8/15 (HUP): alcoholic hepatitis

Late post thanks to boards! A big thanks to Dr. Vandana Khungar for helping us through the case of a young man who presented with jaundice and abdominal pain with a bilirubin of 51 and was ultimately diagnosed with acute alcoholic hepatitis (for which he got a liver transplant).

Key features of alcoholic hepatitis

  1. Even though we often think of alcoholic hepatitis as ‘acute’, its actually more often a manifestation of chronic heavy alcohol intake (>80g/day for a decade or more).

Ever wonder how much alcohol is in a ‘standard’ drink? Take a look!

Screen Shot 2017-08-15 at 8.50.33 AM.png

Remember that alcoholic hepatitis (AH) can be superimposed on underlying cirrhosis/chronic liver disease.

  • Patients can present with fever, tender hepatomegaly and leukocytosis; it can sometimes be difficult to distinguish from other causes of acute hepatitis, as well as sepsis/infection
  • Some series have shown that >50% of patients have abdominal bruits; other stigmata of liver disease (ascites, encephalopathy) may be present either with or without underlying liver disease
  • The AST:ALT ratio will usually be >2:1: thought to be due to hepatic deficiency of pyridoxal 5′-phosphate in alcoholics (a cofactor for the enzymatic activity of ALT); so the ratio is really a failure of ALT to increase appropriately

Risk stratification for alcoholic hepatitis

There are several risk scores used for EtOH hepatitis:

Screen Shot 2017-08-15 at 10.25.34 AM.png
Lucey. NEJM 2009.

 

Maddrey’s discriminant function: estimates EtOH severity; a score >32 is considered severe.
Glasgow score: used to estimate likelihood of benefit from steroids. Rarely used in clinical practice
Lille score: helps decide whether to stop or continue steroids after 1 week (ie which patients won’t benefit from steroids no matter what given the severity of their hepatitis)

How is alcoholic hepatitis managed?

  • Supportive care (fluids, antibiotics if needed, abstinence, nutritional support)
  • The big debate is over the role of prednisolone and pentoxifylline (a TNF-a inhibitor) in the treatment of alcoholic hepatitis. You can read the details of the STOPAH trial below (which compared the two), but the short answer is that it’s not totally clear that one is better than the other.
  • One major flaw of STOPAH may have been that in the groups randomized to steroids, the investigators continued prednisolone for 28 days instead of using the Lille score to stop steroids for those people that wouldn’t have benefited; in doing so, they may have driven up mortality due to infection in the steroid group and diminished any apparent benefit of prednisolone!
  • In clinical practice (at least at Penn), prednisolone is often started after 48 hours of negative infectious workup, as long as they don’t have renal failure (a population that was excluded in STOPAH, due at least in part to concerns about bleeding risk)

See reference #2 below for more information about the role of liver transplant in treating alcoholic hepatitis!

References

  1. Thursz M et al. Prednisolone or Pentoxifylline for Alcoholic Hepatitis (STOPAH). NEJM 2015.
  2. Saberi, B. et al. 2016. Current Management of Alcoholic Hepatitis and Future TherapiesJournal of Clinical and Translational Hepatology. 4, 2 (2016), 113–122.
  3. Lucey et al. 2009. Alcoholic Hepatitis. NEJM.

7/31 PPMC Report: Acute Diarrhea!

Acute Diarrhea

Today’s resident intake report from the effervescent Nancy Aitcheson was a 31 yo M p/w 4 days of nausea, vomiting and diarrhea.

As discussed — the differential is in the HISTORY! Most acute diarrhea can be lumped into inflammatory or non-inflammatory based on history alone and occasionally a quick peek at the stool.

We reviewed that extensive testing, including stool cultures, CDiff, fecal leukocytes and O+P are for the most part unnecessary, but discussed the few times when those tests SHOULD be run.

We also highlighted the treatment options:

  1. Rehydrate the patient! — oral is better than IV. If they can’t keep fluids down (like the case presented) then they are likely to need an admission.
  2. Early re-feeding — don’t keep your patient on a clear liquid diet. It turns out letting them eat what they can ASAP helps reduce bowel permeability and decreases illness duration
  3. Loperamide — we’ve all been nervous about giving this to patients, but if the diarrhea ISN’T bloody and they aren’t at risk for CDiff then go ahead!
  4. Pepto Bismol — it’s a tried and true medicine cabinet staple for a reason. Almost ALL patients can take this medication (even if they have fevers and inflammatory diarrhea)!
  5. Probiotics and Zinc — the data backing this up primarily comes from the pediatric population, but if your patient is at home and needs to feel empowered, go ahead and recommend these two treatments. There’s very little downside and potentially some benefit (studies pending).

7/20 (HUP): C. diff and FMT

Thanks to Dr. Brendan Kelly for guiding us through the case of a 70 year old man with severe pan-colitis and shock who was found to have C. difficile.

Pearls

There are two main diagnostic tests to know:

  1. EIA (aka immunoassay) = assay for C. diff toxin A/B AND/OR glutamate dehydrogenase (GDH)
  2. PCR (aka molecular assay aka NAAT) = PCR for C. diff DNA

Glutamate dehydrogenase (GDH) is an enzyme secreted by the bacterium and is highly sensitive but not as specific for C. diff.

The testing approach shown in this diagram echoes HUP’s testing algorithm:

Screen Shot 2017-07-20 at 3.55.48 PM.png

Interestingly, according to a 2016 analysis in JAMA, patients that are toxin-/PCR+ behave much more similarly to toxin-/PCR- patients (ie those that don’t have any evidence of C. diff), as the following figure shows:

Screen Shot 2017-07-20 at 3.59.03 PM.png
The orange and light blue lines (tox-) are much closer to each other than they are to the darker (tox+) line, implying that phenotypically, toxin production is really what determines disease and those that are just PCR+ may just be colonized w/ C. diff and have some other reason for diarrhea. Polage et al, JAMA 2015.

NB: if the C. diff that you ordered comes back as “positive by immunoassay”, that means their GDH/toxin EIA was positive and they probably have C. diff. But if it says “positive by molecular assay”, it means either the GDH or toxin EIA was negative (usually GDH+/toxin- ), and the ‘tie breaker’ PCR (aka molecular assay) was positive, which should make you question whether they really have C. diff diarrhea, or C. diff colonization with diarrhea for some other reason.

You can think about C. diff management in two categories:

  1. Medical management: oral vancomycin, metronidazole, fidaxomicin, supportive care
  2. ‘Surgical’ management:
  • loop ileostomy w/ colonic lavage (Pittsburgh protocol) > total colectomy
  • fecal microbiota transplant (FMT), even though it’s not surgical

Loop ileostomy (what is that?) is indicated for severe complicated C. diff infection (shock, megacolon, lactic acidosis, renal failure, etc).

Lastly, a note on FMT: it’s still in its infancy, and people are still figuring out how to use it and what populations do and don’t benefit from it (IBD, immunocompromised, etc)). Right now it’s used primarily for the treatment of recurrent C. diff infection, but is sometimes used as a last ditch attempt to stave off total colectomy (as in this case). It can be delivered as a slurry of fresh stool (yum) via nasoenteric tube or colonoscope, or as a capsule.

References

  1. Polage, C. et al. 2015. Overdiagnosis of Clostridium difficile Infection in the Molecular Test Era. JAMA Internal Medicine. PMID 26348734
  2. Neal, M. et al. 2011. Diverting Loop Ileostomy and Colonic Lavage: An Alternative to Total Abdominal Colectomy for the Treatment of Severe, Complicated Clostridium difficile Associated Disease. Annals of Surgery. PMID 21865943

 

7/11 PPMC Report: Chronic Diarrhea

Watery Diarrhea

Today we discussed a great case: 54 yo M with PMH GERD/Barrett’s esophagitis and non-healing duodenal ulcer presenting with chronic watery diarrhea and weight loss. (Orange arrows = today’s case!)

We learned the SIX STEP APPROACH TO DIARRHEA and applied this approach to our differential (1).

  1. Is it REALLY diarrhea? (impaction/incontinence vs. diarrhea)
  2. Review MEDICATIONS – including teas, supplements, etc.
  3. Is the host IMMUNOSUPPRESSED?
  4. Is the diarrhea Acute (<2 weeks) or Chronic (>4weeks)?
  5. What description fits the diarrhea? (watery vs. fatty vs. inflammatory)
  6. Don’t forget to think of factitious diarrhea!

We discussed fecal calprotectin use in the outpatient setting (2). The studies on using it in a primary care office are limited but in this particular study the NPV was 98% and the PPV was 28% — so it may be of use in younger patients (<45 yo) to try to tease out organic from inorganic causes of diarrhea in the right setting. Also check out the article below (3) for an excellent IBS read!

We also learned a bit about GASTRINOMAs and Zollinger-Ellison syndrome. Don’t forget to screen for MEN1 (pancreas, parathyroid and pituitary) if you make this diagnosis!

 

References:

  1. Sweester S. Evaluating the Patient with Diarrhea: A Case Based Approach. Mayo Clin Proc.June 2012;87(6):596-602.
  2. Pavlidis P, Chedgy FJQ, Tibble JA. Diagnositic accuracy and clinical application of faecal calprotectin in adult patients presenting with gastrointestinal symptoms in primary care. Scand J Gastroenterol 2013;48:1048-54.
  3. Ford AC, Lacy BE, Talley NJ. Irritable Bowel Syndrome. NEJM 2017;376:2566-78.