Category Archives: Pediatric Gastroenterology Liver Disease

Drink Up!

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Green tea and coffee have a lot of advocates and a number of articles suggest that each can have beneficial effects for the liver.  This month’s Hepatology describes how a green tea component, epigallocatechin-3-gallate (EGCG), inhibits hepatitis C viral (HCV) entry. ECGC acts by blocking viral attachment to target cells with all HCV genotypes; it does not affect viral replication.  Other components of green tea do not have this effect.  A complete description of green tea components is described in the discussion of the article, Hepatology 2012: 54: 1947-55.  Also, there have been preliminary dosing studies in healthy volunteers which have shown that EGCG is safe at doses of 800mg daily for four weeks.  This would be the equivalent of drinking 8-16 cups of green tea per day (Clin Cancer Res 2003; 9: 3312-19).  In order to eliminate HCV, however, even higher amounts of EGCG would be likely.

 

Coffee also has been studied and has been associated with decreasing liver fibrosis.  In addition, coffee may enhance response to HCV treatments.  To my knowledge, there have not been extensive studies of either coffee or green tea for pediatric patients.

Additional References:

  • -Gastroenterology 2011; 140: 1961. Coffee (3 cups/day) increases response to PEG/RBV in HCV
  • -Hepatology 2009; 51: 201. Coffee decreases fibrosis. n=177.
  • -Hepatology 2009; 50: 1360. Coffee intake associated with slower progression of HCV liver disease
  • -Hepatology 2009; 50: 970. Coffee -2 cups per day decreases risk of liver fibrosis & HCC. Coffee has methylxanthin which inhibits connective tissue growth factor.

Looking for trouble

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Although cirrhosis is an infrequent problem in pediatric gastroenterology, there are several important management aspects.  One of these is surveillance for hepatocellular carcinoma (HCC).  In this month’s Hepatology, Poustchi et al describe the “feasibility of a randomized control trial for liver cancer screening” (Hepatology 2012; 54: 1998 & editorial 1898).  Not surprisingly, the authors conclude that such a trial is not possible with informed consent.  As such, the effectiveness and cost-effectiveness may not be determined.  Although the consensus is in favor of screening, there are potential disadvantages like discovering non-cancer nodules leading towards unnecessary invasive investigations.

The AASLD considers screening for HCC worthwhile in patients with cirrhosis.  When HCC is discovered early, treatment can be effective.  For example, if HCC meets Milan criteria–either 1 tumor <5cm or 2-3 < 3 cm each– OLT has 91% 1 yr survival.

Most U.S. physicians (74%) report that they screen all of their patients with cirrhosis; however,  population-based studies of Medicare patients show only 6.6% receive regular surveillance (Hepatology 2010; 52: 132-41) & only 12% of veterans with HCV-infected cirrhosis (Ann Intern Med 2011; 154: 85-93).  Better ways of consolidating screening can bridge this gap & perhaps catch cases of HCC amenable to treatment.  This may be another area where an EMR can help with patient/doctor reminders.

Current practice recommendations for cirrhotic patients: Ultrasound every 6 months (with or without AFP).  This recommendation is supported by the AASLD, EASL, and APASL.  The efficacy of HCC surveillance is reviewed further in the January “Education Practice” article: Clin Gastro & Hepatatol 2012: 10: 16-21.

Additional references:

  • Gastroenterology 2011; 141: 1240. Risk of HCC from HBV related to ALT and HBV DNA levels.
  • NEJM 2011; 365: 1118. Review. For cirrhotics/advanced liver dz, recs U/S & AFP q6-12months.
  • Hepatology 2010; 53: 1020. updated guidelines from AASLD. Suggests U/S as screen q6months.
  • J Pediatr 2011; 159: 617. BA associated with HCC.
  • Hepatology 2010; 51: 1972. NASH cirrhosis pts develop HCC. 12.8% over .32 yrs (compared with 20.3 % of pts with HCV cirrhosis). Alcohol & age were independent variables that increased risk.
  • Gastroenterology 2009; 137: 110, editorial page 26. AFP has at best 66% sensitivity for HCC.
  • Gastroenterology 2009; 136: 138, 39(ed). HCC occuring c HCV ~1%/yr in HALT-C study. prolonged Rx -not helpful. n=1005. Best surveillance is US. Only 60% of pts c HCC received surveillance. Hepatolgy 2005; 42 : 1208.
  • Gastroenterologyo 2008; 135: 111. DM & obesity associated with increase risk of HCC in patients with HBV/HCV.
  • Gastroenterology 2008; 134: 1612. Increasing LTx for HCC affects others on Tx list.
  • Gastroenterology 2007; 132: 2557. review
  • Clin Gastro & Hep 2006; 4: 252 Review.
  • Hepatology 2005; 42: 1208. AASLD guidelines for management.
  • Gastroenterology 2004 (November) 127; supplement 1:S1–S323. Review of HCC. S108: screen with alpha-fetoprotein AND U/S every 6-12 months in individuals with cirrhosis or advanced disease (not needed in individuals with mild disease).
  • Clinical Gastro & Hep 2003; 1: 10-18. Review.
  • Gastroenterology 2004; 126: 1005. HCC survival improved when detected as part of surveillance.

The cost of progress in treating Hepatitis C

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Background information on Hepatitis C (HCV):

  • —170 million people worldwide infected with HCV, 2.7 milllion people in U.S. infected
  • —27% of worldwide cases of cirrhosis are due to HCV
  • —25% of cases of hepatocellular carcinoma are due to HCV
  • —Established treatment with pegylated interferon (PEG IFN) and ribavirin have ~40% response rates in genotype 1 (74% of HCV in U.S.) and relapses are not uncommon among responders

New treatments for Hepatitis C (in combination with previous treatments):

  • —Two new drugs: Boceprevir (BOC) & Telaprevir (TVR)
  • —Overall sustained viral response (SVR) with BOC combination 63-66% vs 73-79% with TVR combination treatment
  • —Both trials demonstrate marked improvement over previous
  • Mechanism of action: —Protease inhibitor binding to NS3 HCV target
  • —BOC: Wholesale cost $1100/week (20-44 weeks)
  • —TVR: 12weeks cost: $49,000
Previous treatments for hepatitis C typically cost about $5000 per month (http://www.familydrugguide.com/family/ub/view/Consumer_Reports_Health/526033/4/hepatitis_c_drugs).  The addition of these newer drugs could add another $50,000 to the cost of treatment.  In some cases which respond well to the newer treatments, shorter treatment periods will lower the increase in cost.  Although these drugs are expensive, they may be lifesaving and may obviate the need for liver transplantation.  Due to the potential complications of HCV, more medications are in the pipeline.  They may be easier to take but are likely to be expensive as well.  The safety & effectiveness of these medications have not been demonstrated in published pediatric studies.
Article References:
  • Hepatology 2011; 54: 1433.  Updated AASLD HCV treatment guidelines
  • NEJM 2011; 364: 1195-206, Editorial pg. 1272. Addition of boceprevir, in 1097 previously untreated pts increased SVR. In whites, 40%–>67% & in blacks from 23% –>42%. Medication given after lead-in of 4 weeks. More frequent anemia in boceprevir-treated patients (SPRINT-2 study).Boceprevir dosing: 800mg (4 capsules) TID with food. (trying to space out doses evenly).
  • NEJM 2011; 365: 1014. n=540. Telaprevir study: extended SVR 72%. In pts with rapid viral response (RVR) at 4 & 12 weeks (no detectable HCV), Telaprevir12weeksPegRbv24 was as effective as Telprevir12weeksPegRbv48. Dosing for study: Teleprevir 750mg TID, PEGalfa-2a 180mcg/wk, RBV1-1.2gm per day.  Rash in 37% (severe in 5%), anemia in 39% (severe in 6%).
  • NEJM 2011; 364: 2405, 2417, 2429 (review). Telaprevir addition:  up to 75% response in HCV genotype 1 pts. n=1095 in 1st study, n=833 in 2nd study (re-treatment study)
  • Gastroenterology 2011; 140: 746. Summary of results of boceprevir (used with IFN -alfa 2b 1.5/kg) & telaprevir (used with IFN -alfa 2a 180mcg). “Similar effectiveness” thus far. Telaprevir used for 12 weeks without lead-in period.  TVR: most frequent problem -rash & then anemia.  In practice, dosing in adults: Telaprevir will be used at 750mg TID in combination with IFN-2a 180mcg & RBV 1-1.2g/d. & used for 1st 12 weeks of Rx. This will allow ~50% of patients to have shorter Rx duration:  if HCV RNA RVR –>24week total vs 48week total in those w/o RVR.  Both drugs best for genotype 1.