Case 23: Chronically Abnormal Liver Function Tests

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Case 23: Chronically Abnormal Liver Function Tests

A 25-year-old male with a history of Down's syndrome, hypothyroidism and a body mass index of 33.2 presented to the office with his mother due to chronic abnormal liver function tests (LFTs). The mother reports chronic elevation in labs for over one year.

The patient is nonverbal, and the mother reports he has not had any GI complaints. Denies any abdominal pain. No history of liver disease. When asked about medications, the mother relays that the patient was prescribed minocycline for six months for a chronic rash and has been following up with dermatology. He discontinued the medication one month ago due to a lack of response. No other antibiotic use. Denies regular Tylenol use. No supplement use. Denies any ETOH use. Bowel movements are daily, and there is no blood with stool. No recent change in stool form or consistency. No nausea or emesis. No unintentional weight loss, there was a slight weight gain of 5 pounds in the past four months and no change in appetite. No history of EGD or colonoscopy in the past.

He has a brother with ulcerative colitis (UC). No family history of liver disease or GI malignancy.


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Presenting Labs

CMP: TB: 1.3. AST: 89. ALT: 120. Alk Phos: 941. All else normal.

CBC: HGB: 14.2. PLTs: 165. MCV: 105.9

RUQ US: The hepatic parenchyma is diffusely increased in echogenicity consistent with fatty infiltration. No focal parenchymal abnormalities are seen within the liver; however, the hepatic contour appears slightly nodular. The gallbladder appears normal. The common bile duct is not dilated.

In your next step for evaluation, you plan on obtaining labs for chronic liver disease evaluation (consisting of INR, autoimmune labs [ANA, SMA, AMA], viral hepatitis panel, ceruloplasmin and AIAT). What additional laboratory evaluation should you consider obtaining?

A)    PEth blood alcohol test
B)    Tylenol serum level
C)    Celiac screening (TTG IgA)
D)    Triglycerides

The correct answer is C, celiac screening (TTG IgA).

Chronic liver disease labs are negative. TTG IgA is positive. Mild iron deficiency. EGD ordered. Findings from EGD suggest atrophic-appearing mucosa of the duodenal bulb and biopsy confirmed celiac disease. Started on a gluten-free diet at one-month follow-up, mother reports immediate improvement in the chronic rash. Repeat labs: TB: 1.33. AST: 186. ALT: 204. Alk Phos: 1294. Remains iron deficient.

MRI/MRCP ordered. Unable to complete MRI/MRCP due to motion artifact, awaiting timing to reschedule with anesthesia.

Colonoscopy recommended (due to persistent iron deficiency and family history of UC). Findings suggestive of pancolitis; a biopsy confirmed UC.

In the setting of recently diagnosed UC and persistently elevated LFTs despite adherence to a gluten-free diet, what diagnosis remains highest on your differential?

A)    Autoimmune liver disease
B)    Primary biliary cirrhosis
C)    Primary sclerosing cholangitis
D)    Drug-induced liver injury

The correct answer is D, primary sclerosing cholangitis.

Practice Pearls

Celiac Disease

  • The U.S. prevalence of celiac disease is approximately 1:130. High-risk groups include first- and second-degree relatives of patients with celiac disease, type 1 diabetes, autoimmune thyroiditis, and Down and Turner syndromes.1
  • Extraintestinal manifestations include patients without other explanation for iron-deficiency anemia, persistent elevation in serum aminotransferases, dermatitis herpetiformis, fatigue, recurrent headaches, recurrent fetal loss, low birthweight offspring, reduced fertility, persistent aphthous stomatitis, dental enamel hypoplasia, metabolic bone disease and premature osteoporosis, idiopathic peripheral neuropathy or nonhereditary cerebellar ataxia.1

Primary Sclerosing Cholangitis

Epidemiology/Pathophysiology

  • Primary sclerosing cholangitis (PSC) is a progressive disorder of the medium and large ducts of the intrahepatic and extrahepatic biliary tree, characterized by inflammation, fibrosis and stricturing.
  • Approximately 70 percent of patients with PSC are men; the mean age at diagnosis is 40 years old.2
  • Roughly 50 percent of patients have concomitant diagnoses of PSC and inflammatory bowel disease (IBD: 70 percent, UC; 17 percent, Crohn’s disease; 8 percent, intermediate/unspecified IBD).3

Clinical Manifestations

  • Patients may be asymptomatic or have symptoms such as fatigue and pruritus.
  • Patients with PSC also may develop numerous other complications, including fat-soluble vitamin deficiencies (A, D, E and K), metabolic bone disease, dominant biliary strictures, cholangitis and cholelithiasis, cholangiocarcinoma, gallbladder cancer, hepatocellular carcinoma (in patients with cirrhosis) and colon cancer (in patients with concomitant UC).2

Diagnostic Evaluation

  • Liver tests are typically elevated in cholestatic pattern, with elevation of alkaline phosphatase predominantly elevated.2
  • Additional abnormal serologic findings include hypergammaglobulinemia, increased IgM and atypical P-ANCA.2
  • Cholangiography (either MRCP or ERCP) is typically utilized for diagnosis and will demonstrate multifocal stricturing (or “beading”) and dilation of the intrahepatic and/or extrahepatic bile ducts.2

Management

  • In addition to age-appropriate cancer screening, patients with PSC typically undergo screening for gallbladder carcinoma, cholangiocarcinoma, colon cancer and hepatocellular carcinoma. Surveillance for cholangiocarcinoma and gallbladder cancer should be performed in all adult patients 20 years or older with PSC, regardless of disease stage. Surveillance considerations include ultrasound, abdominal computed tomography scan or MRI/MRCP with or without serum levels of the tumor marker cancer antigen 19-9 every six to 12 months.3
  • Surveillance is particularly important in the first year after diagnosis, in patients with UC and those diagnosed at an older age.3

 

 

References

  1. UpToDate. Epidemiology, pathogenesis, and clinical manifestations of celiac disease in adults. Diagnosis of celiac disease. Management of celiac disease. https://www.uptodate.com
  2. Kowdley KV. Primary sclerosing cholangitis in adults: Clinical manifestations and diagnosis. Updated October 23, 2023. UpToDate.  https://www.uptodate.com
  3. Mehta TI, Weissman S, Fung BM, Sotiriadis J, Lindor KD, Tabibian JH. Global incidence, prevalence and features of primary sclerosing cholangitis: A systematic review and meta-analysis. Liver Int. 2021;41:2418-2426. doi: 10.1111/liv.15007

Katelyn Cookson, PA-C, is a physician assistant specializing in gastroenterology at UCHealth Digestive Health Center and is also an instructor at the University of Colorado Anschutz Medical Campus. Katelyn serves as co-chair the ASGE APP Committee.

 

Kimberly Kearns, MS, APN-BC, is a nurse practitioner who specializes in adult gastroenterology for DULY Health and Care in Hoffman Estates, Illinois. She is the co-founder of MIDGUT, a professional society dedicated to the education, mentorship and collaboration of nurse practitioners and physician assistants specializing in gastroenterology and hepatology. Kimberly serves on the ASGE APP Committee.