Protocol Title:

Protocol for the assessment of incidence of disease recurrence in patients who underwent orthotopic liver transplant for NASH or cryptogenic cirrhosis

Principal Investigator: Mary E. Rinella, M.D.Resident Co-Investigator: Lisa B. VanWagner, M.D.

Northwestern University Medical SchoolDept of Hepatology

303 E. Chicago Ave, Tarry Bldg 14-721Chicago, IL 60611

Telephone: 312-503-4592Fax: 312-908-6192

Email: m-rinella@northwestern.edu

TABLE OF CONTENTS

1. Overview

2. Objectives

3. Background

4. Study Population

5. Study Design

6. Inclusion/Exclusion Criteria

7. Methods

8. Confidentiality

9. Future Directions

1. Overview

Approximately 31% of Americans are obese (body mass index [BMI] ≥ 30 kg/m2) and 64% are overweight (BMI ≥ 25 kg/m2).1 With this epidemic comes the increasing incidence of obesity related diseases such as diabetes, hypertension, dyslipidemia and nonalcoholic fatty liver disease (NAFLD).2 NAFLD is the most common cause of liver test abnormalities in the United States.3 Its prevalence has been estimated at 10-24% in various populations and is significantly higher in obese populations (57.5-93%).4 NASH is a subset of NAFLD characterized by fatty change with lobular inflammation, hepatocellular injury, progressive fibrosis and cirrhosis.5

Researchers continue to address risk factors contributing to NAFLD and its progression to NASH, which ultimately can lead to decompensated cirrhosis requiring orthotopic liver transplantation.4-5 Studies have estimated that the development of NASH occurs over decades; however recent studies have demonstrated that in patients who have undergone orthotopic liver transplantation for NASH or cryptogenic cirrhosis, features of disease recurrence occur at an accelerated rate, often within 4-5 years.6-9 One theory underlying this trend is that patients in this population often fail to lose a significant amount of body weight postoperatively, which contributes to exacerbations in poor glucose control and hypertriglyceridemia.10-14 Interestingly, multiple studies conducted in the bariatric surgery population have demonstrated that hepatic histology greatly improves following weight loss surgery.15-21

The purpose of this study is to determine the incidence of disease recurrence in patients who have undergone orthotopic liver transplantation at Northwestern University for NASH or cryptogenic cirrhosis and to identify any modifying risk factors that may contribute to disease recurrence. In addition, we hope to identify a sub-population that has had significant weight loss post transplant and compare the incidence of disease recurrence in that population to age matched controls who failed to decrease their BMI following transplantation. We predict that in those patients who failed to lose a significant amount of body fat postoperatively, features indicative of disease recurrence will occur at an accelerated rate. Futhermore, if this is found to be true, future studies will be designed to develop an intervention to promote weight loss post transplant in the hopes of preventing disease recurrence.

2. Objectives

Primary objectives of study: To determine the incidence of recurrence of NAFLD/NASH in patients who

underwent orthotopic liver transplant for NASH or cryptogenic cirrhosis from June 1993 to March 2007.

To identify modifying risk factors, such as components of the metabolic syndrome and immunosupression that may contribute to disease recurrence in the study population.

Secondary objectives: To identify a possible subpopulation of patients who either underwent weight loss

surgery or experienced a significant amount of weight loss post-transplant. To compare disease recurrence in relation to BMI for patients who experienced

significant weight loss compared to age matched controls.

3. Background

The rapid rise in the prevalence of obesity (body mass index [BMI] ≥ 30 kg/m2) in the United States over the past decade is unprecedented and now a well known epidemic facing the American population.1 Data from two National Health and Nutrition Examination Surveys (NHANES) show that among adults aged 20–74 years the prevalence of obesity increased from 15.0% (in the 1976–1980 survey) to 32.9% (in the 2003–2004 survey).22 Second only to tobacco use, poor diet and physical inactivity are the leading causes of preventable death and are expected to surpass smoking within the coming years.23 As a result, Americans face a public health crisis and an incredible disease burden attributable to poor health behaviors. Obesity has been linked to diseases such as hypertension, dyslipidemia, Type 2 diabetes, coronary artery disease, stroke, gallbladder disease, osteoarthritis, sleep apnea and respiratory problems, and a histological spectrum of obesity-induced liver disease known as nonalcoholic fatty liver disease (NAFLD).2

NAFLD is the most common cause of abnormal liver tests in the United States.3 NAFLD is often found in association with obesity and diabetes and it is expected to become increasingly prevalent as the incidence of these conditions continues to increase.3, 24-25

NAFLD represents a range of diseases from simple fatty deposition in the liver to more aggressive inflammation and fibrosis, termed nonalcoholic steatohepatitis (NASH). The distinction of NASH as an entity within NAFLD is an important one, as the natural history of this disease is different. Ultimately, NASH may progress to cirrhosis in up to 25% of patients, compared to simple steatosis which leads to cirrhosis in only 3% of patients.24-25 In addition, many patients with cryptogenic cirrhosis have risk factors clearly associated with NASH, suggesting that a majority of patients with cryptogenic cirrhosis may have severe end stage NASH.26-27 This theory is consistent with studies indicating that in advanced NASH with prominent bridging fibrosis, histological patterns of NASH may be difficult to detect.26,28 In addition, there is a higher recurrence rate of NAFLD as well as NASH in patients transplanted for cryptogenic cirrhosis as compared to controls.29

The true incidence and prevalence of NAFLD and its subsets (fatty liver and NASH) are unknown, secondary to the fact that the gold standard for diagnosis includes liver biopsy with clinical correlation and exclusion of other causes of liver disease, such as viral, autoimmune or alcoholic. In addition, data comparison between studies is difficult because although there is an accepted histological scoring system for NASH, it is not universally utilized and there is considerable interobserver variability.5 In spite of these limitations, NASH has been estimated at 13-28% in various populations and is

significantly higher in obese populations (57.5-74%).4 Given the rising prevalence of obesity in the general population NAFLD/NASH has become an increasingly important cause of liver-related morbidity and mortality in the next decade.

It is now appreciated that the majority of cases of NAFLD are associated with insulin resistance and that NAFLD represents the hepatic manifestation of a syndrome characterized by resistance to the physiologic effects of insulin.30-33 An association between certain metabolic disorders and cardiovascular disease has been known since the 1940s, however in the 1980s this association became more clearly defined and the term metabolic syndrome (also known as syndrome X) was coined to designate a cluster of metabolic risk factors that come together in a single individual.34 Based on the guidelines from the 2001 National Cholesterol Education Program Adult Treatment Panel (ATP III), any three of the following traits in the same individual meet the criteria for the metabolic syndrome:35

1. Central obesity: a waist circumference over 102 cm (40 in) in men and over 88 cm (35 inches) in women.

2. Serum triglycerides 150 mg/dl or above. 3. HDL cholesterol 40mg/dl or lower in men and 50mg/dl or lower in women. 4. Blood pressure of 130/85 or more. 5. Fasting blood glucose of 110 mg/dl or above. (Some groups say 100mg/dl)

Many studies have indicated that obesity is the condition most often associated with NAFLD and in most studies 69% to 100% of patients with NASH were also obese.30-33, 36

However; other studies have found that only certain components of the metabolic syndrome, such as hyperglycemia and hypertriglyceridemia, are more closely associated with NASH than other components.10, 32, 34

Currently there are very few prospective studies documenting the natural history of NAFLD and available retrospective data provide conflicting results on what the risk factors are for progression of liver disease to cirrhosis. 4-6, 30, 37-39 This information has significant clinical implications given the fact that NASH is one of the leading causes of liver failure necessitating liver transplantation.4-5

What has been demonstrated, however, is that in patients who undergo orthotopic liver transplantation for NASH at least some of the components of steatohepatitis recur within 5 years.7-9 For example, in a recent study of 27 patients with either well-documented NASH or cryptogenic cirrhosis all grafts showed some degree of fatty change within 4-5 years post-transplant vs. only 20-25% of age and gender matched controls with alcoholic liver disease, primary biliary cirrhosis or hepatitis B. Interestingly, only 3 of 27 grafts showed steatohepatitis, suggesting that recurrence of NASH may take longer to develop than steatosis alone post-transplant.6 Based on these data many questions arise. What factors influence the development of steatosis in these patients? Are there certain factors which increase the risk of disease recurrence post-transplant? What interventions might be tried to help reduce the development of steatosis and in turn, NASH?

Several factors may account for NASH recurrence post-transplant. For one, patients often have a persistence of pre-transplant risk factors, such as obesity, Diabetes, hypertension and dyslipidemia. After liver transplantation, patients often develop a dramatic increase in weight, as a result of a combination of medications, poor physical activity, and increase caloric intake.31 In a series of 320 non-obese liver transplant recipients, 21.6% of patients became obese within 2 years from transplantation.32 In addition, immunosuppressive agents, such as steroids and cyclosporine, exacerbate insulin resistance, poor glucose control, dyslipidemia and hypertension. Finally, the incidence and severity of metabolic syndrome features also worsen.10-11, 14-16

In the morbidly obese, up to 95% of patients undergoing bariatric surgery have hepatic steatosis, 47% have NASH and 11% have previously undiagnosed cirrhosis.3, 24-25 The high prevalence of NASH in the bariatric population has made these patients ideal subjects for the study of NAFLD/NASH. Multiple studies have demonstrated that certain weight loss surgeries, such as Roux-en-Y gastric bypass and laproscopic banding, can improve liver histology in these patients.16-20 In addition, a case study of two morbidly obese patients who had undergone orthotopic liver transplant for NASH and had graft dysfunction secondary to disease recurrence underwent Roux-en-Y gastric bypass surgery and at 2 years post-op showed significant improvement in liver histology.21 However, no prospective studies have been conducted to examine this therapy as an option to decrease NAFLD/NASH recurrence in the post orthotopic liver transplant population. In addition, retrospective studies have not looked specifically at weight loss methods employed in the transplant population and their subsequent effect on the incidence of disease recurrence in patients transplanted for NASH or cryptogenic cirrhosis.

The purpose of this study is to initiate a retrospective chart review of all patients transplanted for NASH or cryptogenic cirrhosis at Northwestern University since 1993 in order to direct future prospective research studies. Records indicate that there have been approximately 95 cases of orthotopic liver transplant thought secondary to NASH or cryptogenic cirrhosis. The primary goal of this study is to establish the incidence of steatosis and steatohepatitis recurrence in this transplanted population at Northwestern University. A secondary goal is to examine whether or not BMI and parameters of the metabolic syndrome, such as hypertriglyceridemia, hyperglycemia, HTN, etc, influence recurrence rates and to what extent. In addition, we hope to detect a sub-population that has undergone significant weight loss post-transplant and see if incidence or severity of disease recurrence is less pronounced. We predict that in those patients who failed to lose a significant amount of body fat post-operatively, NASH/NAFLD will occur at an accelerated rate compared to those patients who did lose a significant amount of body fat. Furthermore, if this is found to be true a prospective study will be designed to address weight loss efforts in post-transplant recipients secondary to NASH in hopes of preventing disease recurrence.

References:

1. Strum R. Increases in clinically severe obesity in the United States, 1986-2000. Arch Intern Med 2003; 163:2146-48.

2. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales BS, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 2003; 289:76-79.

3. Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology 2003; 124:71-9.

4. Sass DA, Chang P, Chopra KB. Nonalcoholic fatty liver disease: a clinical review. Dig Dis Sci 2005; 50:171-80.

5. Contos MJ, Sanyal AJ. The Clinicopathologic Spectrum and Management of Nonalcoholic Fatty Liver Disease. Adv Anat Pathol 2002; 9(1): 37-51.

6. Teli MR, James OF, Burt AD, Bennett MK, Day CP. The natural history of nonalcoholic fatty liver: a follow-up study. Hepatology 1995; 22:1714-9.

7. Czaja AJ. Recurrance of nonalcoholic steatohepatitis after liver transplantation [Editorial]. Liver Transpl Surg 1997; 3:185-6.

8. Carson K, Washington MK, Treem WR, Clavien PA, Hunt CM. Recurrance of nonalcoholic steatohepatitis in a liver transplant recipient. Liver Transpl Surg 1997; 3:174-6.

9. Kim WR, Poteruch JJ, Porayko MK, Dickson ER, Steers JL, Wiesner RH. Recurrence of nonalcoholic steatohepatitis following liver transplantation. Transplantation 1996; 62:1802-5.

10. Gholam PM, Flancbaum L, Machan JT, Charney DA, Kotler DP. Nonalcoholic Fatty Liver Disease in Severely Obese Subjects. Am J Gastro 2007;102:399-408.

11. Collantes R. Ong JP. Younossi ZM. Nonalcoholic fatty liver disease and the epidemic of obesity. [Review] Cleveland Clinic Journal of Medicine. 71(8):657-64, 2004 Aug.

12. Reich D, Rothstein K, Manzarbeita C, Munoz S. Common medical diseases after liver transplantation. Semin Gastrointest Dis 1998; 9:110

13. Everhart JE, Lombardero M, Lake JR, Wiesner RH, Zetterman RK, Hoofnagle JH. Weight change and obesity after liver transplantation; incidence and risk factors. Liver Transpl Surg 1998; 4:285.

14. Angelico F, Del Ben M, Francioso S, Hurtova M, Battista S, Palmieri GP, Tisone G, Angelico M. Recurrence of insulin resistant metabolic syndrome following liver transplantation. Eur J Gastro & Hep 2003; 15:99-102.

15. Shaffer EA. Bariatric surgery: a promising solution for nonalcoholic steatohepatitis in the very obese. [Review] Journal of Clinical Gastroenterology. 40(3 Suppl 1):S44-50, 2006 Mar.

16. Frantzides CT, Carlson MA, Moore RE, et al. Effect of body mass index on nonalcoholic fatty liver disease in patients undergoing minimally invasive bariatric surgery. J Gastrointest Surg 2004; 8:849-55.

17. Dallal RM, Mattar SG, Lord JL, et al. Results of laparoscopic gastric bypass in patients with cirrhosis. Obes Surg 2004; 14:47-53.

18. Luyckx FH, Desaive C, Thiry A, et al. Liver abnormalities in severely obese subjects: effect of drastic weight loss after gastroplasty. Int J Obes Relat Metab Disord 1998; 22:222-6.

19. Dixon JB, Bhathal PS, Hughes NR, O'Brien PE. Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss. Hepatology 2004; 39:1647-54.

20. Bugianesi E, Marzocchi R, Villanova N, Marchesini G. Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH): treatment. Best Pract Res Clin Gastroenterol 2004; 18:1105-16.

21. Duchini A, Brunson E. Roux-en-Y gastric bypass for recurrent nonalcoholic steatohepatitis in liver transplant recipients with morbid obesity. Transplantation 2001; 72:156-171.

22. Ogden CL. Carroll MD. Curtin LR. McDowell MA. Tabak CJ. Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. [Journal Article. Research Support, Non-U.S. Gov't] JAMA. 295(13):1549-55, 2006 Apr 5.

23. Mokdad AH, Marks JS, Stroup DF, et al. Actual causes of death in the United States, 2000. JAMA 2004; 291:1238-45.

24. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.Gastroenterology 1999; 116:1413-9.

25. Angulo P, Lindor KD. Non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2002; 17 Suppl:S186-90.

26. Caldwell SH, Oelsner DH, Iezzoni JC, Hespenheide EE, Battle EH, Driscoll CJ. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology 1999; 29:664-9.

27. Poonawala A, Nair SP, Thuluvath PJ. Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: a case-control study. Hepatology 2000; 32:689-92.

28. Powell EE, Cooksley WG, Hanson R, Searle J, Halliday JW, Powell LW. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology 1990; 11:74-80.

29. Contos MJ, Cales W, Luketic VA, et al. Development of nonalcoholic fatty liver disease after liver transplant for cryptogenic cirrhosis. Liver Transpl 2001; 7:363-73.

30. Fong DG, Nehra V, Lindor KD, Buchman AL. Metabolic and nutritional considerations in nonalcoholic fatter liver. Hepatology 2000; 32:3-10.

31. Luyckx FH, Lefebvre PJ, Scheen AJ. Nonalcoholic steatohepatitis: association with obesity and insulin resistance, and influence of weight loss. Diabetes MetabI 2000: 26:98-106.

32. Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome [erratum appears in Hepatology 2003; 38:536]. Hepatology 2003; 37:917-923.

33. Sanyal AJ, Campbell-Sargent C, Mirshahi F, et al. Nonalcoholic steatohepatitis: Association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001; 120:1183-92.

34. Abrams, GA, Kunde SS, Lazenby AJ, Clements RH. Portal fibrosis and hepatic steatosis in morbidly obese subjects: A spectrum of nonalcoholic fatty liver disease. Hepatology 2004; 40:475-483.

35. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001; 285:2486-2497.

36. Wanless IR, Lentz JS. Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology 1990; 11:74-80.

37. Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999; 30:1356-62.

38. Rinella ME, Alonso E, Rao S, et al. Body mass index as a predictor of hepatic steatosis in living liver donors. Liver Transplant 2001; 7:409.

39. Ong JP, Elariny H, Collantes R, et al. Predictors of nonalcoholic steatohepatitis and advanced fibrosis in morbidly obese patients. Obes Surg 2005; 15:310-5.

4. Study Population

This will be a retrospective chart review of approximately 95 patients aged 18-65 years who underwent liver transplantation for either NASH or cryptogenic cirrhosis at Northwestern Memorial Hospital through the liver transplant program between January 1993 and March 2007.

5. Study Design

This will be a retrospective chart review study to determine the prevalence, natural history and coincident risk factors associated with disease recurrence in NASH/NAFLD patients post liver transplant. In addition, the study will identify the prevalence of patients who have undergone bariatric surgery post liver transplantation and determine liver biopsy histological features in those who may have experienced early graft dysfunction secondary to disease recurrence.

6. Inclusion/Exclusion Criteria

Patient medical records must meet the following criteria for entry into the protocol:

Adult subjects 18-65 years of age of any race or gender who underwent liver transplantation secondary to NASH or cryptogenic cirrhosis between January 1993 and March 2007.

Subjects must fulfill the criteria for diagnosis of NASH:٠ Presence of steatosis and evidence of hepatocellular injury as defined by

the NASH activity score (NAS) (Kleiner et al. 2005) ٠ The exclusion of other forms of liver disease such as hepatitis C, hepatitis

B, hemochromatosis, Wilson’s disease, alpha-1-antitrypsin deficiency, and autoimmune hepatitis as referenced below:

Anti - smooth muscle Ab < 1:80, ANA <1:160 (or histological evidence of autoimmune hepatitis)

Serum Hepatitis B surface antigen (HepBsAg) negative. Serum Hepatitis C Antibody (Hep C Ab) negative Iron/TIBC ratio (transferrin saturation) < 45% Alpha-1-antitrypsin level within normal limits Ceruloplasmin level within normal limits. No active drug abuse within 6 months Etoh consumption < 20g/day (males) or < 10 g/day

(females) - Assessed by one physician and confirmed with one family member.

No known diagnosis of malignancy

Subjects must fulfill the criteria for diagnosis of cryptogenic cirrhosis pre-transplant

٠ The exclusion of other forms of liver disease such as hepatitis C, hepatitis B, hemochromatosis, Wilson’s disease, alpha-1-antitrypsin deficiency, and autoimmune hepatitis determined by negative serologies as outlined above.

7. Methods

Subjects: Medical records for all patients aged 18-75 years old who underwent liver transplantation for NASH or cryptogenic cirrhosis from January 1993 to March 2007.

Data Collection: Medical records will be reviewed in a systematic matter for eligibility for inclusion based on the Northwestern University Liver Transplantation database (OTR) and pre- and post- transplant charts. After inclusion/exclusion criteria have been met medical records will be reviewed to determine patient demographic data, number of biopsies obtained preoperatively and postoperatively as well as both preoperative and postoperative metabolic measurements. Additional known risk factors for NAFLD recurrence will be documented, such as cumulative steroid dose given, other immunosuppressive medications and corresponding levels. The incidence of disease recurrence will be determined by biopsy or suggested by abnormal liver enzymes and radiological evidence of steatosis (CT, MRI, ultrasound). Changes in weight and the addition of anti-diabetic, lipid lowering or antihypertensive medications will also be noted (please see attachment).

Analysis: All data will be entered into Microsoft Excel and analyzed for descriptive statistics such as mean, median, and frequency with standard deviations. The main focus of interest is the incidence of disease recurrence and the prevalence of possible modifying risk factors based on metabolic measurements used to diagnosis the metabolic syndrome. We are additionally interested in prevalence of weight gain and weight loss post transplant in association with disease recurrence. Finally, we hope to identify a subpopulation with recurrent disease to better understand the risk factors for disease recurrence. Data will be further analyzed using SPSS software to determine factors that are independently associated with disease recurrence. With these preliminary data, we will design a prospective study to determine the effects of bariatric surgery (Lap Band) on patients at risk for rapid recurrence. We hypothesize that the attenuation of post- transplant weight gain and weight loss in general will decrease the incidence and severity of NASH recurrence.

8. Confidentiality

All study personnel have undergone HIPAA training and will comply with HIPAA guidelines. Medical records will be identified by a unique system subject code only which corresponds to the transplant number listed on Northwestern University’s transplant database. This database is located on a secure password protected computer and specific patient identifying information will only be referenced for the purpose of revisiting specific medical records once the review has been completed for any clarifying information needed to complete the study. Data not yet transferred to the database will be abstracted from paper charts located on the 15th and 17th in locked rooms for pre and post transplant patients, respectively. Data collection results will be entered into a Microsoft Excel spreadsheet and stored in a secured study file located on a dedicated personal computer in a locked office, which can only be reviewed through a password-protected account. Each subject will be identified on the main study personal computer by a unique study code. Subject confidentiality will be maintained. There is no harm or benefit to subjects included in the review because no intervention will be initiated. Only

statistical data will be collected. However, future patients may benefit if this research is able to identify possible methods of intervention to prevent disease recurrence.

9. Future Directions

NAFLD/NASH recurs at an accelerated rate in patients transplanted for NASH or cryptogenic cirrhosis. Major risk factors for NAFLD include those associated with metabolic syndrome, the most important being obesity which often worsens post-transplant. Weight loss surgery has been shown to result in improvement or elimination of features of the metabolic syndrome and both biochemical and histological improvement in NASH. Thus, one would expect that in those patients in whom weight loss surgery is performed the development of steatosis, steatohepatitis and liver failure from recurrent disease would be delayed compared to age matched controls not undergoing weight loss surgery.

This retrospective review will determine the prevalence and rate of recurrent NAFLD/NASH in our post orthotopic liver transplant patients and identify possible modifying risk factors. Therefore, in a prospective study we plan to assess the impact of weight loss surgery (laparoscopic adjustable gastric band) during or post orthotopic liver transplant in obese patients transplanted for NASH cirrhosis.

Appendix A: DATA COLLECTION SHEET

ID #: _________________ MRN: ______________ DOB: ____________________

Age:________ GENDER: M or F Race: _____________ OLT Date:

_______________ MELD: ____________ Diagnosis: NASH

Cryptogenic BOTH Other ____________

Donor: LIVING or CADAVERIC % donor liver fat: _______ Graft

Function: ______________

Pertinent PMH: ( e.g. Diabetes (on or off meds?), HTN, Hyperlipidemia)

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

PRE-OP dx of Metabolic syndrome? Y or N

# criteria met? 1 2 3 4 5

Which criteria?

MEDS:

PRE-OP POST-OP

CUMULATIVE STEROID DOSE and taper period:

________________________________

Other immunosupressants (time used, dose adjustments):

________________________________

SOCIAL HX:

EtOH < 20 g/day (male) or < 10 g/day (female)? Y or NEtOH assessed by 1 physician and confirmed with family member? Y or N

LABS:

Anti-SM AB ANASPEP HepBsAg HepC AbIron/TIBC Alpha-1-antitrypsinCeruloplasmin

PRE-OP POST-OP Date: Date: Date:

HeightWeightWaist circumferenceHip circumferenceWaist-hip ratioCalculated BMISBPDBPBUN/CrCBC w/ plts

HbA1cFasting glucoseOGTT?Total CholTG

LDLHDLASTALTAST/ALT ratioGGTAlk phosTbiliAlbumin

STUDIES:

Date Pre/Post? Indication Result

U/S

CT

MRI

Liver Biopsy history:

Date Pre/Post? Indication Result ( *include % steatosis)

POST-OP COMPLICATIONS?

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

BRIEF POST-OP COURSE

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

____________________________________

DOCUMENTED WEIGHT LOSS EFFORTS?

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

__________________

EVIDENCE OF RECURRENT DISEASE? Y or N

Biopsy:

DATE: ____________________

1) % of steatosis: ___________ grade of steatosis: MILD MOD

SEVERE

2) NAS score

3) Extent fibrosis

OR

Presumptive:

ALT/AST: ____________________________

U/S, MRI or CT with fat:-

____________________________________________________________

TIME TO DIAGNOSIS: (i.e. 1 year post OLT)

_________________________________________________