Bariatric surgery is a routinely performed procedure and is associated with a reduction in all-cause mortality in patients with obesity. However, bariatric surgery has also been linked to increased alcohol use with up to 30% of these patients developing alcohol use disorder (AUD). The mechanism of AUD after bariatric surgery is multifactorial and includes anatomic, metabolic, and neurohumoral changes associated with post-surgical anatomy. These patients are at increased risk of alcohol associated liver disease and, in some cases, require liver transplantation. In this article, we provide a scoping review of epidemiology, pathophysiology, and clinical outcomes of alcohol-related health conditions after bariatric surgery.

Chronic liver disease (CLD) is a leading cause of morbidity and mortality worldwide with a wide etiological spectrum. FibroScan^® is used for follow-up of fibrosis and steatosis. This single-center study aims to review the distribution of indications by referral to FibroScan^®.

Demographic characteristics, CLD etiologies, and FibroScan^® parameters of the patients who were referred to our tertiary care center between 2013 and 2021 were retrospectively evaluated.

Out of 9345 patients, 4946 (52.93%) were males, and the median age was 48 [18-88] years. Nonalcoholic fatty liver disease (NAFLD) was the most common indication (N=4768, 51.02%), followed by hepatitis B (N=3194, 34.18%) and hepatitis C (N=707, 7.57%). Adjusting for age, sex, and CLD etiology, the results revealed that patients with older age (Odds ratio (OR)=2.908; confidence interval (CI)=2.597-3.256; p<0.001) and patients with hepatitis C (OR=2.582; CI=2.168-3.075; p<0.001), alcoholic liver disease (OR=2.019; CI=1.524-2.674, p<0.001), and autoimmune hepatitis (OR=2.138; CI=1.360-3.660, p<0.001) had increased odds of advanced liver fibrosis compared to NAFLD.

NAFLD was the most common indication for referral to FibroScan^®.

The present review spans a broad spectrum of topics dealing with alcoholic liver disease (ALD), including clinical research, translational research, pathogenesis and therapies. A special accent is placed on alcohol misuse, as alcohol is a legally commercialized and taxable product. Drinking alcohol, particularly from a young age, is a major health problem. Alcoholism is known to contribute to morbidity and mortality. A systematic literature search was performed in order to obtain updated data (2008-2015). The review is focused on genetic polymorphisms of alcohol metabolizing enzymes and the role of cytochrome p450 2E1 and iron in ALD. Alcohol-mediated hepatocarcinogenesis is also discussed in the presence or absence of co-morbidities such as viral hepatitis C as well as therapeutic the role of innate immunity in ALD-HCV. Moreover, emphasis was placed on alcohol and drug interactions, as well as liver transplantation for end-stage ALD. Finally, the time came to eradicate alcohol-induced liver and intestinal damage by using betaine.

Liver fibrosis occurs as a consequence of chronic injuries from viral infections, metabolic disorders, and alcohol abuse. Fibrotic liver microenvironment (LME) is characterized by excessive deposition and aberrant turnover of extracellular matrix proteins, which leads to increased tissue stiffness. Liver stiffness acts as a vital cue in the regulation of hepatic responses in both healthy and diseased states; however, the effect of varying stiffness on liver cells is not well understood. There is a critical need to engineer in vitro models that mimic the liver stiffness corresponding to various stages of disease progression in order to elucidate the role of individual cellular responses. Here we employed polydimethyl siloxane (PDMS) based substrates with tunable mechanical properties to investigate the effect of substrate stiffness on the behavior of primary rat hepatocytes. To recreate physiologically relevant stiffness, we designed soft substrates (2 kPa) to represent the healthy liver and stiff substrates (55 kPa) to represent the diseased liver. Tissue culture plate surface (TCPS) served as the control substrate. We observed that hepatocytes cultured on soft substrates displayed a more differentiated and functional phenotype for a longer duration as compared to stiff substrates and TCPS. We demonstrated that hepatocytes on soft substrates exhibited higher urea and albumin synthesis. Cytochrome P450 (CYP) activity, another critical marker of hepatocytes, displayed a strong dependence on substrate stiffness, wherein hepatocytes on soft substrates retained 2.7 fold higher CYP activity on day 7 in culture, as compared to TCPS. We further observed that an increase in stiffness induced downregulation of key drug transporter genes (NTCP, UGT1A1, and GSTM-2). In addition, we observed that the epithelial cell phenotype was better maintained on soft substrates as indicated by higher expression of hepatocyte nuclear factor 4α, cytokeratin 18, and connexin 32. These results indicate that the substrate stiffness plays a significant role in modulating hepatocyte behavior. Our PDMS based liver model can be utilized to investigate the signaling pathways mediating the hepatocyte-LME communication to understand the progression of liver diseases.

Alcoholic liver disease (ALD) is the major liver disease in the developed world and characterized by hepatic iron overload in ca. 50% of all patients. This iron overload is an independent factor of disease progression, hepatocellular carcinoma and it determines survival. Since simple phlebotomy does not allow the efficient removal of excess iron in ALD, a better understanding of the underlying mechanisms is urgently needed to identify novel targeted treatment strategies. This review summarizes the present knowledge on iron overload in patients with ALD. Although multiple sides of the cellular and systemic iron homeostasis may be affected during alcohol consumption, most studies have focused on potential hepatic causes. However, it should not be overlooked that more than 90% of the major iron pool, the hemoglobin-associated iron, is efficiently recycled within the human body and it is also strongly affected by alcohol. The few available studies suggest various molecular mechanisms that involve iron regulatory protein (IRP1), transferrin receptor 1 (TfR1), and the systemic iron master switch hepcidin, but not classical mutations of the HFE gene. Notably, reactive oxygen species (ROS), namely, hydrogen peroxide (H2O2), are powerful modulators of these iron-steering proteins. For instance, depending on the level, H2O2 may both strongly suppress and induce the expression of hepcidin that could partly explain the anemia and iron overload observed in these patients. More studies with appropriate ROS models such as the novel GOX/CAT system are required to unravel the mechanisms of iron overload in ALD to consequently identify molecular-targeted therapies in the future.

Alcoholic liver disease (ALD) is the most common liver disease in the Western world. For many reasons, it is underestimated and underdiagnosed. An early diagnosis is absolutely essential since it (1) helps to identify patients at genetic risk for ALD; (2) can trigger efficient abstinence namely in non-addicted patients; and (3) initiate screening programs to prevent life-threatening complications such as bleeding from varices, spontaneous bacterial peritonitis or hepatocellular cancer. The two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis (AH). The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on a combination of laboratory, clinical and imaging findings. It is not widely conceived that conventional screening tools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca. 40% of manifest alcoholic liver cirrhosis. Non-invasive methods such as transient elastography (Fibroscan), acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of alcoholic cirrhosis. Present algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca. 95% of patients. The correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase levels. Other non-invasive methods such as controlled attenuation parameter, serum levels of M30 or M65, susceptometry or breath tests are under current evaluation to assess the degree of steatosis, apoptosis and iron overload in these patients. Liver biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH.