The high prevalence of nonalcoholic fatty liver disease (NAFLD) has made the condition an important public health issue. Two clinical entities are manifestations of NAFLD, namely nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). The former tends to be benign and non-progressive while the latter can progress to cirrhosis, which in rare cases gives rise to hepatocellular carcinoma. The diagnosis of NAFLD is based on 1) a history of no or limited daily alcohol intake (<20 g for women and <30 g for men), 2) presence of hepatic steatosis by imaging or by histology, and 3) exclusion of other liver diseases. NAFL is defined histologically by the presence of bland, primarily macrovesicular hepatocellular fatty change, while NASH features fatty change with inflammation and evidence of hepatocyte injury, such as ballooning degeneration. Presence of fibrosis is a sign of chronicity. Thus, the diagnosis of NAFL/NASH rests on clincopathological criteria; it always requires both clinical and biopsy-based information. NAFLD could be both the result and the cause of metabolic syndrome, with a vicious cycle operating between these conditions. Remaining challenges are 1) the lack of a clear threshold alcohol intake for defining "nonalcoholic", 2) a lacking consensus for the classification of fatty liver disease, and 3) absence of a histological definition of NASH, which currently remains the gold standard for the diagnosis. Further challenges include the overlap of the criteria for NAFLD and alcoholic liver disease as many obese individuals also consume considerable volumes of alcohol.
One central component in the complex network of processes leading to the development of alcoholic liver disease is the activation of immune cells residing in the liver (i.e., Kupffer cells) by a substance called endotoxin, which is released by bacteria living in the intestine. Alcohol consumption can lead to increased endotoxin levels in the blood and liver. When activated, Kupffer cells produce signaling molecules (i.e., cytokines) that promote inflammatory reactions as well as molecules called reactive oxygen species (ROS), which can damage liver cells. Endotoxin activates Kupffer cells by interacting with a complex of protein molecules that are located on the outside of the Kupffer cell or which extend into the cell. Binding of endotoxin alters the activities of the proteins in this complex so that they trigger a cascade of biochemical signals in the Kupffer cell, resulting in cytokine and ROS production and, ultimately, liver damage. Because alcohol can enhance endotoxin release and, therefore, Kupffer cell activation, novel approaches to inhibit these processes might help prevent or ameliorate alcoholic liver disease.
1.1. The hepatoprotective activity of aqueous-methanolic extract of Cyperus scariosus (Cyperaceae) was investigated against acetaminophen and CCl4-induced hepatic damage.2.2. Acetaminophen produced 100% mortality at a dose of 1 g/kg in mice while pretreatment of animals with plant extract (500 mg/kg) reduced the death rate to 30%.3.3. Acetaminophen at a dose of 640 mg/kg produced liver damage in rats as manifested by the rise in serum levels of alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) to 430 ± 68, 867 ± 305 and 732 ± 212 IU/1 (n = 10) respectively, compared to respective control values of 202 ± 36, 59 ± 14 and 38 ± 7.4.4. Pretreatment of rats with plant extract (500 mg/kg) significantly lowered (P < 0.05) the respective serum ALP, GOT and GPT levels to 192 ± 31, 63 ± 9 and 35 ± 8.5.5. The hepatotoxic dose of CCl4 (1.5ml/kg; orally) raised serum ALP, GOT and GPT levels to 328 ± 30, 493 ± 102 and 357 ± 109 IU/1 (n = 10) respectively, compared to respective control values of 177 ± 21, 106 ± 15 and 47 ± 12.6.6. The same dose of plant extract (500 mg/kg) was able to significantly prevent (P < 0.05) CCl4-induced rise in serum enzymes and the estimated values of ALP, GOT and GPT were 220 ± 30, 207 ± 95 and 75 ± 38, respectively.7.7. The plant extract also prevented CCl4-induced prolongation in pentobarbital sleeping time confirming hepatoprotectivity.8.8. These results indicate that the Cyperus scariosus possesses hepatoprotective activity and thus, rationalizes the folkloric use of this plant in hepato-biliary disorders.
Increased portal blood flow represents a compensatory mechanism preventing hepatic hypoxia after ethanol consumption. In addition, alcohol increases hepatic vascular resistance. Thus, ethanol consumption, by increasing hepatic vascular resistance and portal flow, may worsen portal hypertension in patients with cirrhosis. The aim of this study was to investigate the effects of ethanol consumption on hepatic hemodynamics in patients with alcohol-induced cirrhosis.
Measurements of hepatic venous pressure gradient (HVPG), azygos blood flow, hepatic blood flow, heart rate, and arterial pressure were obtained in 16 patients with alcohol-induced cirrhosis and portal hypertension before and after random administration of a noncaloric fruit drink (250 mL, n = 7) or of an identical beverage plus 0.5 g/kg of ethanol (n = 9).
Vehicle caused no effects. By contrast, ethanol increased HVPG (P < 0.0001). The increase in HVPG was maximum at 15 minutes and remained significant at 45 minutes (P < 0.05 vs. vehicle). Ethanol increased azygos blood flow (P < 0.05) without changes in hepatic blood flow. Heart rate and arterial pressure slightly increased.
Oral ethanol consumption increases portal pressure and portocollateral blood flow in patients with alcohol-induced cirrhosis. These findings suggest that even moderate alcohol consumption worsens the portal-hypertensive syndrome and, therefore, may increase the risk of variceal bleeding in patients with alcohol-induced cirrhosis.
The understanding of how alcohol damages the liver has expanded substantially over the last decade. In particular, the genetics of alcoholism, the genesis of fatty liver, the role of oxidant stress, interactions between endotoxin and the Kupffer cell, and the factors that control activation of the hepatic stellate cell (HSC) have been the focus of a great deal of research. Genetic mechanisms for increasing the risk of alcoholism include alterations in alcohol metabolizing enzymes as well as neurobiological differences between individuals. The development of fatty liver may involve both redox forces, oxidative stress, and alterations in peroxisome proliferator activated receptor function. Oxidative stress is now known to involve both microsomal and mitochondrial systems. Recent studies implicate stimulation of Kupffer cells by portal vein endotoxin as a cause of release of cytokines and chemokines, hepatocyte hyper-metabolism, and activation of HSC. These actions appear to be in part gender-dependent and may explain the susceptibility of women to alcoholic liver disease. Activation of HSC underlies liver fibrosis and cirrhosis of all types; control of this activation might permit control of the progression of fibrosis. These advances suggest a number of new approaches as therapy for alcoholic liver injury.
Udara Rogachikitsa: Ver. 17. Varanasi: Chaukhamba Prakashan
Shastri SB, editor. Yoga Ratnakar, Commentary by Vaidya Sri Laxmipati Shastri. Udara
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Vol 6, Issue 4, 2017.
Alcoholic Liver Disease Med Line Plus: Trusted Health Information for You
George F Longstreth
Longstreth, George F.; Zieve, David (eds.) (18 October 2009). "Alcoholic Liver Disease".
Med Line Plus: Trusted Health Information for You. Bethesda, MD: US National Library
of Medicine & National Institutes of Health. Archived from the original on 22 January
2010. Retrieved 27 January 2010.