Liver Shorts May 2018

VL NG et al. J Pediatr 2018; 196: 139-47. This study with 148 children examined the neurodevelopmental outomes of young children with biliary atresia (ChiLDRen Study). Key finding: Children with their native livers were at increased risk for neurodevelopmental delays at 12 and 24 months.  This risk was more than 4-fold increased among those with unsuccessful Kasai procedure.

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WS Lee et al. J Pediatr 2018; 196: 14-20. Updated review on hepatopulmonary synddrome (HPS) and portopulmonary hypertension (POPH).  Figure 1 graphically shows the difference in pathophysiology.  HPS hallmark is intrapulmonary vascular dilatation.  POPH is characterized by progressive remodeling of the wall (thickening & vasoconstriction) of small pulmonary arteries.

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JA Woo Baidal et al. Hepatology; 2018; 67: 1339-47. This prospective cohort study with 528 children showed that increased Vitamin E intake in early childhood, based on validated food questionnaires, correlated with lower ALT values in mid-childhood.  Children with higher intakes “had lower odds of elevated mid-childhood ALT” (adjusted odds ratio of 0.62) when comparing quartiles 2-4 to the lowest quartile.  The authors note that Vitamin E is present in foods that are more often consumed in “healthful diets, such as wheat germ, almonds, spinach, and broccoli, as well as cooking oils.”

J Pfeiffenberger et al. Hepatology 2018; 67: 1261-69. The retrospective multicenter study with 282 pregnancies in 136 women with Wilson’s disease (WD), showed good outcomes. Aggravation of neurologic symptoms was rare (1%) (though tended to persist), liver test abnormalities (6%) resolved in all cases after delivery. Birth defect rate of 3% and spontaneous abortion rate of 26%; rthough, patients receiving treatment with zinc and D-penicillamine had lower spontaneous abortion rates, (10% and 17%, respectively) than those without treatment.  Chelation therapy resulted in no increase in the rate of birth defects compared to the general population.

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F Bril et al. Clin Gastroenterol Hepatol 2018; 16: 558-66. This prospective study of adults with biopsy-proven NASH (52 with diabetes and 49 with prediabetes) found that pioglitazone treatment was associated with a reduction in the primary outcome, NAFLD activity score by 2 or more points, in 48% of those with type 2 diabetes and 46% of those with prediabetes. And, with a resolution of NASH in 44% and 26% respectively.

 

Big Creek Greenway near McFarland

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HBV Reactivation Risk with HCV DAA Therapy and What to Do About It

A recent prospective study (C-J Liu et al. Gastroenterol 2018; 154: 989-97) provided some reassurance about the likelihood of hepatitis B virus (HBV) reactivation during hepatitis C virus (HCV) treatment with direct-acting antivirals (DAA).

In this study with 111 patients with both HCV and HBV treated with ledpasvir/sofusbuvir, all (100%) of the patients had a sustained virologic response for their HCV infection. Other key findings:

  • Of the 37 patients with baseline HBV DNA < 20 IU.mL, 31 (84%) developed detectable HBV DNA levels through posttreatment week 12.
  • Of the 74 patients with baseline HBV DNA >20 IU/mL, 39 (53%) developed increases in HBV DNA >1 log10 IU/mL through posttreatment week 12.
  • 5 patients developed ALT >2 times ULN and 3 patients were started on HBV therapy.

The associated editorial (pgs 795-8) made the following recommendations:

  • “HBsAg-negative/HBcAb-positive patients should be monitored with ALT alone until SVR12 and should be tested with HBsAg +/- HBV DNA only if ALT increases or fails to normalize on therapy.”
  • “HBsAg-positive patients with undetectable baseline HBV DNA should be considered for preemptive anti-HBV treatment, or monitored with ALT and HBV DNA until SVR12”
  • “HBsAg-positive patients with positive baseline HBV DNA should be started on preemptive anti-HBV treatment until SVR12.”

Using the above management strategy will limit the number of HBV-infected patients who need to be treated.

My take: This study and the associated editorial provide useful information regarding DAA in coinfected HBV/HCV patients; this is important for patients and practitioners, especially given the black box warning on DAA medications.

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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.

Assessment of Organ Donation –MRI Often Precludes Need for a Liver Biopsy

A recent retrospective single-center study (J Satkunasingham et al. Liver Transplantation 2018; 24: 470-77) shows that MRI is a good tool to assess hepatic steatosis.  In total there were 144 liver donor candidates; a subset of 32 underwent liver biopsy.

When examining magnetic resonance spectroscopy (MRS) and MRI -proton pump density fat fraction (PDFF), the authors found that MRS-PDFF and MRI-PDFF had 95% and 100% negative predictive value in identifying patients with clinically  significant histologic steatosis (≥10%).

The associated editorial by James Trotter (pg 457-58) makes several important points:

  • Currently living donor transplantation in the U.S. accounts for 4% of all transplants
  • In his center (and most centers), protocol biopsy are not required prior to liver donation.  The main indications for donor liver biopsy are biochemical dysfunction or steatosis on imaging studies.

My take (borrowed from editorial): “Noninvasive estimation of hepatic steatosis is sufficiently accurate to forgo liver biopsy in most donors, although ultimately this decision will continue to rest with the individual center.”

 

Hepatitis C Infections Increasing -Tied to Opioid Crisis

Just when it looked like new treatments could eliminate/cure hepatitis C virus (HCV), it turns out that with the opioid epidemic, HCV infections are increasing at a rapid pace (TJ Liang, JW Ward. NEJM 2018; 378: 1169-71).

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Estimated number of new Hepatitis B and Hepatitis C Infections in the U.S. from CDC Data.

Ethnicity and Fatty Liver Disease

A recent systematic review and meta-analysis (NE Rich et al. Clin Gastroenterol Hepatol 2018 16: 198: 210) provides a more comprehensive description of how ethnicity impacts the epidemiology of nonalcoholic fatty liver disease (NAFLD) in the U.S. This study identified 34 previous publications with 368,569 unique patients.

Key points:

  • NAFLD prevalence in hispanic persons is higher than white persons with a pooled relative risk of 1.47; whereas compared to white persons, black persons have a pooled relative risk of 0.74
  • Presence of NASH also had an ethnic predilection with a relative risk of 1.09 for hispanic persons, and 0.72 for black persons in comparison to white persons
  • Approximately one in 6 of all Americans have NAFLD

My take: While hispanic persons have a higher rate of NAFLD/NASH, it is still quite high among white persons and even in black persons who have the lowest rates.

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How Successful is Liver Transplantation for Fatty Liver Disease?

A recent guideline update (ZM Younossi. Liver Transplantation 2018; 24: 166-70) provides some useful information about nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and liver transplantation (LT).

Key points:

  • “Despite metabolic comorbidities, posttransplant outcomes of NASH patients are generally good.  In fact, 1-, 3-, and 5-year patient and graft survival rates are …similar to other liver diseases.”
  • NASH/NAFLD can recur following LT…”NASH with significant fibrosis (stage ≥2) occurs in approximately 5% of recipients by 5 years after transplantation.”
  • Additional issues to manage after LT, include weight management, and metabolic conditions including diabetes, hypertension, dyslipidemia, and hypertension.  All of these conditions can be affected by specific immunosuppressants.  For example, calcineurin inhibitors and corticosteroids can exacerbate type 2 diabetes mellitus.

My take: This article indicates better LT outcomes than I expected in patients with NASH/NAFLD.

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Hepatitis C Reactivation with Chemotherapy

There are a lot of reports describing the potential of adverse outcomes due to hepatitis B reactivation with chemotherapy as well as with treatment of hepatitis C; in addition, there are recommendations to prevent this occurrence (see below). With hepatitis C virus (HCV), the issue of reactivation has not garnered the same type of concern.  A recent study (HA Torres et al. Hepatology 2018; 67: 36-47) indicates that HCV can reactivate with chemotherapy, though this may not result in adverse outcomes. The authors prospectively followed HCV-infected patients receiving cancer therapy from 2012-16.  Reactivation was defined as HCV RNA increase >1 log over baseline and hepatic flare as an increase in ALT >3 times ULN.

Key finding:

  • “Reactivation occurred in 23 (23%)…No patient with reactivation experienced liver failure or liver-related death within 36 weeks after initiation of cancer treatment…most had an unremarkable clinical course.”

Related articleM Persico et al. Hepatology 2018; 67: 48-55.  In the Persico study, the authors examined the association of HCV with non-Hodgkin’s lymphoma. In this observational study, all patients underwent antiviral therapy with sofosbuvir/ledipasvir and chemotherapy.  Compared to a historical control group, the antiviral treatment group had similar overall survival but a significantly higher disease-free survival after 52 weeks.  Thus, the authors note that antiviral treatment combined with chemotherapy, “was shown to be safe and effective in influencing remission of aggressive lymphomas in HCV patients.”

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