December 20, 2013

Hep C and Happy Holidays!


December 20, 2013
by Opiferum

Having hepatitis C at this time of the year is not easy. Christmas and New Year’s is typically fuelled by an indulgence of rich foods high in fat, not to mention drenched in alcohol. But the holiday period is also seen as a time during which people get together and celebrate a Hallmark perfect life. No wonder there is yet a card that reads “Merry Christmas” with a picture of someone sitting by the fire-side self-injecting a weekly dose of pegylated interferon. Having to deal with living with the hepatitis C virus is hard enough without the extra burden and stress that Christmas brings. More than any other time of the year, this is when people affected by the hepatitis C are likely to feel the crippling effects of discrimination and isolation. This is because there are some families that simply refuse to have their hepatitis C positive loved one at the Christmas dinner table. So, what can you do to get through the holidays with hep C?

Firstly, be aware of your self-talk. This is a time of year when it is easy to fall into negative-self talk. Factors such as feeling isolated or not measuring up to those picture perfect images on Christmas cards certainly contribute to this. Therefore ask yourself, What is my attitude towards this time of year? It is perfectly ok to acknowledge your feelings about Christmas. There are no “right” or “wrong” feelings to have about Christmas, either. However, if you are drowning in negative self-talk, then maybe it is having a disempowering effect on you that might be causing more stress than is necessary. Instead of using words like “don’t” and “won’t”, for example, try to re-word your phrases to exclude these kinds of negative words. Instead of telling yourself, “I don’t like Christmas at all,” exchange it for a different kind of self-talk, like “Christmas is just another time of the year; I will look for something to like about it no matter how difficult.” It might be as simple as appreciating Christmas lights in the neighbourhood, to feeling a heightened sense of gratitude for the fact you can empathise for those that are in the same position as you.

Be careful of what you eat and drink. At this time of year, there is a universal tendency to overindulge in fatty foods and alcohol. This is because rich food and drinking are all associated with the act of celebrating. Trying to excuse one’s self from not over indulging is difficult, unless you are the sort of person that is lucky enough to be surrounded by people that are aware of the importance diet plays for those living with hepatitis C. If you feel pressure to celebrate Christmas by eating and drinking too much, then prepare for this by bringing your own stash of non-alcoholic beverages for you to have at the dinner table. Another way to help your liver get through the Christmas menu is by requesting smaller portions, or even excusing yourself as a vegetarian. There are plenty of creative ways to get around having to eat too much, or over imbibing in the traditional Christmas drink.

If you are on treatment It is difficult enough to live with the unpleasant side-effects associated with interferon and ribavirin, but having to deal with the extra stress this time of year brings is another thing altogether. If you are on treatment, then make sure you have enough medication to get you through the holiday period. Know exactly when your next doctor’s appointment is, so that you do not have to stress about when it might be. Having people around you that understand your situation is ideal, even though not necessarily the case for everyone. If you are feeling anxious about getting through the holiday period, then consult your local community centre or hepatitis council for the names of support groups that might be able to make a difference. There is someone out there that will listen to your needs, even if it is just by making a post to an on-line support group.

If you are not on treatment A lot of people have put off undergoing treatment for hepatitis C because of the well-known harsh side-effects associated with interferon and ribavirin. However, we are entering a new age of therapy for hepatitis C that are not only proving to show incredibly high rates of success, but with side-effects easier to manage. As well, new treatments for hepatitis C are showing to be very effective with previously harder to treat genotypes (namely 1). Where medical treatment is fully subsidised by the Government (i.e. Australia and New Zealand) then be sure to enrol yourself at the local liver clinic (usually a part of the gastroenterology or infectious diseases department of a hospital). Wherever you are, make the most of the clinical services that are available to you. Get in sooner, as this will not only benefit your liver in the long run, but also secure your right to treatment in the future.

Christmas and New Year are both calendar events that are here to stay. The best form of self-care is awareness and prevention. Stay on top of the silly season by laughing it off, or looking for other safe and healthy things to do. Taking care of both your mental and physical health might be more challenging at this time of the year, but with the right attitude, you can do it. May you all manage the testing time ahead without forgetting to look after your liver.

Wishing you all a very hepatitis C friendly Christmas and New Year,


Hepatitis C Transmission Confirmed in a Dental Setting

by Mary Govoni, CDA, RDA, RDH, MBA

In September, the Centers for Disease Control and Prevention confirmed that the first patient-to-patient transmission of hepatitis C occurred in a dental setting in the U.S. This transmission occurred in the oral surgery practice in Tulsa that was the subject of intense media publicity earlier this year.

Although the CDC was able to match the viruses of two of the patients through genetic testing, they may never be able to determine how the transmission took place. The suspected routes of transmission are improperly sterilized instruments and the use of unsterile needles in multiple dose medication vials. The good news is that there have not been any previously reported cases in dentistry. The bad news is that this occurred.

Once again this news prompts the need to make sure that everything we do to protect our patients is in line with the CDC Guidelines for Infection Control in Dental Health Care Settings. While the majority of practices that I interact with are clear on what must be heat sterilized, there is less clarity about verifying the sterilization process and the importance of quality control protocols in instrument sterilization.

The first of the quality control measures is the recommendation for packaging of instruments prior to sterilization to ensure sterility of the instruments until the point of use. This includes extra instruments that are stored in drawers or cabinets in the treatment rooms and includes orthodontic instruments. The second is the recommendation for using a process indicator in the instrument packages. This measures the parameters for sterilization – time, temperature, and pressure (steam penetration).

Although most sterilization pouches have indicators incorporated into the pouch, they typically measure only one or two of the parameters – time and temperature. In addition, there are indicator strips that can be placed inside instrument packs or cassettes. It is important to note that autoclave tape, which is used to seal packages and cassettes, is a single parameter indicator – temperature only.

There is one pouch, the Sure-Check Pouch from Crosstex, that is cleared by the FDA as a Class IV indicator. This pouch measures two or more of the criteria for sterilization. An indicator strip that is also cleared by the FDA as a Class V integrator is the Steam Sterilization Integrator Strip from Hu-Friedy. This strip measures all of the criteria – time, temperature, and steam penetration.

These indicators are used to make sure that the instrument packs in each sterilizer load have been exposed to the right parameters for sterilization. If the indicator shows a "failure," the instruments must be repackaged and reprocessed.

Many times it is the instruments in the center of the load that are not sterilized, due to overloading of the sterilizer and the inability of the steam to penetrate into the packages. Without the use of sterilization indicators, there is no way to know which instrument packs are at risk.

These indicators are an additional measure to protect patients, but are not a substitute for weekly monitoring of the sterilizer with a biological indicator or spore test. There are a number of in-office monitoring systems such as Attest from 3M, ConFirm from Crosstex, and SporeCheck from Hu-Friedy.

In addition, there are third-party monitoring services including many that are affiliated with dental schools and dental suppliers, as well as companies such as ConFirm, The Dental Advisor, North Bay Bioscience, and others. The dental practice should keep records of the results of these tests. If a sterilizer fails a spore test, that sterilizer must be taken out of service until the reason for the failure is determined and corrected.

Following appropriate guidelines and protocols for sterilization will not only minimize the risk of a patient-to-patient transmission of a bloodborne infectious disease such as hepatitis C; it will go a long way in reassuring patients that it is safe to go to the dentist.

Mary Govoni, CDA, RDA, RDH, MBA, is the owner of Mary Govoni & Associates, a consulting company based in Michigan. She is a member of the Organization for Safety, Asepsis and Prevention. She can be contacted at or


'Serial Infector' Gets 39 Years Linked to Hepatitis C Outbreak



Kwiatkowsi's Victims

In addition to one patient whose death was linked to the hepatitis C infection, other individuals infected with Kwiatkowski’s strain of hepatitis C included:

- A Marine veteran over the age of 50 who, as a result of his infection, has experienced pain, sleeping and weight loss problems, and trouble controlling his diabetes. He has also been unable to travel, something he used to do extensively for his job.

- A male over the age of 70 who has substantial health problems, had to have major surgery, and whose health continues to deteriorate.

- A Navy veteran over the age of 80 with serious health problems, including severe fatigue. He is so fearful of transmitting the hepatitis C virus that he won’t kiss his wife.

- A retiree over the age of 60 who has experienced fatigue and so much stress that she has had to seek counseling.

- An Army veteran over the age of 40 who suffers from fatigue, body aches, loss of appetite, and emotional issues.

- A male over the age of 50 whose health issues are so severe he has been unable to return to work.

The vast majority of health care professionals are dedicated individuals committed to their patients. But in a recent investigation, we came across a hospital worker who was more committed to his own selfish needs than to his patients—he knowingly put patients at risk of exposure to the hepatitis C virus so he could steal and abuse a powerful narcotic prescribed for use during medical procedures.

David Kwiatkowski—who pled guilty to a scheme to divert and obtain the controlled substance fentanyl as well as to product tampering, was sentenced earlier this month to 39 years in prison. Because of Kwiatowski’s actions, at least 45 people became infected with hepatitis C, a virus that attacks the liver and may cause liver damage, liver failure, or cancer. At least one patient died as a result of the infection.

You see, Kwiatkowski himself was infected with hepatitis C. And he admitted that while employed at a New Hampshire hospital and at hospitals in several other states, he stole syringes of fentanyl prepared for patients about to undergo medical procedures, injected himself with the drug, and refilled those same syringes with saline—tainting them with his hepatitis C-positive blood—for use on unsuspecting victims. As a trained health care worker, Kwiatkowski would have known that hepatitis C, a blood-borne viral disease, is primarily transmitted by exposure to infected blood.

How the case began. In May 2012, the New Hampshire Department of Health and Human Services began a public health investigation after it was notified by an area hospital of four patients newly diagnosed with hepatitis C. Three of the individuals had been patients in the hospital’s Cardiac Catheterization Laboratory (CCL), while the fourth was a CCL employee (Kwiatkowski). Although Kwiatkowski led the hospital to believe he had been previously unaware of his hepatitis C status, the investigation showed that he had known of his infection since at least 2010.

Testing confirmed that all four shared a genetically similar virus, indicating a common source of infection. Because Kwiatkowski had previously worked as a traveling technician in multiple hospitals in several states, the information about his activities was shared with those states, which began their own reviews.

The federal Centers for Disease Control and Prevention (CDC) coordinated the overall public health investigation, which ruled out other possible methods of transmission and suspected that a drug diversion scheme was the source of the outbreak. During their investigation, public health authorities recommended that more than 12,000 people who may have crossed paths with Kwiatkowski in various hospitals get tested for possible hepatitis C infection.

In June 2012, the FBI’s Boston Office opened a full criminal investigation into the outbreak…and into Kwiatkowsi. The investigation involved several search warrants and included a search of Kwiatkowski’s vehicle that uncovered needles and syringes. Working with public health agencies along with other federal, state, and local law enforcement partners, we gathered evidence and interviewed dozens of people who either worked with Kwiatkowski or were patients at hospitals that employed him. By July 2012, we were able to arrest him.

According to New Hampshire U.S. Attorney John Kacavas, the 39-year sentence imposed on Kwiatkowski “ensures that this serial infector will no longer be in a position to harm innocent and vulnerable people, extinguishing once and for all the pernicious threat he posed to public health and safety.”

- Press release

Source -  Federal Bureau of Investigation

Predicting Survival after Liver Transplantation Based on Pre-Transplant MELD Score: a Systematic Review of the Literature



Kristin B. Klein, Taenia D. Stafinski, Devidas Menon

Published: December 12, 2013 DOI: 10.1371/journal.pone.0080661


The model for end-stage liver disease (MELD) score is used to stratify candidates for liver transplantation based on objective measures of disease severity. MELD has been validated as a predictor of wait-list mortality in transplantation candidates and has been postulated as a predictor of post-transplant survival. The purpose of this study was to examine the predictive value of the pre-transplantation MELD score on post-transplant survival from relevant existing studies. A systematic review and critical appraisal was performed using Cochrane guidelines. PubMed, the Cochrane Library, Embase, and Web of Science were searched for articles published in the English language since 2005 using a structured search strategy. There were 3058 discrete citations identified and screened for possible inclusion. Any study examining the relationship between pre-transplant MELD and post-transplant survival in the general transplant population was included. Thirty-seven studies met these criteria and were included in the review. Studies were all case series that typically involved stratified analyses of survival by MELD. They represented 15 countries and a total of 53,691 patients. There was significant clinical heterogeneity in patient populations across studies, which precluded performance of a meta-analysis. In 15 studies, no statistically significant association between MELD and post-transplant survival was found. In the remaining 22, some association was found. Eleven studies also measured predictive ability with c-statistics. Values were below 0.7 in all but two studies, suggesting poor predictive value. In summary, while the majority of studies reported an association between pre-transplantation MELD score and post-transplant survival, they represented a low level of evidence. Therefore, their findings should be interpreted conservatively.

Citation: Klein KB, Stafinski TD, Menon D (2013) Predicting Survival after Liver Transplantation Based on Pre-Transplant MELD Score: a Systematic Review of the Literature. PLoS ONE 8(12): e80661. doi:10.1371/journal.pone.0080661

Editor: Evren Alici, Karolinska Institutet, Sweden

Received: May 9, 2013; Accepted: October 5, 2013; Published: December 12, 2013

Copyright: © 2013 Klein et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: Kristin Klein receives funding from the Clinical Investigators program at the University of Alberta. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist


The identification of patients who are most likely to benefit from orthotopic liver transplantation (OLT) is a significant challenge in transplantation medicine. Liver transplantation offers the only curative therapy for patients with end-stage liver disease (ESLD). However, the supply of donor livers remains inadequate to meet the demand, necessitating an effective policy for organ allocation. In order to minimize waitlist mortality, a Model for End-Stage Liver Disease (MELD) - based organ allocation was proposed. First adopted by the United States in February 2002, it has become one of the most widely used approaches to prioritizing liver transplant candidates in countries around the world. The MELD score was initially developed by Malinchoc et al [1] to predict mortality in patients undergoing transjugular intrahepatic portosystemic shunts, but has since been validated as predictor of short-term mortality in patients awaiting transplantation. It uses objective variables (creatinine, bilirubin and the international normalized ratio of prothrombin time (PTINR)) to quantify the severity of ESLD, enabling the prioritization of patients in need of liver transplantation by medical urgency. An ideal system would allocate organs to patients not only at the highest risk of dying without transplantation, but also with the highest likelihood of survival following transplantation.

In recent years, the possibility of using pre-transplant MELD to predict post-transplant survival has been explored in many opinion pieces and expert reviews[2]. However, it has yet to be assessed through a systematic review and critical appraisal of published studies that adheres to internationally accepted systematic review guidelines. The need for such a review is heightened by the lack and infeasibility of RCTs on this topic and the fact that considerable debate over the value of MELD in this context remains. Thus, the aim of this study was to assess the association and predictive value of pre-transplantation MELD score on post-transplantation patient survival through a comprehensive, protocol driven systematic review of studies published to date.


Identification of potentially relevant studies

To identify relevant studies published as of August 2011, a structured search strategy combining relevant controlled vocabulary terms such as Medical Subject Headings (MeSH) and additional non-indexed terms was first developed. Such terms included Model for End-Stage Liver Disease, MELD, liver transplantation, liver failure, and survival. The search strategy was applied to the following electronic bibliographic databases: PubMed (MEDLINE and non-MEDLINE), the Cochrane Library, EMBASE, and Web of Science; and limited to full text, English language studies of adult patients which were published within the past 10 years. For completeness, reference lists of relevant articles were scanned. Also, an internet search for unpublished studies was performed with the Google® search engine. Full search details are provided in Table A in File S1.

Selection of studies for inclusion in the review

Two researchers independently screened the titles and abstracts of citations identified through the literature search using predetermined inclusion criteria (Table 1). The initial search strategy identified studies published in the last ten years, whereas only studies published since 2005 were included in the review.

Parameter Inclusion Criteria Exclusion Criteria
General Full-text articles published in the English language since 2005 Abstracts
Participants Adults patients with liver failure Patient populations not representing the general liver transplant population (ex: patients with HCC or HCV only)
Intervention Patient’s first orthotopic, whole liver, deceased-donor transplant Multi-organ transplants, non-standard donor or living donor transplants, split liver transplants, sequential transplants
Comparator Pre-operative Model for end-stage liver disease score Delta-Meld, MELD-Na, post-operative MELD score
Outcome Post-transplantation patient survival Survival rate not reported by MELD score
Study design Cohort, cross sectional, RCT, quasi-RCT, or controlled studies Case study or series, commentaries, and opinion pieces without primary data

Table 1. Inclusion/exclusion criteria for review.

Since the purpose of this study was to assess the predictive ability of MELD in the general transplant patient population, studies focussing on specific subgroups of patients were excluded, along with those involving only unique transplant conditions, such as multi-organ transplants, split livers, and non-standard donors. However, studies that considered these conditions within the context of the broader transplantation population were included in the review. Corresponding papers of citations deemed potentially relevant were then retrieved for full review. The level of consensus among reviewers was assessed using the Kappa Statistic. A score of 0.98 was achieved, indicating excellent agreement. Discrepancies among reviewers were resolved through discussion without the need for third party adjudication.

Extraction of data from included studies

Information from included studies was systematically extracted using a pre-tested data abstraction form. The abstraction form contained elements related to study design, patient population, comparators, outcomes measured, and findings. All studies were reviewed by the primary author, with a second reviewer extracting information on 50% of the studies. Reviewers subsequently met to compare results. No discrepancies were found. Therefore, a second, independent review of the remaining studies was deemed unnecessary.

Critical appraisal of included studies

Studies were appraised using the Oxford Center for Evidence-based Medicine Levels and Grades of Recommendation[3].

Data analysis and synthesis of results

Extracted data were tabulated to facilitate a comparison of findings across studies. A meta-analysis of pre-transplant MELD on post-transplant survival using a random effects model was also planned (see Results section). Prior to presenting pooled or summary estimates, clinical heterogeneity and statistical heterogeneity using the I2 statistic were assessed.


Results of the literature search are presented in the PRISMA diagram (Figure 1). The search yielded 3058 discrete citations. Forty-eight full-text articles were retrieved for full consideration, of which 37 met the inclusion/exclusion criteria of the review. Among excluded studies, 6 involved inappropriate comparators or outcomes, 4 did not present primary data, and 1 contained data already captured in an included study. The list of excluded studies, along with reasons for exclusion, is presented in Table B in File S1.


Figure 1. Literature search results and study selection for clinical review.

Description of included studies

The 37 studies comprised both prospective and retrospective case series, and collectively included a total of 53,691 patients. In most, the main objective was not to assess the relationship between MELD and post-transplant survival. Instead, studies examined a broad range of pre-transplant factors that may or may not influence survival through exploratory analyses. Studies originated from several countries, including: Belgium (2), New Zealand (1), the United Kingdom (3), Brazil (6), Spain (5), the United States (7), Singapore (1), Turkey (1), China (1), Korea (1), Switzerland (1), Poland (1), Italy (3), Canada (1), and Germany (3). The majority were single centered. Sample sizes ranged from 46 to 21,673 patients (mean = 1451, median = 222), most of whom were male. None used a power calculation to determine sample size. Sampling methods comprised consecutive patients who met inclusion/exclusion criteria, which differed considerably across studies. Therefore, patients comprising the “general transplant population” may have varied. The point at which MELD was measured in patients was inconsistent across studies, with some using time of placement on the transplant list and others using time of transplant. In most of the studies, the relationship between MELD and survival was examined through stratified analyses of survival across sub-groups defined by MELD score, where MELD cut-off points for sub-groups were determined post-hoc. Further, the majority(25) measured the association between MELD and survival based on univariate analyses alone, and, therefore, did not control for potential confounders. Eleven of the studies assessed the predictive ability of the MELD score on post-transplantation survival using a receiver operating characteristic (ROC) curve and the c-statistic. In 4 of the studies, there was partial overlap of patient populations since they included data from the Transplant Scientific Registry (Cywinski et al [4], Freeman et al [5], Rana et al [6] and Yoo & Thuluvath [7]). All of these studies were kept in the review as each used different MELD categories and follow-up times in their analysis. A detailed summary of each study is presented in Table C in File S1.

As mentioned above, the majority of studies grouped patients by MELD. Specifically, MELD, which represents a continuous variable, was converted to a categorical variable for the analyses. The cut-off points for such categories varied widely across studies and were typically determined post-hoc. (Refer to relevant outcome measures in Table C in File S1). Effect measures also differed, ranging from proportions to hazards ratios, odds ratios, and relative risks, and follow-up time periods were inconsistent. Lastly, characteristics of the “general transplant population” varied. Therefore, given such clinical heterogeneity across studies, a meta-analysis was deemed inappropriate, and a statistical assessment of heterogeneity was not performed.

Quality of included studies

Based on the Oxford Center for Evidence-based Medicine Levels of Evidence, the quality of all of the included studies was level IV. The studies, which involved a comparison of pre-transplant MELD scores with post-transplant survival, were all case series and predominantly retrospective in design. All studies recruited consecutive patients over a specified time period, thereby reducing the risk of selection bias.

Association between Pre-Transplant MELD Score and Post-Transplantation Survival

Of the 37 studies, 15 found no association between pre-transplant MELD score and post-transplant patient survival, while 22 reported poorer survival with higher MELD. A detailed description of the results of each study is presented in Table C in File S1. Based on qualitative analyses, there were no clear differences in studies with statistically significant findings compared to those with no statistically significant findings. In both groups, sample sizes varied, as did follow-up times. However, findings from the two largest studies (N >15,000) both suggested that survival decreased with increasing MELD. One observed this relationship only when patients with MELD scores under 9 were compared to those with scores of 30 or greater, while the other had treated MELD as a continuous variable. At the same time, of the 7 other studies that analysed MELD as a continuous variable, all but one found no statistically significant association between MELD and survival. In most of the studies, information presented on patient characteristics was limited. Therefore, it was not possible to identify any differences in patient populations that could explain inconsistencies in the findings.

Predictive ability of MELD score for post-transplantation survival

Eleven studies presented a receiver operating characteristic (ROC) curve to determine the predictive ability of pre-transplant MELD score to determine post-transplantation survival. The area under the curve is used to produce a concordance value called the c-statistic. A c-statistic of 0.50 indicates no predictive ability, and is expected if the results are due to chance alone. In contrast, a c-statistic of 1 represents perfect discrimination. Values under 0.7 suggest poor predictive power, while those greater than 0.70 indicate a useful test, and those higher than 0.80 imply excellent predictive accuracy[2]. Among the 11 studies, 10 reported c-statistics less than <0.7, indicating that MELD poorly predicted post-transplant survival. This included the largest study contributing to the review[6]. In 1 study, the c-statistic decreased over time, from 0.711 for 3-month post-transplant survival to 0.679 for 12-month survival[8]. In the single study with a high c-statistic[9], there was no clear difference in sample size, follow-up time, or patient population when compared to the studies with lower values.


This review assessed the association and predictive ability of pre-transplantation MELD score on post-transplantation survival in adults with end-stage liver disease. It highlighted discrepancies in findings across studies. Such discrepancies may be related to the nature of the studies, The vast majority were retrospective case series that relied upon exploratory stratified analyses of data to detect a relationship between MELD and post-transplant survival. As such, analytical techniques, rather than study design, were used to control for confounding. In addition, most of the studies were single centered, with each site having its own process for prioritizing patients for transplant. Therefore, patients constituting the general transplant population may have varied across studies. Thus, while using pre-transplant MELD to predict post-transplant survival in transplant candidates may be attractive, there is little evidence to support it. Prospective studies designed specifically to examine this relationship are needed. MELD score does appear to have a greater impact on mortality when observed in combination with other known risk factors for post-transplant mortality, including sub-optimal livers, low graft-to-body ratio and presence of Hepatitis C. Further research in the area of particular patient subgroups (such as those with hepatitis C) may show a stronger association between MELD and post-transplant outcome.

Based on the studies conducted to date, which collectively represent a low level of evidence, MELD could be correlated with survival, but appears to have limited predictive ability. The vast majority of studies presenting concordance statistics found that pre-transplant MELD score offered minimal discriminating power for post-transplantation survival. However, the c-statistic may be of limited value in determining the predictive ability[10]. This is because the c-statistic is intended for diagnostic models, rather than prognostic models. The two types differ in that prognostic models add the element of time. Specifically, diagnostic models are designed to determine the current state of the patient and accurately identify an existing disease state. In contrast, prognostic models are designed to estimate the probability of a future state where the outcome is not yet known and subject to chance.

This review is limited by heterogeneity in key parameters of studies used to date, which precluded performance of a meta-analysis. Studies reported different comparators (in terms of MELD categories) and applied time-points for outcomes. Studies comparing standardized MELD categories would be beneficial in determining whether or not there is, in fact, a threshold level at which liver transplantation does not offer sufficient survival to warrant the use of scarce donor livers. A more accurate assessment of post-transplant survival would also need to look at other factors, such as quality of life. Research examining the combinations of patient factors using more appropriate statistical techniques may also be valuable in improving the predictive ability of pre-transplant elements on post-transplant outcome.


This study provides a comprehensive review of recent articles examining the relationship between pre-operative MELDS score and post-transplantation survival. Based on the results of studies conducted to date, it appears that the use of MELD does not serve as a reliable predictor of post-transplantation survival. This may be a reflection of a reliance on less than ideal analytical measures. However, the use of pre-transplant characteristics may always fall short of ensuring optimal organ allocation due to variability in immeasurable patient factors and the complexity of perioperative and postoperative conditions.

Supporting Information

Table A in File S1. Literature Search. Table B in File S1. Excluded Studies. Table C in File S1. Description of Included Studies [Download File S1, Checklist S1]


The authors would like to thank Leigh-Ann Topfer for assistance with the literature search, Mohamed El Shayeb for assistance with manuscript selection, and Andrea Dunn for assistance with data extraction.

Author Contributions

Conceived and designed the experiments: KK TS DM. Performed the experiments: KK TS. Analyzed the data: KK TS. Contributed reagents/materials/analysis tools: N/A. Wrote the manuscript: KK TS.



Transplant vs resection for the management of HCC meeting Milan Criteria in the MELD exception era at a single institution in a UNOS region with short wait times

J Surg Oncol. 2013 Dec 17. doi: 10.1002/jso.23531. [Epub ahead of print]

Squires MH 3rd, Hanish SI, Fisher SB, Garrett C, Kooby DA, Sarmiento JM, Cardona K, Adams AB, Russell MC, Magliocca JF, Knechtle SJ, Staley CA 3rd,Maithel SK.


BACKGROUND: Management of hepatocellular carcinoma (HCC) in the Model for End-Stage Liver Disease (MELD) exception era remains regionally variable. Outcomes were compared for patients undergoing transplant versus resection at a single institution in a UNOS region with short wait times for organ availability.

METHODS: All patients who underwent resection of HCC from January 2000 to August 2012 and patients who underwent transplant post-January 2006, during the Milan Criteria (MC)-based MELD exception policy for HCC, were identified. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS).

RESULTS: Two hundred fifty-seven patients were analyzed, of whom 131 underwent transplant and 126 underwent resection. All transplant patients met MC; 45 (36%) resection patients met MC. Median follow-up time was 30 months. Median wait time to transplant was 55 days; no patients dropped off the waitlist while awaiting an organ. Among patients meeting MC, transplant demonstrated significantly greater 5-year OS (65.7% vs. 43.8%; P = 0.005) and RFS (85.3% vs. 22.7%; P < 0.001) versus resection. For patients with hepatitis C, transplant (n = 87) demonstrated significantly improved 5-year outcomes compared to patients meeting MC who underwent resection (n = 21; OS: 63.5% vs. 23.3%; P = 0.001; RFS: 83.5% vs. 23.7%; P < 0.001).

CONCLUSION: In a region with short waitlist times for organ availability, liver transplant is associated with improved survival compared to resection for HCC within MC and should be considered for all patients meeting MC, particularly those with hepatitis C. J. Surg. Oncol. © 2013 Wiley Periodicals, Inc.

© 2013 Wiley Periodicals, Inc.

KEYWORDS: Milan Criteria, hepatic resection, hepatocellular carcinoma, liver transplant, waitlist time

PMID: 24347475 [PubMed - as supplied by publisher]


Canadian guidelines for management and treatment of HIV/hepatitis C coinfection in adults

Canadian Journal of Infectious Diseases and  Medical Microbiology

Special Article
Winter 2013, Volume 24 Issue 4: 217-238

CIHR Canadian HIV Trials Network Co-Infection and Concurrent Diseases Core: Canadian guidelines for management and treatment of HIV/hepatitis C coinfection in adults -

M Hull | M Klein | S Shafran | A Tseng | P Giguère | P Côté | M Poliquin | C Cooper | on behalf of The CIHR Canadian HIV Trials Network HIV/Hepatitis C Management and Treatment Guidelines Working Group

BACKGROUND: Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians living with HIV, and is responsible for a heavy burden of morbidity and mortality. HIV-HCV management is more complex due to the accelerated progression of liver disease, the timing and nature of antiretroviral and HCV therapy, mental health and addictions management, socioeconomic obstacles and drug-drug interactions between new HCV direct-acting antiviral therapies and antiretroviral regimens.

OBJECTIVE: To develop national standards for the management of HCV-HIV coinfected adults in the Canadian context.

METHODS: A panel with specific clinical expertise in HIV-HCV co-infection was convened by The CIHR HIV Trials Network to review current literature, existing guidelines and protocols. Following broad solicitation for input, consensus recommendations were approved by the working group, and were characterized using a Class (benefit verses harm) and Level (strength of certainty) quality-of-evidence scale.

RESULTS: All HIV-HCV coinfected individuals should be assessed for HCV therapy. Individuals unable to initiate HCV therapy should initiate antiretroviral therapy to slow liver disease progression. Standard of care for genotype 1 is pegylated interferon and weight-based ribavirin dosing plus an HCV protease inhibitor; traditional dual therapy for 24 weeks (for genotype 2/3 with virological clearance at week 4); or 48 weeks (for genotypes 2-6). Therapy deferral for individuals with mild liver disease may be considered. HIV should not be considered a barrier to liver transplantation in coinfected patients.

DISCUSSION: Recommendations may not supersede individual clinical judgement.

Antivirals | Direct-acting antivirals | HCV | HIV | Pharmacokinetics

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