Multidisciplinary Management of Acute Hepatic Porphyria
In this podcast, Akshata Moghe, MD, PhD, discusses the management of acute hepatic porphyrias, including differences in short-term and long-term management, the role of the hepatologist in the care continuum, and the importance of a multidisciplinary team for treatment.
Additional resource:
Moghe A, McGuire BM, Levy C. Acute hepatic porphyrias - a guide for hepatologists. Hepatology. Published online April 12, 2024. https://journals.lww.com/hep/abstract/9900/acute_hepatic_porphyrias_a_guide_for_hepatologists.836.aspx
TRANSCRIPT:
Leigh Precopio: Hello everyone, and welcome to another installment of Podcasts360, your go-to resource for medical news and clinical updates. I'm your moderator, Leigh Precopio, with Consultant360, a multidisciplinary medical information network.
Acute hepatic porphyrias (AHP) are a group of rare genetic disorders that affects the heme biosynthesis pathway. Treatment of acute hepatic porphyrias proves difficult for health care practitioners, as there is a lack of sufficient testing options available, a wide range of symptomatology, and various complications associated with these disorders. As a result, a high level of care from a multidisciplinary team may be necessary for reducing the burden of disease in these patients.
Hepatologists play a key role in this multidisciplinary approach to treatment. Akshata Moghe, MD, joins us to further discuss the role of the hepatologist in the management of acute hepatic porphryias. Dr Moghe is a physician in the Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition at the University of Texas Health Science Center in Houston, Texas.
To begin, could you briefly describe the role of the hepatologist in the diagnosis and management of AHPs? How has that role changed over time?
Akshata Moghe, MD, PhD: I think the hepatologist plays a critical role as a team member on the multidisciplinary team that takes care of patients with acute hepatic porphyrias. But also, I think, hepatologists and gastroenterologists are in a unique position to identify and diagnose these patients for the very first time.
So as a background and a little primer, we know that porphyrias are a group of genetic disorders that arise from defects in the heme biosynthesis pathway. The pathway has eight steps or eight enzymes and a defect in each of these enzymes can lead to a different type of porphyria. Four of these are called the acute hepatic porphyrias. Acute because they present with acute neurovisceral symptoms, but hepatic because the site of both origin and accumulation of porphyrins is in the liver in these cases. They present with I guess a variety of neurovisceral symptoms, but the cardinal symptom is really abdominal pain. And hence, the hepatologist or gastroenterologist might be frequently called upon to consult on these patients. These might be patients with unexplained abdominal pain or undiagnosed abdominal pain that a specialist is called upon for and that would be the hepatologist.
I guess in addition, the hepatologist also plays a role in monitoring these patients for complications over time, because patients with AHPs can develop liver dysfunction or liver damage, including cirrhosis, or even liver cancer, or HCC, hepatocellular carcinoma. So really following these patients over time, monitoring for these complications and then treating those complications if they occur is very much within the purview of the hepatologist.
Leigh Precopio: In your review, you discussed that the diagnosis of AHPs is often missed or delayed. What are some clinical pearls health care practitioners may utilize for prompt diagnosis of AHPs?
Dr Moghe: Yes, so unfortunately I think the porphyrias, especially AHPs, are often misdiagnosed or the diagnosis is delayed for a long time. And there are a few reasons for this, which are important to understand. I think the primary reason is just that physicians believe that porphyrias are disorders that you read about in medical school in a textbook and then you never really see a case in your practice when you start practice, which is really a fallacy. That is not the case.
Secondly, I think there's just not enough for comfort level in knowing what to do, if at all you even think of porphyria as a diagnosis for a patient, how to test, how to diagnose. So that is not very clear to physicians.
And then finally I think it's just hard to diagnose porphyria because it is the presentation can be pretty nonspecific. But one thing that I would kind of remind medical professionals is that even though you see nonspecific neurovisceral symptoms, the presence of abdominal pain, whether it is acute abdominal pain, severe abdominal pain, or just recurrent attacks of abdominal pain, or abdominal pain that has gone undiagnosed for a long time, all these should really trigger you to think about porphyria. And having a high level of suspicion for porphyria and a low threshold to test for porphyria is really the key to improving from diagnosis.
Leigh Precopio: How might the approach to treatment differ for short-term management vs long -term management of AHPs? And how would the role of the hepatologist differ for short-term vs long-term management?
Dr Moghe: Yes, so I think this is a really important question and I could talk about this for a long time, but to put it simply, the short-term management really focuses on the management of an acute attack. So once that attack is diagnosed, managing symptoms is one part of it. And then treating the attack with IV hemin if it's a severe attack is another part of the treatment strategy.
Managing symptoms can be if it's severe pain, then treatment with pain management, whether it's with opioids and other pain management strategies. And management of other manifestations of the attack, hypertension, or tachycardia, or hyponatremia. Managing in the right setting. If it's in a severe attack, then managing in the hospital and the ICU setting. That's kind of covering the management of an acute attack or the short -term management. Also, elimination of any triggers that might have led to that attack is important.
In terms of long term management, I think that really focuses on educating the patient and empowering the patient to know about their condition. So, to know what brings on an attack, how to manage attacks at home. How to prevent further attacks, whether it is, you know, eliminating something that triggered a previous attack or knowing what else can trigger porphyria, whether it's alcohol or smoking, knowing that and preventing future attacks is important.
Sending the patient to a genetic counselor for learning more about the genetic basis of the disease and identifying other family members that might have porphyria is another thing we do in the long-term management. And then finally, monitoring for complications. So, whether it's liver complications or kidney complications, such as the development of chronic kidney disease or neuro complications, monitoring and treating those is important. We do screen these patients for liver cancer once they turn 50. Screening for HCC is something that the hepatologist does when managing these patients long term.
Leigh Preccopio: How might hepatologists work with other health care practitioners to embody a multidisciplinary approach to the treatment and management of these patients?
Dr Moghe: I think it's important to know that you really need a village to take care of patients with acute hepatic porphyrias and it's important for everybody to work as a team. So, you know, the hepatologists might come into the picture right from the time of diagnosis or they might see the patient in clinic after the patient has been referred to them because they were diagnosed elsewhere with porphyria in a different setting. But the hepatologist frequently works with other team members, which could be medical geneticists, or hematologists, or dermatologists, neurologists, sometimes OBGYNs if the patient is contemplating pregnancy or is pregnant. And building a team together and working together so that the patient kind of receives holistic care is really important.
Leigh Precopio: And finally, what is the next step for research in this area?
Dr Moghe: Yes, there's a focus on research in different aspects of the condition. The first is being novel therapies in the treatment of porphyria. So we know that IV hemitin has been the workhorse of management of acute attacks for a long time. And then more recently givosiran was approved for the prophylaxis of acute attacks in AHPs. And we use givosiran in our patients now for prophylaxis and we see that even though we might have normalization of ALA and PBG in these patients, sometimes there are breakthrough attacks, even though overall we see a reduction in attack frequency.
So these breakthrough attacks are really poorly understood and the mechanism behind an attack in spite of normalization of ALA and PBG is being questioned and is the research question that is being discussed in the porphyria community of late. Other novel therapies such as increasing PBGD levels, or delivering PBGD through nanoparticles is being discussed. And then we know that AHP patients can develop HCC, but not much is known about what are the risk factors for development of HCC, when does it develop, does it relate to severity of the disease or attack frequency, and how does the risk of development of HCC change if the patient also has other comorbidities for HCC development such as fatty liver or alcohol use. So, those are interesting questions that I think future research is going to focus on.
Leigh Precopio: Thank you for joining me today.
Dr Moghe: Oh, thank you for bringing up this topic and thank you for having me.