Lean body mass index is a marker of advanced tumor features in patients with hepatocellular carcinoma.

Background: Obesity is an independent risk factor for the development of hepatocellular carcinoma (HCC) and may influence its outcomes. However, after diagnosis of HCC, like other malignancies, the obesity paradox may exist where higher body mass index (BMI) may in fact confer a survival benefit. This is frequently observed in patients with advanced HCC and cirrhosis, who often present late with advanced tumor features and cancer related weight loss.

Procedural-Related Bleeding in Hospitalized Patients With Liver Disease (PROC-BLeeD): An International, Prospective, Multicenter Observational Study.

Background & Aims: Hospitalized patients with cirrhosis frequently undergo multiple procedures. The risk of procedural-related bleeding remains unclear, and management is not standardized. We conducted an international, prospective, multicenter study of hospitalized patients with cirrhosis undergoing nonsurgical procedures to establish the incidence of procedural-related bleeding and to identify bleeding risk factors.

Proof-of-concept study to evaluate the safety and efficacy of saroglitazar in patients with primary biliary cholangitis.

Background & Aim: Saroglitazar is a novel peroxisome proliferator-activated receptor (PPAR) agonist with dual agonistic properties (α/γ). Due to a strong mechanistic rationale, we aimed to test the safety and efficacy of saroglitazar in patients with primary biliary cholangitis (PBC) who were either ursodeoxycholic acid (UDCA) resistant or intolerant.

Methods: In this double-blind, phase II proof-of-concept trial, 37 patients with PBC were randomized to saroglitazar 4 mg (n = 13), saroglitazar 2 mg (n = 14), or placebo (n = 10) daily for 16 weeks.

Late onset CMV disease presenting as a colonic stricture in a liver transplant recipient.

Cytomegalovirus (CMV) is a common opportunistic infection in solid organ transplant (SOT) recipients in the first 6 months after transplant. Late onset CMV infection or disease outside the classical risk period is uncommon and can present with atypical signs and symptoms. Here, we report a case of late onset CMV presenting as a colonic stricture more than 10 years after liver transplantation in the absence of traditional CMV risk factors.

Analysis of Plasma Tenascin-C in Post-HCV Cirrhosis: A Prospective Study.

Background And Aim: Hepatitis C virus (HCV)-related cirrhosis, one of the most common etiologies of liver cirrhosis in the Western world, is a risk factor for hepatocellular carcinoma. To confirm and improve current effectiveness of screening and prognosis of patients with established cirrhosis, a credible, simple plasma biomarker is needed. Hepatic stellate cell activation, a pivotal event in cirrhosis development, results in increased secretion of extracellular matrix proteins, including tenascin-C (TnC).

Adeno-Associated Virus Serotype 2 Vector-Mediated Reintroduction of microRNA-19b Attenuates Hepatic Fibrosis.

Fibrotic liver injury is a significant healthcare burden in the United States. It represents a major cause of morbidity and mortality for which there are no effective Food and Drug Administration-approved treatment strategies. Fibrosis is considered a disruption of the normal wound healing responses mediated by fibroblastic cells, which are triggered and sustained by pro-fibrotic cytokines such as transforming growth factor beta 1 (TGF-β1).

Viral hepatitis and hepatocellular carcinoma: etiology and management.

Chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) are associated with hepatic fibrosis and development of hepatocellular carcinoma (HCC). There are differences and variation with the incidence of HCC worldwide. Additionally, HCC develops via different pathways with these viral hepatitides.

Risk factors for hepatocellular carcinoma in cirrhosis due to nonalcoholic fatty liver disease: A multicenter, case-control study.

Aim: To identify risk factors associated with hepatocellular carcinoma (HCC), describe tumor characteristics and treatments pursed for a cohort of individuals with nonalcoholic steatohepatitis (NASH) cirrhosis.

Methods: We conducted a retrospective case-control study of a well-characterized cohort of patients among five liver transplant centers with NASH cirrhosis with (cases) and without HCC (controls).

Results: Ninety-four cases and 150 controls were included.

Processing of miR17-92 Cluster in Hepatic Stellate Cells Promotes Hepatic Fibrogenesis During Alcohol-Induced Injury.

Background: Exposure to alcohol and its metabolites can initiate hepatic injury and fibrogenesis. Fibrosis is mediated through hepatic stellate cell (HSC) activation, leading to global changes in mRNA and microRNA (miR) expression. miRs are expressed in cells or shuttled to exosomes which can be detected in tissue culture media (TCM) and biological fluids.

Amoxicillin-Clavulanate-Induced Liver Injury.

Background And Aims: Amoxicillin-clavulanate (AC) is the most frequent cause of idiosyncratic drug-induced injury (DILI) in the US DILI Network (DILIN) registry. Here, we examined a large cohort of AC-DILI cases and compared features of AC-DILI to those of other drugs.

Methods: Subjects with suspected DILI were enrolled prospectively, and cases were adjudicated as previously described.

Diet-Induced Obesity Enhances Progression of Hepatocellular Carcinoma through Tenascin-C/Toll-Like Receptor 4 Signaling.

Obesity is an independent risk factor for the development of liver fibrosis/cirrhosis and hepatocellular carcinoma (HCC). Tenascin-C (TnC), an extracellular matrix protein, is transiently expressed during tissue injury and plays a role in fibrogenesis and tumorigenesis. However, the mechanistic role of TnC signaling in the development of HCC remains unknown.

Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis.

Genome-wide association studies (GWASs) have linked genes to various pathological traits. However, the potential contribution of regulatory noncoding RNAs, such as microRNAs (miRNAs), to a genetic predisposition to pathological conditions has remained unclear. We leveraged GWAS meta-analysis data from >188,000 individuals to identify 69 miRNAs in physical proximity to single-nucleotide polymorphisms (SNPs) associated with abnormal levels of circulating lipids.

Changing the face of hepatitis C management - the design and development of sofosbuvir.

The availability of direct-acting antiviral (DAA) therapy has launched a new era in the management of chronic hepatitis C. Sofosbuvir, a uridine nucleotide analog that inhibits the hepatitis C RNA-dependent RNA polymerase, is the backbone of chronic hepatitis C therapy. Acting at the catalytic site of the polymerase, sofosbuvir is highly potent in suppressing viral replication and has a high genetic barrier to resistance.

Recurrent hepatitis C after liver transplant.

End stage liver disease from hepatitis C is the most common indication for liver transplantation in many parts of the world accounting for up to 40% of liver transplants. Antiviral therapy either before or after liver transplantation is challenging due to side effects and lower efficacy in patients with cirrhosis and liver transplant recipients, as well as from drug interactions with immunosuppressants. Factors that may affect recurrent hepatitis C include donor age, immunosuppression, IL28B genotype, cytomegalovirus infection, and metabolic syndrome.

Drug-induced liver injury with autoimmune features.

Drug-induced liver injury (DILI) with features of autoimmunity (AI) represents an important category of hepatotoxicity due to medication exposure. Drugs repeatedly associated with AI-DILI include diclofenac, α-methyl DOPA, hydralazine, nitrofurantoin, minocycline, and more recently statins and anti-TNF-α agents. Usually, symptoms of acute liver injury occur within a few months after initiation of a culprit medication, but a longer latency period is possible.

Hepatitis C treatment: an incipient therapeutic revolution.

An exciting paradigm shift is occurring in the treatment of hepatitis C virus (HCV). We now have the capacity to specifically target therapy to HCV proteins, and thereby directly interrupt the viral life cycle. The first direct-acting antivirals (DAAs), the NS3-4A serine protease inhibitors boceprevir and telaprevir, improved the rate of sustained virologic response (SVR), but their toxicities combined with PEG-IFN and RBV limited their overall efficacy.

Pharmacological inhibition of a microRNA family in nonhuman primates by a seed-targeting 8-mer antimiR.

MicroRNAs (miRNAs) regulate many aspects of human biology. They target mRNAs for translational repression or degradation through base pairing with 3' untranslated regions, primarily via seed sequences (nucleotides 2 to 8 in the mature miRNA sequence). A number of individual miRNAs and miRNA families share seed sequences and targets, but differ in the sequences outside of the seed.

Systemic causes of cholestasis.

Systemic causes of cholestasis constitute a diverse group of diseases across organ systems. The pathophysiology of cholestasis in systemic disease can be a consequence of direct involvement of a disease process within the liver or extrahepatic biliary system or secondary to immune-mediated changes in bile flow. Evaluating a patient with cholestasis for a systemic cause requires an understanding of the patient's risk factors, clinical setting (eg, hospitalized or immunosuppressed patient), clinical features, and pattern of laboratory abnormalities.

Parvin-beta inhibits breast cancer tumorigenicity and promotes CDK9-mediated peroxisome proliferator-activated receptor gamma 1 phosphorylation.

Parvin-beta is a focal adhesion protein downregulated in human breast cancer cells. Loss of Parvin-beta contributes to increased integrin-linked kinase activity, cell-matrix adhesion, and invasion through the extracellular matrix in vitro. The effect of ectopic Parvin-beta expression on the transcriptional profile of MDA-MB-231 breast cancer cells, which normally do not express Parvin-beta, was evaluated.

Identification of genetic variants in endothelial lipase in persons with elevated high-density lipoprotein cholesterol.

Background: Elevated high-density lipoprotein cholesterol (HDL-C) is associated with reduced risk of cardiovascular disease, and variation in HDL-C levels has been shown to be approximately 50% heritable. Overexpression of endothelial lipase (EL), a member of the lipoprotein lipase gene family, markedly reduces HDL-C levels in mouse models. We hypothesized that genetic variation in EL might be associated with elevated HDL-C.

The frequency of the cholesteryl ester transfer protein-TaqI B2 allele is lower in African Americans than in Caucasians.

Cholesteryl ester transfer protein (CETP) mediates the exchange of cholesteryl ester for triglyceride between high density lipoprotein (HDL) and very low density lipoprotein. The B2 allele of the TaqIB polymorphism located in the first intron of the CETP gene occurs with an allele frequency of about 0.40 in Caucasians and is associated with decreased CETP levels and activity and with higher HDL-cholesterol (HDL-C) levels in this racial group.