Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection.

BACKGROUND & AIMS: Chronic infection with hepatitis B or C virus (HBV or HCV) is a leading cause of cirrhosis by unknown mechanisms of pathogenesis. Translocation of gut microbial products into the systemic circulation might increase because of increased intestinal permeability, bacterial overgrowth, or impaired clearance of microbial products by Kupffer cells. We investigated whether the extent and progression of liver disease in patients with chronic HBV or HCV infection are associated with microbial translocation and subsequent activation of monocytes. METHODS: In a retrospective study, we analyzed data from 16 patients with minimal fibrosis, 68 with cirrhosis, and 67 uninfected volunteers. We analyzed plasma levels of soluble CD14 (sCD14), intestinal fatty acid binding protein, and interleukin-6 by enzyme-linked immunosorbent assay, and lipopolysaccharide (LPS) by the limulus amebocyte lysate assay, at presentation and after antiviral treatment. RESULTS: Compared with uninfected individuals, HCV- and HBV-infected individuals had higher plasma levels of LPS, intestinal fatty acid binding protein (indicating enterocyte death), sCD14 (produced upon LPS activation of monocytes), and interleukin-6. Portal hypertension, indicated by low platelet counts, was associated with enterocyte death (P=.045 at presentation, P<.0001 after therapy). Levels of sCD14 correlated with markers of hepatic inflammation (P=.02 for aspartate aminotransferase, P=.002 for ferritin) and fibrosis (P<.0001 for γ-glutamyl transpeptidase, P=.01 for alkaline phosphatase, P<.0001 for α-fetoprotein). Compared to subjects with minimal fibrosis, subjects with severe fibrosis at presentation had higher plasma levels of sCD14 (P=.01) and more hepatic CD14+ cells (P=.0002); each increased risk for disease progression (P=.0009 and P=.005, respectively). CONCLUSIONS: LPS-induced local and systemic inflammation is associated with cirrhosis and predicts progression to end-stage liver disease in patients with HBV or HCV infection.

An apparent homozygous deletion in maltase-glucoamylase, a lesson in the evolution of SNP arrays.

Single nucleotide polymorphism (SNP) arrays possess clinical potential due to their high throughput capacity, sensitivity and versatility. We used such an array to perform a genome-wide SNP analysis of a patient with a multi-system undiagnosed disease involving peripheral neuropathies and food intolerances. The patient had a homozygous deletion within the gene encoding maltase-glucoamylase (MGAM), an intestinal starch digestion enzyme, predicting absence of enzyme activity and potential starch indigestion. We then performed validation testing using a functional MGAM analysis that involved starch ingestion followed by measuring blood glucose and insulin levels as well as hydrogen breath levels. Gastrointestinal tissue was also obtained via endoscopy and immunohistochemical staining for intestinal MGAM was performed. Our results strongly suggest the presence and functioning of MGAM which disproved deficiency predictions based on SNP array analysis findings, classifying the deletion as a functional polymorphism. This study highlights a current clinical limitation of SNP arrays, i.e., distinguishing deleterious genomic alterations from misleading functional polymorphisms. We conclude that novel findings from SNP arrays should be clinically validated and published.

Internet Published Policies Regarding Liver Transplant Eligibility and Substance Use in United States Transplant Centers.

Liver transplant centers in the United States retain great autonomy in determining eligibility criteria for a liver transplant. This study aims to define the availability and content of liver transplant centers' publicly available Internet policies regarding eligibility criteria for liver transplant. Three trained undergraduate students performed a structured pilot-tested assessment of official websites of the United Network for Organ Sharing-registered liver transplant centers. All 141 liver transplant centers had an accessible website. Some account of eligibility criteria was provided by 53% of centers, while 32% of centers discussed substance use. Only 17% discussed their policy regarding alcohol use in candidates with underlying alcohol use disorder, and only 2% stipulated that 6 months of abstinence was required. While exclusion based on substance use or age was discussed infrequently, insurance coverage requirements, the need for social support, and the need for adherence to medical care were mentioned in 21%, 37%, and 23% of centers, respectively. Conclusion: In 2018, half of liver transplant centers provided some information on their official websites regarding eligibility criteria for liver transplant. Detailed information regarding substance use disorders and social health requirements was rare. The Internet is infrequently used by liver transplant centers as a means to publicly share information regarding selection criteria.

Spleen and Liver Volumetrics as Surrogate Markers of Hepatic Venous Pressure Gradient in Patients With Noncirrhotic Portal Hypertension.

Noncirrhotic portal hypertension (NCPH) is a rare disease that may lead to serious clinical consequences. Currently, noninvasive tools for the assessment of NCPH are absent. We investigated the utility of spleen and liver volumetrics as a marker of the presence and severity of portal hypertension in this population. A cohort of NCPH patients evaluated between 2003 and 2015 was retrospectively studied. The association of spleen and liver volumes with the hepatic venous pressure gradient (HVPG) level was evaluated using locally weighted scatterplot smoothing curves. A cohort of patients with viral hepatitis-related liver disease was used as controls. Of the 86 patients with NCPH evaluated during the study period, 75 (mean age, 35 ± 17; 73% males) were included in the final analysis. Patients with portal hypertension had significantly higher spleen and liver to body mass index (BMI) ratios compared to patients with HVPG <5 mm Hg (39.5 ± 27.9 versus 22.8 ± 10.6 cm3/kg/m2, P = 0.003; 91.1 ± 40.1 versus 71.4 ± 16.7 cm3/kg/m2, P = 0.014, for spleen/BMI and liver/BMI, respectively). In contrast to the patients with viral hepatitis, a positive linear correlation was observed in the NCPH cohort between spleen/BMI and liver/BMI (above a cutoff of 25 and 80 cm3/kg/m2, respectively) and HVPG level. Additionally, only in the NCPH cohort was an increase in spleen/BMI range quartile predictive of a higher prevalence of portal hypertension and clinically significant portal hypertension (trend, P = 0.014 and 0.031, respectively). Conclusion: Spleen and liver volumetrics may have utility in the assessment of NCPH as a noninvasive biomarker that can be performed using routine radiologic examinations. Further studies are needed to validate these findings. (Hepatology Communications 2018; 00:000-000).