Liver and spleen stiffness and other noninvasive methods to assess portal hypertension in cirrhotic patients: a review of the literature.

Portal hypertension (PH) is one of the most important causes of morbidity and mortality in patients with chronic liver disease. PH measurement is crucial to stage and predict the clinical outcome of liver cirrhosis. Measurement of hepatic vein pressure gradient is considered the gold standard for assessment of the degree of PH; however, it is an invasive method and has not been used widely. Thus, noninvasive methods have been proposed recently. We critically evaluated serum markers, abdominal ultrasonography, and particularly liver and spleen stiffness measurement, which represent the more promising methods to stage PH degree and to assess the presence/absence of esophageal varices (EV). A literature search was carried out on MEDLINE, EMBASE, Web of Science, and Scopus for articles and abstracts. The search terms used included 'liver cirrhosis', 'portal hypertension', 'liver stiffness', 'spleen stiffness', 'ultrasonography', and 'portal hypertension serum biomarker'. The articles cited were selected on the basis of their relevance to the objective of the review. The results of available studies indicate that individually, these methods have a mild accuracy in predicting the presence of EV, and thus they cannot substitute endoscopy to predict EV. When these tests were used in combination, their accuracy increased. In addition to the PH staging, several serum markers and spleen stiffness measurement can predict the clinical outcome of liver cirrhosis with a good accuracy, comparable to that of hepatic vein pressure gradient. In the future, noninvasive methods could be used to select patients requiring further investigations to identify the best tailored clinical management.

Measurement of spleen stiffness to evaluate portal hypertension and the presence of esophageal varices in patients with HCV-related cirrhosis.

BACKGROUND & AIMS: The hepatic vein pressure gradient (HVPG) is the standard used to determine the degree of portal hypertension (PH) and an important prognostic factor for patients with cirrhosis; HVPG values correlate with the presence of esophageal varices (EV). However, HVPG can only be accurately determined at specialized centers; noninvasive methods are needed to predict HVPG values and the presence of EV. We compared the diagnostic performance of spleen stiffness (SS) measurement by transient elastography with that of liver stiffness (LS) and of other recently proposed noninvasive tests. METHODS: We measured SS and LS in 100 consecutive patients with hepatitis C virus-induced cirrhosis. Patients were also assessed by FibroScan, HVPG, esophagogastroduodenoscopy, and liver biopsy. We also analyzed LS-spleen diameter to platelet ratio score and platelet count to spleen diameter. RESULTS: SS and LS were more accurate than other noninvasive parameters in identifying patients with EV and different degrees of PH. A linear model that included SS and LS accurately predicted HVPG values (R(2) = 0.85). The results were internally validated using bootstrap analysis. CONCLUSIONS: Measurement of SS can be used for noninvasive assessment and monitoring of PH and to detect EV in patients with hepatitis C virus-induced cirrhosis.

Gut microbiota and its pathophysiology in disease paradigms.

The gut flora carries out important functions for human health, although most of them are still unknown, and an alteration of any of them, due to a condition of dysbiosis, can lead to relevant pathological implications. Commensal bacteria in the gut are essential for the preservation of the integrity of the mucosal barrier function and an alteration in the anatomic functional integrity of this barrier has been implicated in the pathophysiologic process of different diseases. The gut microflora plays a role in modulating the intestinal immune system; in fact, it is essential for the maturation of gut-associated lymphatic tissue, the secretion of IgA and the production of antimicrobial peptides. The enteric flora represents a potent bioreactor which controls several metabolic functions, even if most of them are still unknown. The main metabolic functions are represented by the fermentation of indigestible food substances into simple sugars, absorbable nutrients, and short-chain fatty acids. Furthermore, the gut microbiota exerts important trophic and developmental functions on the intestinal mucosa. This overview focuses briefly on the physiological role of the gut microbiota in maintaining a healthy state and the potential role played by disturbances of both the function and composition of the gut microbiota in determining important pathological conditions, such as irritable bowel syndrome, inflammatory bowel disease, metabolic syndrome, obesity, and cancer.

Non-invasive methods can predict oesophageal varices in patients with biliary atresia after a Kasai procedure.

BACKGROUND: After a Kasai procedure, 70% of patients with biliary atresia develop chronic liver disease with portal hypertension and oesophageal varices. AIMS: To investigate the role of new non-invasive parameters in predicting the presence of varices in patients with biliary atresia after a Kasai procedure and to identify the cut-off values of these parameters in predicting the presence of varices. METHODS: 31 patients with biliary atresia who had undergone a Kasai portoenterostomy were studied. Clinical, biochemical and abdominal ultrasound examination, liver stiffness measurement (LSM), LSM-spleen diameter to platelet ratio score (LSPS) and upper digestive endoscopy were performed. RESULTS: 15 (47%) patients had oesophageal varices (Group A) and 16 had no varices (Group B). Median values of LSM (kPa) and LSPS were significantly higher in Group A than in Group B (LSM: 17.0 vs. 7.5, respectively; p=0.0001; LSPS: 19.62 vs. 2.94, respectively; p=0.0001). The optimal cut-offs for predicting oesophageal varices were: LSM>10.6 kPa (sensitivity: 87%, specificity: 87.5%, PPV: 87%, NPV: 87.5%, and AUC: 0.92) and LSPS ≥9.2 (sensitivity: 91%, specificity: 92%, PPV: 91%, NPV: 92%, and AUC: 0.96). CONCLUSIONS: Non-invasive methods can predict the presence of oesophageal varices in patients with biliary atresia; the sequential use of two non-invasive methods improves accuracy.

Pre-operative liver biopsy in cirrhotic patients with early hepatocellular carcinoma represents a safe and accurate diagnostic tool for tumour grading assessment.

BACKGROUND & AIMS: Knowledge of pre-operative tumour grade is crucial in the management of hepatocellular carcinoma (HCC) because it can influence recurrence and survival after surgery. The accuracy of pre-operative needle core biopsy (NCB) in tumour grading has been assessed in only a few studies with conflicting results. Our aim was to determine the long-term safety and the overall accuracy of NCB in assessing tumour grading in subjects who had undergone liver resection for a single HCC. METHODS: Eighty-one cirrhotic patients with HCC who had undergone NCB before liver resection were selected. Only patients with a single HCC and with at least a five-year-follow-up were included. Tumour grading was scored according to a modified Edmondson-Steiner classification: well/moderately (low grade) vs poorly-differentiated (high grade). RESULTS: In the 81 patients with a solitary HCC (mean size 4.1 ± 2.3cm) tumour grade was correctly identified by NCB in 74 out of 81 (91.4%) HCCs. NCB overall sensitivity and specificity were 65% and 98.1%, respectively, with a PPV of 92% and an NPV of 91%. No major complications (in particular tumour seeding) were observed. The overall survival rates at 1, 3, and 5 years were 83%, 62%, and 44%, respectively; the recurrence rate after a 5-year-follow-up was 56.2% for low grade and 82.3% for high grade tumours (p<0.007). CONCLUSIONS: Pre-operative NCB can be performed on early (<5 cm) HCC cirrhotic patients because it provides histologically useful information for HCC management with good accuracy and a low complication rate.