Incidence of primary hepatitis C infection among people who inject drugs during 2012-2020 in Athens, Greece.

One of the World Health Organization's targets for the 2030 viral hepatitis elimination strategy is to reduce new hepatitis C (HCV) infections. In Athens, Greece, people who inject drugs (PWID) have a high HCV prevalence, with increasing trends since the 2000s. This analysis aims to assess primary HCV incidence among PWID during 2012-2020. Two community-based interventions were implemented in 2012-2013 and 2018-2020 with repeated sero-behavioural surveys in each period. Participants enrolled in multiple surveys were identified through linkage. To assess trends in HCV transmission, three indicators were estimated: (i) anti-HCV prevalence among 'new' injectors (those injecting ≤2 years), (ii) indirect HCV incidence among 'new' injectors, assuming infection occurred at the midpoint between initiating injection and the first positive test, and (iii) HCV incidence from repeat participants. There were 431 and 125 'new' injectors, respectively, in 2012-2013 and 2018-2020. Αnti-HCV prevalence [95% CI] declined from 53.6% [48.8%, 58.3%] in 2012-2013 to 40.0% [31.3, 49.1%] in 2018-2020 (25.4% reduction, p = .007). The indirect estimate [95% CI] of HCV incidence among 'new' injectors decreased from 56.1 [49.3, 63.8] to 39.0/100 person-years (PYs) [29.6, 51.5] (30.5% reduction, p = .020). HCV incidence [95% CI] based on seroconversions in repeat participants (16/63 in 2012-2013 and 9/55 in 2018-2020) declined from 64.6 [39.6105.4] to 13.8/100 PYs [7.2, 26.5], respectively (78.6% reduction, p < .001). Primary HCV incidence remains high among PWID in Athens. Consistent implementation of combined interventions, including high-coverage harm reduction programs and initiatives tailored to increase access to HCV treatment, is essential to sustain the declining trends documented during 2012-2020.

HERACLIS-HDV cohort for the factors of underdiagnosis and prevalence of hepatitis D virus infection in HBsAg-positive patients.

BACKGROUND AND AIMS: Hepatitis D virus (HDV) underdiagnosis remains common. We assessed the HDV screening and prevalence rates in HBsAg-positive patients seen at tertiary liver centres throughout Greece as well as factors affecting HDV diagnosis. METHODS: All adult HBsAg-positive patients seen within the last 5 years were included. Non-screened patients who visited or could be recalled to the clinics over a 6-month period were prospectively tested for anti-HDV. RESULTS: Of 5079 HBsAg-positive patients, 53% had anti-HDV screening (41% before and 12% after study initiation). Pre-study (8%-88%) and total screening rates (14%-100%) varied widely among centres. Screening rates were associated with older age, known risk group, elevated ALT, centre location and size and period of first visit. Anti-HDV prevalence was 5.8% without significant difference in patients screened before (6.1%) or after study initiation (4.7%, p = 0.240). Anti-HDV positivity was associated with younger age, parenteral drug use, born abroad, advanced liver disease and centre location. Overall, HDV RNA detectability rate was 71.6% being more frequent in anti-HDV-positive patients with elevated ALT, advanced liver disease and hepatitis B therapy. CONCLUSIONS: Anti-HDV screening rates and recall capabilities vary widely among Greek liver clinics being higher in HBsAg-positive patients of known risk group with active/advanced liver disease seen at smaller centres, while non-medical factors are also important. Anti-HDV prevalence varies throughout Greece being higher in patients born abroad with younger age, parenteral drug use and advanced liver disease. Viremia is more frequently but not exclusively detected in anti-HDV-positive patients with elevated ALT and advanced liver disease.

Spleen stiffness can predict liver decompensation and survival in patients with cirrhosis.

BACKGROUND AND AIM: Liver stiffness measurement (LSM) has been predicting liver decompensation and survival in cirrhotics. The aim of our study was to investigate if spleen stiffness measurement (SSM) by 2D shear-wave elastography could predict better the probability of decompensation and mortality, compared with LSM and other parameters. METHODS: Consecutive cirrhotic patients were recruited between 1/2017 and 12/2021. LSM and SSM were performed at baseline and epidemiological, clinical, and laboratory data were collected. Clinical events were recorded every 3 months. RESULTS: Totally, 177 patients were followed for a mean period of 31 ± 18 months. In Cox regression analysis, only SSM was independently associated with the probability of decompensation (HR: 1.063, 95% CI: 1.009-1.120; P = 0.021), offering an AUROC of 0.710 (P = 0.003) for predicting 1-year liver decompensation (NPV: 81.1% for the cut-off point of 37 kPa). The occurrence of death/liver transplantation was independently associated only with higher SSM (HR: 1.043; 95% CI:1.003-1.084; P = 0.034). The AUROC of SSM for predicting 1-year death/liver transplantation was 0.72 (P = 0.006) (NPV: 95% for the cut-off of 38.8 kPa). The performance of SSM to predict the 1-year death/liver transplantation increased in high-risk patients (CTP: B/C plus MELD >10 plus LSM > 20 kPa), giving an AUROC of 0.80 (P < 0.001). Only 1/26 high-risk patients with SSM < 38.8 kPa died during the first year of follow-up (NPV: 96.4%). CONCLUSIONS: SSM was the only factor independently associated with the probability of decompensation and occurrence of death, showing better diagnostic accuracy for the prediction of 1-year decompensation or death compared with LSM and MELD score.

Comparative Utility of Transient and 2D Shear Wave Elastography for the Assessment of Liver Fibrosis in Clinical Practice.

The aim of the study was to investigate the feasibility and correlation of liver stiffness measurements (LSM) between 2D-shear wave elastography (2D-SWE) and transient elastography (TE) in patients with chronic liver disease. Over 4 months, 421 patients with chronic liver disease of any cause underwent LSM by 2D-SWE and TE (M and/or XL probe) and controlled attenuation parameter at the same visit. LSM was not feasible by TE in 16 (3.8%) and by 2D-SWE in 17 (4.0%) patients. Median LSM were 8.9 and 8.7 kPa with TE and 2D-SWE, respectively, having a strong correlation (r = 0.774, p < 0.001) in the total cohort and in any cause of liver disease (r = 0.747-0.806, p < 0.001). There was a strong agreement on diagnosis of severe fibrosis (k-statistic: 0.841, p < 0.001) or cirrhosis (k-statistic: 0.823, p < 0.001). Both methods had increased failure rates in patients with obesity and/or increased waist circumference. Among 104 obese patients, TE was more feasible than 2D-SWE (92.3% vs 85.6%, p < 0.001]. LSM by 2D-SWE are strongly correlated to LSM by TE independently of the etiology of chronic liver disease, stage of fibrosis, degree of liver steatosis, and patients' characteristics. TE with the XL probe may be superior in a minority of obese patients.

Role of Spleen Stiffness Measurement by 2D-Shear Wave Elastography in Ruling Out the Presence of High-Risk Varices in Cirrhotic Patients.

BACKGROUND AND AIM: To evaluate if spleen stiffness measurement (SSM) can rule out the presence of high-risk varices in patients with cirrhosis, avoiding an upper gastrointestinal endoscopy (UGE). METHODS: We enrolled 71 cirrhotic patients irrespective of liver disease's etiology. 2D shear wave elastography (SWE) of spleen and UGE was performed. High-risk varices (HRV) were defined as esophageal varices ≥ 5 mm and/or red spots and any gastric varices. RESULTS: Esophageal varices were documented in 37 (52.1%) and HRV in 25 (35.2%) patients. SSM was not technically feasible in 7/71 patients (9.8%). From the remaining 64 patients, when those with cholestatic liver disease were excluded (n = 17), SSM < 35.8 kPa was found to exclude well the existence of HRV offering an AUROC of 0.854 (p < 0.001), sensitivity 88.9%, negative predictive value (NPV) 91.3%, specificity 72.4%, and positive predictive value (PPV) 66.7%. Only 2/47 patients (4.3%) were misclassified, and 23 (48.9%) could avoid endoscopy. In the total cohort of 64 patients, SSM < 33.7 kPa was found to exclude well the presence of HRV offering AUROC 0.792 (p < 0.001), sensitivity 91.7%, specificity 60%, NPV 92.3%, and PPV 57.9%. The misclassification rate was 3.1% (2/64), while 26/64 (40.6%) could avoid endoscopy. CONCLUSIONS: 2D-SWE of spleen is a reliable method for ruling out the presence of HRV in cirrhotic patients. If larger studies confirm our results, a large number of endoscopies could be avoided.

Recent advances in cirrhotic cardiomyopathy.

Cirrhotic cardiomyopathy, a cardiac dysfunction presented in patients with cirrhosis, represents a recently recognized clinical entity. It is characterized by altered diastolic relaxation, impaired contractility, and electrophysiological abnormalities, in particular prolongation of the QT interval. Several mechanisms seem to be involved in the pathogenesis of cirrhotic cardiomyopathy, including impaired function of beta-receptors, altered transmembrane currents, and overproduction of cardiodepressant factors, like nitric oxide, tumor necrosis factor α, and endogenous cannabinoids. Diastolic dysfunction is the first manifestation of cirrhotic cardiomyopathy and reflects the increased stiffness of the cardiac mass, which leads to delayed left ventricular filling. On the other hand, systolic incompetence is presented later, is usually unmasked during pharmacological or physical stress, and predisposes to the development of hepatorenal syndrome. The prolongation of QT is found in about 50 % of cirrhotic patients, but rarely leads to fatal arrhythmias. Cirrhotics with blunted cardiac function seem to have poorer survival rates compared to those without, and the risk is particularly increased during the insertion of transjugular intrahepatic portosystemic shunt or liver transplantation. Till now, there is no specific treatment for the management of cirrhotic cardiomyopathy. New agents, targeting to its pathogenetical mechanisms, may play some role as future therapeutic options.

Transjugular intrahepatic portosystemic shunt for recompensating decompensated cirrhosis?

Transjugular intrahepatic portosystemic shunt (TIPS) is a medical procedure that has been used to manage variceal bleeding and ascites in patients with cirrhosis. It can prevent further decompensation and improve the survival of high-risk decompensated patients. Recent research indicates that TIPS could increase the possibility of recompensation of decompensated cirrhosis when it is combined with adequate suppression of the causative factor of liver disease. However, the results of the studies have been based on retrospective analysis, and further validation is required by conducting randomized controlled studies. In this context, we highlight the limitations of the current studies and emphasize the issues that must be addressed before TIPS can be recommended as a potential recompensating tool.

Evaluation of spleen stiffness by 2D shear wave elastography for ruling out high risk varices in patients with chronic advanced liver disease. A systematic review and meta-analysis.

OBJECTIVES: To systematically review the accuracy of spleen stiffness measurement (SSM) by 2D- Shear Wave Elastography (2D-SWE) in predicting high risk for bleeding varices (HRV) in cirrhotic patients. METHODS: PubMed, Embase, Web of Science, Medline, Cochrane, and Google Scholar databases were searched up to 31/05/2023 for all human studies using 2D-SWE to estimate SSM and endoscopy to detect HRV. Meta-analysis was performed using a generalized linear mixed model. Publication bias was evaluated using the funnel plot asymmetry test. The Area Under the Summarized Receiver Operating Characteristic curve (AUSROC) was estimated using the "mada" package. RESULTS: A total of 13 studies and 1970 patients were included. Of them, 27.8 % had HRV. The pooled sensitivity and polled specificity of SSM in detecting HRV were 90 % (95 %CI:87-92 %) and 68 % (95 %CI:58-77 %), respectively, with an AUSROC at 0.86 (95 %CI:0.82-0.90). The median cutoff value of SSM in detecting HRV was 34.2 kPa. In studies including exclusively HBV cirrhotic patients, SSM's polled sensitivity and specificity in predicting HRV was 88 % (95 %CI:82-92 %) and 73 % (95 %CI:68-78 %), respectively. The AUSROC was 0.84 (95 %CI:0.81-0.87). The number of repeated measurements per patient (<5 or ≥ 5) did not affect the method's capability. Using Aixplorer to evaluate SSM had a higher sensitivity in ruling out HRV than other 2D-SWE devices. CONCLUSIONS: Our meta-analysis supports that SSM by 2D-SWE has a good diagnostic performance for ruling out HRV in cirrhosis.

Folic Acid and Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) remain a major cause of morbidity. This narrative mini-review aimed to investigate the potential role of folic acid (FA) in DFUs. Individuals with DFUs exhibit lower levels of FA and lower daily intake, compared to those without DFUs. There is preliminary evidence that FA administration may contribute to improved DFUs healing. In this context, regular evaluation of dietary FA intake may prove important towards reduction or even prevention of DFUs. However, data are still limited and further research is required to enable definitive conclusions and any recommendations.

Female-specific risk factors for cardiovascular disease: an update.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. While it was previously believed that men have greater susceptibility to CVD, recent research suggests that women face an increased risk of CVD after the onset of menopause, primarily due to the loss of the protective effects of estrogens. Premature ovarian insufficiency (POI), polycystic ovarian syndrome (PCOS), and gestational factors, such as gestational diabetes mellitus (GDM), recurrent pregnancy loss, preterm delivery, and preeclampsia, are specific reproductive disorders that may contribute to an elevated risk of CVD at earlier ages, i.e., before the onset of menopause. This suggests that women with these conditions should be closely monitored for CVD risk factors even before reaching menopause. Such early intervention may help reduce the incidence of CVD and improve overall cardiovascular health in this population. The precise pathophysiological mechanism underlying the development of CVD in women with menopause, premature POI, PCOS, and gestational factors remains elusive. This review article seeks to elucidate the latest research on the relationship between these conditions and CVD in women, aiming to explore the underlying pathogenic mechanisms contributing to this association.

Gonadal dysfunction in women with diabetes mellitus.

It is well known that both type 1 and type 2 diabetes mellitus (DM) are related to increased risk for cardiovascular (CV) and chronic kidney disease (CKD). However, besides these prominently presented complications, DM has also been associated with reproductive dysfunctions. It seems that these disorders are met in up to 40% of women with DM and consist of delayed menarche, all types of menstrual disorders, such as amenorrhea, oligomenorrhea, menstrual irregularity, as well as menorrhagia, infertility, characteristics of polycystic ovary syndrome (PCOS) and early (or rarely late) menopause. In type 1 DM (T1DM), insulin treatment, although it has reduced the rates of insulinopenic-induced hypogonadotropic hypogonadism, an entity commonly presented in many women with the disease in the past decades, when it is used in excess it can also promote hyperandrogenism. Regarding type 2 DM (T2DM), insulin resistance (IR) and hyperinsulinemia have mainly been implicated in the pathogenesis of reproductive dysfunctions, as insulin can act as gonadotropin on the theca cells of the ovary and can lead to hyperandrogenism and inhibition of proper ovulation. This review aims to detail the reproductive dysfunctions associated with DM and provide scientific data to enlighten the underlying pathogenetic mechanisms.

The role of low glycemic index and load diets in medical nutrition therapy for type 2 diabetes: an update.

The increasing prevalence of type 2 diabetes mellitus (T2DM) and its microvascular and macrovascular complications necessitate an optimal approach to prevention and management. Medical nutrition therapy serves as the cornerstone of diabetes care, reducing reliance on diabetic medications for glycemic control and mitigating cardiovascular risk. The broadening field of research in the effect of low glycemic index (GI) and/or glycemic load (GL) diets on individuals with T2DM has yielded promising results in the existing literature. Adopting low-GI and GL dietary patterns contributes to minimizing fluctuations in blood glucose levels, thus presenting a good strategy for achieving enhanced glycemic control. Furthermore, the above dietary practices may offer a viable alternative and practical approach to weight management in individuals with T2DM. However, clinical practice guidelines for diabetes dietary management show inconsistency regarding the certainty of evidence supporting the implementation of low-GI/GL nutritional patterns. This review aims to thoroughly evaluate the available data on the effectiveness of low-GI and low-GL diets in managing glycemic control and reducing cardiovascular risk factors.

Peripheral Neuropathy in Patients with Hepatitis C Infection-Reversibility after HCV Eradication: A Single Center Study.

Chronic hepatitis C virus (HCV) infection is characterized by a variety of extra-hepatic manifestations; peripheral neuropathy (PN) is one of the most common, especially when mixed cryoglobulinemia (MCG) is present. The prevalence and risk factors of HCV-related PN in the absence of MCG are largely unknown. We conducted a prospective, single-center study, examining the prevalence and reversibility of HCV-associated neuropathy in the absence of MCG. Nerve fiber density in the epidermis was evaluated through skin biopsy and electroneurography (ENG) before HCV-treatment initiation and 1 year post sustained virological remission (SVR). Forty HCV-infected individuals (nine HIV co-infected) with no other neuron-harming factors were included; four other HCV mono- and three HIV co-infected individuals were excluded due to presence of diabetes, B12 insufficiency, or neurotoxic drugs. Twelve consecutive controls with no neuron-harming conditions were also recruited; eight more were excluded due to meeting exclusion criteria. Four patients had ENG signs of polyneuropathy (two with HCV mono- and two with HIV co-infection), while seven more (five with HCV mono- and two with HIV co-infection) had signs of mono-neuropathy, leading to PN prevalences of 22.5% and 44% for mono- and co-infection, respectively (p value 0.179). The two patients with HCV mono-infection and polyneuropathy and the one with ulnar nerve damage showed ENG improvement 1 year post SVR. Regarding intraepidermal nerve density, HCV infection, irrespective of HIV co-infection, was correlated with a lower intraepidermal neuron density that improved 1 year post SVR (p value 0.0002 for HCV and 0.0326 for HCV/HIV co-infected patients). PN is common in HCV infection; successful eradication of HCV leads to PN improvement.

Food Cravings and Obesity in Women with Polycystic Ovary Syndrome: Pathophysiological and Therapeutic Considerations.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, constitutes a metabolic disorder frequently associated with obesity and insulin resistance (IR). Furthermore, women with PCOS often suffer from excessive anxiety and depression, elicited by low self-esteem due to obesity, acne, and hirsutism. These mood disorders are commonly associated with food cravings and binge eating. Hypothalamic signaling regulates appetite and satiety, deteriorating excessive food consumption. However, the hypothalamic function is incapable of compensating for surplus food in women with PCOS, leading to the aggravation of obesity and a vicious circle. Hyperandrogenism, IR, the reduced secretion of cholecystokinin postprandially, and leptin resistance defined by leptin receptors' knockout in the hypothalamus have been implicated in the pathogenesis of hypothalamic dysfunction and appetite dysregulation. Diet modifications, exercise, and psychological and medical interventions have been applied to alleviate food disorders, interrupting the vicious circle. Cognitive-behavioral intervention seems to be the mainstay of treatment, while the role of medical agents, such as GLP-1 analogs and naltrexone/bupropion, has emerged.

Elevated FIB-4 Is Associated with Higher Rates of Cardiovascular Disease and Extrahepatic Cancer History in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is often complicated by steatotic liver disease, cardiovascular disease (CVD), and extrahepatic cancer. We investigated whether FIB-4, an indicator of liver fibrosis, is associated with a higher risk of CVD and extrahepatic cancer history in T2DM. METHODS: Two hundred and nine of 244 diabetics admitted to our center in one year were included and retrospectively evaluated. RESULTS: One hundred and fifty-two (72.7%) were males and 57 (27.3%) females. The mean age and FIB-4 were 64.3 ± 11 years, and 1.15 ± 0.5, respectively. One hundred and fifty patients (71.8%) had FIB-4 ≤ 1.3, and 59 (28.2%) had FIB-4 > 1.3. A history of CVD was presented in 76 (36.4%) patients, and of extrahepatic cancer in 39 (18.7%). Patients with CVD were significantly older than those without (68.4 ± 8.5 vs. 63.2 ± 11.5 years; p = 0.002), with significantly higher FIB-4 (1.26 ± 0.5 vs. 1.08 ± 0.5; p = 0.012). Patients with cancer were older, with higher FIB-4 compared to those without (68.2 ± 9.5 vs. 64.4 ± 10.9 years; p = 0.098 and 1.37 ± 0.6 vs. 1.1 ± 0.5; p = 0.004, respectively). FIB-4 > 1.3 was associated with a 2.1-fold probability for CVD (χ2 = 5.810; p = 0.025) and 2.7-fold probability for cancer history (χ2 = 7.603; p = 0.01). CONCLUSIONS: FIB-4 ≥ 1.3 is associated with a higher probability of CVD or extrahepatic cancer history. FIB-4 could potentially discriminate patients at risk, justifying stricter surveillance.

High levels of all-cause mortality among people who inject drugs from 2018 to 2022.

BACKGROUND: Mortality among people who inject drugs (PWID) is high, with overdose and HIV infection being the main causes of death. In Greece, there have been no data on mortality, and two HIV outbreaks have been recorded in this population in the past decade. In this study, we aim to estimate the all-cause crude mortality rate and the standardised mortality ratio in this population during 2018-2022. METHODS: PWID recruited from two community-based programs in Athens and Thessaloniki during 2018-2021 were interviewed and tested for HIV/HCV. Data on vital status (deceased/alive) and date of death were obtained from death registries through December 31, 2022. All-cause crude mortality rates (CMR) and standardised mortality ratios (SMR) were estimated. Determinants of mortality were assessed using Cox proportional-hazards model. RESULTS: Of 2,530 participants, 301 died over 8,543 person-years (PYs) of follow-up. The CMR (95 % CI) was 3.52 (3.15-3.94) deaths per 100 PYs; 3.10 per 100 PYs (2.68-3.58) in Athens and 4.48 per 100 PYs (3.74-5.37) in Thessaloniki. An increasing trend in CMR was identified over 2018-2022 in Athens (from 2.90 to 4.11 per 100 PYs, 41.5 % increase, p = 0.018). The pooled SMR (95 % CI) was 15.86 (14.17-17.76) for both cities and was particularly increased in younger individuals, females, those injecting daily, not enrolled to opioid agonist treatment and HIV-infected individuals. Older age, living in Thessaloniki, Greek origin, homelessness, history of injection in the past 12 months, and HIV infection were independently associated with higher risk of death. CONCLUSION: Mortality among PWID in the two largest cities (Athens and Thessaloniki) in Greece in 2018-2022 was high, with the population in Thessaloniki being particularly affected. The increasing trend in mortality in Athens may reflect the long-term impact of the COVID-19 pandemic. Preventive programs such as take-home naloxone, screening and treatment for HIV, are urgently needed.

Frequency and severity of cirrhotic cardiomyopathy and its possible relationship with bacterial endotoxemia.

BACKGROUND: The cardiac dysfunction presented in cirrhotic patients is already known as cirrhotic cardiomyopathy. The pathogenesis of this entity is not fully understood. AIMS: The aim of this study was to evaluate the frequency and characteristics of cirrhotic cardiomyopathy and to investigate the possible role of bacterial endotoxemia on its aggravation. METHODS: Forty-five cirrhotics were studied by a tissue Doppler imaging echocardiography at rest and after stress. The diagnosis of left ventricular diastolic dysfunction was based on the latest guidelines of the American Society of Echocardiography, whereas its severity was defined by the E/e'av ratio. Endotoxemia was estimated by measuring the serum levels of lipopolysaccharide-binding protein (LBP) and cytokines. RESULTS: None of the patients had systolic dysfunction, but 17/45 (37.8 %) had a diastolic one. Patients with grade II diastolic dysfunction had significantly longer QTc (p = 0.049), larger left atrium volume (p = 0.013), higher Brain Natriuretic Peptide levels (p = 0.007) and higher LBP levels (p = 0.02), compared to those with normal cardiac function, without differences in the systemic hemodynamics and the cytokines' levels. Moreover, the severity of diastolic dysfunction as reflected by the E/e'av. was significantly correlated with the LBP levels (p = 0.002). On the multivariate analysis, the LBP was independently associated with the presence of diastolic dysfunction. CONCLUSIONS: Cirrhosis is commonly complicated by cardiac dysfunction. Patients with severe cirrhotic cardiomyopathy have higher LBP levels, which are significantly correlated with the degree of diastolic dysfunction. Our findings support a potential role of bacterial endotoxemia on the aggravation of cardiomyopathy in cirrhotic patients.

Systemic Treatment in Intermediate Stage (Barcelona Clinic Liver Cancer-B) Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) represents an entity of poor prognosis, especially in cases of delayed diagnosis. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, patients in BCLC-A are the most suitable for potentially curative treatments (surgery or radiofrequency ablation), whereas those in BCLC-C should be treated only with systemic treatment, as locoregional interventions are ineffective due to the tumor's extensiveness. For patients in the BCLC-B stage, trans-arterial chemoembolization (TACE) is the reference treatment, but the role of systemic treatment has been constantly increasing. As this group of patients is extremely heterogeneous, a case-by-case therapeutic strategy instead of a one-fits-all treatment is certainly required to achieve adequate results against HCC. The decision of selecting among immune checkpoint inhibitors (ICIs), tyrosine kinase inhibitors (TKIs), TACE, or a combination of them depends on the patient's tumor load, the severity of liver dysfunction, the general performance status, and the presence of concomitant extrahepatic diseases. The objective of this review is to critically appraise the recent data regarding the systemic treatment of BCLC-B HCCs, aiming to emphasize its potential role in the management of these difficult-to-treat patients.

Spleen stiffness: a predictive factor of dismal prognosis in liver cirrhosis.

Portal hypertension (PH) is a major complication of liver cirrhosis, as it predisposes to the development of serious clinical manifestations such as ascites, hepatic encephalopathy and variceal bleeding, aggravating the prognosis of patients. Hepatic vein pressure gradient (HVPG) is considered the reference method for the estimation of the presence and severity of PH, but this procedure is available only in specialized centers. Alternatively, many non-invasive methods have been proposed in order to substitute HVPG. Among them, liver stiffness measurement (LSM) has been widely used, as it has been shown to correlate well with HVPG, though this relationship seems to weaken in values of HVPG higher than 12 mmHg, the threshold of serious complications development. Several studies supported the use of spleen stiffness measurement (SSM) instead of LSM, anticipating to a more adequate assessment of this advanced stage of PH. The aim of this paper is to critically appraise and summarize the literature about the role of SSM as a predictive tool of liver decompensation and prognosis, highlighting the strengths and the potential limitations of the studies published so far. EXPERT'S OPINION: The utility of SSM in ruling out high risk for bleeding varices in cirrhotic patients has been demonstrated, driving the Baveno VII consensus to encompass SSM in its last recommendations, though its use in patients with non-viral cirrhosis remains to be validated. We believe that in the near future, SSM alone or combined with other tests, will being used not only for sparing upper endoscopies, but also for predicting decompensation and prognosis in advanced compensated cirrhotic patients, regardless of liver disease's etiology. Herein, we present the data that support this consideration, pointing out these issues that should further be investigated in order to elucidate and intensify the value of SSM in the management of patients with liver cirrhosis.