Ep 43: A 32-year-old with fever and abdominal pain

Harrison's PodClass provides engaging, high-yield discussions of key topics commonly found on rotational and board exams in internal and family medicine.

Transcript

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♪ (music) ♪(Cathy) Hi, welcome to <i>Harrison's Podclass</i> where we discuss important concepts in internal medicine. I'm Cathy Handy.(Charlie) And I'm Charlie Wiener, and we're coming to you from the Johns Hopkins School of Medicine.

(Cathy) Welcome to Episode 43: 0:17

A 32-Year-Old with Fever and Abdominal Pain.

(Charlie) Here's the case: 0:22

A 32-year-old woman is admitted to the hospital with fever, abdominal pain, and jaundice. She drinks approximately six beers per day but has recently increased her alcohol intake to more than 12 beers daily over the last 3 months. She has no other substance abuse history and has no prior history of liver disease or pancreatitis. She's not taking any medications. On physical examination, she appears ill and disheveled with a fruity odor to her breath.(Cathy) You know, fruity breath always comes up in questions, but it really is quite difficult to detect unless the patient is really, really sick, like in the ICU. But if you do notice it, it suggests ketonemia or ketoacidosis which could be due to starvation in a nondiabetic patient, such as this one.(Charlie) Okay, let's hear more about this case. She's tachycardic with a heart rate of 122, a blood pressure of 95/56, a respiratory rate of 22, a temperature of 101.2, and an oxygen saturation of 98% on room air. She has scleral icterus with poor capillary refill, spider angiomata are present on the trunk, her JVP is flat while supine, and the cardiac and lung examination is normal. Her liver edge is palpable 10 cm below the right costal margin, and it's smooth and tender to palpation. There's no palpable splenomegaly. She also has no ascites or lower extremity edema.(Cathy) So, it does sound like she is really sick and probably in the ICU. What about any relevant labs that we have on her?(Charlie) Her relevant laboratory studies show an AST of 431 IU/L, an ALT of 198 IU/L, a bilirubin of 8.6 mg/dL, an alkaline phosphatase of 201 IU/L, an amylase of 88 U/L and a lipase of 50 U/L. Her total protein is 6.2. Her albumin is 2.8. Her prothrombin time is 29 seconds with a control of 13 seconds, and her INR is 2.2.(Cathy) So, it sounds like, in addition to being acutely sick, she has sequela of heavy and chronic alcohol use with the spider angiomata and the hepatomegaly. In a case like this, the hepatomegaly may be due to fatty infiltration of the liver, and we see that in over 90% of heavy drinkers. I'm also concerned about acute alcoholic hepatitis, given the labs that you mentioned.

(Charlie) The question asks: 2:45

"What is the best approach to the treatment of this patient?" Option A is administer IV fluids, thiamine, and folate. Observe for improvement in laboratory tests in clinical condition. Option B says, administer prednisolone, 40 mg daily for 4 weeks before beginning a taper. Option C is consult surgery for management of acute cholecystitis, and option D says, perform an abdominal CT with IV contrast to assess for necrotizing pancreatitis.(Cathy) In reality, we would probably do a combination of these choices. So, for example, IV fluids would be started, and as we talked about it in episode 41, if you're starting IV glucose-containing fluids, you would also need thiamine supplementation in someone with a heavy alcohol history.(Charlie) Yeah, I agree. In this case, based on her heart rate, blood pressure and physical examination, first thing she really needs is aggressive volume resuscitation with normal saline.(Cathy) I agree, and there's also some suggestion that she has problems with poor nutrition, given that she has an albumin that's low at 2.8. And I would also probably do a CT scan, although necrotizing pancreatitis wouldn't be the first thing on my differential, given the lab values that she has and the physical exam findings. Same goes for the surgery consults. I think we can hold off on that now because it doesn't sound like she has an acute abdomen, and acute cholecystitis isn't the highest on my differential diagnosis.(Charlie) Okay, so it sounds like you're leaning that this lady probably has acute alcoholic hepatitis.(Cathy) Yes, I am. So, for the real answer to the question, I would probably choose answer B which is to start prednisolone, once we've ruled out an infection. But first, I'd also volume resuscitate like we mentioned before, start good nutrition, and then, obviously, continue supportive care, and probably even antibiotics while we're waiting for culture results.(Charlie) Okay, so tell me more about prednisolone and acute alcoholic hepatitis. How do you assess the severity of acute alcoholic hepatitis and who should get prednisolone?(Cathy) The severity of alcoholic hepatitis is conventionally defined by the Maddrey's discriminant function, which is calculated using the prothrombin time and the patient's serum bilirubin level. So, the formula is 4.6 times the patient's prothrombin time in seconds minus the control plus the patient's serum bilirubin level in mg/dL. And once you calculate that, if you have a value that's 32 or higher, it indicates severe alcoholic hepatitis, and that carries a very adverse prognosis. The mortality there can be 20-30% within one month after presentation, and even higher than that up to 30-40% within 6 months after presentation. In our patient, she has a Maddrey's score over 80, so she definitely qualifies as severe disease, and that's a very poor prognostic category.(Charlie) What about MELD scores? Are they used in these kinds of situations?(Cathy) Yeah, absolutely. That's another measure of liver dysfunction that's commonly used for transplant evaluation, and that includes the serum bilirubin, the creatinine and the INR. We don't have her creatinine here, but her bili and her INR are elevated, so her MELD score wouldn't be in the normal range, and the short-term mortality among patients with severe disease even by the MELD score exceeds 30%.(Charlie) Okay, tell me a little bit more about the prednisolone since we've decided that that's what we're going to start in her.(Cathy) So, since her Maddrey's discriminant function is high, over 32, we would start prednisolone, and it's probably the most widely-used option, although not all of the data support an overall survival benefit with this, and there have been meta-analyses, and they've been mixed, but in general, this is still the preferred treatment option. It's important to use prednisolone instead of prednisone because prednisone requires conversion to prednisolone in the liver, which can be impaired in these acute cases. The other important thing to consider before starting is to make sure that there aren't any contraindications or other concerning factors that you would need to manage before starting long-term steroids. So, you'd think about GI bleeding, renal failure, pancreatitis, and you would also want to have hepatology on board.(Charlie) Okay, I've also heard mention of pentoxifylline for this disorder?(Cathy) So, that is another option that's been discussed for acute alcoholic hepatitis. It's a nonspecific TNF inhibitor, and the data there have been mixed too. So, this isn't my first choice. One of the big trials to know about is the STOPAH trial. It was published in 2015 in the <i>New England Journal of Medicine.</i> That trial showed no mortality benefit from pentoxifylline when compared to placebo, but there was a trend towards improvement in mortality with steroids over placebo. Either way, hepatology should be consulted on this patient and involved for the short- and long-term management of this person's disease. Alcohol cessation is also key to the long-term health. I would also say that neither N-acetylcysteine nor TNF inhibitors have shown consistently positive results in trials.(Charlie) Yeah, I was going to ask about those, so I'm glad you mentioned those, too. So, the teaching point here is that in patients with acute alcoholic hepatitis, in addition to volume resuscitation, in patients who have severe disease, prednisolone but not prednisone can also be added. Other medications have not shown consistent benefit, and that while the data is not compelling for prednisolone, it is commonly used in patients like this.(Cathy) And to read more, you can go to <i>Harrison's</i> Disorders of the Gastrointestinal System, and the most recent meta-analysis that was published in <i>Gastroenterology</i> on the benefit of steroids for the short-term decrease in mortality can be found in the journal<i>Gastroenterology</i>, published in 2018, in August.♪ (music) ♪