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Liver biopsy is most accu- rate in disorders causing diffuse changes throughout the liver and is subject to sampling error in focal disorders. Liver biopsy should not be the initial procedure in the diagnosis of cholestasis. The biliary tree should first be assessed for signs of obstruction. Contraindications to performing a percutaneous liver biopsy include significant ascites and prolonged INR. Under these circumstances, the biopsy can be per- formed via the transjugular approach.

Ultrasonography is the first diagnostic test to use in patients whose liver tests suggest cholestasis, to look for the presence of a dilated intrahepatic or extrahepatic biliary tree or to identify gallstones. In addition, it shows space-occupying lesions within the liver, enables the clinician to distinguish between cystic and solid masses, and helps direct percutaneous biopsies. Ultrasound with Doppler imaging can detect the patency of the portal vein, hepatic artery, and hepatic veins and determine the direction of blood flow. This is the first test ordered in patients suspected of having Budd- Chiari syndrome.

The pathology of alcoholic liver disease consists of three major lesions, with the progressive injury rarely existing in a pure form: (1) fatty liver, (2) alcoholic hepatitis, and (3) cirrhosis.

Although there are genetic predispositions for alcoholism (Chap. 445), gender is a strong determinant for alcoholic liver disease. Women are more susceptible to alcoholic liver injury when compared to men. They develop advanced liver disease with substantially less alcohol intake.

The clinical manifestations of alcoholic fatty liver are subtle and charac- teristically detected as a consequence of the patient's visit for a seemingly unrelated matter. Previously unsuspected hepatomegaly is often the only clinical finding. Occasionally, patients with fatty liver will present with right upper quadrant discomfort, nausea, and, rarely, jaundice. Differenti- ation of alcoholic fatty liver from nonalcoholic fatty liver is difficult unless an accurate drinking history is ascertained. In every instance where liver disease is present, a thoughtful and sensitive drinking history should be obtained.

Alcoholic hepatitis is associated with a wide gamut of clinical features. Fever, spider nevi, jaundice, and abdominal pain simulating an acute abdomen represent the extreme end of the spectrum, while many patients will be entirely asymptomatic. Portal hypertension, ascites, or variceal bleeding can occur in the absence of cirrhosis. Recogni- tion of the clinical features of alcoholic hepatitis is central to the initiation of an effective and appropriate diagnostic and therapeutic strategy. It is important to recognize that patients with alcoholic cirrhosis often exhibit clinical features identical to other causes of cirrhosis.

Patients with alcoholic liver disease are often identified through routine screening tests. The typical laboratory abnormalities seen in fatty liver are nonspecific and include modest elevations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transpeptidase (GGTP), often accompanied by hypertriglyceridemia and hyperbiliru- binemia. In alcoholic hepatitis and in contrast to other causes of fatty liver, AST and ALT are usually elevated two- to sevenfold. They are rarely >400 IU, and the AST/ALT ratio is >1 (Table 335-2). Hyperbilirubinemia is accompanied by modest increases in the alkaline phosphatase level. Derangement in hepatocyte synthetic function indicates more serious disease. Hypoalbuminemia and coagulopathy are common in advanced liver injury. Ultrasonography is useful in detecting fatty infiltration of the liver and determining liver size. The demonstration by ultrasound of portal vein flow reversal, ascites, and intraabdominal venous collaterals indicates serious liver injury with less potential for complete reversal.

Complete abstinence from alcohol is the cornerstone in the treatment of alcoholic liver disease. Improved survival and the potential for reversal of histologic injury regardless of the initial clinical pre- sentation are associated with total avoidance of alcohol ingestion. Referral of patients to experienced alcohol counselors and/or alco- hol treatment programs should be routine in the management of patients with alcoholic liver disease. Attention should be directed to the nutritional and psychosocial states during the evaluation and treatment periods. Because of data suggesting that the pathogenic mechanisms in alcoholic hepatitis involve cytokine release and the perpetuation of injury by immunologic processes, glucocorti- coids have been extensively evaluated in the treatment of alcoholic hepatitis. Patients with severe alcoholic hepatitis, defined as a dis- criminant function >32 or MELD >20, should be given prednisone, 40 mg/d, or prednisolone, 32 mg/d, for 4 weeks, followed by a ste- roid taper (Fig. 335-1). Exclusion criteria include active gastrointesti- nal bleeding, renal failure, or pancreatitis. Patients with infection can be concurrently treated with antibiotics and steroids. Women with encephalopathy from severe alcoholic hepatitis may be particularly good candidates for glucocorticoids. A Lille score >0.45, at http:// www.lillemodel.com, uses pretreatment variables plus the change in total bilirubin at day 7 of glucocorticoids to identify those patients unresponsive to therapy.

Liver transplantation is an accepted indication for treatment in select patients with complications of cirrhosis secondary to alcohol abuse. Outcomes are equal or superior to other indications for trans- plantation. In general, transplant candidacy should be reevaluated after a defined period of sobriety. Patients presenting with alcoholic hepatitis have been largely excluded from transplant candidacy because of the perceived risk of increased surgical mortality and high rates of recidivism following transplantation.

Because the vast majority of these subjects deny hazardous levels of alcohol consumption (defined as greater than one drink per day in women or two drinks per day in men), they are considered to have NAFLD. NAFLD is strongly associ- ated with overweight/obesity and insulin resistance. However, it can also occur in lean individuals and is particularly common in those with a paucity of adipose depots (i.e., lipodystrophy). Ethnic/racial factors also appear to influence liver fat accumulation; the documented prev- alence of NAFLD is lowest in African Americans (~25%), highest in Americans of Hispanic ancestry (~50%), and intermediate in American whites (~33%). NAFLD encompasses a spectrum of liver pathology with different clinical prognoses. The simple accumulation of triglyceride within hepatocytes (hepatic steatosis) is on the most clinically benign extreme of the spectrum. On the opposite, most clinically ominous extreme, are cirrhosis (Chap. 337) and primary liver cancer (Chap. 78). The risk of developing cirrhosis is extremely low in individuals with chronic hepatic steatosis, but increases as steatosis becomes complicated by histologically conspicuous hepatocyte death and inflammation (i.e., nonalcoholic steatohepatitis [NASH]). NASH itself is also a heteroge- neous condition; sometimes it improves to steatosis or normal histol- ogy, sometimes it remains relatively stable for years, but sometimes it results in progressive accumulation of fibrous scar that eventuates in cirrhosis. Once NAFLD-related cirrhosis develops, the annual inci- dence of primary liver cancer can be as high as 3%

NAFLD is defined as the presence of hepatic steatosis (fatty liver) in individuals who do not consume alcohol or do so in small quantities and who do not have another cause of secondary hepatic fat accumulation

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NAFLD is associated with obesity, diabetes mellitus type 2, and hyperlipidemia, all components of the metabolic syndrome

Central adiposity is a key feature of the syn- drome, and the syndrome’s prevalence reflects the strong relationship between waist circumference and increasing adiposity. However, despite the importance of obesity, patients who are of normal weight may also be insulin-resistant and may have the metabolic syndrome. This phenotype is particularly evident for populations in India, South- east Asia, and Central America.

Individuals with the metabolic syn- drome are twice as likely to die of CVD as those who do not, and their risk of an acute myocardial infarction or stroke is threefold higher. The approximate prevalence of the metabolic syndrome among patients with coronary heart disease (CHD) is 60%, with a prevalence of ~35% among patients with premature coronary artery disease (≤age 45) and a particularly high prevalence among women. With appropriate cardiac rehabilitation and changes in lifestyle (e.g., nutrition, physical activity, weight reduction, and—in some cases—pharmacologic therapy), the prevalence of the syndrome can be reduced.

Lipodystrophic disorders in general are associ- ated with the metabolic syndrome. Moreover, it is quite common for such patients to present with the metabolic syndrome. Both genetic lipodystrophy (e.g., Berardinelli-Seip congenital lipodystrophy, Dun- nigan familial partial lipodystrophy) and acquired lipodystrophy (e.g., HIV-related lipodystrophy and in HIV patients receiving certain antiretroviral therapies) may give rise to severe insulin resistance and many of the components of the metabolic syndrome.

No single gene explains the complex phenotype called the metabolic syndrome. However, using genome wide association and candidate gene approaches, a number of genetic variants are asso- ciated with the metabolic syndrome. Although many of the loci have unknown function, many others relate to body weight and composi- tion, insulin resistance, and lipid and lipoprotein metabolism.

he metabolic syndrome affects nearly 50% of the U.S. popu- lation aged >60, and at >60 years of age women are more often affected. The age dependency of the syndrome’s prevalence is seen in most populations around the world.

Diagnosing NAFLD requires demonstration of increased liver fat in the absence of hazardous levels of alcohol consumption. Thresholds for potentially dangerous alcohol ingestion have been set at more than one drink per day in women and two drinks per day in men based on epidemiologic evidence that the prevalence of serum aminotransferase elevations increases when alcohol consumption habitually exceeds these levels. In those studies, one drink was defined as having 10 g of ethanol and, thus, is equivalent to one can of beer, 4 ounces of wine, or 1.5 ounces (one shot) of distilled spirits. Other causes of liver fat accumulation (particularly exposure to certain drugs; Table 336-2) and liver injury (e.g., viral hepatitis, autoimmune liver disease, iron or cop- per overload, α 1 antitrypsin deficiency) must also be excluded.

Establishing the severity of NAFLD-related liver injury and related scarring (i.e., staging NAFLD) is more difficult than simply diagnosing NAFLD. Staging is critically important, however, because it is neces- sary to define prognosis and thereby determine treatment recommen- dations. The goal of staging is to distinguish patients with NASH from those with simple steatosis and to identify which of the NASH patients have advanced fibrosis.

Most subjects with NAFLD are asymptomatic. The diagnosis is often made when abnormal liver aminotransferases or features of fatty liver are noted during an evaluation performed for other reasons. NAFLD may also be diagnosed during the workup of vague right upper quadrant abdominal pain, hepatomegaly, or an abnormal-appearing liver at time of abdominal surgery. Obesity is present in 50–90% of sub- jects. Most patients with NAFLD also have other features of the meta- bolic syndrome (Chap. 401). Some have subtle stigmata of chronic liver disease, such as spider angiomata, palmer erythema, or splenomegaly. In a small minority of patients with advanced NAFLD, complications of end-stage liver disease (e.g., jaundice, features of portal hyperten- sion such as ascites or variceal hemorrhage) may be the initial findings. The association of NAFLD with obesity, diabetes, hypertriglyceri- demia, hypertension, and cardiovascular disease is well known. Other associations include chronic fatigue, mood alterations, obstructive sleep apnea, thyroid dysfunction, and chronic pain syndrome. NAFLD is an independent risk factor for metabolic syndrome (Chap. 401). Longitudinal studies suggest that patients with NASH are at two- to threefold increased risk for the development of metabolic syndrome. Similarly, studies have shown that patients with NASH have a higher risk for the development of hypertension and diabetes mellitus. The presence of NAFLD is also independently associated with endothe- lial dysfunction, increased carotid intimal thickness, and the number of plaques in carotid and coronary arteries. Such data indicate that NAFLD has many deleterious effects on health in general.

Treatment of NAFLD can be divided into three components: (1) specific therapy of NAFLD-related liver disease; (2) treatment of NAFLD- associated comorbidities; and (3) treatment of the complications of advanced NAFLD.

Treatment of the complications of advanced NAFLD involves manage- ment of the complications of cirrhosis and portal hypertension, includ- ing primary liver cancers.

the current approach to NAFLD management focuses on treatment to improve the risk factors for NASH (i.e., obesity, insulin resistance, metabolic syndrome, dyslipidemia). Based on our understanding of the natural history of NAFLD, only patients with NASH or those with features of hepatic fibrosis on liver biopsy are considered currently for targeted pharmacologic therapies.

1. Which one does NOT belong to sex cord cell tumnors: A. granulosa cell tumor B. teratoma C. thecoma D. sertoli cell tumor E. leydig cell tumor

B. teratoma

Which one is NOT characteristic for complete hydatidiform mole: A. maternal chromosomes only B. diploid zygote C. giving rise to choriocarcinoma in 2~3% D. villi without vasculature E. incidence before 20 and after 40 years of age

Reddened, moist or scaly lesions like eczema on the nipple or areola is a typical manifestation of: A. medullary carcinoma of the breast B. lobular carcinoma in situ C. invasive lobular carcinoma D. Paget disease of the breast E. Intraductal papilloma

Budd–Chiari syndrome (BCS) is a condition principally affecting young females, in which the venous drainage of the liver is occluded by hepatic venous thrombosis or obstruction from a venous web. As a result of venous outflow obstruction, the liver becomes acutely congested, with the development of impaired liver function and, subsequently, portal hyperten- sion, ascites and oesophageal varices.

6. Which neoplasm of the thyroid has the worst prognosis: A. papillary carcinoma B. anaplastic carcinoma C. follicular carcinoma D. medullary carcinoma E. large B-cell lymphoma

P is the