Non-Invasive Assessment of Liver Fibrosis in Hepatitis B Patients.

The aim of this review is to provide updated information on the clinical use of non-invasive serum and imaging-based tests for fibrosis assessment in chronic hepatitis B (CHB) virus infection. In recent years, non-invasive tests (NIT) have been increasingly used to determine eligibility for treatment. Liver biopsy is still considered the gold standard for assessing inflammatory activity and fibrosis staging, but it is an invasive procedure with inherent limitations. Simple serum markers such as APRI and FIB-4 are limited by indeterminate results but remain useful initial tests for fibrosis severity if imaging elastography is not available. Point-of-care US-based elastography techniques, such as vibration-controlled transient elastography or 2D shear wave elastography, are increasingly available and have better accuracy than simple serum tests for advanced fibrosis or cirrhosis, although stiffness cut-offs are variable based on E-antigen status and inflammatory activity. Current NITs have poor diagnostic performance for following changes in fibrosis with antiviral therapy. However, NITs may have greater clinical utility for determining prognosis in patients with CHB that have advanced disease, especially for the development of hepatocellular carcinoma and/or liver decompensation. Algorithms combining serum and imaging NITs appear promising for advanced fibrosis and prognostic risk stratification.

Predictors of Respiratory Failure Development in a Multicenter Cohort of Inpatients With Cirrhosis.

INTRODUCTION: Hospitalized patients with cirrhosis can develop respiratory failure (RF), which is associated with a poor prognosis, but predisposing factors are unclear. METHODS: We prospectively enrolled a multicenter North American cirrhosis inpatient cohort and collected admission and in-hospital data (grading per European Association for the Study of Liver-Chronic Liver Failure scoring system, acute kidney injury [AKI], infections [admission/nosocomial], and albumin use) in an era when terlipressin was not available in North America. Multivariable regression to predict RF was performed using only admission day and in-hospital events occurring before RF. RESULTS: A total of 511 patients from 14 sites (median age 57 years, admission model for end-stage liver disease [MELD]-Na 23) were enrolled: RF developed in 15%; AKI occurred in 24%; and 11% developed nosocomial infections (NI). At admission, patients who developed RF had higher MELD-Na, gastrointestinal (GI) bleeding/AKI-related admission, and prior infections/ascites. During hospitalization, RF developers had higher NI (especially respiratory), albumin use, and other organ failures. RF was higher in patients receiving albumin (83% vs 59%, P < 0.0001) with increasing doses (269.5 ± 210.5 vs 208.6 ± 186.1 g, P = 0.01) regardless of indication. Admission for AKI, GI bleeding, and high MELD-Na predicted RF. Using all variables, NI (odds ratio [OR] = 4.02, P = 0.0004), GI bleeding (OR = 3.1, P = 0.002), albumin use (OR = 2.93, P = 0.01), AKI (OR = 3.26, P = 0.008), and circulatory failure (OR = 3.73, P = 0.002) were associated with RF risk. DISCUSSION: In a multicenter inpatient cirrhosis study of patients not exposed to terlipressin, 15% of patients developed RF. RF risk was highest in those admitted with AKI, those who had GI bleeding on admission, and those who developed NI and other organ failures or received albumin during their hospital course. Careful volume monitoring and preventing nosocomial respiratory infections and renal or circulatory failures could reduce this risk.

Management of hepatorenal syndrome in liver cirrhosis: a recent update.

Hepatorenal syndrome (HRS) is a serious form of renal dysfunction in patients with cirrhosis and ascites. It is an important component of the acute-on-chronic liver failure (ACLF) syndrome. Significant recent changes in the understanding of the pathophysiology of renal dysfunction in cirrhosis include the role of inflammation in addition to hemodynamic changes. The term acute kidney injury (AKI) is now adopted to include all functional and structural forms of acute renal dysfunction in cirrhosis, with various stages describing the severity of the condition. Type 1 hepatorenal syndrome (HRS1) is renamed HRS-AKI, which is stage 2 AKI [doubling of baseline serum creatinine (sCr)] while fulfilling all other criteria of HRS1. Albumin is used for its volume expanding and anti-inflammatory properties to confirm the diagnosis of HRS-AKI. Vasoconstrictors are added to albumin as pharmacotherapy to improve the hemodynamics. Terlipressin, although not yet available in North America, is the most common vasoconstrictor used worldwide. Patients with high grade of ACLF treated with terlipressin are at risk for respiratory failure if there is pretreatment respiratory compromise. Norepinephrine is equally effective as terlipressin in reversing HRS1. Recent data show that norepinephrine may be administered outside the intensive care setting, but close monitoring is still required. There has been no improvement in overall or transplant-free survival shown with vasoconstrictor use, but response to vasoconstrictors with reduction in sCr is associated with improvement in survival. Non-responders to vasoconstrictor plus albumin will need liver transplantation as definite treatment with renal replacement therapy as a bridge therapy. Combined liver and kidney transplantation is recommended for patients with prolonged history of AKI, underlying chronic kidney disease or with hereditary renal conditions. Future developments, such as the use of biomarkers and metabolomics, may help to identify at risk patients with earlier diagnosis to allow for earlier treatment with improved outcomes.

Raised plasma levels of H2S and nitrate predict intrapulmonary vascular dilations: A preliminary report in patients with cryptogenic cirrhosis.

BACKGROUND AND AIMS: The role of vasoactive chemicals in the pathogenesis of hepatopulmonary syndrome (HPS), a disorder characterized by intrapulmonary vascular dilation (IPVD), is only vaguely elucidated. We aimed to study the association between plasma H2S, nitrate levels, and presence and severity of IPVD and HPS. METHODS: Consecutive adult patients with cryptogenic cirrhosis were evaluated for IPVD (by contrast echocardiography) and for hypoxemia (by arterial blood gas analysis). Plasma H2S and nitrate levels were measured in these patients. RESULTS: Fifty-eight patients with cryptogenic cirrhosis (male, 45; median age, range, 45, 16-74 years; Child's class; A, 30; B, 18; C, 10) were enrolled in this study. Thirty-four of the 58 (59%) patients had IPVD and 13 (22%) had HPS (mild, 4; moderate, 5; severe, 2; very severe, 2). Plasma H2S levels were significantly higher in patients with IPVD (19.6, 5.7-83 µmol/L) as compared to patients who had no IPVD (12.3, 0-47 µmol/L; p-value 0.03) with an area under receiver operating characteristic curve of 0.68 (95% CI 0.53-0.84). Plasma H2S levels were higher in patients with IPVD irrespective of liver disease severity. There was a trend for higher plasma nitrate levels in patients with IPVD (47, 15.8-126.4 nmol/mL) as compared to patients who had no IPVD (32.3, 6.9-51.4 nmol/mL; p-value 0.1). Raised plasma H2S and nitrate levels had an additive effect on the presence of IPVD. Neither plasma H2S nor plasma nitrate levels correlated with the degree of hypoxemia. CONCLUSION: Raised plasma H2S and nitrate levels predict the presence of IPVD in patients with cryptogenic cirrhosis.

Tissue Xpert™ MTB/Rif assay is of limited use in diagnosing peritoneal tuberculosis in patients with exudative ascites.

BACKGROUND: Xpert™ MTB/Rif is a multiplex hemi-nested real-time PCR-based assay to detect presence of M. tuberculosis within 2 hours of sample collection. The present study aimed at assessing efficacy of Xpert™ MTB/Rif assay for diagnosing peritoneal tuberculosis. METHODS: Patients with exudative ascites, fluid negative for acid-fast bacilli on auramine O fluorescence staining and unyielding fluid cytology for malignant cells, were included. Ultrasound-guided omental biopsy samples were obtained in all. Xpert™ MTB/Rif assay on tissue samples was assessed against a composite "reference" standard for diagnosis of peritoneal tuberculosis, defined as presence of any of the three-culture showing M tuberculosis, granulomatous inflammation on histology or resolution of ascites with 2 months of antitubercular therapy. RESULTS: During January 2012-July 2013, 28 patients (age:43 ± 15 years; mean ± SD; male:20) were recruited. Serum ascitic albumin gradient was <1.1 in all except in four patients with underlying cirrhosis. Twenty-one of the 28 patients had peritoneal TB as diagnosed by composite reference standard (histology:18; culture:4; treatment response:3). Seven patients (25%) had an alternative diagnosis (metastatic carcinoma 2, adenocarcinoma 2, mesothelioma 2, and systemic lupus erythematous 1). Xpert™ MTB/Rif assay was positive in 4/21 patients with peritoneal tuberculosis and in none of the 7 patients with alternative diagnosis. Thus, sensitivity, specificity, positive, and negative predictive values for tissue Xpert™ MTB/Rif assay in diagnosing peritoneal tuberculosis were 19% (95% C.I: 6% to 42%), 100% (95% C.I: 59% to 100%), 100% (40% to 100%), and 29% (95% C.I: 13% to 51%), respectively. INTERPRETATION AND CONCLUSION: Tissue Xpert™ MTB/Rif assay was of limited use in diagnosing peritoneal tuberculosis.