Celiac Hepatopathy 2019

A recent retrospective study (E Benelli et al. JPGN 2019; 68: 547-51) examines a large cohort of patients (=700) who were diagnosed with celiac disease (CD) from 2010-2016 and had available liver transaminases.

Key findings:

  • ALT values >40 U/L were elevated in only 3.9% (27/700)
  • Younger age (<4.27 years) correlated with a higher risk of liver involvement with OR 3.73
  • Of these 27 patients with elevated ALT, 18 had adequate followup.  All but 3 patients normalized ALT values after at least 1 year; of these, 1 was diagnosed with sclerosing cholangitis. In the other two, one was thought to be nonadherent with gluten-free diet and one had dropped ALT to 47 U/L.
  • Thus, definitive autoimmune liver disease was identified in only one patient

My take: This study shows a lower rate of liver involvement than previous studies.

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Liver Shorts April 2019

CL Mack et al. JPGN 2019; 68: 495-501. This multicenter prospective open-label phase I/III trial of IVIG in biliary atresia patients status-post Kasai indicated that the infusions were tolerated.  However, though this study was not powered to detect efficacy, survival with native liver was LOWER among patients who had received IVIG (n=29): 58.6% compared to the comparison placebo group 70.5% (n=64).  Thus, despite the theoretical advantages of IVIG which targets aspects of the immune system and improvement in a murine model, in practice IVIG does not appear promising for biliary atresia.

D Kim et al. Hepatology 2019; 69: 1064-74. This study shows that despite improvements in hepatitis C mortality rates associated with newer treatments, there is an overall increase in mortality rates from cirrhosis and hepatocellular carcinoma.  This increase is driven by increasing prevalence and severity of both alcoholic liver disease and nonalchoholic fatty liver disease. The overall cirrhosis-related mortality increased from 19.77/100,000 persons in 2007 to 23.67 in 2016 with an annual increase of 2.3%. Similarly, the overall HCC-related mortality increased from 3.48/100,000 persons in 2007 to 4.41 in 2016 at annual increase of 2%. The editorial on page 931 (TG Cotter and MR Charlton) notes that each year there are more than 40,000 deaaths associated with chronic liver disease.

H Park et al. Hepatology 2019; 69: 1032-45. This study, using Truven Health MarketScan Cata, examined the outcomes of more than 26,000 patients with newly-diagnosed hepatitis C virus (HCV) infection.  Among the 30% who received oral direct-acting antiviral (DAA) therapy, there were improved outcomes in those with and without cirrhosis. In those with cirrhosis (n=2157), DAA was associated with a 72% and 62% lower incidences of HCC and DCC [decompensated cirrhosis] respectively. In noncirrhotic HCV patients (n=23,948), DAA was associated with a 57% and 58% lower incidence of HCC and DCC respectively.  In addition to improved health outcomes, DAA treatment resulted in decrease health care costs, especially for patients with cirrhosis.

Z Kuloglu et al. JPGN 2019; 68: 371-6.  In this multicenter Turkish study, the authors identified 810 children (median age 5.6 years) with unexplained transaminase elevation (62%),unexplained organomegaly (45%), obesity-unrelated liver steatosis (26%) and cryptogenic fibrosis or cirrhosis (6%).  LAL-D [lysosomal acid lipase deficiency] activity was deficient in 2 siblings (0.2%); both had LDL ~155.  Overall, even in at risk groups, LAL-D is rare.

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Best Predictor for Mortality from Biliary Atresia Liver Transplantation Candidates –Cardiomyopathy?

Briefly noted: A recent study (NM Gorgis et al. Hepatology 2019; 69: 1206-18, editorial 940-2 by Elizabeth Rand) indicates that cirrhotic cardiomyopathy (CCM) is very important factor for survival for biliary atresia (BA) patients requiring liver transplantation.

CCM was defined based on two-dimensional echocardiographic criteria: LV mass index ≥95 g/meter-squared or relative wall LV thickness of LV ≥0.42.

Key points:

  • Overall, 11 of 69 patients died, 4 while awaiting liver transplantation and 7 following transplantation.
  • 34 of 69 BA patients in this cohort had BA-CCM
  • All 11 who died had BA-CCM compared with no deaths in the 35 patients without CCM.

My take: Severe BA-CCM needs to be examined further; if severe, it may merit changing allocation policy.

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Biliary Atresia and Bile Lakes

A retrospective study (DA Ginström et al. JPGN 2019; 488-94) review cholangitis associated with biliary atresia and the role of bile leaks.  This study encompasses a ~30 year period (1987-2016) and 61 patients.

Key findings: 

  • 54% had survived with their native liver at a median of 7.3 years; 28 (46%) had ≥ 1 cholangitis episodes/year
  • Cholangitis bouts were >5 times higher among patients with bile lakes
  • Management of bile lakes after 1995 (n=6) was with operative intestinal drainage (bile-lake jejunostomy) which resulted in disappearance or regression of bile lakes in all patients.  Associated with this, yearly cholangitis bouts decreased from 8.8 (4.2-14) to 1.1 (0.2-3.2). Prior to 1995, two patients were managed with PTCD; both died within one year.
  • Among patients who had surgical drainage of their bile lakes, 4 have survived jaundice-free and 2 received liver transplants at 1.3 and 4.9 years after intestinal drainage.

My take: This report provides insight into the management of bile lakes (also referred to as intrahepatic biliary cysts) indicating that bile-lake jejunostomy is effective in symptomatic patients.

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Pediatric Livers Bypassing Needy Children

A recent study (J Ge, EK Hsu, J Bucuvalas, JC Lai. Hepatology 2019; 69: 1231-41) provides data showing that current liver allocation policy allow pediatric donor organs to bypass desperately ill children in favor of adult liver transplant recipients. The authors utilized national registry data over a 5-year period to follow the allocation of pediatric liver donor organs.

Key points:

  • About 60 children (~12% of waitlist candidates) die awaiting liver transplantation each year
  • From 2010-2014, 3318 pediatric donor livers were transplanted; 45% of these organs went to adults.
  • 390 of the 1569 adult recipients received a pediatric organ that was NEVER offered to a child
  • In this group of 390, 71% of these adults were lower acuity with MELD <35 and non-status 1A.

These data identify a deviation from the policy goal that pediatric organs are offered first to pediatric recipients.

My take: this study adds more data showing that children <12 years of age are disadvantaged with current allocation policies.  This is despite the fact that children have lower posttransplant mortality, indicating that organ transplantation is more likely to be truly life-saving in children.

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How Progressive Familial Intrahepatic Cholestasis (PFIC) Recurs After Liver Transplantation

A recent case-report study (D Krebs-Schmitt et al. JPGN 2019; 68: 169-74) describes how progressive familial intrahepatic cholestasis (PFIC) due to bile salt export pump (BSEP) deficiency can recur after liver transplantation.

BSEP deficiency due to mutations in ABCB11 gene causes the development of PFIC type 2.  In this case report, the authors describe recurrence of BSEP-deficiency following liver transplantaion in 3 patients.

Key points:

  • Following liver transplantation, patients with PFIC 2 can develop antibodies to BSEP as this antigen was not present in the pretransplant period.  Since initial reports, more than 20 patients have been described. “In most of these cases, intensifying the immunosuppression led to normalization of graft function.”
  • In this case report, the 3 patients ultimately required retransplantation due to recurrent disease and one patient died (following retransplantation). One patient also received stem cell transplantation after a complicated course.

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Are Liver Tests Needed in Pediatric Patients Receiving Statin Therapy?

A recent study (NK Desai et al. JPGN 2019; 68: 175-81) showed excellent safety of statins with regard to hepatotoxicity. This study utilized prospectively collected ALT values from the Preventive Cardiology Program at Boston Children’s and their lipid program from 2010 until 2014.  They included 943 patients (mean age 14 years) with 111 always on statin, 97 started on statin, and 735 never on a statin.

Key findings:

  • In this cohort with dyslipidemia, there was no higher burden of ALT elevations among pediatric patients receiving statin therapy compared to those who did not receive statin therapy.
  • Patients with ALT values ≥5 times ULN were not increased among patients receiving statins (n=3) compared to those who did not receiving statins (n=13)
  • Mean ALT was actually greater in the non-statin cohort by 2 U/L but likely related to the increased frequency of obesity in the non-statin group.

My take: Due to the high prevalence of nonalcoholic fatty liver disease (NAFLD), it is likely that most patients who need statin therapy would get liver biochemistries; however, this study suggests that additional monitoring is not required in asymptomatic patients who receive statins for dyslipidemia.

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