Liver stiffness and the prediction of clinically significant portal hypertension and portal hypertensive complications.

OBJECTIVE: Clinically significant portal hypertension (CSPH) is associated with increased risk of liver disease complications, but its identification requires invasive methods. Liver stiffness (LS) measurement via transient elastography correlates with the presence of CSPH. We, therefore, evaluated LS as a noninvasive tool in the prediction of CSPH and portal hypertensive complications. MATERIAL AND METHODS: Ninety-five consecutive patients successfully underwent measurement of hepatic venous pressure gradient (HVPG) and LS on the same day. Recent laboratory tests were correlated. Patients were followed up for development of portal hypertensive complications. Predictors of CSPH and complications were identified. RESULTS: Seventy-six (80%) were male and mean age was 56.8 ± 9.3 years. Ninety-three percent and 72% of patients had cirrhosis and esophageal varices, respectively. Only LS (r(2) = 0.38; p < 0.0001) and international normalized ratio (r(2) = 0.21; p = 0.02) were independently associated with HVPG. An LS >29.0 kilopascal (kPa) predicted CSPH with 71.9% sensitivity, 100% specificity, 100% positive predictive value (PPV), and 56.0% negative predictive value (NPV). An LS <25.0 kPa in those with platelet count >150 × 10(9)/L excluded CSPH with 91.7% sensitivity, 100% specificity, 100% PPV, and 90% NPV. Ninety patients were followed up for a median duration of 15.1 months. CSPH and LS >34.5 kPa predicted portal hypertensive complications with 100% and 75.0% sensitivity, 40.3% and 69.4% specificity, 43.1% and 52.5% PPV, and 100% and 86.2% NPV, respectively. CONCLUSION: LS shows promise as a noninvasive marker of CSPH and portal hypertensive complications. Combining LS with platelet count improves diagnostic accuracy in the exclusion of CSPH.

Non-cirrhotic portal hypertension in HIV mono-infected patients.

BACKGROUND AND AIM: Unexplained liver injury including fibrosis and portal hypertension has rarely been reported among patients with HIV in the absence of co-infection with hepatitis B (HBV) or hepatitis C (HCV). We describe a series of HIV mono-infected patients with evidence of non-cirrhotic portal hypertension. METHODS: HIV-infected patients with evidence of portal hypertension who were anti-HBV and anti-HCV negative and HBV and HCV RNA polymerase chain reaction (PCR) negative were identified from patients managed by the Victorian statewide HIV referral service located at The Alfred Hospital, Melbourne. Portal hypertension was defined as either radiological or endoscopic evidence of varices, portal vein flow obstruction, or elevated hepatic venous pressure gradient (HPVG). RESULTS: Five patients were found to have portal hypertension. These patients were male, aged 41 to 65 years, with known duration of HIV infection between 11 to 25 years. All had been treated with antiretroviral therapy, including didanosine. Tests for metabolic, autoimmune, and hereditary causes of liver disease failed to establish an etiology for the liver injury. All had radiological or endoscopic findings of varices, and four patients had radiological features of portal vein obstruction or flow reversal. Only one patient underwent HPVG measurement, which was elevated. Non-invasive fibrosis assessment revealed increased liver stiffness in three (out of four) patients, and no cirrhotic features were found on those who underwent liver biopsy. CONCLUSIONS: To our knowledge, this is the largest published series of non-cirrhotic portal hypertension in HIV mono-infected patients in Australia. Further research is needed to understand what relationship, if any, HIV or its treatments might have on liver injury over time.

Norfloxacin treatment for clinically significant portal hypertension: results of a randomised double-blind placebo-controlled crossover trial.

BACKGROUND: While selective intestinal decontamination (SID) can alter the hyperdynamic circulatory state of cirrhosis, the impact of SID on portal pressure remains unclear especially in the setting of clinically significant portal hypertension. AIMS: To examine the impact of SID with norfloxacin on portal pressure in subjects with clinically significant portal hypertension and explore the potential mechanisms by which norfloxacin exerts its haemodynamic effects. METHODS: Randomised, double blind, placebo-controlled, crossover trial of norfloxacin 400 mg twice daily for 4 weeks. The portal pressure was assessed by hepatic venous pressure gradient (HVPG). Endotoxaemia was assessed by the Limulus amebocyte lysate (LAL) assay. l-arginine (l-Arg) transporter function was assessed in peripheral blood mononuclear cells (PBMCs). Plasma levels of urotensin II (UII) and tumour necrosis factor were measured before and after therapy. RESULTS: Sixteen subjects with clinically significant portal hypertension (16.5+/-1.1 mmHg) completed the study. Norfloxacin therapy was not superior to placebo in reducing HVPG (13.8+/-1.0 mmHg vs 13.6+/-1.2 mmHg, P=0.3). Furthermore, no alteration in l-Arg transport was detected after 4 weeks of norfloxacin therapy. Plasma UII levels correlated positively with HVPG (P=0.01) and the Child-Pugh score (P<0.05). However, UII levels following therapy did not parallel HVPG changes. CONCLUSIONS: Norfloxacin is not superior to placebo in reducing HVPG in subjects with clinically significant portal hypertension. Furthermore, norfloxacin does not appear to modulate the l-Arg transporter mechanism in this patient population. Although plasma UII correlates positively with HVPG, UII does not appear to have a direct role in modulating HVPG.

Transient simulations of nitrogen load for a coastal aquifer and embayment, Cape Cod, MA.

A time-varying, multispecies, modular, three-dimensional transport model (MT3DMS) was developed to simulate groundwater transport of nitrogen from increasing sources on land to the shore of Nauset Marsh, a coastal embayment of the Cape Cod National Seashore. Simulated time-dependent nitrogen loads at the coast can be used to correlate with current observed coastal eutrophic effects, to predict current and ultimate effects of development, and to predict loads resulting from source remediation. A time-varying nitrogen load, corrected for subsurface loss, was applied to the land subsurface in the transport model based on five land-use coverages documenting increasing development from 1951 to 1999. Simulated nitrogen loads to Nauset Marsh increased from 230 kg/yr before 1930 to 4390 kg/yr in 2001 to 7130 kg/yr in 2100, assuming future nitrogen sources constant at the 1999 land-use rate. The simulated nitrogen load per area of embayment was 5 times greater for Salt Pond, a eutrophic landward extension of Nauset Marsh, than for other Nauset Marsh areas. Sensitivity analysis indicated that load results were little affected by changes in vertical discretization and annual recharge but much affected by the nitrogen loss rate assumed for a kettle lake downgradient from a landfill.

Urotensin II: a novel vasoactive mediator linked to chronic liver disease and portal hypertension.

BACKGROUND/AIMS: Urotensin II (UII) is recognised as the most potent human vasoconstrictor; however, its role in chronic liver disease (CLD) is unknown. AIM: We sought to determine serum UII levels in CLD and explore its relationship with clinical features and outcomes of patients with CLD and portal hypertension. METHODS: UII was analysed by radio-immunoassay on cirrhotic patients undergoing hepatic venous pressure gradient (HVPG) determination and age- and sex-matched controls. Follow-up data were prospectively recorded. RESULTS: From 1997 to 2004, 80 patients (male/female: 74/6) underwent a total of 94 HVPG assessments. UII was higher in cirrhotic patients compared with controls (2.05+/-0.06 and 1.55+/-0.09 pmol/L, P<0.001) and was correlated with HVPG (r=+0.35, P=0.001) and severity of CLD (r=+0.6, P<0.001). UII was higher in patients who developed refractory ascites (2.45+/-0.13 vs. 1.7+/-0.12 pmol/L, P<0.001) and in those who died during the follow-up period (2.27+/-0.15 pmol/L vs. 1.95+/-0.08 pmol/L, P<0.05). CONCLUSION: Serum UII is elevated in patients with CLD, and is associated with the severity of the underlying liver disease and the degree of portal hypertension. Baseline levels can predict future complications such as refractory ascites and patient survival.