This case illustrates the clinical presentation of symptomatic hereditary hemochromatosis (HHC), one of the most common autosomal recessive disorders. HHC is a disorder of iron storage, whereby an inappropriate increase in intestinal iron absorption results in deposition of excessive quantities of iron in parenchymal cells, with eventual tissue damage and functional impairment. The liver is usually the first affected organ. Hepatomegaly develops and, when hepatic iron concentration reaches a threshold of 400 µmol/g dry weight, cirrhosis is common. The iron threshold is lower in patients with other risk factors for liver diseases, such as heavy alcohol consumption or chronic hepatitis. Splenomegaly develops in 50% of symptomatic patients. Manifestations of portal hypertension and esophageal varices occur less commonly than in alcoholic cirrhosis. HCC develops in 30% of those with cirrhosis and is the most common cause of death among treated patients. Clinical HHC is only present in the setting of iron overload. The serum ferritin level defines the point at which hemochromatosis is expressing iron overload and treatment should be initiated. Treatment involves removal of mobilizable iron stores. Weekly phlebotomy is usually required for 2 to 3 years. When the transferrin saturation and ferritin level become normal, phlebotomy is performed at the time intervals required to maintain levels in the normal range. Chelating agents, such as deferoxamine, are more expensive and less effective than phlebotomy, but may play a role in HHC when anemia or hypoproteinemia are severe enough to preclude further blood removal. When treatment is initiated before the development of hepatic cirrhosis or diabetes, patients with HHC appear to have a normal life expectancy. In the case example, elevations in INR, bilirubin, and transaminases suggest that liver damage and cirrhosis have already occurred. Once hepatic cirrhosis develops, no treatment is available to alter the risk of HCC.

Weight loss in obese patients, the control of elevated triglycerides and diabetes, and the avoidance of alcohol are recommended. Of several treatment strategies tested in clinical trials, weight loss (at least 5% to 10% of total body weight) seems to be the most effective. Weight loss in obese patients with steatohepatitis has shown to be associated with normalization of liver enzymes and improved hepatic histology. Newer studies are targeting insulin resistance as a potential underlying mechanism of fatty liver. Clinical trials assessing the use of insulin-sensitizing agents developed for patients with type 2 diabetes mellitus are currently under way.

Several studies suggest that steroids improve survival for patients with severe alcoholic hepatitis without gastrointestinal (GI) bleeding. The definition of severity requires an evaluation of the bilirubin level and the pro time. The so-called discriminant function value identifies a group of patients at substantial risk for dying from alcoholic hepatitis.

4.6 (pro time – control [in seconds]) + (serum bilirubin [mg/dL]) = 32

When severely ill patients with a discriminant function score of ≥32 (without GI hemorrhage) are given 40 mg of prednisone daily for 28 days, survival is nearly twice as likely.

Immune globulin provides protection against hepatitis A. Formerly, preexposure prophylaxis was recommended for those who travel internationally to endemic regions, but currently such persons are advised to receive active immunization. Postexposure prophylaxis with immune globulin is recommended for (a) household and sexual contacts under the age of 12 months or over the age of 40 years (for those between 12 months and 40 years, hepatitis A vaccine is preferred); (b) in day care centers (if children in diapers attend) but not to elementary or secondary school contacts unless an outbreak (more than a single case) has been identified; (c) within institutions to contacts only; and (d) in hospitals only if an outbreak occurs. Immune globulin is not recommended for coworkers in offices or factories. Restaurant-exposed persons also may get immune globulin unless the contact was more than 2 weeks previous, in which case no vaccine is recommended. Postexposure prophylaxis is not needed for persons who have been immunized.

Cardiomyopathy is not an extrahepatic manifestation of hepatitis C. All other choices can be seen along with the addition of lymphoproliferative disorders and leukocytoclastic vasculitis.

Cirrhotic ascites is similar to serum, except it contains less protein. The SAAG is usually >1.1. This ratio is calculated by subtracting the albumin concentration of ascites from that of serum (albumin serum minus albumin ascites). Cardiac ascites will have a similarly high gradient. The SAAG has been established as a clinical valuable test with high specificity to differentiate ascites due to portal hypertension (cirrhosis, Budd-Chiari syndrome, or right heart failure) from other causes of ascites. Low gradients (<1.1) suggest a noncirrhotic (and a noncardiac) cause for ascites, such as malignancy and infection.

This man has symptoms suggesting complicated acute pancreatitis. A contrast-enhanced CT is indicated to determine the presence of pancreatic necrosis. The presence of necrosis on CT requires prompt evaluation for infection. Fine needle aspiration (FNA) with Gram stain has been shown to be most effective at determining the presence or absence of microorganisms.

The CT scan done 2 days prior to the acute episode had already shown the presence of pancreatic necrosis. The development of fever and hypotension should raise suspicion for infected pancreatic necrosis. FNA of the necrotic material is the best way to detect infection. Intravenous antibiotic therapy would be indicated for infected necrosis.

This woman has the classic presentation of hereditary pancreatitis: acute bouts of abdominal pain starting in childhood with the eventual development of chronic pancreatitis. Her family history is positive for pancreatitis. Patients with hereditary pancreatitis have a fivefold greater risk of pancreatic cancer than the risk in the average population.

This man has painless jaundice, which along with a palpable, nontender gallbladder (Courvoisier sign) and his age (over 50 years old) is strongly suggestive of pancreatic cancer. Acute cholecystitis, chronic pancreatitis, and choledocholithiasis are usually associated with abdominal pain. Although chronic pancreatitis and choledocholithiasis can very rarely present this way, pancreatic cancer is more likely.

Dysphagia for solids suggests an anatomic (i.e., structural) rather than a functional (i.e., motility) disorder. Dysphagia resulting from a motor source is usually manifested by difficulty with both solids and liquids.

All these medications are associated with pill-induced esophagitis. However, the most frequent culprit is doxycycline, as it is a widely used antibiotic. Classically, young adults taking doxycycline for acne present with dysphagia and odynophagia because they take their medication either with a minimal amount of water or immediately before bedtime.

More than 50% of patients with noncardiac chest pain have GERD. Extraesophageal presentations of GERD include damage to the lungs (i.e., asthma) and oropharynx (e.g., hoarseness, vocal cord granulomas, dental erosions, and laryngeal cancer) secondary to high acid reflux.

Helicobacter pylori is the most common cause for ulcer disease— especially duodenal ulcer (70% to 75%). NSAIDs are causative in approximately 25% of ulcer disease. Ulcers increase with age because these two risk factors increase with age. Cardiac prophylactic doses of aspirin are a risk factor but have a low incidence of ulcer disease (1%). COX-2-selective inhibitors (0.5%) have the same ulcer risk as placebo.

The most appropriate approach in uncomplicated dyspepsia in this young patient would be H. pylori breath testing. This test-and-treat method is warranted as a cost-effective approach for a young patient with new-onset dyspepsia, as breath testing is noninvasive. A short course of a PPI is a reasonable strategy, but a full 8-week course would not be warranted. No justification ever exists for treating anyone for H. pylori without proof of infection.

Patients younger than 45 to 50 years of age with new-onset dyspepsia without alarm symptoms such as hematemesis, melena, anemia, nausea, vomiting, and weight loss do not warrant immediate upper endoscopy, and the incidence of gastric cancer is low. This patient’s symptoms could be related to gastroparesis. However, a gastric-emptying study would not be the best initial diagnostic study.

Dyspeptic symptoms frequently may persist long after the course of H. pylori eradication therapy. Symptoms, therefore, cannot help to determine if eradication has been achieved. Breath testing would not be accurate this soon after eradication therapy due to the decreased sensitivity from the use of antibiotics and a PPI. Although confirmation of eradication by all testing is most reliable 4 weeks after treatment, fecal antigen testing has the advantage of being a more prompt test to determine treatment failure and can be used as soon as 7 days after the completion of therapy. Quadruple therapy is appropriate as a first-, second-, or even a third-line option. However, in this recently treated patient, it should be initiated only when it has been determined that eradication was unsuccessful.

This is an unstable patient with risk factors for adverse outcomes with ulcer disease. Medical stabilization is most appropriate, then endoscopy. Intravenous PPI therapy and H. pylori eradication are beneficial but not as helpful in this acute bleed as is prompt endoscopic intervention. Rebleeding after initial endoscopic management occurs in 20% to 25% of cases. Repeat endoscopy is very successful, and combined with the use of intravenous PPIs, surgery is needed significantly less often. In addition, interventional radiology procedures in many centers have essentially replaced surgery for intractable GI bleeding.

This is a low-risk patient who should do well with simply starting an NSAID. Starting on a COX-2-selective inhibitor is reasonable, but cost is a concern. Test and treat for H. pylori in this asymptomatic patient is not the appropriate management. Prophylaxis with a PPI and NSAID has an equivalent ulcer risk to that of a COX-2-selective inhibitor but may be more costly. Neither of these regimens is warranted in this low-risk patient. Because NSAID use is so widespread, the economic consequences of universal prophylaxis are prohibitive. Therefore, prophylaxis is warranted only in high-risk patients, such as those who are older than 60 years, have had prior peptic ulcer disease, or are taking a high dosage of or more than one NSAID, use corticosteroids or anticoagulants concurrently with an NSAID, or have a serious systemic disorder. A COX-2-selective inhibitor and PPI is the least appropriate therapy in this low-risk patient.

Until further studies are performed, all patients with an adenoma detected by flexible sigmoidoscopy should undergo a full colonoscopy to detect synchronous, more proximal neoplasms, as well as polypectomy of all detected polyps.

All patients with ulcerative pancolitis who have had the diagnosis for more than 8 years are at increased risk for colorectal dysplasia and cancer. Yearly colonoscopy with four-quadrant biopsy every 10 cm to detect dysplasia is indicated.

Patients with IBS and no risk factors are at average risk for colorectal cancer. Colonoscopy every 10 years (or a flexible sigmoidoscopy every 5 years or annual fecal occult blood testing) is an appropriate screening method for patients at average risk.