Scarring of the liver cirrhosis Around 1 in 5 heavy drinkers have scarring of their liver cirrhosis. Cirrhosis may not cause symptoms. Reducing the risk of liver damage You can reduce the risk of liver damage by cutting down or giving up alcohol.
If you have significant liver scarring or cirrhosis, you should not drink alcohol. Back to top. Welcome to the Quit smoking Live Chat. Please accept functional cookies to use live chat Read our cookies policy to find out more about cookies and how we use them. Manage Cookies. Talk to a breastfeeding expert. Manage cookie preferences.
Options Chat. Alcoholic liver disease is caused by heavy use of alcohol. If you drink more than it can process, it can become badly damaged. Fatty liver can happen in anyone who drinks a lot.
Alcoholic hepatitis and alcoholic cirrhosis are linked to the long-term alcohol abuse seen in alcoholics. Research suggests there may be a genetic link, but this is not yet clear. The effects of alcohol on the liver depend on how much and how long you have been drinking alcohol. These are the most common symptoms and signs:. The symptoms of alcoholic liver disease may look like other health problems.
Always see a doctor for a diagnosis. Your healthcare provider will do a complete health history and physical exam. Other tests used to diagnose alcohol-induced liver disease may include:. The goal of treatment is to restore some or all normal functioning to the liver. This may involve an alcohol treatment program, diet changes, or other methods. Others have hepatitis B virus. Your provider will test you for both and treat you if needed. Those with cirrhosis often develop kidney problems, intestinal bleeding, fluid in the belly, confusion, liver cancer, and severe infections.
Health Home Conditions and Diseases. Many heavy drinkers progress through these 3 types over time: Fatty liver. Fatty liver is the build-up of fat inside the liver cells. It leads to an enlarged liver. Alcoholic hepatitis. Alcoholic hepatitis is an acute inflammation of the liver. There is death of liver cells, often followed by permanent scarring. Alcoholic cirrhosis. A major factor in the initiation of the inflammatory response by resident macrophages of the liver i.
Enhanced circulating endotoxin levels in alcoholic hepatitis are caused by alcohol-induced qualitative and quantitative changes in the bacteria that inhabit the gut i.
These cells produce reactive oxygen species ROS as well as proinflammatory cytokines and chemokines that together with alcohol contribute to hepatocyte damage.
Other factors contributing to hepatocyte damage include alcohol-induced activation of various immune cells i. Other factors can exacerbate liver inflammation. Prominent among these are MAA adducts that are produced in alcohol-exposed hepatocytes. These adducts are taken up by scavenger receptors on KCs Ambade and Mandrekar , further promoting the proinflammatory response. The resulting release of small vesicles i.
Apoptotic hepatocytes are engulfed by KCs, thereby switching their phenotype to M1, which exacerbates inflammation. Inflammation-associated release of chemokines, in turn, attracts circulating macrophages, T-cells, and neutrophils an additional source of oxidative stress to the liver. These immune cells, by releasing proinflammatory cytokines and chemokines with direct cytotoxic effects, further promote hepatocyte cell death and the persistence of alcoholic hepatitis.
Recently, it was reported that HSCs also play a dual i. An important function of HSCs is to transmit signals from sinusoid cells to the liver parenchyma. The proinflammatory cytokines and chemokines produced by activated KCs stimulate the production of proinflammatory cytokines by HSCs. The dual role of KCs in the regulation of inflammation is not only related to production of proinflammatory substances.
At the stage of the resolution of inflammation, KCs produce anti-inflammatory substances, such as prostaglandin D2, which is sensed by HSC receptors. Schematic depiction of the role of Kupffer cells KCs and hepatic stellate cells HSCs in promoting alcohol-induced inflammatory changes and progression to fibrosis and cirrhosis. These factors attract immune cells e. Activated HSCs secrete abundant extracellular matrix proteins e.
HSCs are the key players in the development of fibrosis. These cells normally reside in the space of Disse as quiescent, lipid retinyl-ester -storing cells figure 8. Following hepatic injury, HSCs undergo a complex activation process figure 9 and become the principal source for the increased and irregular deposition of extracellular-matrix components that characterize fibrosis.
Activated HSCs also contribute to the inflammatory response, coordinating the recruitment and stimulation of leukocytes by releasing chemokines and proinflammatory cytokines as well as expressing adhesion molecules.
The leukocytes, in turn, not only attack and destroy hepatocytes, but also activate quiescent and activated HSCs, thereby exacerbating the fibrogenic response Friedman Hepatic stellate cells HSCs are key players in the development of fibrosis.
HSCs normally reside in the space of Disse as quiescent, lipid retinyl-ester -storing cells. Chronic ethanol consumption initiates a complex activation process that transforms these quiescent HSCs into an activated state. Activated HSCs secrete copious amounts of the scar-forming extracellular matrix proteins. This, in turn, contributes to structural changes in the liver, such as the loss of hepatocyte microvilli and sinusoidal endothelial fenestrae, ultimately causing the deterioration of hepatic function.
Pathways of hepatic stellate cell HSC activation. Following hepatic injury, HSCs undergo a complex activation process involving numerous signaling molecules that is characterized by loss of retinoids, increased proliferation, contractility, and chemotaxis. These activated cells are the principal cell source of increased and irregular deposition of extracellular matrix components, which characterize fibrosis.
Activated HSCs also contribute to the inflammatory response by coordinating the recruitment and stimulation of white blood cells WBCs by releasing chemokines and proinflammatory cytokines, as well as expressing adhesion molecules.
Hepatic fibrosis is a transient and reversible wound-healing response, which may be restored to normal in some patients if alcohol intake ceases. The main pathological feature of cirrhosis is the formation of regenerative nodules of hepatic parenchyma surrounded by fibrous septa. Cirrhosis development progresses from a compensated phase, in which part of the liver remains undamaged and functionally compensates for the damaged regions, to a decompensated phase, in which scar tissue fully envelops the organ.
Among problem drinkers, only about 35 percent develop advanced liver disease. This is because modifiers, as listed below, exist that exacerbate, slow, or prevent ALD disease progression. Pattern of Consumption and Beverage Type. The most important factors determining the progression of liver disease are the beverage type consumed and the amount and pattern of drinking e. Epidemiologic data show that women are more susceptible to alcohol-related liver damage than men.
This appears to be related to higher blood alcohol concentrations in women than in men who ingest the same amount of alcohol, resulting from a lower proportion of body water in females compared with males of equal weight Mumenthaler et al. There also are reports that women possess a lower capacity than men to oxidize ethanol in the gut, a process called first-pass metabolism Frezza et al.
This deficit in women allows greater quantities of ethanol into the portal circulation, thereby exposing their livers to higher ethanol concentrations. Further, gender-based differences in the sensitivity of KCs to endotoxins and hepatic inflammatory responses have been related to higher susceptibility to ALD progression in females than in males Frezza et al. It is not completely clear how age modifies ALD progression.
It is, however, a predictor for ALD Masson et al. Ethnicity is a major factor affecting the age at and severity of presentation of different subtypes of ALD Levy et al. The reason s for these differences are not clear. Both genetic and epigenetic influences govern the initiation and progression of ALD. Genome-wide association studies have identified specific genetic markers i.
Most recently, an allele of patatin-like phospholipase domain-containing protein 3 PNPLA3 IM , a triglyceride-degrading enzyme, was identified as an independent risk factor for alcoholic cirrhosis Anstee et al. Nutritional Factors. Dietary fat is a macronutrient and dietary modifier for ALD.
In rodents, dietary saturated fat seems to protect against alcohol-induced liver damage, whereas dietary unsaturated fat that is enriched in linoleic acid reportedly promotes such damage Kirpich et al. Alcohol and other drugs including prescription medications, over-the-counter agents, and illicit drugs interact to enhance hepatotoxicity. For example, as described earlier, acetaminophen hepatotoxicity can be exacerbated by alcohol abuse. Population-based studies have indicated a significant correlation between the risk of liver damage and alcohol consumption in people with a high body mass index Ruhl and Everhart Cigarette smoking can adversely affect certain hepatic functions and is associated with higher risk of alcoholic cirrhosis in humans Klatsky and Armstrong Viral Infections.
The course of hepatitis C HCV and hepatitis B HBV viral infections is worsened in alcohol-abusing patients, causing rapid progression to fibrosis, cirrhosis, and even hepatocellular carcinoma Szabo et al.
Several common mechanisms of viral infection and alcohol-induced damage have been suggested Zakhari ; however, the exact mechanisms for this rapid disease progression are not completely understood. HCV and alcohol are the two most widespread causes of liver disease worldwide.
Almost all patients with a history of both HCV infection and alcohol abuse develop chronic liver injury.
Some studies report that In HCV-positive alcohol abusers, cirrhosis prevalence is even higher at A daily intake of 80 grams of alcohol increases liver-cancer risk 5-fold over that of nondrinkers, whereas heavy alcohol use by HCV-infected individuals increases cancer risk by fold over uninfected heavy drinkers.
There are multiple mechanisms by which alcohol potentiates HCV-infection pathogenesis. For example, HCV proteins induce oxidative stress by binding to the outer membranes of mitochondria, stimulating electron transport and increasing the generation of cellular ROS e. Coupled with the ethanol-induced depletion of the antioxidant glutathione and ROS-induced suppression of proteasome activity, this compromises cell viability Osna et al.
There currently is little information on whether heavy drinking affects the outcomes of HCV treatment with the new generation of antiviral agents Keating Ethanol metabolites appear to stimulate HCV replication. However, this rise is only temporarily sustained Seronello et al. The resulting cell fragments i. In addition to apoptotic bodies, another type of cell-derived vesicles i.
Because ethanol exposure also increases hepatic miRNA levels Bala et al. Innate immunity is the first line of antiviral protection in the liver. HCV commandeers this line of defense, and ethanol metabolism potentiates its takeover. There are other published examples of how ethanol consumption interferes with the immune response to HCV infection Ganesan et al.
Thus, HCV and ethanol synergize in thwarting protective mechanisms that include both innate and adaptive immunity by increasing oxidative stress in liver cells, thereby accelerating the onset of cell death and facilitating the spread of the virus. The following therapies currently are used for optimal ALD management. Drinking cessation is considered the most effective therapy in patients with ALD. Abstinence from alcohol not only resolves alcoholic steatosis but also improves survival in cirrhotic patients Sofair et al.
The effectiveness of abstinence is enhanced when it is combined with lifestyle modifications e. Corticosteroid treatment, including the use of prednisolone, has been the most extensively used form of therapy, especially for moderate to severe alcoholic hepatitis, based on their ability to suppress the immune response and proinflammatory cytokine response Mathurin et al. However, outcomes with steroids have been variable Thursz et al. Current guidelines suggest discontinuation of therapy if there is no indication of a decrease in bilirubin levels by day 7 of treatment European Association for the Study of the Liver Nearly all patients with severe alcoholic hepatitis and cirrhosis are malnourished and their degree of malnutrition correlates with disease severity and complications, such as variceal bleeding, ascites, infections, encephalopathy, and hepatorenal syndrome Halsted ; Mendenhall et al.
Deficiencies in micronutrients e. According to the current guidelines of the American Association for the Study of Liver Diseases, all patients with alcoholic hepatitis or advanced ALD should be assessed for nutritional deficiencies and treated aggressively with enteral nutritional therapy. A protein intake of 1. Micronutrient supplementation should be considered if deficiencies are detected. Supplementation with one such micronutrient, zinc, has been shown to be therapeutic in animal models of alcoholic liver injury.
Mechanistic studies have revealed that its protection is mediated by blocking or attenuating most mechanisms of liver injury, including increased gut permeability, oxidative stress, increased TNF production, and hepatocyte apoptosis Mohammad et al. The few clinical studies conducted to date suggest that zinc supplementation could be an effective therapeutic approach for humans because liver function of ALD and HCV patients improved with 50 mg of elemental zinc Mohammad et al.
This procedure remains the standard of care for patients with end-stage liver disease. Some patients with ALD are not listed for the replacement of their own liver by a donor organ i. As a result, transplantation candidates with ALD often are screened for common malignancies and must undergo a formal medical and psychiatric evaluation.
They also must abstain from alcohol for 6 months before being considered for liver transplantation. Data show that fewer than 20 percent of patients with histories of alcohol use as the primary cause of end-stage liver disease receive liver transplants Lucey However, patient and organ survival is excellent in this patient population, with considerable improvement in their quality of life Singal et al.
Following transplantation, ALD patients return to consuming alcohol at rates similar to those transplanted for other reasons, although ALD patients may consume greater amounts Bergheim et al.
Because all transplant recipients exhibit increased levels of alcohol use over time, post-transplant interventions are deemed extremely valuable in supporting patients to maintain abstinence Donnadieu-Rigole et al.
Patients often turn to natural and herbal therapies based on their potential for hepatoprotection. An extract of milk-thistle seeds silymarin and garlic were reported as the most commonly used herbs for liver disease, followed by ginseng, green tea, gingko, echinacea, and St. As indicated in a recent review Kim et al. This review is the result of work supported with resources and the use of the facilities at the Omaha Veterans Affairs Medical Center. Financial Disclosure.
National Center for Biotechnology Information , U. Journal List Alcohol Res v. Alcohol Res. Natalia A. Osna , Ph. Donohue, Jr. Kharbanda , Ph. Author information Copyright and License information Disclaimer. Osna, Ph. Terrence M. Kusum K. Kharbanda, Ph. Copyright notice. Unless otherwise noted in the text, all material appearing in this journal is in the public domain and may be reproduced without permission.
Citation of the source is appreciated. This article has been cited by other articles in PMC. Abstract Excessive alcohol consumption is a global healthcare problem. Keywords: Alcohol consumption, heavy drinking, alcohol effects and consequences, abstinence, alcoholic liver disease, liver injury, hepatic lesions, steatosis, hepatitis, fibrosis, cirrhosis, treatment, pharmacological therapy, nutritional therapy, liver transplantation.
Hepatic Alcohol Metabolism Beverage alcohol i. Open in a separate window. Figure 1. Spectrum of ALD Heavy ethanol consumption produces a wide spectrum of hepatic lesions, the most characteristic being fatty liver i. Figure 2. Figure 3. Mechanisms Involved in Alcoholic Steatosis As the preceding section on ethanol metabolism stated, ethanol and acetaldehyde oxidations generate higher levels of NADH, which alters the cellular redox potential and enhances lipid synthesis i.
Figure 4. Alcohol Accelerates Hepatic Lipogenesis Enhanced lipid synthesis results from a higher expression of lipogenic enzymes and cytokines see table 2 that are encoded by genes regulated by two transcription factors, sterol regulatory element binding protein-1c SREBP-1c and early growth response-1 Egr Figure 5. Alcohol Decelerates Hepatic Lipid Breakdown Because most lipids in hepatocytes are stored in lipid droplets, these organelles must first be degraded to extract the lipids for their subsequent oxidation.
Alcohol Causes Defective Hepatic Lipid Export It is well known that the liver exports triglycerides and cholesterol only as constituents of very low density lipoprotein VLDL particles; any impairment in either the synthesis or export of VLDL particles therefore contributes to fat accumulation within hepatocytes.
Mechanisms Involved in Alcoholic Hepatitis Alcoholic hepatitis occurs in about 30 to 40 percent of individuals reporting chronic alcohol abuse. Figure 6. Figure 7. Figure 8. Figure 9. Abstinence Drinking cessation is considered the most effective therapy in patients with ALD.
Natural and Artificial Steroids Corticosteroid treatment, including the use of prednisolone, has been the most extensively used form of therapy, especially for moderate to severe alcoholic hepatitis, based on their ability to suppress the immune response and proinflammatory cytokine response Mathurin et al.
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