During this issue of IBC Newsletter, Dr. Farah Husain with her fellow Dr. Priya Rajdev defend their practice of selective liver biopsy during bariatric surgery. On the other hand, Dr. Laura Doyon explains her more liberal approach in obtaining liver biopsies intraoperatively. An expert commentary is provided by Dr. Cori McBride along with her fellow Dr. Michael Cudworth.
The more conservative approach (Dr. Husain and Dr. Rajdev)
What kind of evaluation do you do before bariatric surgery to assess liver anatomy and function (if you do any)?
Preoperative labs include transaminases, platelet count, and coagulation studies are routinely performed on all candidates for bariatric surgery. Symptoms and risk factors on initial visit are also explored such as: dietary habits, substance use/abuse, medication history, viral exposures, h/o hepatitis, and personal history of cancer. Any prior imaging is reviewed as well.
Does the diagnosis of NASH affect you leaning towards one procedure or another? What about Cirrhosis?
If the patient has non-alcoholic steatohepatitis suspected on routine lab work (elevated AST/ALT) or on abdominal imaging, we counsel the patient regarding their options. It is our practice to refer these patients for FibroScan or MR elastography prior to offering an invasive test. Patients will only receive a liver biopsy if labs and imaging support the need for liver biopsy.1 Currently, of the two most common operations at our institution, Laparoscopic Roux-en-y gastric bypass offers slightly increased and more durable weight loss than sleeve gastrectomy. Historically, we have tended to recommend RYGB to patients with very high BMI (>50), those who have GERD, diabetic patients, and those with multiple sequelae of obesity, such as NASH, that may most benefit from dramatic and sustained weight loss. However, there is mounting evidence fatty changes to the liver may be equally well-addressed by sleeve gastrectomy alone.2 Sleeve gastrectomy may offer a lower-risk operation in cirrhotic patients or those who are on the transplant list. MELD score will play a role in determining risk of operative morbidity and mortality, guiding perioperative counseling of the patient, and selecting appropriate surgical candidates.
When do you perform liver biopsy during bariatric surgery? Planned vs non planned? Consented or not?
Most planned liver biopsies will occur when the patient is being actively worked up by GI/Hepatology for abnormal LFTs; indeed, a referral to bariatric surgery may be a result of hepatology workup. In these cases, patients are consented preoperatively if they have not yet had a liver biopsy, and the referring hepatologist requests biopsy. Otherwise, liver biopsy is not routinely performed, even when fatty or “nutmeg” liver is grossly observed. In general, we expect fatty liver disease to improve after bariatric surgery, and therefore the benefit of quantifying degree of steatosis at the time of operation is unclear. Liver biopsy adds time to the case, has risk involved, and poses an additional cost to the patient in pathology fees. If preoperative transaminases, platelets, and INR are within normal limits, we do not pursue liver biopsy.
What kind of liver biopsy (if needed) do you perform? And why? Have you had any complications once performed?
A Tru-cut core needle biopsy is done. This is generally used to obtain several cores. The goal is to obtain cores between 15-30mm in length, as this size is needed to adequately assess fibrosis. Liver biopsies have limitations, the most notable being sampling error. If the sample obtained is too small, it can lead to under or over-staging. In addition, the right lobe vs left lobe of the liver can have differing pathology. It is recommended that larger gauge needles, longer biopsies, multiple biopsies, and pathologist with specific training in analyzing fibrosis are needed to optimize results. 3 To date, we have seen one bleeding complication of liver biopsy and one hepatic abscess that was likely a biopsy site that became infected from adjacent surgical procedure.
Have you had to change a bariatric procedure or abort one, after a liver intarop finding? If not, what finding would in the future?
We have not aborted a case due to cirrhosis. We gauge the extent of hepatic dysfunction prior to proceeding, such as presence of ascites, evidence of varices, or any concern for portal hypertension. Being at an academic institution, we also do have the luxury of hepatobiliary and transplant specialists who are available for intraoperative consultation. As such, our threshold for case cancellation is much higher than it might be in other settings. Cases can be aborted if the left liver lobe is too heavy or large to be effectively retracted to expose the gastric fundus and hiatus. Isolated findings, such as evidence of malignancy or metastases, would prompt us to change or abort a procedure.
What kind of follow up these patients get after a liver biopsy is done? Do you believe a hepatologist referral would change anything in the future care?
If our intraoperative suspicion of clinically latent fatty liver disease is present, we will perform and follow-up the results of the liver biopsy. If pathology demonstrates fibrosis, we will refer the patient to hepatology. After this referral, the patient may undergo further workup, such as follow-up Fibro-Scan or MRI. With judicious referral to hepatology, based on preoperative suspicion, intraoperative biopsy have been very limited. It is important that select patients at high risk of clinically significant NASH/NAFLD have follow-up with appropriate specialists. The natural history of disease can show progression in approximately 1/3 of patients. With the best intervention being weight loss, bariatric surgery is a key to halting progression, if not improving fibrosis.
References
1. Sporea I, Cirli R, Deleanu A, Tudora A, Curescu M, Cornianu M, Lazăr D. Comparison of the liver stiffness measurement by transient elastography with the liver biopsy. World J Gastroenterol 2008; 14(42): 6513-6517
2. W. K. Karcz, D. Krawczykowski, S. Kuesters, et al. Influence of sleeve gastrectomy on NASH and Type 2 Diabetes Mellitus. Journal of Obesity 2011; 1-7.
3. Brunt EM, Tiniakos DG. Histopathology of nonalcoholic fatty liver disease. World J Gastroenterol 2010 November 14; 16(42): 5286-5296.Tapper EB, Lok AS. Use of liver imaging and biopsy in clinical practice. N Engl J Med 2017; 377:756-768 DOI: 10.1056/NEJMra1610570
The more liberal approach (Dr. Doyon)
What kind of evaluation do you do before bariatric surgery to assess liver anatomy and function (if you do any)?
All preoperative patients have a panel of labwork to check nutritional status, as well as for routine surgical planning. Included in that panel is a comprehensive metabolic panel which assess liver function tests – transaminases, alkaline phosphatase, and bilirubin. Unexplained elevated transaminases are treated as presumed NAFLD. These patients will be offered liver biopsy at the time of their surgery.
We do not routinely check right upper quadrant ultrasound except in cases with convincing enough history for biliary colic or other firm indication for cholecystectomy. However, we see many patients who had started their workup at an outside hospital. If they have an ultrasound or CT that comments on fatty changes to the parenchyma, we will offer that patient a liver biopsy as well.
There is increasing data that there can be occult NALFD/NASH in the absence of bloodwork abnormalities, and visual cues for steatosis in the operating room can be unreliable. This is the rationale for offering liver biopsy to all patients undergoing bariatric surgery as some centers do.
Does the diagnosis of NASH affect you leaning towards one procedure or another? What about Cirrhosis?
I can count on one hand the number of patients who have come in with a preoperative diagnosis of NAFLD/NASH that was biopsy proven (the gold standard). We have discussed the greater metabolic advantage of a gastric bypass with those patients, but ultimately do not force patients to have either a sleeve or a bypass based on this alone. For patients with more advanced Cirrhosis, a sleeve would likely be a safer choice. The diagnosis that we are discussing in this forum is a postoperative diagnosis and is not intended to influence choice of surgery.
When do you perform liver biopsy during bariatric surgery? Planned vs non planned? Consented or not?
We obtain consent for this in advance whenever possible. It is almost always planned based on criteria above. However, if they have evidence of marked steatosis which is obvious, we will do a biopsy at that time and I inform the patient and family once surgery is completed. The patient and their family are notified immediately postop when this occurs. We are moving towards a process where all patients get an intraoperative liver biopsy given that NAFLD/NASH can be occult and not show in the preoperative workup, in combination with the elevated risk in our patient population.
ADA guidelines indicate that all patients with T2DM and prediabetes should be screened for NAFLD, given that there is a prevalence in this population of up to 70%. Traditional methods of screening (bloodwork, ultrasound) have low sensitivity, and few patients get percutaneous biopsies due in part to the risk of bleeding or other morbidity with that type of biopsy. As bariatric surgeons we have a unique role in the overall health of our obese patients. We commonly screen for other comorbid conditions, for example obstructive sleep apnea, which most primary care physicians don’t have the time or awareness to address.
What kind of liver biopsy (if needed) do you perform? And why? Have you had any complications once performed?
We perform a small <1cm laparoscopic wedge liver biopsy. We use laparoscopic scissors to excise a small triangle of parenchyma from the inferior edge of the left lateral lobe of the liver. Hemostasis is easily achieved with hook electrocautery. We are able to reassess the site for hemostasis by the end of the procedure. I have never seen bleeding or other complication from this type of biopsy.
Have you had to change a bariatric procedure or abort one, after a liver intraop finding? If not, what finding would in the future?
We are not getting frozen pathology at the time of these biopsies. The diagnosis of NALFD/NASH should not affect whether they can be successful or recover safely from surgery. Again, the intention is not to determine whether the patient may go ahead with surgery. Personally, I think that would be devastating to the patient who had put months of effort and hope into preparing for this procedure. The goal is to identify previously undiagnosed NAFLD/NASH since we have a unique opportunity to safely perform a biopsy that would otherwise carry more risk and morbidity when done as a percutaneous biopsy.
What kind of follow up these patients get after a liver biopsy is done? Do you believe a hepatologist referral would change anything in the future care?
For patients who have fibrosis level of 3 or 4 found on the biopsy, they are referred out to a hepatologist. These patients will undergo regular surveillance, often with a fibroscan, to assess for progression of the disease, which may occur even despite weight loss. Additionally, for the ~15% of patients which the ASMBS now believes are likely to have significant weight regain after bariatric surgery, NAFLD will almost certainly progress and/or not improve. Additionally, at least anecdotally, we have seen cases of patients with F3 and above that, upon receiving the news, will double down on their lifestyle changes, and make certain to remain abstinent from alcohol which can encourage further disease progression. Disease progression can result in cirrhosis and hepatocellular carcinoma, and can lead to a higher risk of cardiovascular events. It is believed that the current trajectory of the incidence of NASH will soon result in the leading cause of liver transplant in the US. Current treatments aside from weight loss are still evolving. The current standard of care is to encourage a weight loss of ideally >10%, which is certainly reached by most postoperative surgical patients. However, only 65% of patients have been found to have improvement in Fibrosis level postop, and that at later time points of >5 years, that number drops to 50% or less. This again speaks to the need for identification. Medical treatment for resistant cases could include vitamin E, Pioglitazone, or SGLT-2 inhibitors. There are additional therapies that are currently being researched and will likely be coming soon, therefore this may be the best time to identify these patients.
The expert commentary (Dr. McBride and Dr. Cudworth)
A case for selective liver biopsy during Bariatric Surgery
Non-alcoholic fatty liver disease (NAFLD) as well as its progression, Non-alcoholic steatohepatitis (NASH) are a major cause of chronic liver injury, and after alcoholic and viral hepatitis, one of the most common causes of liver failure and cirrhosis. (1) NAFLD and NASH are increasing in prevalence worldwide and in the United States, where the prevalence has been estimated to be between 20% and 30%, similar to the prevalence of Obesity, and over the upcoming decades it is expected to be the leading cause of liver transplantation. (2,3) NAFLD and NASH are ubiquitous in obesity, with the prevalence of NAFLD in the general population being reported as ranging from 2.8-53%, in the obese population up to 70-88% have NAFLD, and 33-56% have NASH. (4, 5).
NASH has no overt signs and symptoms, nor is there any trustworthy non-invasive diagnostic test, which makes its diagnosis challenging. (4,6) However, identifying these patients is critically important, as NASH can progress to liver failure and cirrhosis. Identifying these patients may allow a window of opportunity in which to intervene, and establish treatment and surveillance to attempt prevention of progression to liver failure. (8) The gold standard for diagnosis of NASH has been liver biopsy.(9) Intraoperative liver biopsy (IOLB) is a relatively safe procedure, which in conjunction with the substantial prevalence of NALD has led some to recommend routine liver biopsy in bariatric and morbidly obese patients during abdominal procedures. (4,10,11,12)
Indeed, the Longitudinal Assessment of Bariatric Surgery (LABS) studies suggested that lack of routine biopsies result in missed diagnosis in 86% of patients with NASH and 88% with advanced fibrosis. (4,10) However, overall these studies showed a low rate of serious liver disease, with only 4.2% of biopsies showing bridging fibrosis or cirrhosis, with 13.7% showing a NAS (NAFLD activity score) of 5 or greater. In terms of diagnostic categorization, this cohort had 16.2% showing definite steatohepatitis, and an additional 17.4% with borderline steatohepatitis. IOLB is also associated with additional risks of complications, costs and increased operating room time, which in conjunction with the overall low rate of serious liver disease render the routine use of IOLB in all obese patients undergoing abdominal surgery an impractical proposition. (12,13,14) The holds true for bariatric surgery as well, and may be contributing factors as to why most bariatric surgeons do not currently routinely perform IOLB. (4,12,13)
A better case may be made for selective IOLB. A combination of visual inspection during laparoscopy and targeted biopsy may be higher yield. Prior reports have showed visual diagnosis of cirrhosis at the time of laparoscopy to be superior to targeted liver biopsy for diagnosis of liver cirrhosis and increased the sensitivity of diagnosis by more than 30% compared to laparoscopically targeted biopsy alone. (13, 15) Jalan et al showed a combination of visual inspection during laparoscopy and histology provides the diagnosis in most cases. In this cohort, the authors reported laparoscopy had a sensitivity of 100% and a specificity of 97.1% in diagnosing cirrhosis. Histology with laparoscopic visual assessment of the liver would miss diagnosis in 6.1% in this cohort. (16)
An interesting report by Ooi et al described a structured tool based on assigning scores to the visual appearance of the liver during laparoscopy, based on color, size, and surface components, thus stratifying patients into low, intermediate and high-risk categories based on the VLS (Visual Liver Score, calculated by a sum of color, size, and surface scores, total score 0-8). This was correlated with histology, and found to be a reliable indicator of steatosis, NASH, and fibrosis. Per the authors, a low-risk score (VLS ≤ 1) would indicate an IOLB is unnecessary, with a high negative predictor value (NPV 79.8–100%). Conversely, an intraoperative liver biopsy would be recommended in those with a high-risk score (VLS ≥ 4), and should be considered for those with an intermediate score (VLS 2–3). This approach seems to offer a reasonable risk-benefit ratio, and thus the VLS could be considered a useful adjunct in clinical practice. (4) As a conclusion to the aforementioned discussion, in our practice we have adopted a selective approach to IOLB.
References
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Sarwar R, Pierce N, Koppe S. Obesity and nonalcoholic fatty liver disease: current perspectives. Diabetes Metab Syndr Obes. 2018 Sep 25;11:533-54
Neuschwander-Tetri BA. Non-alcoholic fatty liver disease. BMC Med. 2017;15(1):45
Ooi GJ, Burton PR, Earnest A, Laurie C, Kemp WW, Nottle PD, McLean CA, Roberts SK, Brown WA. Visual Liver Score to Stratify Non-Alcoholic Steatohepatitis Risk and Determine Selective Intraoperative Liver Biopsy in Obesity. Obes Surg. 2018 Feb;28(2):427-436
Angulo P. GI epidemiology: nonalcoholic fatty liver disease. Aliment Pharmacol Ther. 2007;25:883–9.
Ooi GJ, Burton PR, Doyle L, et al. Modified thresholds for fibrosis risk scores in nonalcoholic fatty liver disease are necessary in the obese. Obes Surg. 2017;27(1):115–25.
Bugianesi E, Leone N, Vanni E et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 2002; 123: 134-40.
Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology. 2012;142(7):1592–609.
Bacon BR, Farahvash MJ, Janney CG et al. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology 1994; 107: 1103-9.
Kleiner DE, Berk PD, Hsu JY, et al. Hepatic pathology among patients without known liver disease undergoing bariatric surgery: observations and a perspective from the longitudinal assessment of bariatric surgery (LABS) study. Semin Liv Dis. 2014;34(1):98–107.
Teixeira AR, Bellodi-Privato M, Carvalheira JB, et al. The incapacity of the surgeon to identify NASH in bariatric surgery makes biopsy mandatory. Obes Surg. 2009;19(12):1678–84.
Shalhub S, Parsee A, Gallagher SF, et al. The importance of routine liver biopsy in diagnosing nonalcoholic steatohepatitis in bariatric patients. Obes Surg. 2004;14(1):54–9.
Mahawar KK, Parmar C, Graham Y, et al. Routine liver biopsy during bariatric surgery: an analysis of evidence base. Obes Surg. 2016;26(1):177–81.
Dallal RM, Samuel G, Lord JL, et al. Hemobilia: a rare complication after routine liver biopsy during gastric bypass. Surg Obes Relat Dis. 2007;3(1):91–3.
Helmreich-Becker I, Schirmacher P, Denzer U, et al. Minilaparoscopy in the diagnosis of cirrhosis: superiority in patients with Child-Pugh A and macronodular disease. Endoscopy. 2003;35(1):55–60.
Jalan R, Harrison DJ, Dillon JF, et al. Laparoscopy and histology in the diagnosis of chronic liver disease. QJM. 1995;88(8):559–64.
