digestivo.El documento establece: como debería ser la formación, en que indicaciones, que requerimientos mínimos de material y como debe documentarse la exploración para que la ecografía realizada por el especialista de digestivo sea útil y segura.

Over recent years, ultrasonography has been used increasingly in various medical specialties and is now an indispensable diagnostic tool. In gastroenterology, bedside or point-of-care ultrasound allows the early diagnosis and monitoring of multiple intraabdominal conditions. Ultrasound guidance is also highly useful in certain therapeutic procedures, increasing procedural safety.Ultrasound is a non-invasive technique but has the drawback of being very operator dependent. Therefore, it is necessary to ensure that the professionals who perform ultrasonography have a sufficient level of training in the technique.In Catalonia, abdominal ultrasound is usually carried out by radiologists and has not yet been incorporated as an investigation performed by gastroenterologists. In view of this, the Societat Catalana de Radiologia and the Societat Catalana de Digestologia judged it necessary to develop a consensus framework document on ultrasound use and training for gastroenterologists.The document establishes the suggested format for training, the appropriate indications, the minimum material requirements and appropriate documentation of the procedure to ensure that gastroenterologist-performed ultrasound is useful and safe.

Joint position statement of the Societat Catalana de Digestologia and the Societat Catalana de Radiologia on gastroenterologist-led ultrasound in Catalonia. / Documento de posicionamiento de la Societat Catalana de Digestologia y la Societat Catalana de Radiologia: ecografía para especialistas en enfermedad digestiva en Catalunya.

Over recent years, ultrasonography has been used increasingly in various medical specialties and is now an indispensable diagnostic tool. In gastroenterology, bedside or point-of-care ultrasound allows the early diagnosis and monitoring of multiple intraabdominal conditions. Ultrasound guidance is also highly useful in certain therapeutic procedures, increasing procedural safety. Ultrasound is a non-invasive technique but has the drawback of being very operator dependent. Therefore, it is necessary to ensure that the professionals who perform ultrasonography have a sufficient level of training in the technique. In Catalonia, abdominal ultrasound is usually carried out by radiologists and has not yet been incorporated as an investigation performed by gastroenterologists. In view of this, the Societat Catalana de Radiologia and the Societat Catalana de Digestologia judged it necessary to develop a consensus framework document on ultrasound use and training for gastroenterologists. The document establishes the suggested format for training, the appropriate indications, the minimum material requirements and appropriate documentation of the procedure to ensure that gastroenterologist-performed ultrasound is useful and safe.

Liver cancer risk after HCV cure in patients with advanced liver disease without non-characterized nodules.

BACKGROUND & AIMS: Recognition of non-characterized liver nodules (NCLN) prior to direct-acting antivirals (DAAs) is associated with increased hepatocellular carcinoma (HCC) risk in patients with HCV. The risk of HCC has not been defined in F3/F4 patients in whom NCLN have been ruled-out before starting DAAs and at sustained virological response (SVR). This study aimed to estimate HCC incidence in this population. METHODS: We performed a prospective study including HCV-infected patients with F3/F4 fibrosis, without a history of HCC, and who achieved SVR after DAAs. Patients were only included if they had undergone ultrasound imaging that excluded the presence of HCC/NCLN within 30 days after SVR. All patients were evaluated every 6 months until developing primary liver cancer, death or withdrawal of informed consent. HCC incidence was expressed per 100 patient-years (/100PY). Adherence to screening program was calculated every 6 months for the first 48 months. RESULTS: A total of 185 patients (63/122, F3/F4) were included. Among those with cirrhosis, 92% were Child-Pugh A and 42.7% had clinically significant portal hypertension (CSPH). Albumin-bilirubin score was 1 in 84.9% and 2 in 15.1% of patients, respectively. The median clinical and radiologic follow-up was 52.4 months and 48 months, respectively. Ten patients developed HCC: HCC incidence was 1.46/100PY (95% CI 0.79-2.71) in the whole cohort, 2.24/100PY (95% CI 1.21-4.17) in F4 only and 3.63/100PY (95% CI 1.95-6.74) in patients with CSPH. No HCC was registered in patients with F3. Median time between SVR and HCC occurrence was 28.1 months; 12 non-primary liver cancers were also identified. CONCLUSIONS: Patients with cirrhosis without NCLN at SVR remain at risk of HCC development. The absence of HCC in patients with F3 reinforces their marginal cancer risk, but prospective studies are needed to exclude them from screening programs. LAY SUMMARY: Patients with HCV-related cirrhosis, without non-characterized liver nodules at sustained virologic response, remain at risk of hepatocellular carcinoma despite viral cure. However, the cancer risk after successful direct-acting antiviral treatment is marginal in patients with F3 fibrosis without non-characterized liver nodules. If confirmed in larger prospective studies, current screening recommendations may need to be revisited in this group of patients.

Risk of non-tumoural portal vein thrombosis in patients with HCV-induced cirrhosis after sustained virological response.

BACKGROUND & AIMS: Sustained virological response (SVR) to direct-acting antivirals ameliorates portal hypertension, improves hepatic function and may reverse the procoagulant state observed in patients with cirrhosis. However, an unexpected incidence of portal vein thrombosis (PVT) immediately after antiviral therapy has recently been reported. Therefore, we analysed the long-term impact of SVR on the development of non-tumoural PVT. METHODS: Our study comprised of two well-characterized prospective cohorts (hepatitis C virus '(HCV)-Cured': n = 354/'HCV-Active': n = 179) of patients with HCV cirrhosis who underwent standardized ultrasound surveillance. In the main analysis, the event of interest was de novo non-tumoural PVT and events known to modify its natural history (orthotopic liver transplantation, transjugular intrahepatic portosystemic shunt, death, tumoural PVT and anticoagulation) were considered as competing risk. Adjusted models were built using propensity scores for baseline covariates. Moreover, predictive factors were investigated by conventional multivariate analysis. RESULTS: Ten (2.8%) patients in the 'HCV-Cured' cohort developed a non-tumoural PVT during a median follow-up of 37.1 months, while 8 (4.5%) patients in the 'HCV-Active' cohort were diagnosed with non-tumoural PVT during a median follow-up of 42.2 months. High Child-Pugh score was the only independent risk factor for non-tumoural PVT development and stage A patients were at low risk. Importantly, HCV cure did not decrease the risk of non-tumoural PVT in inverse probability of treatment-weighted (IPTW) analysis (subdistribution hazard ratio: 1.31 (95% confidence interval [95% CI]: 0.43-3.97); P = .635). In contrast, SVR was associated with a substantial reduction in mortality (IPTW-adjusted sHR: 0.453 [95% CI: 0.287-0.715]; P < .001). CONCLUSIONS: The risk of non-tumoural PVT persists after HCV cure in patients with cirrhosis, despite improving survival. Even after aetiological cure, severity of liver disease remains the main determinant of non-tumoural PVT development.

Early diarrhoea under sorafenib as a marker to consider the early migration to second-line drugs.

BACKGROUND: Despite atezolizumab and bevacizumab (A + B) is currently the first-line treatment for hepatocellular carcinoma (HCC) patients, some patients will not be adequate for this combination. In the setting of sorafenib some adverse events have been proposed as prognostic factors. OBJECTIVE: To characterize the early diarrhoea development as prognostic factor in 344 HCC patients. METHODS: The development of early diarrhoea in sorafenib treatment defined as patients who developed diarrhoea and needed dose modification within the first 60 days of treatment (e-diarrhoea) and 3-grouping variables were analysed: Patients with e-diarrhoea, patients who developed diarrhoea after the first 60 days of treatment (L-diarrhoea) and patients that never developed diarrhoea (never diarrhoea). RESULTS: The median overall survival in sorafenib treated patients was significantly different across groups (6.8 months for e-diarrhoea, 26.7 months for L-diarrhoea and 13.3 months for never-diarrhoea). The emergence of e-diarrhoea was associated with poor outcomes (hazard ratio [HR] 1.84 [95%CI 1.15-2.95]), while there was no increased/decreased risk of dismal evolution in patients with L-diarrhoea (HR 0.66 [95%CI 0.42-1.03]). CONCLUSION: The emergence of e-diarrhoea in HCC patients treated with sorafenib is an early predictor of dismal evolution under this therapy. Thus, prompt identification of these non-responders may be useful for an early switch to second-line therapies.

Evaluation of LI-RADS 3 category by magnetic resonance in US-detected nodules ≤ 2 cm in cirrhotic patients.

OBJECTIVES: Liver Imaging Reporting and Data System (LI-RADS) for hepatocellular carcinoma (HCC) diagnosis in high-risk patients is a dynamic system, which was lastly updated in 2018. We aimed to evaluate the accuracy for HCC diagnosis of LI-RADS v2018 with magnetic resonance imaging (MRI) with extracellular contrast for solitary nodules ≤ 20 mm detected during ultrasound (US) surveillance in cirrhotic patients, with particular interest in those observations categorized as LI-RADS 3. METHODS: Between November 2003 and February 2017, we included 262 consecutive cirrhotic patients with a newly US-detected solitary ≤ 20-mm nodule. A LI-RADS (LR) v2018 category was retrospectively assigned. The diagnostic accuracy for each LR category was described, and the main MRI findings associated with HCC diagnosis were analyzed. RESULTS: Final diagnoses were as follows: 197 HCC (75.2%), 5 cholangiocarcinoma (1.9%), 2 metastasis (0.8%), and 58 benign lesions (22.1%); 0/15 (0%) LR-1, 6/26 (23.1%) LR-2, 51/74 (68.9%) LR-3, 11/12 (91.7%) LR-4, 126/127 (99.2%) LR-5, and 3/8 (37.5%) LR-M were HCC. LR-5 category displayed a sensitivity and specificity of 64% (95% CI, 56.8-70.7) and 98.5% (95% CI, 91.7-100), respectively. Considering also LR-4 as diagnostic for HCC, the sensitivity slightly increased to 69.5% (95% CI, 62.6-75.9) with minor impact on specificity (96.2%; 95% CI, 89.3-99.6). Regarding LR-3 observations, 51 out of 74 were HCC, 2 were non-HCC malignancies, and 20 out of 21 LR-3 nodules > 15 mm (95.2%) were finally categorized as HCC. CONCLUSIONS: The high probability of HCC in US-detected LR-3 observations (68.9%) justifies triggering an active diagnostic work-up if intended to diagnose HCC at a very early stage. KEY POINTS: • In cirrhotic patients with nodules ≤ 20 mm detected during US surveillance, 51 out of 74 (68.9%) of LR-3 nodules by MRI corresponded to an HCC. • In LR-3 nodules, HCC diagnosis was closely related to baseline tumor size. All 5 nodules smaller than 1 cm were diagnosed as benign. Oppositely, 20 out of 21 LR-3 observations > 15 mm (95.2%) were diagnosed as HCC. • The high probability of HCC in US-detected LR-3 observations justifies triggering an active diagnostic work-up if intended to diagnose HCC at a very early stage.

Next-generation sequencing in the diagnosis of non-cirrhotic splanchnic vein thrombosis.

BACKGROUND & AIMS: Myeloproliferative neoplasms (MPNs) are the most frequent cause of non-tumoural non-cirrhotic splanchnic vein thrombosis (NC-SVT). Diagnosis of MPN is based on blood cell count alterations, bone marrow histology, and detection of specific gene mutations. Next-generation sequencing (NGS) allows the simultaneous evaluation of multiple genes implicated in myeloid clonal pathology. The aim of this study was to evaluate the potential role of NGS in elucidating the aetiology of NC-SVT. METHODS: DNA samples from 80 patients (75 with idiopathic or exclusively local factor [Idiop/loc-NC-SVT] and 5 with MPN and NC-SVT [SVT-MPN] negative for Janus kinase 2 gene [JAK2] [V617F and exon 12], calreticulin gene [CALR], and thrombopoietin gene [MPL] mutations by classic techniques) were analysed by NGS. Mutations involved in myeloid disorders different from JAK2, CALR, and MPL genes were categorised as high-molecular-risk (HMR) variants or variants of unknown significance. RESULTS: In 2/5 triple-negative SVT-MPN cases (40%), a mutation in exon 12 of JAK2 was identified. JAK2-exon 12 mutation was also identified in 1/75 patients with Idiop/loc-NC-SVT. Moreover, 28/74 (37.8%) of the remaining Idiop/loc-NC-SVT had at least 1 HMR variant. Sixty-two patients with Idiop/loc-NC-SVT were not receiving long-term anticoagulation and 5 of them (8.1%) had recurrent NC-SVT. This cumulative incidence was significantly higher in patients with HMR variants than in those without. CONCLUSIONS: NGS identified JAK2-exon12 mutations not previously detected by conventional techniques. In addition, NGS detected HMR variants in approximately one-third of patients with Idiop/loc-NC-SVT. These patients seem to have a higher risk of splanchnic rethrombosis. NGS might be a useful diagnostic tool in NC-SVT. LAY SUMMARY: Next-generation sequencing (NGS) performs massive sequencing of DNA allowing the simultaneous evaluation of multiple genes even at very low mutational levels. Application of this technique in a cohort of patients with non-cirrhotic non-tumoral portal vein thrombosis (NC-SVT) and a negative study for thrombophilic disorders was able to identify patients with a mutation in exon 12 not previously detected by conventional techniques. Moreover, NGS detected High Molecular Risk (HMR)-variants (Mutations involved in myeloid disorders different from JAK2, CALR and MPL genes) in approximately one third of patients. These patients appear to be at increased risk of rethrombosis. All these findings supports NGS as a potential useful tool in the management of NC-SVT.

Pancreatic Insufficiency in Patients Under Sorafenib Treatment for Hepatocellular Carcinoma.

GOALS: To describe the occurrence of malabsorption (MA) in hepatocellular carcinoma (HCC) patients under sorafenib, the potential relationship with pancreatic insufficiency (PI), and the role of pancreatic enzymes supplementation. BACKGROUND: With the increasing options of second-line systemic therapies for HCC, the recognition of drug intolerance using practical tools is crucial. It has been proposed that a MA syndrome could be due to sorafenib-induced pancreatic dysfunction. STUDY: All sorafenib-treated patients with suspicion of MA (defined as decreased stool consistency lasting >4 wk or presenting ≥10% body weight loss without HCC progression) were prospectively evaluated by serum markers, endoscopy, and imaging techniques. RESULTS: We evaluated 81 sorafenib-treated patients and 21 developed MA suspicion (85.7% male, 81.5% Child-Pugh A, 52.4% BCLC-B, and 47.6% BCLC-C) within a median 5.9 months after starting sorafenib. The median treatment duration, follow-up, and overall survival after MA suspicion were 5.9, 20.3, and 20.3 months, respectively. Nine of them (42.9%) presented hyperparathyroidism secondary to vitamin D deficiency and 8 with PI. A gradual decrease in pancreatic volume of up to 19% was observed among patients with PI. Six of the 8 patients with PI received pancreatic enzymes, with complete recovery from MA symptoms and stabilization of pancreatic volume. CONCLUSIONS: We validated the association between MA and PI in 10% of sorafenib-treated patients. Pancreatic enzymes supplementation successfully led to symptomatic recovery. Awareness of this adverse event can help in the management of sorafenib irrespective of cancer type and likely, of other tyrosine kinase inhibitors for HCC patients.

Pharmacokinetics and pharmacogenetics of sorafenib in patients with hepatocellular carcinoma: Implications for combination trials.

BACKGROUND & AIMS: Sorafenib and lenvatinib are the first-line treatments approved in hepatocellular carcinoma (HCC), but information is lacking about the relationships between their pharmacokinetics, patients pharmacogenetic profiles, adverse events (AE) and overall survival. We aimed to elucidate these relationships of tyrosine Kinase Inhibitors, such as sorafenib, in order to improve the design of trials testing it in combination with checkpoint inhibitors. METHODS: We assessed the pharmacokinetics of sorafenib and its N-oxide metabolite at day-0, day-7, day-30, day-60, day-90, day-120, day-150 and day-180 and nine single-nucleotide polymorphisms (SNP) in five genes related to sorafenib metabolism/transport to identify the best point for starting the combination between tyrosine kinases and checkpoint inhibitors. RESULTS: We prospectively included 49 patients (96% cirrhotic, 37% hepatitis-C, 82% Child-Pugh-A and 59% BCLC-C). Pharmacokinetic values peaked at day-7 and progressively declined until day-60. In the 16 patients without further dose modifications after day-60, pharmacokinetic values remained stable through day-180 (sorafenib P = .90; N-oxide P = .93). Pharmacokinetic values were higher in patients with early dermatological adverse events and lower in patients with early diarrhoea. Sorafenib and N-oxide pharmacokinetic values varied linearly with different alleles of MRP2*3972. CONCLUSIONS: Sorafenib's pharmacokinetics is heterogeneous across HCC patients. This heterogeneity affects adverse events development and must be taken into account in setting the dose and timing of its combination with checkpoint inhibitors.

Does transient arterial-phase respiratory-motion-related artifact impact on diagnostic performance? An intra-patient comparison of extracellular gadolinium versus gadoxetic acid.

OBJECTIVE: To compare the frequency of transient arterial-phase respiratory-motion-related artifacts in liver MRI after extracellular gadolinium and gadoxetic acid injection, and to determine the impact of these artifacts on the detection of focal areas of enhancement on arterial-phase images. MATERIALS AND METHODS: Intra-patient comparison of 82 cirrhotic patients who prospectively underwent liver MR with extracellular gadolinium and with gadoxetic acid within 1 month. Two readers independently assessed the quality of dynamic T1-weighted MR images (pre-contrast, arterial, and portal-venous phases), rating respiratory-motion-related artifacts on four-point scale (0 [none]-3 [non-diagnostic]). We dichotomized these assessments, which were compared using McNemar's test, defining transient arterial-phase respiratory-motion-related artifacts as a study with a pre-contrast score < 2 and arterial-phase score ≥ 2. Readers also recorded whether at least one focal area of enhancement ≥ 10 mm on arterial phase was present. RESULTS: The quality of arterial-phase images was worse when obtained after gadoxetic acid than after extracellular gadolinium (p < 0.01), and transient arterial-phase respiratory-motion-related artifacts were more common after gadoxetic acid than after extracellular gadolinium (p < 0.02). At least one area of arterial-phase enhancement ≥ 10 mm was detected more often after extracellular gadolinium than after gadoxetic acid. We observed significant differences on the comparison of the distributions of the presence of arterial-phase artifacts against the presence of arterial-phase enhancement ≥ 10 mm between the two contrast agents (p < 0.0001). CONCLUSION: In cirrhotic patients, transient arterial-phase respiratory-motion-related artifacts are more common after gadoxetic acid than after extracellular gadolinium. Worse detection of arterial-phase enhancement on gadoxetic acid is only partly due to these artifacts. KEY POINTS: • In a patient-by-patient analysis, the quality of arterial-phase liver MR images was significantly worse with gadoxetic acid than with extracellular gadolinium. • The frequency of transient arterial-phase artifacts was significantly higher after gadoxetic acid injection than after extracellular gadolinium injection. • Differences in the detection of areas of arterial-phase enhancement between MRI studies done with extracellular gadolinium and those done with gadoxetic acid might not be related only to image quality.

Time association between hepatitis C therapy and hepatocellular carcinoma emergence in cirrhosis: Relevance of non-characterized nodules.

BACKGROUND & AIMS: Despite direct-acting antivirals being highly effective at eradicating hepatitis C virus infection, their impact on the development of hepatocellular carcinoma (HCC) remains controversial. We analyzed the clinical and radiological outcome of cirrhotic patients treated with interferon-free regimens to estimate the risk of developing HCC. METHODS: This was a retrospective multicenter study focusing on cirrhotic patients treated with direct-acting antivirals until December 2016. Clinical and radiologic characteristics were collected before the start of antiviral therapy, at follow-up and at HCC development. Diagnosis of HCC was centrally validated and its incidence was expressed as HCC/100 person-years. RESULTS: A total of 1,123 patients were included (60.6% males, 83.8% Child-Pugh A) and 95.2% achieved a sustained virologic response. Median time of follow-up was 19.6 months. Seventy-two patients developed HCC within a median of 10.3 months after starting antiviral treatment. HCC incidence was 3.73 HCC/100 person-years (95% CI 2.96-4.70). Baseline liver function, alcohol intake and hepatic decompensation were associated with a higher risk of HCC. The relative risk was significantly increased in patients with non-characterized nodules at baseline 2.83 (95% CI 1.55-5.16) vs. absence of non-characterized nodules. When excluding these patients, the risk remained increased. CONCLUSION: These data expose a clear-cut time association between interferon-free treatment and HCC. The mechanisms involved in the increased risk of HCC emergence in the short term require further investigation. LAY SUMMARY: In this cohort of cirrhotic patients, interferon-free therapies achieved a high rate of sustained virologic response (>95%); however, we reported a risk of de novo hepatocellular carcinoma of 3.73 per 100 person-years and a clear-cut time association with antiviral therapy. The time association between starting direct-acting antivirals and developing hepatocellular carcinoma, together with the association with the presence of non-characterized nodules at baseline ultrasound, suggests that antiviral therapy elicits a mechanism (probably immune-related) that primes the growth and clinical recognition of hepatocellular carcinoma early during follow-up. As a result, short-term liver cancer risk is significantly increased.

Diagnosis and staging of hepatocellular carcinoma (HCC): current guidelines.

One of the key strategies to improve the prognosis of HCC, beside prevention, is to diagnose the tumor in early stages, when the patient is asymptomatic and the liver function is preserved, because in this clinical situation effective therapies with survival benefit can be applied. Imaging techniques are a key tool in the surveillance and diagnosis of HCC. Screening should be based in US every 6 months and non-invasive diagnostic criteria of HCC based on imaging findings on dynamic-MR and/or dynamic-CT have been validated and thus, accepted in clinical guidelines. The typical vascular pattern depicted by HCC on CT and or MRI consists on arterial enhancement, stronger than the surrounding liver (wash-in), and hypodensity or hyposignal intensity compared to the surrounding liver (wash-out) in the venous phase. This has a sensitivity of around 60% with a 96-100% specificity. Major improvements on liver imaging have been introduced in the latest years, adding functional information that can be quantified: the use of hepatobiliary contrast media for liver MRI, the inclusion of diffusion-weighted sequences in the standard protocols for liver MRI studies and new radiotracers for positron-emission tomography (PET). However, all them are still a matter of research prior to be incorporated in evidence based clinical decision making. This review summarizes the current knowledge about imaging techniques for the early diagnosis and staging of HCC, and it discusses the most relevant open questions.