Lack of Survival Benefit With MELD Exception Points in Hepatocellular Carcinoma

Posted on October 24, 2015 by gutsandgrowth

Briefly noted:

Another study also looks at transplant utility by showing the use of MELD exception points for hepatocellular carcinoma provides almost no survival benefit: K Berry, GN Ioannou. Gastroenterol 2015; 149: 669-80, editorial 531-34. The article states that the “survival benefit of patients with HCC was similar to that of patients without HCC who had the same actual MELD score…a much lower mean 5-year survival benefit was achieved by providing liver transplants to patients with HCC (0.12 years/patient) than patients without HCC (1.47 years/patient).”

How is this possible?

When patients are transplanted at lesser illness acuity, it takes longer to achieve a transplant benefit because they can live longer without a transplant. In essence, the survival clock starts ticking much later than the transplant date.

Why this is important (from editorial):

The proportion of patients undergoing liver transplantation for HCC has increased from “4.6% before the introduction of MELD exception to 16.5% currently.” And, “the results, put simply, suggest that allocating donor livers and performing liver transplantation in patients with HCC MELD exception points produces almost no survival benefit.”

My take: Liver allocation policies need to be modified. This study suggests that prioritizing HCC patients does not make much sense.

Atlanta Botanical Garden

Should Younger Transplant Patients Receive Better Organs?

Posted on October 23, 2015 by gutsandgrowth

Many physicians are unhappy with the current liver transplantation allocation system. A recent article (A Cucchetti et al. Liver Transl 2015; 21: 1241-49, editorial LB Vanwagner, AI Skaro. Liver Transpl 2015; 21: 1235-37) suggests that there should be adjustments to consider age in liver organ allocation. While this issue is not new, the article does suggest the idea of “age-mapping” which is a different twist on this subject.

The editorial notes that the current MELD system as been a poor predictor of post transplant outcomes and “does little to promote utility in organ allocation.” Because age is not a factor in MELD, “there is a subsequent loss of equity in the current system because younger recipients receive fewer opportunities to achieve a full lifespan compared with older recipients.” However, age matching is prohibited by discrimination laws.

“Age mapping differs from age matching.” With age mapping, all candidates would have an “equal chance of getting a liver” but the probability of receiving a ‘better organ’ (donor ≤35 years) would be more likely for younger recipients.

My take: The scarcity of organ availability compounded with the possible decline in organ quality leads to these discussions. Who really can balance unfair against unfortunate?

Related blog posts:

Days of Future Past and Declining Liver Graft Quality

Posted on August 18, 2015 by gutsandgrowth

In the most recent ‘X-men’ movie (Days of Future Past), the disastrous future is averted by having Wolverine go back in time to correct a mistake. Overall, while there are a good number of movies that have used this trick, this particular movie is pretty clever. For whatever reason, this movie came to mind as I was reading a recent study: “Declining Liver Graft Quality Threatens the Future of Liver Transplantation in the United States” (ES Orman et al. Liver Transpl 2015; 21: 1040-50). The authors extrapolate data from UNOS to assess what the liver transplantation (LT) picture may look like in 2030. Their results/conclusion:

“If donor liver utilization practices remain constant, utilization will fall from 78% to 44% by 2030, resulting in 2230 fewer LTs.” “The transplant community will need to accept inferior grafts and potentially worse post transplant outcomes and/or develop new strategies for increasing organ donation.”

The authors note that the national epidemics of diabetes and obesity will result in more cases of NAFLD-related liver failure while at the same time worsen the quality of available grafts. In the associated editorial, (RH Wiesner, pages 1011-12) the author emphasizes that the future is not quite so set.

the prevalence of diabetes and obesity in donors for 2030 might not be as great as feared; in addition, medical/surgical advances may diminish the complications associated with obesity
there will be a marked decrease in transplants due to hepatitis C virus related cirrhosis and hepatocellular cancer

His conclusion: “in the future, we will be using donor livers that we have never used before and will be achieving similar excellent results as we have today.” Which vision of the liver transplantation future is correct?

Bison, Yellowstone

What is Driving Racial Disparities in Access to Living Donor Liver Transplants

Posted on August 13, 2015 by gutsandgrowth

Recent articles highlight a huge gap in the availability of living donor liver transplants (LDLTs) when examined based on racial/ethnic background.

YR Nobel et al. Liver Transpl 2015; 21: 904-13.
A Doyle et al. Liver Transpl 2015; 21: 897-903.

What is the reason for this inequality?

The first study examined UNOS data from 2002-2014 among adult liver transplant recipients. Of 35,401 recipients, 2171 (6.1%) received a LDLT.

Key findings:

Cholestatic liver disease: When compared with white patients, the odds ratios of receiving LDLT were 0.35 for African American, 0.58 for Hispanic, and 0.11 for Asian.
Noncholestatic liver disease: When compared with white patients, the odds ratios of receiving LDLT were 0.53 for African American, 0.78 for Hispanic, and 0.45 for Asian.
LDLT recipients were more likely to have private insurance

The second study did not look at racial/ethnic background but instead focused on other recipient factors. Using a retrospective cohort of 491 consecutive patients, they determined that all of the following resulted in a lower likelihood of LDLT:

Single — OR 0.34
Divorced –OR 0.53
Immigrant — OR 0.38
Low income quintile — OR 0.44

Together these studies allow speculation on why there is such a disparity.

Financial costs, including lost wages, could preclude those with lower socioeconomic status from being available as donors
Distrust of donation system and/or fear of surgery

Bottomline: Racial/ethnic differences and financial resources are associated with significant access inequality to living donor liver transplantation.

Related blog posts:

Cascade Canyon, Grand Tetons

EXCEPTIONal Outcomes and Liver Allocation

Posted on January 23, 2015 by gutsandgrowth

A recent study (Hepatology 2015; 61: 285 & editorial 28-31) takes a closer look at US liver organ allocation and outcomes.

The editorial notes that our allocation in the US is targeted towards “need.” Since February 2001, the MELD score was adopted with “the stated aim of reducing deaths on the waiting list.” Other potential aims:

Equity –so any one who might benefit from a graft has an equal chance and a first-come, first-served approach is adopted
Utility –organs are allocated to the recipient who is likely to have the best outcomes
Benefit –organs are allocated to the patient who has the greatest benefit, so taking into account the risks of dying with and without a transplant
Fairness — ‘an ill-defined combination of all the approaches’

The editorial notes that “despite the concerns the approach has been highly effective in achieving its goal in reducing waiting list mortality.”

“Like any system, it can be manipulated and, given the life-saving nature of transplantation, it is scarcely surprising that both legal and illegal methods have been adopted to artificially raise the MELD score and distort allocation.”

The study reviewed 78,595 adult liver transplant candidates (2005-2012). 27.3% of the waiting list was occupied by candidates with exceptions.

Candidates with exceptions fared much better on the waiting list compared to those without exceptions in mean days waiting (HCC 237 versus non-HCC 426), transplantation rates (HCC 79.1% versus non-HCC 40.6%), and waiting list death rate (HCC 4.5% versus non-HCC 24.6%).

The editorialists recommend that “we should consider diverting some of the resources used to develop and implement a perfect allocation scheme into increasing the number of donors and livers used for transplant and, in the longer term, finding treatments and interventions that will render liver transplantation a treatment of historic interest.” Now that’s a lofty goal.

Related blog posts:

John Snow and Hepatology Potpouri

Posted on November 17, 2014 by gutsandgrowth

If you mention the name “John Snow,” I bet most people would think about one of the characters from Game of Thrones. However, a more important John Snow is referenced in a recent Hepatology review (Hepatology 2014; 60: 1124-25). “In 1855, the physician and epidemiologist John Snow used the technique of medical geography to stem the cholera epidemic in London. By mapping the number of choleras case and the local water supply, he found that the Broad Street pump station was responsible and after the pump handle was removed, incident cases declined.”

Hepatology 2014; 60: 1150-59, editorial 1124-25. Using spatial (clustering) epidemiology, the authors show that parenteral antischistosomal therapy (PAT) alone cannot explain the high HCV prevalence in Egypt. Other iatrogenic exposures and poor infection control are likely contributing factors.

Hepatology 2014; 60: 1222-30, editorial 1130. In a prospective study (western Europe), the authors show that vitamin D (25-OH) levels were inversely associated with the risk of hepatocellular carcinoma (HCC). What is remarkable about this study is the levels were obtained on average 6 years before HCC diagnosis. Also, this study uses tertiles -comparing those in the top third to those in the lowest third.

Hepatology 2014; 60: 1399-1408. More data showing injury from Herbals and dietary supplements. Liver injury caused by bodybuilding herbal supplements (often anabolic steroids) were typically less severe than liver injury induced in non-bodybuilding herbals (predominantly middle-aged women). Table 3 identifies by name many of the herbal supplements/dietary supplements associated with death or liver transplantation. “Contrary to popular belief, this study demonstrates that HDS products are not always safe.”

Cognitive Outcomes after Liver Transplantation

Posted on August 7, 2014 by gutsandgrowth

An important measure of liver transplantation (LT) is cognitive/academic outcomes. Previous studies have indicated increased intellectual deficits but were not optimally-designed. A recent study (J Pediatr 2014; 165: 65-72) overcomes many of the limitations of previous studies.

Study design: Prospective, multicenter longitudinal cohort of neurocognitive functioning after pediatric liver transplantation. 144 participants, ≥2 years after liver transplantation -recruited through Studies of Pediatric Liver Transplantation (SPLIT). Tested with multiple cognitive test at two separate time points.

Key findings:

At the time 2, 29% had full scale IQ (FSIQ) between 71-85 (compared to 14% expected); 7% had FSIQ <71 (compared with 2% expected)
42% received special education.
Pretransplant markers of nutritional status and operative complications predicted intellectual outcome
Having a primary care provider with a college education was a protective factor.

One limitation of the study was that only 55% of those approached to participate were enrolled; however, the authors noted similar demographics between those who enrolled and those who did not.

AASLD/NASPGHAN 2014 Guidelines for Evaluation of Pediatric Liver Transplantation

Posted on July 11, 2014 by gutsandgrowth

I want to congratulate the authors of a recent AASLD/NASPGHAN report (Hepatology 2014; 60: 362-98 & JPGN 2014; 59: 112-31) and in particular Rene Romero who has been a terrific colleague in Atlanta. I’m grateful for his timely advice to me and my colleagues along with the excellent care that he has provided to children referred for liver transplantation (LT).

The link to full article, Evaluation of Pediatric Liver Transplantation, and other AASLD practice guidelines can be accessed from this website: AASLD guidelines.

Some of the useful recommendations include the following:

For biliary atresia, “patients who are post hepatoportoenterostomy (HPE) should be promptly referred for LT evaluation if the total bilirubin is greater than 6 mg/dL beyond 3 months from HPE” and should be considered if total bilirubin is ≥2 mg/dL. According to the authors in the Hepatology article, ‘84% of those with a total bilirubin <2 mg/dL will survive with native liver beyond 2 years of age whereas only 16% will if total bilirubin is >6 mg/dL.’ [Interestingly, this information is stated differently in the JPGN article where the authors state “up to 70% of patients with BA may have prolonged transplant-free survival if the total serum bilirubin falls below 2 mg/dL” w/in 3 months following HPE.]
For biliary atresia: HPE is recommended as 1st line treatment except in infants with “evidence of decompensated liver disease.”
Ascites management: can be managed with an aldosterone antagonist. Reserve more aggressive measures (paracentesis, TIPS, surgical shunt) for those with compromised respiratory effort or severely impaired quality of life.
Recurrent disease: families should be informed that autoimmune hepatitis, PSC, and bile salt excretory pump disease can recur post-LT.
Recommends screening with use of pulse oxygen with the patient in upright position in all patients with possible portosystemic shunting.
Discusses immunizations for child and for family members (all family members need to fully immunized).
The review provides recommendations specific for virtually each liver condition, including Alagille, Wilson’s, Tyrosinemia, PFIC, hemangioendothelioma, Cystic fibrosis, urea cycle defects, autoimmune hepatitis, PSC, Hepatoblastoma, Alpha-1 Antitrypsin deficiency, Bile Acid Synthesis Disorders, Glycogen Storage Disease, Fatty Acid Oxidation defects, Parenteral Nutrition-Associated Liver Disease (PNALD), and many others.
Contraindicated for LT: Alper’s syndrome/valproate-associated liver failure, mitochondrial disease with severe extrahepatic disease, Hepatocellular carcinoma with extrahepatic disease and rapid progression, uncontrolled systemic infection, Niemann-Pick Disease Type C, and severe medically-refractory portopulmonary hypertension

Take-home message: This practice guideline is an excellent resource in the evaluation of pediatric liver transplantation and pre-transplant management. The ease of accessing the entire report online is a big plus too.

Related posts:

“More to It Than Meets the BMI”

Posted on March 7, 2014 by gutsandgrowth

This blog post title is quoted from a clever editorial which reviews the use of BMI and the effect of obesity with outcomes after liver transplantation (Liver Transpl 2014; 20: 253-54, related article pages 281-90.)

Key points from editorial and study:

Study enrolled 202 consecutive adult (mean 51 years) patients (200-2010) as part of cohort study. Data was obtained at time of transplantation and reviewed with retrospective analysis. NAFLD was transplant indication in 7%.
“Use of BMI as a marker of obesity is flawed.” Authors showed only 86% agreement between calculated BMI and percent body fat as measured with DXA.
Patients with high BMI due to greater lean muscle mass may have improved outcomes. Sarcopenia (loss of muscle mass) likely has greater effect on outcomes.
The study shows that the combination of diabetes and obesity increases the risk of complications and prolongs hospital stays (5.81 days, P<0.01).
Metabolic risk factors had no effect on 30-day, 1-year, or 5-year patient survival.

Another article in same issue: Liver Transpl 2014; 20: 311-22. This study retrospectively examined 148 normal-weight, 148 overweight, and 74 obese patients who underwent living donor liver transplantation. Key finding: “there were no differences in graft survival [hazard ratio (HR) =0.955] or recipient survival [HR = 0.90]” between these groups. Obese patients do require larger grafts which can delay identifying suitable donor.

Bottomline from editorial: “this study shows us that the combination of diabetes and obesity dramatically increases the risk of complications” but not survival. “If there comes a day when the cost of a human life is less than the cost of a 6- to 7-day hospital stay, that is the day to reckon. None of us may survive.”

gutsandgrowth

Pediatric Gastroenterology

Tag Archives: liver transplantation