Fatty Liver Disease

Fatty liver is a top cause of liver disease world-wide; it includes alcoholic and non-alcoholic etiologies. Often asymptomatic, but patients may have hepatomegaly; vague RUQ pain. Imaging with ultrasound, CT, MRI. See imaging: Steatosis vs Healthy Gold standard is biopsy. To grade disease activity, use the Liver Fibrosis Score Calculator Generalized progression: First, fat accumulates in hepatocytes, which bloats the cells and displaces their nuclei. Then, lipotoxicity from the accumulated fat causes inflammation and necrosis, which triggers repair processes; we may see Mallory-Denk bodies, which are cytoplasmic hyaline inclusions found in many chronic liver diseases. Cycles of damage and repair lead to fibrosis, which, over time, can create scarring and impair liver functioning – this is cirrhosis, stage 3 liver disease. Review Liver Disease Stages & Cirrhosis Damage from liver disease is accumulative and progressive, and we can describe it according to stages:

• Stage 1 is characterized by inflammation; hepatic tissues are inflamed from fighting infection or healing injuries.
• Stage 2 is characterized by fibrosis, in which scar tissue replaces normal hepatic tissue.
• Stage 3 is characterized by cirrhosis, which is scarring is so extensive that liver function is impaired; at this point, signs and symptoms of liver damage might start to appear (sometimes referred to as decompensation).
• Stage 4 is liver failure, which requires urgent medical attention.

Be aware that this progression does not occur in all individuals; the reasons for this are under investigation. Alcoholic liver disease occurs in patients with chronic or binge drinking habits. Lab results will show elevated AST to ALT ratios. Alcoholic liver disease exists on a spectrum of mild to severe: 1. Alcoholic fatty liver refers to the accumulation of fat in the hepatocytes; it is often asymptomatic. 2. Alcoholic steatohepatitis refers to fatty liver with inflammation and fibrosis. 3. Alcoholic hepatitis is the most severe form; patients may start to experience signs and symptoms of cirrhosis and portal hypertension, with possible fever. Chronic Hepatitis C infection is an important co-morbidity. Alcohol cessation is always recommended. In the early stages, alcohol cessation can allow the liver to heal itself. Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder associated with insulin resistance. Patients should be checked for other metabolic disorders, and alcohol use should be ruled out. Non-alcoholic fatty liver disease has essentially two pathways: 1. Triglycerides accumulate in the hepatocytes and cause bloating and cell distortion. 2. In some individuals, NAFLD progresses to non-alcoholic steatohepatitis (NASH), in which fat accumulation leads to lipotoxicity with eventual fibrosis and possibly cirrhosis (similar to the transition from alcoholic steatohepatitis to hepatitis). Unfortunately, there are no broadly applicable treatments available for non-alcoholic fatty liver disease; weight loss is thought to reduce hepatic fat deposits and inflammation, and some pharmaceutical options are available for select patients (anti-diabetic drugs and vitamin supplements, which are not appropriate for everyone). Central obesity, Type II diabetes, metabolic syndrome, dislipidemia. Impaired synthesis and storage can lead to coagulopathy, which results from decreased storage of vitamin K and synthesis of clotting factors. Impaired hepatic degradation, detoxification and clearance can lead to hepatic encephalopathy and asterixis. Hepatic encephalopathy is the result of toxin build-up in the blood; ammonia, specifically, is thought to be a key culprit. Asterixis, aka, "flapping hand tremor" or "liver flap" is the inability for a patient to sustain a posture due to involuntary, brief, "shock-like" movements. To test for this, have a patient sit with closed eyes, outstretched arms, dorsiflexed wrists, and spread fingers – if they suddenly "flap" their hands, this is asterixis (which is indicative of metabolic encephalopathy, and not specific to hepatic dysfunction). Drug reactions and sensitivities can lead to, for example, elevated estrogen levels, which can cause spider angiomas (spider-looking collections of blood vessels visible beneath the skin), palmar erythema (reddening of the palms and fingers), and gynecomastia (enlargement of breast tissue in males). Impaired bile flow can lead to hyperlipidemia, jaundice, and malabsorption of GI contents. Glucose metabolism is dynamically altered in liver damage so that patients can be hyper- or hypoglycemic. The complications we've addressed so far are largely the result of hepatic tissue dysfunction. Next, let's consider vascular changes that result from portal hypertension, which causes systemic vasodilation and hypotension (via complicated mechanisms that are beyond the scope of this tutorial).

• Varices are collateral blood vessels that form to provide alternative blood flow routes; these pose a

significant risk for hemorrhage, and are an important cause of GI bleeding.

• Ascites & Edema: Ascites refers to the accumulation of fluid in the peritoneum caused by systemic dilation that allows fluid leakage. Ascites is a main complication of cirrhosis, and can lead to peritonitis.

• Spontaneous Bacterial Peritonitis (SBP) is an acute infection resulting from bacteria and endotoxins leaking from the GI tract, and can lead to septic shock if not treated promptly.

• Renal insufficiency and failure are the result of local vasoconstriction (in response to systemic hypotension) and inflammatory processes that reduce filtration. New research shows that spontaneous bacterial peritonitis is often a trigger for renal failure, as it induces the release of pro-inflammatory molecules that contribute to renal dysfunction.

• Hepatopulmonary syndrome, in which pulmonary vasodilation leads to a ventilation/perfusion mismatch, reduced oxygenation, and hypoxemia.

• Increased risk of liver cancer.