gastroenterology observership 2

40 year old female has hepA infection, jaundice at young age, no family history of liver disease, she had her liver enzyme up and down since 10 years ago, recently high alt ast, high cholesterol, TG, her weight is stable, recently ultrasound show mild fatty liver
NASH? LIVER BIOPSY?

NASH nonalcoholic steatohepatitis (NASH)
Patients with nonalcoholic fatty liver disease (NAFLD) have hepatic steatosis, with or without inflammation and fibrosis. In addition, no secondary causes of hepatic steatosis are present.
NAFLD is subdivided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). In NAFL, hepatic steatosis is present without evidence of significant inflammation, whereas in NASH, hepatic steatosis is associated with hepatic inflammation that may be histologically indistinguishable from alcoholic steatohepatitis.

Prevalence — Nonalcoholic fatty liver disease (NAFLD) is seen worldwide and is the most common liver disorder in Western industrialized countries, where the major risk factors for NAFLD, central obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome are common.
In the United States, studies report a prevalence of NAFLD of 10 to 46 percent, with most biopsy-based studies reporting a prevalence of NASH of 3 to 5 percent.
Worldwide, NAFLD has a reported prevalence of 6 to 35 percent (median 20 percent).

Patients with NAFLD (particularly those with NASH) often have one or more components of the metabolic syndrome.
■Obesity
■Systemic hypertension
■Dyslipidemia
■Insulin resistance or overt diabetes

Laboratory findings — Patients with NAFLD may have mild or moderate elevations in the aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Patients with NAFLD may have an elevated serum ferritin concentration or transferrin saturation . There is evidence that a serum ferritin greater than 1.5 times the upper limit of normal in patients with NAFLD is associated with a higher nonalcoholic fatty liver disease activity score (and thus, NASH) and with advanced hepatic fibrosis.

Rule out other disorders — Differentiating NAFLD from the other items in the differential diagnosis begins with a thorough history to identify potential causes such as significant alcohol use, starvation, medication use, and pregnancy-related hepatic steatosis.

We test all patients with hepatic steatosis for hepatitis C virus infection. We also test for hepatitis A and B. We do this to both to rule out these infections in patients with elevated aminotransferases and to determine immunity to guide future immunizations.
We also rule out other chronic liver diseases such as autoimmune hepatitis and hemochromatosis.
We obtain the following tests in all patients:
■Anti-hepatitis C virus antibody
■Hepatitis A IgG
■Hepatitis B surface antigen, surface antibody, and core antibody
■Plasma iron, ferritin, and total iron binding capacity
■Serum gammaglobulin level, antinuclear antibody, antismooth muscle antibody, and anti-liver/kidney microsomal antibody-1

Radiographic examinations:obtain an ultrasound

Role of liver biopsy: While liver biopsy is the gold standard for diagnosing NAFLD, in many cases a presumptive diagnosis can be made based upon the patient's history, laboratory tests, and imaging findings, provided other disorders have been excluded. However, some patients will continue to have an unclear diagnosis following a noninvasive evaluation. In such cases, a liver biopsy is indicated.

STAGES OF FIBROSIS — Noninvasive tests of hepatic fibrosis attempt to predict the stage of hepatic fibrosis that would be seen histologically. There are several histologic scoring systems for chronic liver disease. Many use five-point scales, such at the Metavir score (see "Histologic scoring systems for chronic liver disease", section on 'Metavir score'):
■F0: No fibrosis
■F1: Portal fibrosis without septa
■F2: Few septa
■F3: Numerous septa without cirrhosis
■F4: Cirrhosis 
Patients are typically considered to have significant fibrosis if their fibrosis score is ≥F2.

SEROLOGIC TESTS for fibrosis— A variety of serologic markers have been evaluated to predict the degree of fibrosis in the liver, and panels have been developed that combine assays of multiple markers to improve predictive ability.

The most studied panels are the aspartate aminotransferase (AST) to platelet ratio (APRI), FibroTest/FibroSure, Hepascore, and FibroSpect.

Panels of indirect markers of fibrosis: AST to platelet ratio index — The APRI is based on the AST level and platelet count and is easy to calculate. The APRI is calculated using the AST elevation (which is the AST level divided by the upper limit of normal [ULN] for the lab) and the platelet count per mm3 divided by 1000.
APRI = (AST elevation/platelet count) x 100
As an example, a patient with an AST level of 90 int. unit/L in a lab with an ULN = 45 int. unit/L and a platelet count of 120,000/mm3 would have an APRI of: (2/120) x 100 = 1.67

FibroTest, FibroSure, and ActiTest:FibroTest involves assessment of alpha-2-macroglobulin, alpha-2-globulin (haptoglobin), gammaglobulin, apolipoprotein A1, GGT, and total bilirubin Hepascore — Hepascore involves a combination of bilirubin, GGT, hyaluronic acid, alpha-2-macroglobulin, age, and sex. 

AST/ALT ratio — The AST/ALT ratio is approximately 0.8 in normal subjects. Some studies have suggested that a ratio >1 suggests the presence of cirrhosis.

RADIOLOGIC TESTS: Ultrasound-based transient elastography Magnetic resonance elastography (MRE) Acoustic radiation forse impulse (ARFI) imaging

COMBINING TESTS — Using multiple serologic panels or combining serologic panels with radiographic imaging may improve the ability to correctly assess the degree of a patient's fibrosis [14,166,167]. In addition, it may be possible to improve the diagnostic performance of these panels if they are used in stepwise combination. We typically use a combination serologic testing and tissue elastography. The specific tests chosen will depend on local availability. (See 'Choice of test' above.) The aspartate aminotransferase (AST) to platelet ratio (APRI) has been combined with FibroTest/FibroSure, a strategy referred to as "SAFE" biopsy (sequential algorithm for fibrosis evaluation). In one study, the combination had good overall accuracy for significant fibrosis and reduced the need for liver biopsy in patients with chronic hepatitis C virus (HCV). (See 'FibroTest, FibroSure, and ActiTest' above.) FibroTest has also been evaluated in combination with ultrasound-based transient elastography. In a study of 183 patients with chronic HCV, the combination of these tests demonstrated an area under the ROC curve of 0.88 for F ≥2, 0.95 for F ≥3, and 0.95 for F = 4. When the elastography and FibroTest results agreed, liver biopsy examination confirmed the stage of fibrosis in 84 percent of cases for F ≥2 fibrosis, in 95 percent for F ≥3 fibrosis, and in 94 percent for F = 4 fibrosis. Thus, it is likely that a combination of serum biomarkers and elastography will improve the accuracy of fibrosis detection.

Which patients to biopsy — Specifically, we obtain a biopsy if the patient:
■Has peripheral stigmata of chronic liver disease (suggestive of cirrhosis)
■Has splenomegaly (suggestive of cirrhosis)
■Has cytopenias (suggestive of cirrhosis)
■Has a serum ferritin >1.5 times the upper limit of normal (suggestive of NASH and advanced fibrosis)
■Is >45 years of age with associated obesity or diabetes (increased risk of advanced fibrosis)

NAFLD activity score — The NAFLD activity score (NAS) is a validated score that is used to grade disease activity in patients with NAFLD. The NAS is the sum of the biopsy's individual scores for steatosis (0 to 3), lobular inflammation (0 to 2), hepatocellular ballooning (0 to 2), and fibrosis (0 to 4). An NAS of 1 or 2 corresponds to NAFL, 3 to 4 corresponds to borderline NASH, and a score ≥5 corresponds to NASH.

DIFFERENTIAL DIAGNOSIS Alternative causes of hepatic steatosis — There are multiple causes of hepatic steatosis that should be considered in a patient with suspected nonalcoholic fatty liver disease (NAFLD).
Causes of hepatic steatosis in addition to NAFLD include:
■Alcoholic liver disease
■Hepatitis C (particularly genotype 3)
■Wilson disease
■Lipodystrophy
■Starvation
■Parenteral nutrition
■Abetalipoproteinemia
■Medications (amiodarone, methotrexate, tamoxifen, glucocorticoids, valproate, anti-retroviral agents for HIV)
■Reye syndrome
■Acute fatty liver of pregnancy
■HELLP (hemolytic anemia, elevated liver enzymes, low platelet count) syndrome
■Inborn errors of metabolism (LCAT deficiency, cholesterol ester storage disease, Wolman disease) A standard drink in the United States (12 oz [360 mL] of beer, 5 oz [150 mL] of wine, 1.5 oz [45 mL] of 80-proof spirits) contains approximately 14 grams of alcohol (figure 1), so the limits above roughly translate to >15 drinks per week for men and >10 drinks per week for women.

SUMMARY AND RECOMMENDATIONS
■Nonalcoholic fatty liver disease (NAFLD) refers to the presence of hepatic steatosis when no other causes for secondary hepatic fat accumulation (eg, heavy alcohol consumption) are present. NAFLD may progress to cirrhosis and is likely an important cause of cryptogenic cirrhosis. (See 'Definitions' above.) NAFLD is subdivided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). In NAFL, hepatic steatosis is present without evidence of significant inflammation, whereas in NASH, hepatic steatosis is associated with hepatic inflammation that may be histologically indistinguishable from alcoholic steatohepatitis.
■Most patients with NAFLD are asymptomatic, although some patients with NASH may complain of fatigue, malaise, and vague right upper abdominal discomfort. Patients are more likely to come to attention because laboratory testing revealed elevated liver aminotransferases or hepatic steatosis was detected incidentally on abdominal imaging.
■Patients with NAFLD may have mild or moderate elevations in the aspartate aminotransferase and alanine aminotransferase, although normal aminotransferase levels do not exclude NAFLD.
■Radiographic findings in patients with NAFLD include increased echogenicity on ultrasound, decreased hepatic attenuation on computed tomography, or an increased fat signal on magnetic resonance imaging.
■A definitive diagnosis of NAFLD requires all of the following: •Demonstration of hepatic steatosis by imaging or biopsy •Exclusion of significant alcohol consumption •Exclusion of other causes of hepatic steatosis
■Other causes of hepatic steatosis include (see 'Differential diagnosis' above): •Significant alcohol use •Hepatitis C (particularly genotype 3) •Wilson disease •Lipodystrophy •Starvation •Parenteral nutrition •Abetalipoproteinemia •Medications •Reye syndrome •Acute fatty liver of pregnancy •HELLP (hemolytic anemia, elevated liver enzymes, low platelet count) syndrome •Inborn errors of metabolism
■Radiologic findings are often sufficient to make a diagnosis of NAFLD, provided other causes of hepatic steatosis have been excluded. However, liver biopsy may be indicated if the diagnosis is not clear or to assess the degree of hepatic injury.