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.
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.
•The diagnostic accuracy of SSM by 2D-SWE in detecting HRV has not been validated.•SSM by 2D-SWE showed excellent accuracy in predicting HRV in cirrhosis.•The proposal of a specific SSM threshold for ...ruling out HRV is still unsafe.•Large and well-designed studies are needed in order to specify this issue.
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.
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.
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.
Our meta-analysis supports that SSM by 2D-SWE has a good diagnostic performance for ruling out HRV in cirrhosis.
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.
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.
Background and aim
The aim of this study is to evaluate the performance of 2D-shear wave elastography (2D-SWE) in patients with nonalcoholic fatty liver disease (NAFLD) and compare it to transient ...elastography.
Methods
Over 6 months, 552 patients with NAFLD underwent liver stiffness measurement (LSM) by both 2D-SWE and transient elastography with controlled attenuation parameter (CAP) at the same visit.
Results
LSM was not feasible by transient elastography (M/XL probe) in 18 (3.3%) and by 2D-SWE in 26 (4.7%) patients. The median LSM of transient elastography was 5.5 (2.8–75) kPa and of 2D-SWE 6.2 (3.7–46.2) kPa. LSMs by transient elastography and 2D-SWE were correlated regardless of the obesity status (
r
, 0.774;
P
< 0.001;
r
, 0.774;
P
< 0.001;
r
, 0.75;
P
< 0.001 in BMI <25, 25–30 and ≥30 kg/m
2
respectively), or the degree of liver steatosis (
r
= 0.63;
P
< 0.001 and
r
= 0.743;
P
< 0.001 in mild and moderate/severe steatosis, respectively). According to transient elastography, 88 (15.9%) patients were classified with at least severe fibrosis (≥F3) and 55 (10%) with cirrhosis. By using the 2D-SWE, 85 (15.4%) patients had at least severe fibrosis and 52 (9.4%) cirrhosis. The correlation between the two methods was strong in patients with at least severe fibrosis (
r
, 0.84;
P
< 0.001) or cirrhosis (
r
, 0.658;
P
< 0.001). When transient elastography was used as reference, 2D-SWE showed an excellent accuracy of 98.8 and 99.8% in diagnosing severe fibrosis and cirrhosis, respectively.
Conclusions
In NAFLD, 2D-SWE and transient elastography have comparable feasibility and clinical applicability providing LSMs with strong correlation, even in overweight/obese patients, independently of the severity of liver steatosis and fibrosis. Thus, either of the two methods can be effectively used for the assessment of fibrosis in this setting.
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.
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.
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 (
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 (
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.
BackgroundWe estimated the frequency of cirrhotic cardiomyopathy (CCM) using all of the proposed diagnostic criteria, to describe the whole spectrum of cardiac alterations, and to investigate the ...role of stress in unmasking latent cases of CCM.MethodsNinety consecutive patients were recruited. CCM was evaluated using the Montreal, the American Society of Echocardiography 2009 criteria, and the 2019 modified criteria of the CCM consortium. A dobutamine stress test was also performed.ResultsLeft ventricular diastolic dysfunction (LVDD) was identified in 72 (80%), 36 (40%), and 10 (11.1%) patients based on the above criteria, respectively. None of the patients had right ventricular systolic dysfunction, either at rest or after stress. The dobutamine stress test revealed left systolic dysfunction in 4 (4.5%) patients. There was agreement among the 3 criteria that the presence of LVDD was not associated with the severity of liver disease, using Child-Pugh stage. However, patients with Child-B/C had longer QTc intervals (P=0.004), higher levels of brain natriuretic peptide (P=0.016), and greater echocardiographic E/e' ratio (P<0.001) and E/e'(s) (P=0.003), compared to Child-A patients, while a significant correlation was demonstrated between Child-Pugh score and E/e' (P<0.001), or E/e'(s) (P=0.002).ConclusionsThe prevalence of LVDD seems to be lower than previously considered. Right ventricular function seems to remain unimpaired. A dobutamine stress uncovered only a small percentage of patients with left systolic dysfunction. Nevertheless, the aggravation of several sonographic variables during stress, particularly in Child-B/C patients, potentially indicates a higher risk for clinical heart failure during stressful invasive interventions.