Liver Shorts -May 2020 & CDC Recommendations for Office (NY Times Summary)

NY Times:  C.D.C. Recommends Sweeping Changes to American Offices


FDA Approves Hepatitis C Pangenomic Treatment for Children (Mar 19, 2020):

The U.S. Food and Drug Administration today approved a supplemental application for Epclusa (sofosbuvir and velpatasvir) to treat hepatitis C virus (HCV) in children ages 6 years and older or weighing at least 37 pounds (17 kilograms) with any of the six HCV genotypes—or strains—without cirrhosis (liver disease) or with mild cirrhosis.

Review: NAFLD in China 1999-2018 J Zhou et al. Hepatology 2020; 71: 1851-4.

  • NALFD increased by 8-9% in prevalence, to 29.1%.  This means there are more than 230 million individuals with NAFLD in China.

Use of HCV-positive donors for liver transplantation to HCV-negative recipients. N Anwar et al. Liver Transplantation 2020; 26: 673-80. Key finding: HCV-positive organs had similar outcomes regarding graft function, patient survival and post-LT complications.

Recent Decline in Hepatocellular Carcinoma Rates in U.S. MS Shiels, TR O’Brien. Gastroenterol 2020; 158: 1503-5. Using SEER-21 population based cancer registries covering 37% of U.S. population, the authors found a recent decline in rates of HCC:

  • 2000-2016: 119,078 cases of HCC in SEER-21 registries, 5.84/100,000
  • Rates increased b 5.6% per year from 2000-2007, then by 2.7% per year from 2007 to 2013, subsequent rate reached a plateau and declined with drop of 1.4% per year (P=.12)
  • Improvement could have been due in part to improvement in viral hepatitis treatment; a less favorable explanation could be that the drop occured due to a death from another cause (eg. non-HCC death due to cirrhosis, opioid-related death

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Potential Treatment for Nonalcoholic Steatohepatitis N Chalasani et al. Gastroenterol 2020; 158: 1334-45. The study explored the use of Belapectin, an inhibitor of Galectin-3, in patients with nonalcoholic steatohepatitis and cirrhosis. n=162, phase 2 randomized, double-blind study. Key finding: 1 year of every 2 week infusions were safe but not associated with significant reductions in hepatic venous pressure gradient (HVPG) or fibrosis. However, in a subgroup without varices, there was lowered HVPG and lowered risk of new varices.

Treatment Options for Minimal Hepatic EncephalopathyRK Dhiman et al. Clin Gastroenterol Hepato 2020; 18: 800-12.  This meta-analysis which included 25 trials (n=1563) found the following:

  • For reversing minimal hepatic encephalopathy (MHE), rifaximin (OR 7.53) and lactulose  (OR 5.39) were effective with moderate quality evidence.  Probiotics had OR 3.89 and L-ornithine L-aspartate had OR 4.45 —both with low quality evidence.
  • For prevention of HE, L-ornithine L-aspartate had OR 0.19 (‘high moderate’ quality), and lactulose had OR 0.22 (moderate quality) were effective. Probiotics had OR 0.27 with low quality evidence.
  • The authors conlude that lactulose is the most effective agent for prevention and reversal of MHE.

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Curbside Humor

 

Which is Safer and More Effective –Miralax (PEG 3350) or Lactulose?

A recent randomized multicenter study (D Jarzebicka et al. JPGN 2019; 68: 318-24) compared polyethylene glycol 3350 (PEG, aka Miralax) and lactulose for functional constipation in a cohort of 102 patients (12 weeks of treatment and 4 weeks of follow-up).

Dosing:

  • PEG 3350 dosing divided into 2 doses:
    • <8 kg:  5 g/day
    • 8-12 kg: 10 g/day
    • 12-20 kg: 15 g/day
    • >20 kg: 20 g/day
  • Lactulose was given as 1 mL/kg twice a day

A “good clinical outcome” was considered if there were three or more stools per week and an improvement in stool consistency of at least 2 types in the Bristol scale.

Key findings:

  • At week 12, a good clinical outcome was noted in 98% of PEG group compared with 90% in the lactulose group
  • PEG group had increased defecations relative to lactulose: 7.9 vs. 5.7, less stool retention: 7% vs 10%, and fewer hard stools 7% vs 13%
  • Side effects, mainly abdominal pain and bloating, were reported more frequently with lactulose than with PEG: 23 vs 15, P=0.02)

My take: This study showed that PEG 3350 was more effective and had fewer side effects than lactulose for constipation in children between 6 months of age and 6 years.

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From Civil and Human Rights Museum, Atlanta

Breath Testing for Bacterial Overgrowth

A recent review (Clin Gastroenterol Hepatol 2014; 12: 1964-72) provides useful advice on testing for bacterial overgrowth and explains the limitations/obstacles in determining whether bacterial overgrowth is present.

Their recommendations:

  • Preparation: avoid antibiotics for 4 weeks prior to testing, avoid bismuth for 2-4 weeks, avoid probiotics for 2-3 weeks before testing, avoid consumption of non absorbable carbohydrates (eg. pasta, bread, fiber cereal, beans) the night prior
  • Glucose substrate for hydrogen breath testing is likely most suitable.  50 g in 250 mL.  Check baseline and then every 15 minutes over 120 minute testing interval.  Positive study: increase of 12 ppm (or more) over baseline and/or baseline >20 ppm (if proper test conditions)
  • Glucose breath test (GBT): sensitivity 20-93%, specificity 30-86%.  False-positive results can occur with rapid small-bowel transit.  GBT may not detect distal small bowel bacterial overgrowth.  Lactulose breath test (LBT) generally has lower specificity.
  • If breath testing is not available, small-bowel aspiration for quantitative culture is a reasonable consideration (challenging methodology).  Alternatively, a trial of empiric antibiotics may be considered if pretest probability is high.

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PEG vs Lactulose in Hepatic Encephalopathy

In a study (JAMA Intern Med. Published online September 22, 2014. doi:10.1001/jamainternmed.2014.4746) with 50 participants, PEG was more effective than standard therapy of lactulose for hepatic encephalopathy.  PEG vs Lactulose (HELP study) Abstract.

Here’s an excerpt:

Design, Setting, and Participants  The HELP (Hepatic Encephalopathy: Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution) study is a randomized clinical trial in an academic tertiary hospital of 50 patients with cirrhosis (of 186 screened) admitted for HE.

Interventions  Participants were block randomized to receive treatment with PEG, 4-L dose (n = 25), or standard-of-care lactulose (n = 25) during hospitalization…

Results  Thirteen of 25 patients in the standard therapy arm (52%) had an improvement of 1 or more in HESA score, thus meeting the primary outcome measure, compared with 21 of 23 evaluated patients receiving PEG (91%) (P < .01)… The median time for HE resolution was 2 days for standard therapy and 1 day for PEG (P = .01). Adverse events were uncommon, and none was definitely study related.

Conclusions and Relevance  PEG led to more rapid HE resolution than standard therapy, suggesting that PEG may be superior to standard lactulose therapy in patients with cirrhosis hospitalized for acute HE.

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Hepatology Update (Part 2) -Summer 2014

Hepatology 2014; 60: 715-33.  This publication is the AASLD Practice Guideline for Hepatic Encephalopathy in Chronic Liver Disease.  The recommendations are too extensive to summarize.  Here’s one: despite concerns about efficacy, “lactulose is the first choice for treatment of episodic” overt hepatic encephalopathy.  Rifaximin is an effective add-on therapy to lactulose for prevention of OHE recurrence. AASLD Guidelines Website

Hepatology 2014; 60: 679-86. Using the Drug-Induced Liver Injury Network between 2004-2012, the authors identified 22 cases of hepatotoxicity attributed to statins.  Median age was 60 years.  The latency to onset of symptoms varied from 34 days to 10 years with a median of 155 days. Nine patients had a cholestatic hepatitis pattern and 12 had hepatocellular injury, including six with an autoimmune phenotype. Severity: nine required hospitalization, four had evidence of hepatic failure and one died.

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