Using Less Steroids for Autoimmune Hepatitis

A recent retrospective study (S Pape et al. Clin Gastroenterol Hepatol 2019; 17: 2068-75) with 451 adults (1978-2017) examined outcomes among patients based on steroid dosing.

A high-dose group (n=281) with initial prednisone/prednisolone dose of ≥0.5 mg/kg/day was compared with a low dose group (n=170) <0.5 mg/kg/day.  The low dose group had higher rates of cirrhosis (25.9% vs. 15.3%) but lower median ALT values (7.1 ULN vs. 13.4 ULN) and lower median bilirubin values (48 vs 29 micromol/L).

Key findings:

  • There was no difference in rates of transaminase normalization at 1 year: 76.2% vs 77.6%
  • Transaminase normalization was lower in patients with cirrhosis 58.1% compared to 70.7% with cirrhosis
  • Most patients were receiving low-dose steroids at 6 months, 87.4% in high-dose group compared to 83.5% in low-dose group
  • Cumulative steroid dose was lower in low-dose group, with median of 2573 mg over 6 months compared to 3780 mg

Though, not studied in this report, AASLD has recommended use of immunoglobulin levels may help with immunosuppression titration. The editorial (pg 1948-49) notes that budesonide is another alternative for AIH without cirrhosis, though “long-term outcomes including histologic remission and appropriate tapering strategy for budesonide are currently lacking.”

My take: Particularly in patients without severe inflammation, lower steroid doses can be considered for autoimmune hepatitis.

Related blog posts:

Atlanta Botanical Garden

Need Liver, Will Travel (2019)

A recent study (AJ Kwong et al Clin Gastroenterol Hepatol 2019; 17: 2347-55) quantifies the potential advantage of moving to receive a liver transplant. This had been discussed in 2016 blog post as well (Need Liver, Will Travel)

During the study period (2004-2016), there were 104,914 waitlist registrations.

Key findings:

  • 60.985 patients received a liver transplant during the study period
  • 2930  (2.8%) pursued listing at a distant center
  • Distant listing was associated with a 22% reductinon in the risk of death within 1 year

My take: this study highlights socioeconomic disparity in acquiring a liver transplant along with potential geographic disparities.

Related article:

“Transplantation Traffic –Geography as Destiny for Transplant Candidates” NEJM 2014; 271: 2450-52.  Describes ongoing geographic inequality in organ distribution and obstacles to improving allocation.

Related blog posts:

Botanical Garden,, Chicago

How Reliable is an Acetaminophen Level in Patients with Acetaminophen Overdose?

A recent study (TM Leventhal et al. Clin Gastroenterol Hepatol 2019; 17: 2110-6) provides more data indicating that acetaminophen levels are frequently undetectable even in patients suspected of developing acute liver failure (ALF) due to acetaminophen overdose.

The authors performed a retrospective study with 434 subjects from the ALF study group who met criteria for either ALF (coagulopathy and hepatic encephalopathy w/in 26 weeks of first symptoms) or Acute Liver Injury (ALI) (severe liver injury with coagulopathy but no encephalopathy).  In this group, all of the patients had liver disease attributed to acetaminophen (APAP) toxicity.

Key findings:

  • 227 patients (52%) had undetectable acetaminophen levels
  • Transplant-free survival rate was 79.5% (including both ALF and ALI patients)
  • APAP-protein adduct data was available for 37 patients in cohort; all patients with this assay had evidence of APAP toxicity regardless of whether APAP level was detected

Discussion Points:

  • Symptoms from APAP toxicity frequently emerge >24 hours after ingestion.  APAP, though, has a short half-life, approximately 2-2.5 hours.  Thus, most patients will have APAP clearance from plasma in 18 hours
  • Unintentional overdose, often with multiple doses over therapeutic limit of 4 g/day (in adults), more frequently is associated with an undetectable APAP level than a single large intentional overdose which results in a higher peak level

My take: This study shows that APAP levels are unreliable in determining APAP ingestions and not predictive of ALF.  The use of N-acetylcysteine should not be determined by APAP levels in patients with suspected overdose.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

Atlanta Botanical Garden

Improving Fatty Liver Disease Nomenclature

Those who follow this blog regularly know that I have frequently agreed with articles suggesting improving/updating nomenclature for many conditions including the following:

A recent commentary (M Eslam et al. Gastroenterol 2019; 157: 590-3) suggests that fatty liver diseases could use a nomenclature makeover as well.

In pediatrics, the issue of alcoholic and nonalcholic fatty liver disease (NAFLD) overlap is fairly minor in many ways.  In fact, when I am seeing a young teen with NAFLD, parents will often chuckle when I tell them that ‘Johnny’ needs to lay off the booze (now and in the future).  However, it is difficult to fully differentiate nonalcoholic fatty liver disease from alcoholic fatty liver disease, especially in adults.

Full Text: Toward More Accurate Nomenclature for Fatty Liver Diseases

Key points:

  • “Light (1.0-9.9 g/d) or moderate (10.0–29.9 g/d; 10.0–19.9 g/d for women) alcohol consumption in patients with NAFLD is not uncommon…The negative impact of alcohol intake also extends to nonalcoholic steatohepatitis resolution.”
  • “it is time for clinicians to recognize that, within the spectrum of fatty liver disease, there will be patients with true alcohol-related liver disease (AFLD), those with predominant AFLD compounded by metabolic cofactors, those with true NAFLD in whom alcohol consumption is near zero and disease progression is due to metabolic factors, and perhaps a majority with fatty liver disease owing to an abnormal metabolic milieu but with alcohol intake of ≤30 g/d.”
  • ” An updated and more appropriate nomenclature and classification system is required to reflect the nuances of disease etiology within the spectrum of fatty liver disease…”
    • MPFL: metabolic dysfunction predominant fatty liver;
    • APFL, alcohol predominant fatty liver;
    • MPFL/A and MPFL/N: metabolic dysfunction predominant fatty liver with, and without alcohol intake that is anything more than ceremonial
    • APFL/M and APFL/N: alcoholic predominant fatty liver with metabolic dysfunction or with no metabolic dysfunction.

My take: The authors present a good rationale for updating fatty liver disease –will this be adopted?

Related blog posts:

 

Sad Truth: Job Security in Hepatology

A recent study (ND Parikh et al. Hepatology 2019; 70: 487-95, and associated editorial JA Marrero. 459-61) provide a forecast of increasing liver disease and liver disease severity, driven mainly by fatty liver disease and obesity.

Key findings:

  • Nonalcoholic fatty liver disease (NAFLD) related additions to the liver transplant waitlist expanded from 391 in 2000 to 1605 in 2014.  This corresponded to an overall increase in obesity of 44.1% during that time period.
  • NAFLD-related wait-list additions were predicted by the prevalence of obesity 9 years prior.
  • The authors anticipate that obesity population will increase to over 92 million adults by 2025.
  • The authors project that NAFLD-related wait-list additions will increase to 2104 by 2030, a 55% increase

Because the decrease in complications related to new treatments for Hepatitis C is not expected “until well into the next decade,” the burden of chronic liver disease will continue to rise.

The editorial notes that overall graft survival rates for obese patients with BMI less than 40 do not appear different than those of lean individuals.  Those with BMI >40 had reduced 5-year graft and survival rates.  Also, obese patients have higher morbidities, even in those without reduced survival.

My take: This study identifies a marked increase in end-stage liver disease in the growing population of obese patients.

Related blog posts:

Sclerosing Cholangitis-Like Changes Due to Drug Induced Liver Injury

A recent study (J Ahmad et al. Clin Gastroenterol Hepatol 2019; 17: 789-90) reviewed subjects in enrolled in drug-induced liver injury (DILI) prospective cohort to determine the frequency of sclerosing cholangitis (SC)-like changes in this population.  SC-like changes have previously been noted in up to 10% of DILI cases (Dig Liv dis 2015; 47: 502-7). In this study, 233 of 1487 subjects had underwent an MRI.

Key findings:

  • Four of 56 (7%) with adequate quality images had SC-like images (4 with intrahepatic stricture and 1 with a common hepatic duct stricture as well)
  • Patients with SC-like changes had a more severe initial injury noted and were more likely to develop chronic injury as noted by persistent lab abnormalities at 6 months

My take: This study indicates that a severe DILI can result in secondary sclerosing cholangitis.

Related blog posts:

 

Liver Briefs -June 2019 part 2

E Cowell et al. JPGN 2019; 68: 695-99. This study reviewed 61 cases of pediatric hepatocellular carcinoma to determine predisposing conditions  (in Houston TX).  The majority did NOT have recognizable predisposing conditions.  25 of 61 (41%) had a predisposing condition including cryptogenic cirrhosis/steatosis (9), genetic (7), biliary pathology (4), viral hepatitis (1), and other (4).  Those without a recognizable predisposing condition were diagnosed later and with more advanced disease/decreased survival.

VA McLin et al. JPGN 2019; 68: 615-22. Useful review on congenital portosystemic shunts.

DE Kaplan et al. Gastroenterol 2019; 156: 1693-1706. This large study form the VA with more than 70,000 patients examined the relationship between statin exposure and survival in patients with cirrhosis.  “Each cumulative year of statin exposure was associated with an independent 8-8.7% decrease of mortality of patients with cirrhosis of Child-Turcotte-Pugh classes A and B.”

AG Singal et al. Gastroenterol 2019; 156: 1683-1692. Direct-acting antiviral therapy was not associated with recurrent hepatocellular carcinoma (HCC) in a multicenter cohort study with 793 patients with HCV-associated HCC. Thus, DAAs appear safe in patients who have achieved a complete response to HCC Rx