Ultrasonography as a diagnostic tool for sarcopenia in patients with cirrhosis: Examining the pros and cons.

Sarcopenia has emerged as a significant prognostic factor in liver disease, posing a significant risk to patients in terms of morbidity and mortality. However, the evaluation of skeletal muscle mass and quality remains challenging, as cross-sectional imaging is not a suitable screening tool. In order to better include this crucial variable in the routine risk stratification of patients with chronic liver disease, there is an urgent need for simple and reliable non-invasive diagnostic tools for sarcopenia. Therefore, the use of ultrasound techniques has garnered attention as a promising alternative for detecting sarcopenia and muscle abnormalities. This narrative review aims to provide an overview of the current literature on the use of ultrasound as a diagnostic tool for sarcopenia, with particular focus on patients with cirrhosis, emphasizing its potential limitations and future prospects

Current treatment options of refractory ascites in liver cirrhosis - A systematic review and meta-analysis.

BACKGROUND Refractory ascites is a severe complication of liver cirrhosis and treatment options consist in large volume paracentesis, transjugular intrahepatic portosystemic shunt, alfapump®, peritoneovenous shunt and permanent indwelling peritoneal catheter. AIM Our aim was to assess the efficacy, mortality and complications of each treatment. METHODS We performed a systematic review using Pubmed and Embase. Frequencies were summarized with Comprehensive Meta-Analysis Software. RESULTS Seventy-seven studies were included. In patients with transjugular intrahepatic portosystemic shunt, 1-year mortality was 33% (95% CI 0.29-0.39, I2=82.1; τ2 = 0.37; p<0.001) with lower mortality in newer studies (26% vs. 44%). At 6 months, mortality in patients with alfapump® was 24% (95% CI 0.16-0.33, I2=0.00; τ2 = 0.00; p = 0.83), 31% developed acute kidney injury (95% CI 0.18-0.48, I2=44.0; τ2 = 0.22; p = 0.15). Mortality at 12 months was 44% (95% CI 32%-58%, I2=76.7, τ2 = 0.44, p<0.001) in peritoneovenous shunts and 45% (95% CI 38%-53%, I2=61.4, τ2 = 0.18, p = 0.003) in large volume paracentesis, respectively. Overall mortality in patients with permanent indwelling catheters was 66% (95% CI 33%-89%, I2=82.5, τ2 = 1.57, p = 0.001). DISCUSSION Mortality in patients with transjugular intrahepatic portosystemic shunt was lower in newer studies, probably due to a better patient selection. Acute kidney injury was frequent in patients with alfapump®. Permanent indwelling catheters seemed to be a good option in a palliative setting

Porto-sinusoidal vascular disorder.

It is well established that portal hypertension can occur in the absence of cirrhosis, as reported in patients with immune disorders, infections and thrombophilia. However, similar histological abnormalities primarily affecting the hepatic sinusoidal and (peri)portal vasculature have also been observed in patients without portal hypertension. Thus, the term porto-sinusoidal vascular disorder (PSVD) has recently been introduced to describe a group of vascular diseases of the liver featuring lesions encompassing the portal venules and sinusoids, irrespective of the presence/absence of portal hypertension. Liver biopsy is fundamental for PSVD diagnosis. Specific histology findings include nodular regenerative hyperplasia, obliterative portal venopathy/portal vein stenosis and incomplete septal fibrosis/cirrhosis. Since other conditions including alcohol-related and non-alcoholic fatty liver disease, or viral hepatitis, or the presence of portal vein thrombosis may occur in patients with PSVD, their relative contribution to liver damage should be carefully assessed. In addition to histology and clinical diagnostic criteria, imaging and non-invasive tests such as liver and spleen stiffness measurements could aid in the diagnostic workup. The introduction of PSVD as a novel clinical entity will facilitate collaborative studies and investigations into the underlying molecular pathomechanisms encompassed by this term

Noninvasive Detection of Clinically Significant Portal Hypertension in Compensated Advanced Chronic Liver Disease.

Patients with compensated advanced chronic liver disease have different prognoses depending on the presence of portal hypertension. Current non-invasive diagnostic methods allow identification of clinically significant portal hypertension. Portosystemic collaterals on imaging or liver stiffness of more than 20 to 25 kPa by using transient elastography identifies patients with clinically significant portal hypertension. Patients with liver stiffness of less than 20 kPa and platelet count of greater than 150 g/L can avoid endoscopy. This rule could be expanded using spleen stiffness. Methods to risk stratify for portal hypertension in compensated advanced chronic liver disease and successfully treated chronic hepatitis C and B are subject of research

Transjugular intrahepatic portosystemic shunt in patients with hepatocellular carcinoma: A systematic review.

BACKGROUND/AIMS Transjugular intrahepatic portosystemic shunts (TIPS) in patients with hepatocellular carcinoma (HCC) may improve access to curative therapies, treat portal hypertension (PH)-related complications without worsening liver function, and increase overall survival. Data on the efficacy and safety of TIPS to treat PH complications in HCC patients, as well as the HCC treatment response, were evaluated. METHODS Studies reporting efficacy in controlling bleeding/ascites or response to HCC therapy, safety, and survival in patients with HCC and TIPS were searched systematically on PubMed and Embase. An extraction of articles using predefined data fields and quality indicators was used. RESULTS We selected 19 studies and found 937 patients treated for ascites/bleeding and 177 evaluating HCC treatment response. Over half were under 5 cm and solitary lesions, and most studies included tumours with portal vein thrombosis. Regarding PH studies, TIPS resolved bleeding/ascites in >60% of patients, more effective for bleeding. There were no lethal complications reported and procedural bleeding occurred in 40% rate in half of the studies. CONCLUSIONS In the published studies, TIPS is effective in treating PH complications in patients with HCC. Prospective studies on TIPS placement in patients with HCC are urgently needed to evaluate the efficacy and safety of TIPS in this setting

Bacillus licheniformis BlaR1 L3 Loop Is a Zinc Metalloprotease Activated by Self-Proteolysis

In Bacillus licheniformis 749/I, BlaP β-lactamase is induced by the presence of a β-lactam antibiotic outside the cell. The first step in the induction mechanism is the detection of the antibiotic by the membrane-bound penicillin receptor BlaR1 that is composed of two functional domains: a carboxy-terminal domain exposed outside the cell, which acts as a penicillin sensor, and an amino-terminal domain anchored to the cytoplasmic membrane, which works as a transducer-transmitter. The acylation of BlaR1 sensor domain by the antibiotic generates an intramolecular signal that leads to the activation of the L3 cytoplasmic loop of the transmitter by a single-point cleavage. The exact mechanism of L3 activation and the nature of the secondary cytoplasmic signal launched by the activated transmitter remain unknown. However, these two events seem to be linked to the presence of a HEXXH zinc binding motif of neutral zinc metallopeptidases. By different experimental approaches, we demonstrated that the L3 loop binds zinc ion, belongs to Gluzincin metallopeptidase superfamily and is activated by self-proteolysis

Predictors and management of post-banding ulcer bleeding in cirrhosis: A systematic review and meta-analysis.

BACKGROUND AND AIMS Post-banding ulcer bleeding (PBUB) is an understudied complication of oesophageal varices endoscopic band ligation (EBL). This systematic review with meta-analysis aimed at: (a) evaluating the incidence of PBUB in patients with cirrhosis treated with EBL in primary or secondary prophylaxis or urgent treatment for acute variceal bleeding and (b) identifying predictors of PBUB. METHODS We conducted a systematic review of articles in English published in 2006-2022 using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Searches were made in eight databases including Embase, PubMed and Cochrane Library. Random-effects meta-analysis was used to determine the incidence, mean interval and predictors of PBUB. RESULTS Eighteen studies (9034 patients) were included. The incidence of PBUB was 5.5% (95% CI 4.3-7.1). The mean time for it to occur was 11 days (95% CI 9.94-11.97). Model for End-stage Liver Disease (MELD) score (OR 1.162, 95% CI 1.047-1.291) and EBL done in emergency setting (OR 4.902, 95% CI 2.99-8.05) independently predicted post-ligation ulcer bleeding. Treatment included drugs, endoscopic procedures and transjugular intrahepatic portosystemic shunt. Refractory bleeding was treated with self-expandable metallic stents or balloon tamponade. Mortality was on average 22.3% (95% CI 14.1-33.6). CONCLUSIONS Patients with high MELD score and receiving EBL in an emergency setting are more prone to develop PBUB. Prognosis is still poor and the best therapeutic strategy to address remains to be ascertained

Non-invasive tools for compensated advanced chronic liver disease and portal hypertension after Baveno VII - an update.

Non-invasive tests (NITs) and liver stiffness measurement (LSM) in particular, have entered clinical practice over 20 years ago as point-of-care tests to diagnose liver fibrosis in patients with compensated chronic liver disease. Since then, NITs use has evolved thanks to a large number of studies in all major etiologies of liver disease, and they have become important tools to stratify the risk of portal hypertension and liver-related events. The Baveno VII consensus workshop provided several novel recommendations regarding the use of well-established and novel NITs in the specific setting of portal hypertension screening, diagnosis and follow-up. The Baveno VII expert panels paid special attention to summarizing the existing data into simple clinical rules able to guide clinicians in their practice. The "rule of five" for LSM is a tool to stratify the risk of liver-related events, and LSM alone or in combination with platelet count, can be used now to rule-in and rule-out compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension, as well as to rule-out high-risk varices. Use of NITs in obese subjects with non-alcoholic fatty liver disease (NAFLD) and patients with viral hepatitis C that has been successfully treated, require specific knowledge. This review will update the reader on these aspects