Liver Articles: Short Takes

DBE van Wessel et al. JPGN 2017; 65: 370-74.  This retrospective study showed an increase in biliary atresia incidence in preterm infants compared with full-term: 1.06 per 10,000 compared with 0.52/10,000. In addition, 4-year transplant-free survival rates were significantly worse at 21%, whereas 4-year survival rates was 61%. Clearance of jaundice (with Kasai) was achieved in only 23%.

Related post: Biliary Atresia More Common in Preterm Infants

ES Björnsson et al. Clin Gastroenterol Hepatol 2017; 15: 1635-36. This study examined response to steroids in 18 patients with drug-induced autoimmune hepatitisKey findings: 14 patients had elevated antinuclear antibodies & there were none with elevated smooth muscle antibodies. Infliximab was most frequent agent (n=11) and nitrofurantoin was other frequent agent (n=3).  Overall, 40% improved after discontinuation of medication, the remainder had prompt responses to corticosteroids.  Relapse did not occur when corticosteroids were discontinued.  Among the infliximab group, there was no evidence of liver injury after transitioning to alternative tumor necrosis factor-α inhibitor.

M Balwani et al. Hepatology 2017; 66: 1314-22. Acute Hepatic Porphyrias -Review. Current recommendations include gene sequencing to confirm all biochemical cases. Biochemical tests are spot urine testing of porphobilinogen (PBG), 5-aminolevulinic acid (ALA), and porphyrins. A normal urine PBG in symptomatic patients “excludes the three most common acute hepatic porphyrias.”  For those with abnormal studies, this reference is a handy.

S Wirth et al. Hepatology 2017; 66: 1102-10.  This study examined the effectiveness of sofosbuvir and weigh-based ribavirin dosing in 12-17 year olds with genotype 2 & 3 Hepatitis C infection.  Duration of treatment was 12 weeks for genotype 2 and 24 weeks for type 3.  Overall, SVR12 was achieved in 51 of 52 (98%); one patient with genotype 3 did not achieve SVR12.

Related post: New HCV Treatment Effective in Adolescents (Genotype 1 study)

F Kanwal et al. Gastroenterol 2017; 153: 996-1005. This study, a retrospective cohort of 22,500 VA patients treated for hepatitis C infection, showed that direct-acting antivirals (DAAs) lowered, but did not eliminate, the risk of hepatocellular carcinoma (HCC). Among the 87% who achieved an SVR, the adjusted hazard ratio for HCC was 0.28.  This was true as well as among patients with cirrhosis.. Hazard ratio for those with compensated cirrhosis was 0.32 compared with 0.18 among those without cirrhosis.

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#NASPGHAN17 Annual Meeting Notes (Part 2): Year in Review

This blog entry has abbreviated/summarized this presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

This first slide shows the growth in NASPGHAN membership:

Year in Review

Melvin Heyman  Editor, JPGN

This lecture reviewed a number of influential studies that have been published in the past year.  After brief review of the study, Dr. Heyman summarized the key take-home point.

 

What Can Be Done for Patients with Hepatitis C Who Do Not Respond to the Newest Medications

While the emergence of multiple highly-active agents for Hepatitis C has been a terrific advance, there are a small subset of patients who have not responded to them in almost all clinical trials.  A recent study (M Bourliere et al. NEJM 2017; 376: 2134-46) has identified a highly-effective combination regimen for this population: sofosbuvir/velpatasvir/voxilaprevir x 12 weeks

The authors conducted two phase 3 trials in patients who had not responded to a direct-acting antiviral (DAA) regimen previously.  POLARIS-1 and POLARIS-4. 46% of patients had compensated cirrhosis Key findings:

  • POLARIS-1: 96% of combination group had a sustained virologic response (SVR) compared with 0% of patients receiving placebo
  • POLARIS-4: the triple combination had a SVR of 98%, whereas 90% had SVR with dual therapy (sofosbuvir-velpatasvir)
  • Among patients receiving active treatment, less than 1% discontinue treatment due to advers events.

My take: This triple therapy is highly effective in patients who were  previously-treated with DAA for HCV.

Related blog posts:

Arthur Ravenel Jr Bridge, Charleston

 

Finding Residual Hepatitis C Virus in Liver Explants

A recent report (M Gambato et al. Gastroenterol 2016; 151: 633-6) provides some insight into the importance of the presence of residual hepatitis C virus (HCV) RNA in the liver of patients undergoing liver transplantation.

The authors note that many patients with cirrhosis due to HCV do not complete a full course of antiviral therapy before liver transplantation as the waiting time is unpredictable.  The authors studied whether there was HCV RNA in the liver of 39 of these patients and tried to assess whether its presence was associated with relapse after liver transplantation.

Background:

  • Only 6 patients (15%) had completed treatment prior to liver transplantation.
  • Most patients (68%) had undetectable serum HCV RNA.
  • Treatment was most commonly sofusbuvir/ribavirin (n=30)

Key findings:

  • HCV RNA was detected in 26 of 39 liver explants (67%). Higher levels were detected in those who had received a shorter course of treatment at time of liver transplantation. Interestingly, HCV RNA was also detected in 2 (20%) of controls who had an SVR after completing an interferon-free treatment regimen.
  • 33 of 39 (85%) achieved a post-transplantation virologic response (pTVR) and 6 (15%) had recurrent HCV infection.  Thus, the persistence of HCV RNA in liver explant did not preclude pTVR.
  • Among the 26 patients with residual HCV RNA in the liver explant, a HCV RNA concentration was higher in the 4 patients that relapsed (23 vs 3 median copies/mcg total RNA).
  • Another unexpected finding was that among the 6 who relapsed, two had undetectable HCV RNA in liver explant –both patients carried mutations which could have rendered treatment less effective.  The authors note that HCV RNA could have been present at concentrations below detection or distributed unevenly (which could have affected testing).

The authors speculate that the presence of HCV RNA may have been sequestered in membranous webs which allowed the virus to avoid degradation/host defenses.

My take (borrowed from the authors): The presence of HCV RNA in the liver explant does not seem to be associated with treatment failure/virologic relapse after liver transplantation, except in case with high concentrations.

Maine’s oldest lighthouse: Portland Head Light

Portland Head Light

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