Supersonic shear imaging for the diagnosis of liver fibrosis and portal hypertension in liver diseases: a meta-analysis

Background and aims: The meta-analysis aimed to summarize the technical success rate of supersonic shear imaging (SSI) and to evaluate the diagnostic performance of liver and spleen stiffness measurement (LSM and SSM) with SSI for the detection of liver fibrosis, portal hypertension, and gastroesophageal varices in liver diseases.

Methods: PubMed, EMBASE, and Cochrane Library databases were searched. Technical success rate of SSI was pooled. Area under curve (AUC), sensitivity, and specificity with corresponding 95% confidence interval (CI) were calculated.

Results: Included studies regarding the diagnostic performance of SSI for liver fibrosis, portal hypertension, and esophageal varices numbered 28, 4, and 4 respectively. The pooled technical success rates of LSM and SSM were 95.3% and 75.5%, respectively. The AUC, sensitivity, and specificity of LSM/SSM for different stages of liver fibrosis were 0.85–0.94, 0.7–0.89, and 0.82–0.92, respectively. The AUC, sensitivity, and specificity of LSM were 0.84 (95%CI = 0.8–0.86), 0.79 (95%CI = 0.7–0.85), and 0.82 (95%CI = 0.72–0.88) for clinically significant portal hypertension, 0.85 (95%CI = 0.82–0.88), 0.8 (95%CI = 0.68–0.88), and 0.8 (95%CI = 0.6–0.92) for any varices, and 0.86 (95%CI = 0.83–0.89), 0.86 (95%CI = 0.76–0.92), and 0.61 (95%CI = 0.35–0.83) for high-risk varices, respectively.

Conclusions: LSM with SSI had a high diagnostic accuracy for liver fibrosis, but a moderate diagnostic accuracy for portal hypertension and esophageal varices.     

Evaluation of liver stiffness by 2D-SWE in combination with non-invasive parameters as predictors for esophageal varices in patients with advanced chronic liver disease

Background/aims: Esophageal varices (EV) are common complications in patients with advanced chronic liver disease (ACLD). Non-invasive parameters to exclude EV in patients with ACLD would be desirable. The aim of this study was the evaluation of liver stiffness measurement (LSM) using 2D-shear wave elastography (GE Logiq E9) and other non-invasive parameters as predictors for EV.

Methods: Hundred patients with ACLD were enrolled. Abdominal sonography, including measurement of gall bladder wall thickness (GBWT), spleen diameter and LSM, gastroscopy and blood test results were evaluated. Statistical analyses were performed for the association between EV and non-invasive parameters.

Results: Fifty-one per cent of the patients had EV. The mean LSM (14.6?kPa) and GBWT (3.88?mm) in the group with EV were significantly higher than in the group without EV (10.6?kPa; 2.94?mm; p?<?.01). Performing area under the receiver operating characteristic curve, LSM has a better diagnostic performance (0.781) than GBWT (0.707), spleen diameter (0.672) and platelet count (0.635). Combining LSM (cut-off 13.58?kPa) and GBWT (cut-off 3.07?mm) resulted in a sensitivity of 86.3% and a specificity of 71.4% for the presence of EV. A sensitivity of 100% (negative predictive value 1.0) was achieved at LSM >9?kPa or GBWT >4?mm. Following these criteria in our current study population, 18% of the gastroscopies could have been avoided.

Conclusions: Combining LSM with non-invasive parameters, especially GBWT, improves the diagnostic accuracy for predicting EV. We suggest reconsidering screening gastroscopy in patients with ACLD who show LSM <9?kPa and GBWT <4?mm due to the very low risk of having varices.     

The use of obeticholic acid for the management of non-viral liver disease: current clinical practice and future perspectives

Introduction: Farnesoid X nuclear receptor is involved in the regulation of lipid and glucose metabolism, though mainly in the homeostasis of bile acids. Indeed, the agonists of farnesoid X nuclear receptor represent promising drugs.

Areas covered: Obeticholic acid, a novel semisynthetic analogue of the naturally occurring bile acid, has led to encouraging preliminary results in both cholestatic and metabolic liver disease. In patients with primary biliary cholangitis, obeticholic acid determines a significant biochemical improvement although the effects on liver fibrosis are lacking. Obeticholic acid has been suggested for the treatment of nonalcoholic liver disease with good laboratory results. In cirrhotic animal models, the drug seems to reduce both portal hypertension and gut bacterial translocation.

Expert commentary: The use of obeticholic acid for the treatment of primary biliary cholangitis shows satisfying results. However, some open questions remain unresolved. Herein, we provide an overview of the current knowledge about the use of obeticholic acid in the field of nonviral chronic liver diseases. We tried to give a global point of view using a translational approach.     

Utility of point shear wave elastography in characterisation of focal liver lesions

Background: The present study aimed at evaluation of the usefulness of point shear wave elastography (pSWE) in characterization of FLL(s) by quantifying their stiffness.

Methods: In total, 197 patients (mean age was 56.57 years) with FLL(s) on conventional ultrasound were included. Final diagnoses, confirmed by imaging and/or biopsy whenever possible, included hepatocellular carcinoma (HCC) (n = 143), metastasis (n = 36), hemangioma (n = 16), and focal nodular hyperplasia (n = 2). Stiffness evaluation was performed by pSWE. Stiffness ratio (lesion to background liver) was calculated. ROC analysis was performed to evaluate the diagnostic accuracy of the stiffness value and stiffness ratio and to extract the optimal cutoff values for characterisation of FLL(s).

Results: HCC was significantly softer than its surrounding liver parenchyma [5.43 (3.03) vs. 17.05 (8.53) kPa, p <0.001]. However, the stiffness values for the other examined FLLs were comparable to their surrounding liver parenchyma. No significant difference was detected across different types of metastases or between metastases and surrounding liver (p>0.05). Stiffness ratio was superior to stiffness value in discrimination of HCC from metastasis (AUROC, 0.91 vs. 0.51 respectively).

Conclusion: pSWE could provide a complementary information about FLLs especially in differentiation between HCCs from metastases.     

Gender interaction of uric acid in the development of hypertension

Aim: The present study explored the gender interaction on the risk of uric acid in the new development of hypertension.

Study Design: A longitudinal retrospective cohort.

Subjects & Methods: A total of 5,807 individuals with an average age of 38 ± 7 years old were recruited. Individuals whose blood pressure rose more than 140/90mmHg or those who newly commenced antihypertensive treatment were defined as a new onset of hypertension. Cox regression analysis was employed for the analysis.

Results: During the 10-years follow-up, 42.8% of men and 22.2% of women had developed hypertension. Factors to predict the hypertension development were male gender, older age, higher BMI, higher uric acid, and higher mean blood pressure. An association between higher uric acid levels and higher incidence of hypertension remained statistically significant in women in a multivariate model adjusted for various clinical variables (Hazard ration (HR), 1.180; 95%CI, 1.018 to 1.369), whereas such association was not found in men (HR, 1.034; 95%CI, 0.994 to 1.075). The interaction between the two genders reached statistical significance (p for interaction = 0.007).

Conclusion: Higher uric acid is associated with the incident hypertension in the both genders. Women are more susceptible to the development of hypertension than men.     

Bacterial translocation in patients with liver cirrhosis: physiology,clinical consequences,and practical implications

Introduction: The gut liver axis is an operative unit that works to protect the human body against potentially harmful substances and microorganisms, maintaining the homeostasis of the immune system. Liver cirrhosis profoundly alters this complex system. The intestine becomes more permeable allowing the translocation of bacteria, bacterial products and fragments into the portal circulation, triggering an abnormal local and systemic inflammatory response and a condition of perpetual immunologic alarm. This immune-inflammatory disorder related to dysbiosis is involved in the development of liver damage and liver cirrhosis complications and increases intestinal permeability in a vicious circle.

Areas covered: The most relevant studies on bacterial translocation, the mechanism of intestinal barrier dysfunction and its consequences in patients with liver cirrhosis have been revised through a PubMed search. Data have been discussed with particular regard to their significance in clinical practice.

Expert commentary: The assessment of bacterial translocation and intestinal permeability is not currently used in clinical practice but may be useful to stratify patients’ prognosis.     

Acid suppression in patients treated with endoscopic therapy for the management of gastroesophageal varices: a systematic review and meta-analysis

Background and aim: Endoscopic therapy is the cornerstone choice for the management of varices and variceal hemorrhage. The aim of the present systematic review and meta-analysis was to evaluate the efficacy of acid suppression in patients treated with endoscopic therapy for gastroesophageal varices.

Methods: All eligible studies were searched via the PubMed, EMBASE, and Cochrane Library databases. Incidence of bleeding, mortality, ulcers, chest pain, and dysphagia after endoscopic therapy and length of stay were analyzed. Subgroup analyses were performed according to the types and major indications of endoscopic treatments. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated.

Results: Nine studies with 1470 patients were included. Acid suppression could significantly decrease the incidence of bleeding (OR = 0.39, 95%CI: 0.19–0.81, P = 0.01) and diminish the ulcer size (OR = 0.78, 95%CI: 0.38–1.57, P = 0.48) after endoscopic therapy. The subgroup analyses showed that acid suppression could significantly decrease the incidence of bleeding in patients undergoing prophylactic EVL, rather than in patients undergoing therapeutic EVL. There was no significant difference in the incidence of mortality, ulcers, chest pain, and dysphagia and length of stay between patients treated with and without acid suppression.

Conclusion: Acid suppression might be considered in patients undergoing prophylactic EVL for gastroesophageal varices.     

Clinical characteristics and outcomes of traditional Chinese medicine-induced liver injury: a systematic review

Backgrounds: Traditional Chinese medicine (TCM) is becoming increasingly popular and related adverse events are often ignored or underestimated.

Aims: This systematic review aimed to evaluate the clinical characteristics and outcomes of TCM-induced liver injury (TCM-ILI) and to estimate the proportion of TCM-ILI in all drug-induced liver injuries (DILI).

Methods: China National Knowledge Infrastructure, Wanfang, VIP, PubMed, and Embase databases were searched. Demographic, clinical, and survival data were extracted and pooled. Factors associated with worse outcomes were calculated. For the proportion meta-analyses, the data were pooled by using a random-effects model.

Results: Overall, 21,027 articles were retrieved, of which 625 were finally included. There was a predominance of female and older patients. The proportion of liver transplantation was 2.18% (7/321). The mortality was 4.67% (15/321). Male, higher aspartate aminotransferase and direct bilirubin, and lower albumin were significantly associated with an increased risk of death/liver transplantation in TCM-ILI patients. The proportion of TCM-ILI in all DILI was 25.71%. The proportion was gradually increased with year.

Conclusions: Our work summarises current knowledge regarding clinical presentation, disease course, and prognosis of TCM-ILI. TCM can result in hepatotoxicity, even death or necessitate life-saving liver transplantation. Governmental regulation of TCM products should be strictly established.     

Patients with liver cirrhosis show worse survival if decompensation occurs later during course of disease than at diagnosis

Objectives: Liver cirrhosis is characterized by a silent phase until decompensation, which is defined by onset of ascites, variceal bleeding, or encephalopathy. Although it is presumed that the survival of decompensated patients is the same regardless of when decompensation occurs, data to support this are scarce. We aimed to study the impact of time of decompensation on the clinical course and survival of patients with cirrhosis in a large population-based cohort.

Materials and methods: We used medical registries to define a 10-year cohort of 1317 patients with incident liver cirrhosis in the Scania region of Sweden. Medical records were reviewed. Patients were followed until December 2011, and for death or transplantation until December 2014.

Results: In the cohort, 629 patients were decompensated at diagnosis, of which 505 had ascites and 44 variceal bleeding only. During follow-up, 228 patients developed ascites and 39 variceal bleeding as first complication. Patients with ascites as first complication showed worse survival than patients who had ascites at diagnosis. (5-year survival 33% vs. 15%, HR 1.60 (95% CI 1.34–1.90)). This difference persisted after adjustment for confounders, including hepatocellular cancer (HR 1.38 (95% CI 1.15–1.67)). Worse survival was also seen when bleeding from varices occurred during follow-up rather than at diagnosis.

Conclusions: Our results provide evidence for an association between transplantation-free survival after decompensation and the time of decompensation in liver cirrhosis, with worse survival when decompensation occurs during follow-up, thus challenging the generally held, view that the survival after decompensation is independent of when decompensation occurs.     

Inhospital and delayed mortality after upper gastrointestinal bleeding: an analysis of risk factors in a prospective series

Background: Detailed analyses of mortality after upper gastrointestinal (GI) bleeding are lacking. Follow-up rarely extends beyond 30 days.

Aims: Our aim was to analyze in-hospital and delayed 6-months mortality, identifying risk factors.

Methods: This was a prospective study on patients with upper GI bleeding over 36 months. Clinical outcomes were in-hospital and delayed-6 month-mortality.

Results: Four hundred and forty-none patients were included. Overall inpatient mortality was 9.8% but mortality directly related to bleeding was 5.1%. Patients who died presented lower systolic blood pressures, platelet recounts, prothrombin times and lower levels of hemoglobin, calcium, albumin, urea, creatinine and total proteins. Cirrhosis and neoplasms determined a higher in-hospital mortality. Albumin levels were protective, whereas creatinine and an active bleeding were risk factors for in-hospital death in multivariate analysis. Up to 12.6% of patients discharged died in the first 6 months. Neoplasms, chronic kidney disease, coronary disease and esophageal varices were related to delayed mortality. Coronary disease and neoplasms were independent risk factors for mortality, but albumin levels were protective in multivariate analysis.

Conclusion: Comorbidities were risk factors for delayed mortality, whereas albumin levels were a protective factor for in-hospital and delayed deaths. Six months mortality is proportionately as important as in-hospital mortality. Half of the delayed deaths might be preventable.     

High-Sensitivity Cardiac Troponin T levels in prehypertensive patients

Background: High-sensitivity cardiac troponin T (hs-cTNT) is an important non-invasive laboratory-based marker of subclinical myocardial injury. Prehypertension, which may be a precursor of hypertension, is a major public health issue. Our aim was to evaluate the importance of serum hs-cTnT as a marker predicting prehypertension.

Methods: A total of 100 subjects (45 women and 55 men) consisting of 50 consecutive prehypertensive patients with blood pressures between 120/80 and 139/89 mmHg and 50 normotensive patients with blood pressures < 120/80 mmHg were enrolled prospectively. The hs-cTNT level was calculated and compared between the two groups. Echocardiographic examinations were performed in all patients.

Results: The hs-cTnT level was significantly higher in the prehypertensive group (p < 0.001) and was positively correlated with prehypertension (r = 0.625, p < 0.001). Hs-cTnT was an independent predictor of prehypertension (odds ratio = 1.043, 95% confidence interval [CI] 1.019–1.067, p < 0.001). An Hs-cTnT level of 0.55 ng/L was predictive of prehypertension with a sensitivity of 86% and specificity of 60% (area under the curve = 0.861; 95% CI, 0.787–0.935; p < 0.001).

Conclusion: hs-cTnT may complement other diagnostic biomarkers in predicting prehypertension.

Abbrevations: high-sensitivity cardiac troponin T, prehypertension, subclinical myocardial injury     

Clinical relevance of liver histopathology and different histological classifications of NASH in adults

Introduction: Nonalcoholic fatty liver disease (NAFLD) encompasses simple steatosis and steatohepatitis (NASH) with or without fibrosis/cirrhosis and hepatocellular carcinoma. NAFLD occurs epidemically in most areas of the world, contributes to cardiovascular events and liver-related mortality and therefore exacts a major economic toll.

Areas covered: Here we summarize what clinicians should know about NAFLD histopathology in adults. We report on the individual histological features and scoring systems of NAFLD: the NAFLD activity score (NAS) introduced by the NASH-Clinical Research Network, the ‘Fatty Liver Inhibition of Progression’ algorithm and Steatosis, Activity, and Fibrosis (SAF) score. Pros and cons of histological classifications in NASH are discussed. Special emphasis is given to liver histopathology in some high-risk patient groups, such as those with severe obesity and type 2 diabetes. Moreover, we also examine the relationship between liver histopathology and clinical features, and the impact of liver histopathology on the long-term prognosis of NAFLD. Finally, we propose an integrated diagnostic approach which utilizes both non-invasive tools and liver biopsy in those individual patients with suspected NAFLD.

Expert commentary: Based on expert opinions, we conclude with a research agenda on NAFLD which focuses on the most burning topics to be addressed over the next five years.     

Contrast enhanced ultrasound (CEUS) imaging of solid benign focal liver lesions

Introduction: Ultrasound is well accepted worldwide for imaging of the liver. Absences of radiation exposure, low cost and large diffusion are some of the advantages that make this technique the first to be used in the assessment of focal liver lesions (FLL).

Areas covered: Contrast enhanced ultrasound (CEUS) has been introduced more than twenty years ago, and its detection rate is comparable to that of contrast enhanced magnetic resonance imaging (CEMRI) and contrast enhanced computed tomography (CECT). In this narrative review, we discuss the main CEUS features of benign liver lesions and controversies in published results including the gold standard chosen and the quality and knowledge of the preferred techniques.

Expert commentary: CEUS is safe and allows an immediate evaluation of the nature of FLL. CEUS permits differentiation between malignant and benign FLL in healthy liver parenchyma by analysing the arterial, portal venous and late phases. CEMRI and CECT are reliable to characterize FLL but higher costs, radiation exposure, nephrotoxicity (in particular for CECT) and absence of real time imaging limit the appropriate evaluation of FLL. Therefore CEUS can be preferred in most clinical situations, and when results are unclear or suggestive for malignant FLL, biopsy and histological examination can be directly initiated avoiding unnecessary additional imaging.     

Book reviews

The School Years. Current Issues in the Socialization of Young People John C. Coleman (Ed.) London, Routledge, 1992 (2nd edn) 208 pp.; £10.99 (paperback)

AIDS and the Hospice Community Madalon O'Rawe Amenta & Clair B. Tehan Binghampton, NY, Harrington Park Press, 1991 186 pp. + index

Social Care & HIV/AIDS The Hull York Research Team London, HMSO, 1993 214 pp., £13.70 (paperback)

Private Risks and Public Dangers Sue Scott, Gareth Williams, Stephen Platt & Hilary Thomas (Eds) Aldershot, Avebury, 1993 205 pp., £34.95 (hb)

AIDS: a problem for sociological research Michael Pollak, Geneviève Paicheler & Janine Pierret London, Sage Publications, 1992 124 pp., £10.95 (paperback)

AIDS: The Winter War Arthur D. Kahn Philadelphia, Temple University Press, 1993 236 pp., U£27.95 (hardback)

AIDS: Facing the Second Decade Peter Aggleton, Peter Davies & Graham Hart (Eds) Taylor & Francis, 1993 215 pp., £12.95 (Pb)

Women and AIDS: Psychological Perspectives Corrine Squire (Ed.) London, Sage Publications, 1993 196 pp., £12.95 (paperback)     

Book reviews and books received

Practices of Freedom: Selected writings on HTV/AIDS Simon Watney London, Rivers Oram Press, 1994 328 pp., £11.95 (paperback): £30 (hardback)

AIDS: The Challenge—Understanding Education and Care N. Small Aldershot, Avebury, 1993 172 pp.

Sex, Gay Men and AIDS P. M. Davies, F. C. I. Hickson, P. Weatherburn & A. J. Hunt London, Falmer Press, 1993 199 pp., £12.95

AIDS: Working with young people Peter Aggleton, Kim Rivers & Ian Warwick Horsham, West Sussex, Avert, 1993 162 pp., £ 18.95 (paperback)

ABC of AIDS. Third Edition Michael W. Adler (Ed.)London, BMJ Publishing Group, 1993 86 pp., £ 12.95 (paperback)

Guidelines for Management of Children with HTV Infection Diana Gibb & Sam Walters Horsham, West Sussex, AVERT, 1993 29 pp., £ 4 (paperback)

A Guide to HIV Infection and Child-bearing Danielle Mercey, Susan Bewley & Peter Brocklehurst Horsham, West Sussex, AVERT, 1993 25 pp., £ 3 (paperback)

Essential AIDS Information Resources AHRTAG/WHO, 1994 £ 5.00/US $10.00(Free to readers in developing countries)     

Book Review

Acquainted with the Night Allegra Taylor, 1989 London, Fontana £3.99 (paperback)

The AIDS Handbook Carl Miller 1990 Penguin Books 159pp. £4.99 (paperback)

Caring for Someone with AIDS Edited by David Yelding, 1990 Published for the Research Institute for Consumers Affairs by the Consumers Association and Hodder & Stoughton £6.95 (paperback)

AIDS. A Pocket Book of Diagnosis and Management Edited by A. Mindel, 1990 London, Arnold 244 pp. £12.95

AIDS and its Metaphors Susan Sontag, 1989 Harmondsworth, Penguin 98 pp. £3.99 (paperback)     

The importance of frontal QRS-T angle for predicting non-dipper status in hypertensive patients without left ventricular hypertrophy

Background: Frontal QRS-T angle is a novel marker of myocardial repolarization, and an increased frontal QRS-T angle associated with adverse cardiac outcomes. Non-dipper hypertension is also associated with adverse cardiac outcomes. This study aimed to investigate the relationship between frontal QRS-T angle and non-dipper status in hypertensive patients without left ventricular hypertrophy (LVH).

Methods: This study included 122 hypertensive patients without LVH. Patients were divided into two groups: dipper hypertension and non-dipper hypertension. The frontal QRS-T angle was calculated from 12-lead electrocardiography.

Results: Frontal QRS-T angle (47.9° ± 29.7° vs. 26.7° ± 19.6°, P < 0.001) was significantly higher in patients with non-dipper hypertension than in patients with dipper hypertension. In addition, frontal QRS-T angle was positively correlated with sleeping systolic (r = 0.211, P = 0.020), and diastolic (r = 0.199, P = 0.028) blood pressures (BP), even if they were weak. Multivariate analysis showed that the frontal QRS-T angle was independent predictor of non-dipper status (QR: 1.037, 95% CI: 1.019–1.056, P < 0.001).

Conclusion: Frontal QRS-T angle is independent predictor of non-dipper status in hypertensive patients without LVH.     

Pazopanib for renal cell carcinoma leads to elevated mean arterial pressures in a murine model

Background: In the setting of metastatic RCC (mRCC), pazopanib is approved as first line therapy. Unfortunately treatment may lead to cardiotoxicity such as hypertension, heart failure, and myocardial ischemia.

Objective: Define the in vivo role of pazopanib in the development of cardiotoxicity.

Methods: Wild type mice were dosed for 42 days via oral gavage, and separated into control and treatment (pazopanib) groups. Baseline ECG’s, echocardiograms, and blood pressures were recorded. At the conclusion of the study functional parameters were again recorded, and animals were used for pathological, histological, and protein analysis.

Results: After 2 weeks of dosing with pazopanib, the treatment group exhibited a statistically significant increase in mean arterial pressure compared to control mice (119 ± 11.7 mmHg versus 108 ± 8.2 mmHg, p = 0.049). Treatment with pazopanib led to a significant reduction in the cardiac output of mice.

Conclusion: Our findings in mice clearly demonstrate that treatment with pazopanib leads to a significant elevation in blood pressure after 2 weeks of dosing and this persists for the duration of dosing. The continued development of the cardio-oncology field will be paramount in providing optimal oncologic care while simultaneously improving cardiac outcomes through further investigation into the mechanisms of CV toxicity.     

Pattern of tumour growth of the primary colon cancer predicts long-term outcome after resection of liver metastases

Objective: To identify significant predictive factors for overall survival (OS) and disease-free survival (DFS) after liver resection for colon cancer metastases, with special focus on features of the primary colon cancer, such as lymph node ratio (LNR), vascular invasion, and perineural invasion.

Methods: Patients operated for colonic cancer liver metastases between 2006 and 2014 were included. Details on patient characteristics, the primary colon cancer operation and metastatic disease were collected. Multivariate analysis was performed to select predictive variables for OS and DFS.

Results: Median OS and DFS were 67 and 20 months, respectively. 1-, 3- and 5-year OS were 97, 76, and 52%. 1-, 3- and 5-year DFS were 65, 42, and 37%. Multivariate analysis showed LNR to be an independent predictive factor for DFS but not for OS. Other identified predictive factors were vascular and perineural invasion of the primary colon cancer, size of the largest metastasis and severe complications after liver surgery for OS, and perineural invasion, number of liver metastases and preoperative CEA-level for DFS. Traditional N-stage was also considered to be an independent predictive factor for DFS in a separate multivariate analysis.

Conclusions: LNR and perineural invasion of the primary colon cancer can be used as a prognostic variable for DFS after a concomitant liver resection for colon cancer metastases. Vascular and perineural invasion of the primary colon cancer are predictive for OS.