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Hepatitis C and MELD 12

for Health Care Providers

4: Hepatitis C and MELD 12: How often should lab values be monitored, and does comorbid hemosiderosis exclude this patient from transplant?

Background

The patient is a 51-year-old African American male with chronic hepatitis C virus (HCV) genotype 1A, hemosiderosis, porphyria, and persistent pruritus.

He was asymptomatic with no known prior illnesses until 3 years ago, when he noticed his eyes were yellow. His initial laboratory values were as follows:

  • Alanine aminotransferase (ALT): 370 U/L
  • Aspartate aminotransferase (AST): 358 U/L
  • HCV antibodies: positive

The patient underwent liver biopsy, which revealed grade 2, stage 3 disease. In addition, he underwent endoscopic retrograde cholangiopancreatography (ERCP), with findings of a type 1-C choledochal cyst. An abdominal computed tomography (CT) scan revealed 4 "hypodensities" on the liver.

The patient has a past history of intravenous drug abuse. He is a nonsmoker, and denies alcohol use.

Further laboratory workups revealed a serum ferritin level of 232 µg/L, and the results of his liver function tests (LFTs) remained a matter of concern, with measurements as follows:

  • Total bilirubin: 3.1 mg/dL
  • ALT: 207 U/L
  • AST: 211 U/L
  • Albumin: 3.3 g/dL
  • Alpha-fetoprotein (AFP): 26 µg/L

Serial phlebotomies were initiated along with cholestyramine and ultraviolet A (UVA) treatments for porphyria. For treatment of HCV, he received 30 weeks of pegylated interferon (Peg-Intron) + ribavirin, but did not achieve a virologic response.

Almost 2 years after diagnosis, the patient reported no change in pruritus. Successive CT scans of the abdomen consistently found the 4 unchanged hypodensities and a prominent spleen. Otherwise, there were no significant findings.

The patient's most recent laboratory test results were as follows:

  • Albumin: 2.8 g/dL
  • Prothrombin time: 12.9 seconds
  • International normalized ratio (INR): 1.6
  • Total bilirubin: 2.2 mg/dL
  • Platelet count: 65,000 cells/µL
  • AFP: 22 µg/L
  • Ferritin: 214 µg/L
  • Creatinine: 1.0 mg/dL

Questions

  1. How often should LFTs be monitored to assess declining liver function?
  2. Does the patient need a repeat liver biopsy?
  3. Is the patient a candidate for transplant given his comorbidities and, if so, when should the evaluation process be initiated? (last calculated Model for End-Stage Liver Disease [MELD] score: 12)

Discussion

Speaker 1: The patient is a 51-year-old African American with HCV, porphyria, and pruritus. He appears to be cirrhotic as well, but the liver biopsy indicated stage 3, which is not quite considered cirrhosis. Nonetheless, I strongly suspect that this patient is really cirrhotic because he has a very low albumin level, an INR of 1.6, and a total bilirubin measurement of 2.2 mg/dL. So I really think this is a case of cirrhosis, despite the biopsy interpretation.

The patient's main complaint is pruritus, and it is a bit difficult to sort out which process is causing the pruritus. He has porphyria and he also has a choledochal cyst. But without a recent alkaline phosphatase measurement, we cannot say whether he is really cholestatic because of the cyst. We know that his pruritus has persisted despite phlebotomy, cholestyramine, UVA treatment of the porphyria, and Peg-Intron + ribavirin treatment of his HCV.

Question 1: How often should LFTs be monitored to assess declining liver function?

Speaker 1: There are no guidelines to address this question. When there is compensated cirrhosis or when the MELD score is less than 10, my approach is to assess LFTs every 6-12 months. I try to do that every 6 months because you also need an ultrasound scan and an AFP measurement for HCC screening. For patients with decompensated cirrhosis, it depends on the degree of decompensation. I see patients who are semi-decompensated every 4-6 months and order lab tests. If their MELD score is between 19 and 24, I see them monthly with lab testing. If the MELD score is rising and the creatinine level is rising, then I see them every week. Obviously, you also would be scheduling visits more frequently if you were adjusting the dosage of beta-blockers or diuretics; so you are really tailoring the frequency of visits to the specific circumstances of individual patients.

Question 2: Does the patient need a repeat liver biopsy?

Speaker 1: I would not repeat a liver biopsy. You do not need another liver biopsy unless you are considering a change in your management strategy. If you are not planning to change management in some way, there is no sense in repeating a liver biopsy.

Question 3: Is the patient a candidate for transplant given his comorbidities and, if so, when should the evaluation process be initiated?

Participant 1: I presented this case and I was told this patient would not be a candidate for transplant because of his hemosiderosis.

Participant 2: Some transplant surgeons are concerned that excess iron, or hemosiderosis, is a risk factor for cardiac operative death.

Speaker 2: Let's clarify. It is clear that hemochromatosis--genetic hemochromatosis--is associated with very poor outcomes for transplant recipients. It is not clear whether depleting iron with phlebotomy and excluding cardiomyopathy can lower the risks, and some centers do perform transplants for patients with hemochromatosis, although the cardiac risks are certainly a cause for concern. Also, there are very few African Americans with true genetic HFE-positive hemochromatosis.

As for hemosiderosis, I do not believe there are data to suggest that it is associated with severe complications. The vast majority of patients with high ferritin does not have hemochromatosis and would not be prohibited from transplant.

Speaker 3: In Portland, if a patient does have a high ferritin level, we do a liver biopsy. We perform cardiac biopsy only if the liver iron content is 3-4+.

Speaker 4: Would everybody test for HFE gene mutation in this patient to confirm whether or not he has genetic hemochromatosis? I think that would be reasonable. Remember, you need 2 copies of the bad gene, particularly C282Y, and it is available as a send-out in most of our laboratories.

Speaker 3: As for the pruritus, why is it that men who have pruritus from cirrhosis usually do not even use Vaseline Intensive Care or some other lotion? If you can get them to do that 2 or 3 times a day, the pruritus decreases!

Summary Points

  1. Patients with stable cirrhosis can have laboratory values monitored every 6-12 months, ideally alongside the HCC screening at these intervals.
  2. Patients with decompensated cirrhosis should have laboratory values monitored more often, such as every 3-6 months, depending on the degree of severity.
  3. Hemosiderosis does not necessarily exclude a patient from consideration for transplant. Hemochromatosis may exclude a patient from consideration for transplant, and different centers may have different approaches to managing such patients. Ruling out cardiomyopathy is critical, as the biggest concern is perioperative cardiac complications if the myocardium is involved.
  4. Pruritus can be attributed to several causes, including cholestasis, hepatitis or cirrhosis with hyperbilirubinemia, and hemosiderosis. Disease-specific treatments exist for each of these, but nonspecific treatments for symptom control (eg, topical moisturizers) should be considered as well.

Facilitators/Speakers

  • Sue Currie, MA, Epidemiologist, Associate Director, San Francisco, HCRC
  • Alexander Monto, MD, Hepatologist, Director, San Francisco, HCRC
  • Guadalupe Garcia-Tsao , MD, Hepatologist, Director, Connecticut, HCRC
  • Joseph Awad, MD, Liver Transplant Program Director, Nashville VAMC
  • Anna Sasaki, MD, Hepatologist, Portland, VAMC
  • Thomas Cacciarelli, MD, Liver Transplant Program Director, Pittsburgh VAMC
  • Brenda Salvas, Senior Program Manager, VA National Transplant Program
  • Douglas Heuman MD, Liver Transplant Program Director, Richmond, VAMC
  • Bashar Aqel, MD, Hepatologist, Minneapolis, VA, HCRC
  • HoChong Gilles, RN, MS, FNP, Clinical Coordinator, Richmond, VAMC
  • Kristine Stick, NP, Liver Transplant Coordinator, San Francisco VAMC

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