Non-invasive diagnosis and biomarkers in alcohol-related liver disease.

Even though alcohol-related liver disease (ALD) is a major cause of severe liver disease worldwide, most patients with ALD are diagnosed at the decompensation stage. Liver biopsy is still considered the gold standard for establishing a definite diagnosis and assessing the fibrosis stage of ALD, but it is an invasive procedure, associated with significant morbidity. During the last decade, non-invasive tests have been developed to estimate the severity of liver fibrosis and steatosis.

[The role of Cytochrom P4502E1 in Alcoholic Liver Disease and alcohol mediated carcinogenesis].

Various factors are involved in the pathogenesis of alcoholic liver disease (ALD) and ethanol-mediated carcinogenesis. In addition to genetic, epigenetic and immunologic mechanisms, acetaldehyde-associated toxicity, oxidative stress as well as cytokine-mediated inflammation are of major importance. Oxidative stress, with the generation of reactive oxygen species (ROS), develops either in inflammation (alcoholic hepatitis) or during oxidation of ethanol via cytochrome P4502E1 (CYP2E1).

Nuclear Translocation of RELB Is Increased in Diseased Human Liver and Promotes Ductular Reaction and Biliary Fibrosis in Mice.

Background & Aims: Cholangiocyte proliferation and ductular reaction contribute to the onset and progression of liver diseases. Little is known about the role of the transcription factor nuclear factor-κB (NF-κB) in this process. We investigated the activities of the RELB proto-oncogene NF-κB subunit in human cholangiocytes and in mouse models of liver disease characterized by a ductular reaction.

Suppressed Fat Mobilization Due to PNPLA3 rs738409 -Associated Liver Damage in Heavy Drinkers: The Liver Damage Feedback Hypothesis.

PNPLA3 variant rs738409 has been identified as important progression factor in patients with ALD and NAFLD, the most common liver diseases worldwide. These findings point towards similarities between metabolism of alcohol and fat with regard to the PNPLA3 gene. However, despite many efforts, neither the mechanisms of PNPLA3-related liver damage nor the physiological role of PNPLA3 are fully understood.

Liver stiffness reversibly increases during pregnancy and independently predicts preeclampsia.

Aim: To study liver stiffness (LS) during pregnancy and its association with complications during pregnancy.

Methods: In this observational, diagnostic study, 537 pregnant women were prospectively enrolled at the Department of Obstetrics and Gynecology, University hospital Heidelberg and Salem Medical Center. LS was measured using the Fibroscan device (Echosens, Paris) in all women and in 41 cases 24 h after delivery.

Publisher Correction: Alcoholic liver disease.

The originally published article contained an error in figure 8 part a, in which cut off values for F3 fibrosis, cirrhosis, and screening for oesophageal varices and HCC were incorrectly presented as <8 kPa, <12.5 kPa and <20 kPa, respectively. These cut off values have been corrected in the HTML and PDF versions of the manuscript to >8 kPa for F3 fibrosis, >12.

Alcoholic liver disease.

Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease worldwide. ALD can progress from alcoholic fatty liver (AFL) to alcoholic steatohepatitis (ASH), which is characterized by hepatic inflammation. Chronic ASH can eventually lead to fibrosis and cirrhosis and in some cases hepatocellular cancer (HCC).

Non-invasive diagnosis of liver fibrosis in patients with alcohol-related liver disease by transient elastography: an individual patient data meta-analysis.

Background: The value of transient elastography for the non-invasive diagnosis of alcohol-related liver fibrosis is subject to debate. We did an individual patient data (IPD) meta-analysis to determine specific diagnostic cutoff values for liver stiffness in alcohol-related fibrosis, and to assess the effect of aminotransferase concentrations, bilirubin concentrations, and presence of asymptomatic and non-severe alcoholic hepatitis on liver stiffness.

Methods: We searched for studies that included patients with alcohol-related liver disease, liver biopsy, and transient elastography, and with a statistical method for determining the diagnostic cutoffs for alcohol-induced liver fibrosis on the basis of the FibroScan results, in PubMed between Jan 1, 2000, and Sept 30, 2017.

Pharmacological decrease of liver stiffness is pressure-related and predicts long-term clinical outcome.

Liver stiffness (LS) as measured by transient elastography is increasingly used to noninvasively assess liver fibrosis. However, LS is efficiently modulated by confounders like arterial and portal pressure (PP). We here study the effect of acute hemodynamic changes on LS (measured by µFibroscan) in a rodent model of cirrhosis in response to pharmacological modulation of PP by losartan, nitric oxide donors, and propranolol.

Hypoxia enhances HO-mediated upregulation of hepcidin: Evidence for NOX4-mediated iron regulation.

The exact regulation of the liver-secreted peptide hepcidin, the key regulator of systemic iron homeostasis, is still poorly understood. It is potently induced by iron, inflammation, cytokines or HO but conflicting results have been reported on hypoxia. In our current study, we first show that pronounced (1%) and mild (5%) hypoxia strongly induces hepcidin in human Huh7 hepatoma and primary liver cells predominantly at the transcriptional level via STAT3 using two hypoxia systems (hypoxia chamber and enzymatic hypoxia by the GOX/CAT system).

Controlled attenuation parameter and alcoholic hepatic steatosis: Diagnostic accuracy and role of alcohol detoxification.

Background & Aims: Controlled attenuation parameter (CAP) is a novel non-invasive measure of hepatic steatosis, but it has not been evaluated in alcoholic liver disease. Therefore, we aimed to validate CAP for the assessment of biopsy-verified alcoholic steatosis and to study the effect of alcohol detoxification on CAP.

Methods: This was a cross-sectional biopsy-controlled diagnostic study in four European liver centres.

Evaluation of laboratory tests for cirrhosis and for alcohol use, in the context of alcoholic cirrhosis.

Laboratory tests can play an important role in assessment of alcoholic patients, including for evaluation of liver damage and as markers of alcohol intake. Evidence on test performance should lead to better selection of appropriate tests and improved interpretation of results. We compared laboratory test results from 1578 patients between cases (with alcoholic cirrhosis; 753 men, 243 women) and controls (with equivalent lifetime alcohol intake but no liver disease; 439 men, 143 women).

Association of Proteinuria with Central Venous Catheter Use at Initial Hemodialysis.

Context: Central venous catheter (CVC) use is associated with increased mortality and complications in hemodialysis recipients. Although prevalent CVC use has decreased, incident use remains high.

Objective: To examine characteristics associated with CVC use at initial dialysis, specifically looking at proteinuria as a predictor of interest.

Does Hypoxia Cause Carcinogenic Iron Accumulation in Alcoholic Liver Disease (ALD)?

Alcoholic liver disease (ALD) is a leading health risk worldwide. Hepatic iron overload is frequently observed in ALD patients and it is an important and independent factor for disease progression, survival, and the development of primary liver cancer (HCC). At a systemic level, iron homeostasis is controlled by the liver-secreted hormone hepcidin.

Increase in liver stiffness after transjugular intrahepatic portosystemic shunt is associated with inflammation and predicts mortality.

Unlabelled: Transjugular intrahepatic portosystemic shunt (TIPS) efficiently treats complications of portal hypertension. Liver and spleen stiffness might predict clinically significant portal hypertension. This prospective study investigated liver stiffness in patients receiving TIPS regardless of indication.

Rapid change of liver stiffness after variceal ligation and TIPS implantation.

Liver stiffness (LS) as measured by transient elastography is widely used to screen for liver fibrosis. However, LS also increases in response to pressure changes like congestion but no data on portal pressure are available. We study here the effect of rapid portal pressure changes on LS.

Peroxiredoxin-2: A Novel Regulator of Iron Homeostasis in Ineffective Erythropoiesis.

Aims: Iron overload (IO) is a life-threatening complication of chronic hemolytic disorders such as β-thalassemia. IO results in severe cellular oxidative damage, leading to organ failure. Peroxiredoxin-2 (Prx2), a typical 2-cysteine-(Cys)-peroxiredoxin, is an important component of the cytoprotective system, but its response to IO is still to be fully defined.

Sensitive and non-invasive assessment of hepatocellular iron using a novel room-temperature susceptometer.

Background & Aims: Liver iron accumulates in various chronic liver diseases where it is an independent factor for survival and carcinogenesis. We tested a novel room-temperature susceptometer (RTS) to non-invasively assess liver iron concentration (LIC).

Methods: Two hundred and sixty-four patients with or without signs of iron overload or liver disease were prospectively enrolled.

Caspase-cleaved keratin-18 fragments increase during alcohol withdrawal and predict liver-related death in patients with alcoholic liver disease.

Unlabelled: Noninvasive assessment of disease activity in patients with nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) is still unsettled, but essential for the evaluation of disease progression. We here studied the association of total (M65) and caspase-cleaved (M30) serum keratin-18 fragments (n = 204) with histological parameters (n = 106) in heavy drinkers primarily admitted for alcohol withdrawal before and after alcohol detoxification. An age-, sex-, and fibrosis-stage matched NAFLD cohort (n = 30) was used for comparison.

Does pressure cause liver cirrhosis? The sinusoidal pressure hypothesis.

Independent of their etiology, all chronic liver diseases ultimately lead to liver cirrhosis, which is a major health problem worldwide. The underlying molecular mechanisms are still poorly understood and no efficient treatment strategies are available. This paper introduces the sinusoidal pressure hypothesis (SPH), which identifies an elevated sinusoidal pressure (SP) as cause of fibrosis.

Primary liver injury and delayed resolution of liver stiffness after alcohol detoxification in heavy drinkers with the variant I148M.

Aim: To investigate the influence of genotype in heavy drinkers on serum markers and liver stiffness (LS) during alcohol withdrawal and its association with histology.

Methods: Caucasian heavy drinkers ( = 521) with a mean alcohol consumption of 192.1 g/d (median alcohol consumption: 169.

Arterial pressure suffices to increase liver stiffness.

Noninvasive measurement of liver stiffness (LS) has been established to screen for liver fibrosis. Since LS is also elevated in response to pressure-related conditions such as liver congestion, this study was undertaken to learn more about the role of arterial pressure on LS. LS was measured by transient elastography (μFibroscan platform, Echosens, Paris, France) during single intravenous injections of catecholamines in anesthetized rats with and without thioacetamide (TAA)-induced fibrosis.

Inflammation-adapted liver stiffness values for improved fibrosis staging in patients with hepatitis C virus and alcoholic liver disease.

Background & Aims: It is well known that inflammation increases liver stiffness (LS) in patients with chronic hepatitis C (HCV) and alcoholic liver disease (ALD) independent of fibrosis stage, but no inflammation-adapted cut-off values have been settled so far. An early identification of rapid fibrosers, however, is essential to decide whom to treat first with the novel but expensive antiviral drugs.

Methods: Liver stiffness, biopsy-proven fibrosis stages F0-F4 (METAVIR or Kleiner score) and routine laboratory parameters were studied in 2068 patients with HCV (n = 1391) and ALD (n = 677).