Pathy's Principles and Practice of Geriatric Medicine - Группа авторов

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hepatitis and is the most often‐occurring idiosyncratic prescription drug‐induced liver injury. Isoniazid is the second most common idiosyncratic prescription cause of DILI and is hepatocellular hepatitis. INH‐induced hepatitis prevalence increases markedly with age. Herbal and dietary supplements can also cause drug‐induced hepatitis, and in 20% of cases, two or more of these substances are involved.

      Once a substance is implicated as resulting in an idiosyncratic liver injury, it should not be reused; substances like acetaminophen, which result in liver injury due to overdosage, can be reused, but the dose of acetaminophen should not exceed 2 g daily in alcoholics or 4 g daily in others.19

      Alcohol abuse is common, with 18% lifetime prevalence in all ages, including the geriatric population. Not many studies are done on the prevalence of alcohol use disorder in the geriatric population. In a New York community, 6% of people over age 60 had more than two drinks daily.20 30% of older hospitalized patients on a medical ward and 50% of those on a psychiatry unit had alcohol use disorder.21 A standard drink is 14 g of alcohol; about 1% of people drinking 30–60 g/day will develop alcoholic cirrhosis, and 6% of those drinking 120 g daily will develop cirrhosis.22

      Primary biliary cholangitis (PBC), previously called primary biliary cirrhosis, is an autoimmune disease where T‐cells attack the small liver bile ducts and gradually cause destruction. It is a relatively rare disease with a prevalence of 1:50,000 and occurs primarily in women (90%), usually starting between the ages of 30 and 65. 60% of patients are asymptomatic at presentation, and the disease is suspected on inspection of liver enzymes showing elevation of alkaline phosphatase and sometimes bilirubin. 40% present with symptoms of fatigue and pruritus, and some patients present with clinical manifestations of cirrhosis. Physical signs include hyperpigmentation, jaundice, xanthomas, xerosis (dry skin), dermatographism, fungal infections of the feet or nails, and enlargement of the spleen in the absence of cirrhosis due to non‐portal hypertension. Like most autoimmune diseases, PBC is associated with other autoimmune diseases, especially Sjögren's syndrome, thyroid disease, scleroderma, and rheumatoid arthritis.

      The disease should be looked for in any patient with elevated alkaline phosphatase, which is liver derived; this can be ascertained by fractionating the alkaline phosphatase or getting a gamma‐glutyl‐transferase (GGT) level that is also elevated. An ultrasound should be done to rule out an obstructive cause for the abnormality. If alkaline phosphatase is at least 1.5 times the upper limit of normal, blood tests should be done for antimitochondrial antibodies (AMA), or sp100 or gp210 antibodies if AMA is absent. A liver biopsy is often helpful, as it can show destruction of interlobular bile ducts and is relatively specific. The prognosis of this disease is usually good, and progress of the disease can be slowed with treatment with ursodeoxycholic acid or, if this does not lower alkaline phosphatase, with fenofibrate and obeticholic acid.

      It is important for the geriatric physician to recognize this disease, as early treatment prevents end‐stage liver disease, patients can present with variceal bleeding in the absence of cirrhosis, and osteoporosis is more prevalent in PBC.25

      Mutations in the HFE gene are the cause of most cases of hemochromatosis. Homozygous C282Y mutation or C282Y and H63D combined mutation account for most cases. However, most patients with these mutations do not develop iron overload, as other factors play a role, such as iron consumed and lost and alcohol use. Patients with the genetic defect absorb about 3 mg of iron daily compared to 1 mg in normal people on a typical Western diet. People become symptomatic when total body iron stores are greater than 20 g, usually after age 40 in men and 60 in women. The mutation occurs in 7% of the Caucasian population, for a prevalence of 0.3–0.7% in this population, and much less frequently in other ethnic groups.26

      Patients present with multiple manifestations reflecting iron deposition in multiple organs. Symptoms include fatigue, hepatomegaly, increased transaminase, cirrhosis, hepatocellular cancer, diabetes, cardiomyopathy, hypopituitarism, and arthropathy. There should be a low threshold for testing for hemochromatosis in anyone with suggestive manifestations, as screening tests are easily obtained and treatment will prevent progression. Screening tests are iron, iron‐binding/transferrin, and ferritin. An iron saturation of greater than 45% or ferritin greater than 200 should prompt further testing with a genotype, liver biopsy with iron determination, or an MRI, which can accurately detect iron overload.

      Treatment consists of determining the stage by estimating fibrosis with liver biopsy and other means and then phlebotomy weekly or biweekly until the ferritin is less than 50.27 If caught and treated in time, hepatic and other manifestations of the disease will not occur. This disease often has its first manifestation after age 65, particularly in females.

      Autoimmune hepatitis (AIH), as the name implies, is an autoimmune disease of the liver that can present as acute elevations in liver enzymes, fulminant hepatic failure, chronic elevations, or cirrhosis. Often there are serologic markers of positive antinuclear antibodies, smooth muscle antibodies, and hypergammaglobulins. Histologically shows hepatitis with a plasma cell infiltrate. Although AIH is considered a disease of children and adolescents, about 20% of adults with AIH develop the disease after age 60.28 The male‐to‐female ratio is 1:3 in elderly patients with AIH. This disease must always be looked for as it can often be readily treated with prednisone, azathioprine, and/or budesonide. Drug‐induced AIH hepatitis usually resolves within one to three months after the offending medication is discontinued and must always be considered, especially in the elderly. Nitrofurantoin, statins, minocycline, and diclofenac are known to cause drug‐induced AIH‐like hepatitis.29 In patients with cirrhosis, treatment should include prednisone; but in noncirrhotics, budesonide can be used. Portal hypertension will shunt budesonide around the liver.

      Primary sclerosing cholangitis is a rare disorder, more often seen in males, with a prevalence rate of about 1 in 10,000. It is characterized by hepatic ductal stricturing, which leads to progressive jaundice and cirrhosis.30 It is often associated with inflammatory bowel disease, usually ulcerative colitis. It usually presents before age 40, but if it presents after 50 is less likely to be associated with inflammatory bile disease. It is best diagnosed by MRI cholangiogram or endoscopic cholangiogram, and there is no effective treatment. In jaundice of unclear aetiology, the bile ducts must be visualized to look for primary sclerosing cholangitis or other causes of bile duct obstruction like pancreatic carcinoma or common bile duct stones.

      Hepatocellular carcinoma (HCC) incidence peaks in men age 70–74, while patients older than 75 account for 22%.31 In North America, hepatocellular carcinoma is predominantly a disease of older adults, with 50% of cases occurring in adults over 60. In contrast, the peak incidence of HCC in Sub‐Saharan Africa and China occurs in young to middle adulthood. Older adults are more likely to present with advanced disease,

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