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Budesonide is a glucocorticoid characterized by its local action, with a low systemic bioavailability. Since the original trial comparing budesonide with prednisone in 2010, it is recommended as an effective alternative for the treatment of non-severe acute or chronic autoimmune hepatitis. In this document, we review the general pharmacologic properties of glucocorticoids, the available evidence for the use of budesonide as first line option for autoimmune hepatitis as well as the safety profile of the drug.

Cytogenetic assessment in myelofibrosis is essential for risk stratification and patient management. However, an informative karyotype is unavailable in a significant proportion of patients. Optical genome mapping (OGM) is a promising technique that allows for a high-resolution assessment of chromosomal aberrations (structural variants, copy number variants, and loss of heterozygosity) in a single workflow. In this study, peripheral blood samples from a series of 21 myelofibrosis patients were analyzed via OGM. We assessed the clinical impact of the application of OGM for disease risk stratification using the DIPSS-plus, GIPSS, and MIPSS70+v2 prognostic scores compared with the standard-of-care approach. OGM, in combination with NGS, allowed for risk classification in all cases, compared to only 52% when conventional techniques were used. Cases with unsuccessful karyotypes (n = 10) using conventional techniques were fully characterized using OGM. In total, 19 additional cryptic aberrations were identified in 9 out of 21 patients (43%). No alterations were found via OGM in 4/21 patients with previously normal karyotypes. OGM upgraded the risk category for three patients with available karyotypes. This is the first study using OGM in myelofibrosis. Our data support that OGM is a valuable tool that can greatly contribute to improve disease risk stratification in myelofibrosis patients.

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., Key Summary Established knowledge on this subject Diarrhoea is a frequent adverse event of sorafenib and its emergence has been associated to better outcomes. What are the significant and/or new findings of this study? Early diarrhoea (e‐diarrhoea) in hepatocellular carcinoma patients treated with sorafenib is an early predictor of dismal evolution.Diarrhoea under sorafenib should not be taken as a predictive parameter of lack of benefit.E‐diarrhoea could be used as clinical biomarker for switching to second‐line therapies.

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.

Inflammatory bowel diseases (IBD) belong to the group of immune-mediated diseases (IMIDs). The effect of associated IMIDs in the prognosis in IBD is nowadays unknown. To describe IMIDs associated to IBD patients and evaluate differences linked to the presence or absence of IMIDs. A unicentric retrospective descriptive study was designed. A cohort of 1,448 patients were categorized according to the presence of IMIDs. Clinical characteristics were obtained from IBD database. Univariate and multivariate analysis were performed. 385 patients were diagnosed with associated IMIDs while 1,063 had no associated IMIDs. A prevalence of 26.6% IMIDs associated to IBD was observed. Asthma, skin psoriasis and rheumatoid diseases were most commonly found. Factors associated to the presence of IMIDs were women (OR 1.48; 95 CI 1.17–1.87) and Crohn’s disease (OR 1.35; 95 CI 1.07–1.70). Patients with associated IMIDs required more immunomodulator (OR 1.61; 95 CI 1.27–2.43) and biological treatment (OR 1.81; 95 CI 1.47–2.43). More surgical risk was observed in multivariate analysis in those patients diagnosed with IMIDs prior to the onset of IBD (OR 3.71; 95% CI 2.1–6.56). We considered the presence of IMIDs a poor prognostic factor and suggest a closer monitoring of these patients.

Purpose To assess the effectiveness, safety, and overall survival (OS) of thermal ablation as upfront treatment of intrahepatic colangiocarcinoma (ICC) in patients with cirrhosis. Materials and Methods This was a retrospective analysis of all biopsy-confirmed ICC in cirrhotic patients treated in the authors’ unit from 2001 to 2017. Baseline characteristics, ablation procedures, and complications were recorded, and time to recurrence (TTR) and OS were calculated. Twenty-seven patients were identified. Seventy percent had Child-Pugh A disease, and most had clinically significant portal hypertension. Median tumor size was 21 mm. Twenty-one cases were uninodular, and 10 were single ≤ 2 cm. Results Complete radiologic necrosis was achieved in 25 cases (92.6%). Median OS was 30.6 months (95% confidence interval [CI], 22.6–46.5), and recurrence was detected in 21 cases (77.8%) with a TTR of 10.1 months (95% CI, 7.7–20.9). In those patients with single ≤ 2-cm ICC, the OS was 94.5 months (95% CI, 11.7–not reached). Differences in OS were statistically significant between patients with single ICC ≤ 2 cm and patients with single ICC > 2 cm (P = .04) and between patients with single ICC > 2 cm and patients with multinodular ICC (P = .02). Only 1 patient had a treatment-related complication. Conclusions Thermal ablation is a safe and effective treatment for ICC in patients with cirrhosis who are not candidates for surgery. The OS is similar to that reported in surgical series, but the initial treatment success is hampered by a high rate of tumor recurrence. Encouraging long-term survival after thermal ablation is achieved in patients with single ≤ 2-cm ICC.

Background & Aims: Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population. Methods: We report a multicenter study comprising patients from Latin America and Europe. Patients treated with sorafenib were enrolled; demographics, dose modifications, adverse events (AEs), treatment duration, and outcome of patients undergoing dialysis were recorded. Results: As of March 2018, 6156 HCC patients were treated in 44 centres and 22 patients were concomitantly under dialysis (0.36%). The median age was 65.5years, 40.9% had hepatitis C, 75% had Child-Pugh A, and 85% were Barcelona Clinic Liver Cancer-C. The median time to first dose modification, treatment duration and overall survival rate were 2.4months (interquartile ranges [IQR], 0.8-3.8), 10.8months (IQR, 4.5-16.9), and 17.5months (95% CI, 7.2-24.5), respectively. Seventeen patients required at least 1 dose modification. The main causes of first dose modification were asthenia/worsening of Eastern Cooperative Oncology Group-Performance Status and diarrhoea. At the time of death or last follow-up, four patients were still on treatment and 18 had discontinued sorafenib: 14 were due to tumour progression, 2 were sorafenib-related, and 2 were non-sorafenib-related AE. Conclusions: The outcomes observed in this cohort seem comparable to those in the non-dialysis population. Thus, to the best of our knowledge, this is the largest and most informative dataset regarding systemic treatment outcomes in HCC patients undergoing dialysis.

Background and aim Safety of regorafenib in hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) has been recently demonstrated. We aimed to assess the survival benefit of regorafenib compared to best supportive care (BSC) in LT-patients after sorafenib discontinuation. Methods This observational multicenter retrospective study included LT-patients with HCC-recurrence who discontinued first-line sorafenib. Group-1 was constituted by regorafenib-treated patients, while control group was selected among patients treated with best supportive care (BSC) due to unavailability of second-line options at the time of sorafenib discontinuation and who were sorafenib-tolerant progressors (group-2). Primary endpoint was overall survival (OS) of group-1 compared to group-2. Secondary endpoints were safety and OS of sequential treatment sorafenib+regorafenib/BSC. Results Among 132 LT-patients who discontinued sorafenib included in the study, 81 patients were sorafenib-tolerant: 36 received regorafenib (group-1) and 45 (group-2) received BSC. Overall, 24 (67%) patients died in group-1 and 40 (89%) in group-2: the median OS was significantly longer in group-1 than in group-2 (13.1 vs 5.5 months; p=0.002). Regorafenib treatment was an independent predictor of reduced mortality (HR 0.37, 95%CI 0.16-0.89, p=0.02). Median treatment duration with regorafenib was 7.0 (95%CI 5.5-8.5) months; regorafenib dose was reduced in 22 (61%) patients for adverse events and discontinued for tumor progression in 93%. The median OS calculated from sorafenib start was 28.8 months (95%CI: 17.6-40.1) in group-1 vs 15.3 months (95%CI: 8.8-21.7) in group-2 (p=0.002). Conclusions Regorafenib is an effective second-line treatment after sorafenib in patients with HCC-recurrence after LT.

Eradication of the hepatitis C virus (HCV) with interferon-free therapies (DAAs) has modified the course of the disease, as the rate of patients with compensated cirrhosis who achieve a sustained virological response exceeds 95%. However, the impact on development of hepatocellular carcinoma (HCC) is currently in dispute. This argument could be divided into different key points: the impact of DAA on rate of HCC recurrence, the temporal link between starting DAAs and HCC recurrence, and finally, the aggressive pattern of HCC. Therefore, the aim of this review is to analyse the available results in this population of patients from a clinical perspective where the risks and benefits of HCV eradication with DAA therapies are evaluated in patients with complete response of HCC.

Summary: The management of hepatocellular carcinoma (HCC) has evolved considerably over the last decade. Surveillance of cirrhotic patients and refinements to imaging techniques have enabled a relevant proportion of patients to be diagnosed at an early stage, when effective therapies are feasible. Resection, transplantation and ablation are all options in patients with early stage HCC. Thus, there is some controversy regarding which is the best treatment approach in challenging scenarios. There have also been major developments in locoregional therapies, particularly in intra-arterial approaches. Finally, the systemic treatment for HCC has changed dramatically following the demonstration of a survival benefit with sorafenib; there are currently several first-line (sorafenib and lenvatinib) and second-line (regorafenib, cabozantinib and ramucirumab) treatments that have shown a survival benefit. Expectations for immune checkpoint inhibitors are high, with the results of the ongoing phase III trials eagerly awaited. In this review we discuss some of the controversies in the management of HCC, focussing in particular on systemic therapy. Keywords: Hepatocelullar carcinoma, Diagnosis, Surgery, Liver transplantation, Locoregional therapy, Systemic therapy

Background The positive results of the REFLECT trial in terms of survival (sorafenib vs lenvatinib) offer a new first-line option for hepatocellular carcinoma. Additionally, the expected results of immunotherapy could change the first-line treatment in hepatocellular carcinoma or the clinical trial design in first and second-line. Aims To evaluate the impact of dermatologic adverse events under sorafenib in hepatocellular carcinoma patients as a clinical marker to predict prognosis and critically evaluate outcomes within trials. Methods A systematic search of original articles published until October 2018 was performed using PubMed/MEDLINE and a meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results A total of 393 studies were identified and 13 articles with 2035 patients (79.5% Child-Pugh-A, 73.2% BCLC-C) were selected for qualitative and quantitative analysis. The main type of dermatologic adverse events was hand-foot skin reaction (47.7%) but other dermatologic adverse events were reported in 31.7% of the cases. Presence of dermatologic adverse events was associated with a lower mortality when compared with those patients without them (pooled Hazard Ratio for the univariate analysis 0.45 (95% CI: 0.38-0.53) and there was no heterogeneity for the analysis (P = 0.511; I2 = 0.0%). Refuting this association would require the future report of 1370 negative studies. Conclusions This meta-analysis shows a clinically meaningful association between dermatologic adverse events and a higher probability of longer survival. These data support the use of dermatologic adverse events in the clinical decision-making when informing the prognosis and when systemic treatment is decided.

Resumen La difusion del conocimiento en hepatologia, y la interaccion entre pares, esta viviendo un cambio disruptivo en los ultimos anos propiciado por las capacidades que ofrecen las redes sociales, que en el ambito sanitario y de investigacion biomedica se estan organizando en Twitter. Estos cambios se han acelerado siguiendo un patron exponencial durante la pandemia de SARS-CoV-2. Este articulo analiza estos cambios y las oportunidades que se estan abriendo en el ambito de la difusion del conocimiento e investigacion en hepatologia.

Background/aim Dermatological adverse events (DAE) in hepatocellular carcinoma (HCC) patients treated with sorafenib predicts better outcome. Some turn into skin lesions (SL) requiring pathology examination. We describe incidence, characteristics and molecular profile of SL in HCC patients treated with sorafenib. Materials and methods SL were prospectively collected in 311 HCC patients who started sorafenib. SL from sorafenib cohort were compared to those from a control patient group selected to match SL type and demographics. HRAS, KRAS and BRAF mutations were analyzed by CAST-PCR, mutated p53 and MAPK pathway activation by immunohistochemistry and immune infiltration by hematoxylin-eosin staining. Results Eighty-eight out of 311 patients developed DAE and 7.4% SL required histological assessment. Most frequent lesions were keratoacanthomas (n = 4), squamous-cell carcinomas (SCC)(n = 5), basal-cell carcinomas (BCC)(n = 3) and seborrheic keratosis (n = 5). HRAS and KRAS mutations were detected in 4 SL, while no mutations showed in control SL. Nuclear pERK immunostaining was identified in 33.3% of cases versus 5.3% of controls. Most SL (90%) from patients with DAE were proliferative with intense immune infiltration (73%). Conclusions The onset of SL and their molecular profile did not impact negatively on patient's prognosis, but intense proliferation of SL may reflect compensatory activation of MAPK pathway and warrants their close monitoring.

Background: Cholangiocarcinoma (CCA) encompasses a heterogeneous group of malignant tumors with dismal prognosis and increasing incidence worldwide. Both late diagnosis due to the lack of early symptoms and the refractory nature of these tumors seriously compromise patients’ welfare and outcomes. Summary: During the last decade, immunotherapy and, more specifically, modulation of immune checkpoints-mediated signaling pathways have been under the spotlight in the field of oncology, emerging as a potential therapeutic approach for the treatment of several cancers, including CCA. Generally, high expression levels of immune checkpoints in patients with CCA have been associated with worse clinical outcomes, particularly with shorter overall survival and relapse-free survival. Thus, immune checkpoint inhibitors (ICIs), which mainly constitute different monoclonal antibodies, have been developed in order to hamper the immune checkpoint-mediated pathways. Interestingly, chemotherapy may increase the expression of immune checkpoints, while other therapeutic approaches such as ablative and targeted therapies may enhance their antitumor activity. In this sense, several clinical trials evaluated the safety and efficacy of ICIs for CCA, both as a monotherapy and in combination with other ICIs or loco-regional and systemic therapies. Additionally, many other clinical trials are currently ongoing and results are eagerly awaited. Here, we summarize the key aspects of immune checkpoint molecules as prognostic factors and therapeutic targets in CCA, highlighting the most recent advances in the field and future research directions. Key Messages: (1) Effective therapeutic approaches for CCA are urgently needed. (2) Expression levels of immune checkpoints in patients with CCA have been proposed to be related with clinical outcomes. (3) Combination of different ICIs may outperform the efficacy of ICI monotherapy for CCA treatment. (4) Recent studies point toward the combination of ICIs and other common therapies, especially chemotherapy, as a promising strategy for treatment of CCA patients.

The ways in which information is shared, regardless of its origin, are constantly undergoing major changes. These shifts affecting how people interact and exchange knowledge have been subject to disruptive changes in recent years, due to the possibilities created by social media. The SARS-CoV-2 pandemic has exponentially accelerated these changes and innovations. In health and biomedical settings, Twitter is a key tool. This document aims to depict and describe the nascent opportunities in the field of knowledge dissemination and research on hepatology.

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. 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. 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. 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. • 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.

We would like to highlight that the non-invasive criteria for HCC diagnosis, defined by the presence of hyperenhancement in the arterial phase (wash-in) followed by hypoenhancement (wash-out) in venous phases on MRI and/or CT, have been validated by multiple cohort studies and meta-analysis. These criteria are only applicable when the pre-test probability is high (lesions > 1 cm in patients diagnosed of liver cirrhosis or chronic hepatitis B). In addition, for an adequate use of these criteria, other processes such as active (or past) neoplasms must be ruled out. In this scenario, non-invasive criteria have repeatedly demonstrated a diagnostic specificity and positive predictive value close to 100 %. Moreover, we would like to remark the transversality in the consensus of the non-invasive diagnosis of HCC, since not only the hepatology societies recommend its use, but also the oncology and radiology ones.

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.

Objective To determine the diagnostic accuracy and predictive value of gadoxetic acid liver MRI (Gd-EOB-DTPA MRI) alone or in combination with diffusion-weighted imaging (DWI) as a second-line tool for detecting early hepatocellular carcinoma (HCC) recurrence in cirrhotic patients with previous HCC treated with resection or ablation. Methods Between 2014 and 2017, we prospectively included 34 cirrhotic patients with complete response to resection and/or ablation of early HCC in whom a new focal lesion enhancing in the arterial phase without washout was detected during follow-up with EC-MRI. After signing the informed consent, all patients underwent DWI and Gd-EOB-DTPA MRI; two readers analyzed signal intensities on each phase of dynamic study and on DWI. The final diagnosis was established by histology or follow-up EC-MRI. We used cross-tabulation to calculate indices of diagnostic accuracy. Results We evaluated 34 patients (7 women; 73.5% with hepatitis C virus) with a total of 53 new arterial-phase-enhancing foci (median size, 10 [IQR 9-14] mm). The final diagnosis, reached by histopathology in 15 (35.7%) lesions and EC-MR follow-up in 27 (64.3%), was HCC in 42 (79.2%) and benign conditions in 11 (21.8%). Hepatobiliary-phase hypointensity on Gd-EOB-DTPA MRI plus hyperintensity on DWI yielded 54.8% sensitivity, 90.9% specificity, 95.8% positive predictive value, and 34.5% negative predictive value for diagnosing HCC recurrence. Conclusion Among potential indices, combining hypointensity on hepatobiliary-phase Gd-EOB-DTPA MRI and hyperintensity on DWI has the highest specificity and positive predictive value to optimally detect HCC recurrence prior to confident diagnosis by conventional imaging criteria on EC-MRI in cirrhotic liver. Key points • In patients at risk of HCC recurrence, the use of gadoxetic acid liver MRI and DWI may improve the differentiation of unspecific new arterial-enhancing foci from early hypervascular HCC recurrence in patients with non-conclusive findings on extracellular liver MRI. • Combined findings on hepatobiliary-phase gadoxetic acid-enhanced liver MRI and DWI had high specificity (90.9%) and positive predictive value (95.8%) for detecting early hypervascular HCC recurrence, but limited sensitivity. • Combining hepatobiliary-phase hypointensity on gadoxetic acid MRI and hyperintensity on diffusion-weighted imaging allows early diagnosis of hypervascular hepatocellular carcinoma and may help select patients for salvage therapy.

Hepatocellular carcinoma (HCC) appears mainly in patients with underlying liver disease and it is recognized as one of the most important causes of death in this population. Early detection by surveillance has been suggested as an effective tool for reducing cancer-specific mortality and the most accepted strategy is semiannual abdominal ultrasound in those patients at risk of HCC development. The benefit of HCC surveillance is proven by a randomized-controlled study, several prospective or retrospective analyses, and multiple modeling studies and according to the current scientific evidence, surveillance of HCC should be recommended and widely implemented. Major efforts should be done for improving the diagnostic accuracy of the screening tools and for better identifying those patients at risk of HCC development in whom a surveillance program would be cost-effective.

The principal advancements in the treatment of hepatocellular carcinoma (HCC) are the use of new systemic treatments, such as lenvatinib in first-line treatment and regorafenib, cabozantinib, and ramucirumab in second-line treatment, because of their benefits in terms of overall survival. In addition, nivolumab as a second-line agent was approved by the US Food and Drug Administration in 2017 based on improved radiological response data. Physicians and patients alike will greatly benefit from this expanded arsenal of treatments once all these new drugs for the treatment of HCC finally become available. Unfortunately, in our review of the available data, we found a conspicuous lack of approved systemic treatments for HCC in the distinct setting of after liver transplantation (LT). Careful evaluation of the clinical trials for approved systemic treatments of HCC is crucial when considering the best options for those with HCC recurrence after LT. Although several first-line or second-line treatments have been shown to be effective for HCC, each of these trials was composed of its own specific populations, and those with HCC recurrence after LT were excluded. We have also summarized from a critical and clinical point of view the issues involved in the management of patients who are candidates for systemic treatment in this era of multiple drugs for the same indication.

Hepatitis C represents a serious health issue. Approximately 185 million people are infected with the virus and 350,000 people die every year as a consequence of this disease. New direct-acting antiviral agents achieve viral eradication in more that 90 % of the treated patients. More importantly, patients with advanced liver disease or those non-responders to a previous course of treatment with an interferon-based therapy will also have the chance of curing hepatitis C (HCV) infection with these new drugs. In compensated cirrhosis, effective antiviral therapies may improve liver outcomes avoiding the development of clinical decompensation or hepatocellular carcinoma. However, information about the effectiveness and safety of antiviral drugs in patients with more advanced disease (Child-Pugh B or C) is scarce and it is still unclear whether viral eradication translates into an improvement of liver function or cirrhosis regression.

BACKGROUND AND AIMS: Diagnostic yield of Small Bowel Capsule Endoscopy (SBCE) for the assessment of small bowel (SB) lesions is higher than radiologic imaging techniques. However, magnetic resonance enterography (MRE) data are scarce and inconclusive. Colon Capsule Endoscopy (CCE) is a new capsule modality. The primary aim of our study was to compare MRE and capsule endoscopy (CE) for the assessment of Crohn’s disease (CD). The secondary objectives were to compare the diagnostic accuracy of both CE modalities and changes in Montreal classification after each examination. METHODS: We included 47 patients with established (n = 32) or suspected CD (n = 15). MRE was performed first to rule out strictures. In patients with a suspected stricture by MRE, an Agile Patency Capsule was performed. SB disease activity was measured by MaRIA score (MRE) and Lewis Index (CE). RESULTS: SB lesions were found in 36 of47 patients with CE and in 21 of47 patients with MRE (76.6% vs 44.7%, P = 0.001). Jejunal inflammation was detected by CE in 31.9% of patients and by MRE in 6.4% of patients (15/47 vs 3/47; P = 0.03); lesions in ileum were detected in 57.4% of patients by CE, and in 21.3% of patients by MRE (27/ 47 vs 10/ 47; P = 0.04). Finally, in terminal ileum, CE showed lesions in 68.1% (32/47) of patients, whereas MRE detected lesions in 38.3% (18/ 47 patients), (P = 0.001). The original Montreal classification was changed in 53.1% of patients (25/ 47) based on CE findings and in 12.7% of patients (6/47) based on MRE findings (P < 0.05). CONCLUSIONS: In our cohort CE was significantly superior to MRE for detecting SB lesions, mainly superficial and proximal lesions. CE is useful for a appropriate patients’ classification according to Montreal classification.

Sorafenib is the first-line systemic treatment in hepatocellular carcinoma (HCC). The benefits of sorafenib in HCC show an improvement in overall survival and delay of radiologic tumor progression. These benefits were demonstrated in the absence of a high rate of overall response and the magnitude of this improvement varies considerably from patient to patient. Several hypotheses have tried to address the reason for this variability, giving birth to the emerging field of sorafenib resistance. The aim of this chapter is to discuss the clinical evolutionary events such as early dermatologic adverse events, pattern of progression or serum biomarkers modification that have an impact both on the patient’s outcome as well as in the patient’s management. The pattern of progression classifies patients in four different groups: (1) intra-hepatic (2) extra-hepatic increase in tumor size (3) new intra-hepatic lesion and (4) new extra-hepatic lesion and it is correlated with the post-progression overall survival. Hence, careful evaluation of patients characteristics and their evolutionary events during sorafenib treatment are key to identify the best candidates to continue on sorafenib, those who should receive regorafenib as second-line treatment, second-line trials or best supportive care. In addition, the design of second- and third-line clinical trials should consider all the components discussed in this chapter.

Biliary complications after liver transplantation (LT) are an important cause of morbidity and mortality. In most cases, an anastomosis of the bile duct is performed as a duct-to-duct reconstruction, which makes endoscopic therapy with endoscopic retrograde cholangiography (ERC) feasible. Biliary anastomotic strictures (AS) are the most common cause of biliary complications. The early detection of an AS, which can sometimes be challenging given that its clinical presentation is often subtle, is of key importance to obtain high treatment success. In this review, we focus on the management of AS after LT with a special emphasis on ERC.