Hepatic Decompensation After Gastric Bypass Surgery

Digestive Diseases and Sciences,Vol.49,No.10(October2004),pp.1563–1568(C 2004)CASE REPORTHepatic Decompensation After Gastric Bypass Surgery for Severe ObesitySCOTT J.COTLER,MD,*JOSEPH M.VITELLO,MD,†GRACE GUZMAN,MD,‡GIULIANO TESTA,MD,§ENRICO BENEDETTI,MD,§and THOMAS YDEN,MD*KEY WORDS:gastric bypass;obesity;nonalcoholic fatty liver disease;cirrhosis;hepatic decompensation.Obesity is a pervasive and growing problem in the United States.A Centers for Disease Control and Prevention sur-vey conducted in2000estimated that20%of the U.S.pop-ulation was obese(body mass index[BMI],≥30kg/m2), up from12%in1991(1,2).The prevalence of severe obe-sity(BMI,≥40kg/m2)was2%(1).The rise in obesity has fueled an increasing demand for bariatric surgery. Jejuno-ileal bypass was performed in the late1960s through the early1980s to achieve long-term weight loss (3).The procedure was abandoned due to complications including diarrhea,electrolyte abnormalities,nephrolithi-asis,cholelithiasis,metabolic bone disease,and mortality related to acute liver failure and cirrhosis(4–6).Gastric re-striction procedures such as gastric stapling,gastric band-ing,Roux Y gastric bypass(RNY-GBP),and biliopan-creatic diversion have provided means to achieve weight loss without severe metabolic complications.Roux Y gas-tric bypass is currently the most commonly performed procedure.A study of the Swedish Obese Subjects Co-hort showed that persons who underwent RNY-GBP had a greater weight loss than those who had other gastric restriction procedures or biliopancreatic diversion(7).A number of reports have described the presence of nonalcoholic fatty liver disease(NAFLD)including cir-rhosis in liver biopsy specimens obtained at the time of bariatric surgery(8–12).Hepatic decompensation was re-ported in a patient18months after biliopancreatic di-version(13).However,limited information is available regarding whether RNY-GBP predisposes to progressive liver injury(8).We describe three patients who developed Manuscript received May20,2004;accepted June8,2004.From the*Section of Hepatology,†Division of General Surgery,‡Department of Pathology,and§Division of Transplantation Surgery, the University of Illinois at Chicago,Chicago,Illinois,USA. Address for reprint requests:Scott Cotler,MD,Section of Hepatology (MC787),840South Wood Street,Chicago,Illinois60612,USA; scotler@.hepatic decompensation after RNY-GBP with an extended Roux limb for severe obesity.CASE REPORTSSurgical Technique.Three hundred thirty-two RNY-GBP with an extended Roux limb were performed at our institution for the treatment of severe obesity between January2001and June2003.A225-cm Roux limb was used based on data show-ing superior weight loss with extended versus short Roux limbs in severely obese patients(14).According to standard proce-dure,the stomach was divided,creating a30-ml gastric pouch. The small bowel was divided approximately4ft distal to the lig-ament of Treitz and a225-cm Roux limb was created.A side-to-side jejunojejunostomy was performed to reestablish intestinal continuity.The Roux limb was brought into a retrocolic and ret-rogastric position and an anastomosis was performed to the gas-tric pouch.Three of332patients(0.9%)presented with evidence of severe hepatic dysfunction,7to17months after operation.Patient1.A34-year-old woman with a BMI of86kg/m2 underwent a RNY-GBP with an extended Roux limb.She pre-sented17months later with marked muscle wasting,weakness, fatigue,tender hepatomegaly,and anasarca.Her oral intake was limited to water and small amounts of pureed food.She had lost 128kg since her operation,or51%of her body weight.Laboratory data are listed in boratory tests for viral and autoimmune causes of chronic liver disease were neg-ative.The patient did not drink alcohol.An abdominal ultra-sound showed ascites and splenomegaly.Steatosis with steato-hepatitis and cirrhosis were present on a transjugular liver biopsy (Figures1a and1b).The right atrial-wedged hepatic vein gradi-ent was elevated,at30mm Hg.Parenteral nutrition was provided briefly,followed by nasoen-teral feedings.There was a modest improvement in laboratory parameters(Table1).However,the patient’s course has been complicated by persistent ascites requiring large volume para-centesis every6to8weeks,and two episodes of spontaneous bacterial peritonitis.She is awaiting liver transplantation.Patient2.A37-year-old woman with a history of hyperten-sion and a BMI of61kg/m2underwent a RNY-GBP with an extended Roux limb.She presented7months later with jaun-dice,hepatic encephalopathy,and renal insufficiency.The pa-tient had a48-kg weight loss(27%of body weight)from theDigestive Diseases and Sciences,Vol.49,No.10(October2004)15630163-2116/04/1000-1563/0C 2004Springer Science+Business Media,Inc.COTLER ET AL.T ABLE1.L ABORATORY V ALUES FOR P ATIENT1Total bilirubin Direct bilirubin Total Protein Albumin BUN Creatinine Platelets (mg/dl)(mg/dl)(g/dl)(g/dl)INR AST(U/L)ALT(U/L)(mg/dl)(mg/dl)(×103/mm3) Admission 1.60.87.5 1.6 2.17421120.9916mo later0.80.2 4.8 1.6 1.4168110.6157 Note.Normal ranges:total bilirubin(0–1.2mg/dl),direct bilirubin(0–0.2mg/dl),total protein(6.0–8.0g/dl),albumin(3.6–5.0g/dl),INR(0.9–1.2), AST(10–40U/L),ALT(10–50U/L),BUN(6–20mg/dL),creatinine(0.4–1.2mg/dL),and platelets(150–400×103/mm3).No liver enzymes were available from before the time of bariatric surgery.The preoperative platelet count was253×103/mm3.time of her operation and had very limited oral intake during the weeks leading up to her admission.She had severe muscle wasting and tender hepatomegaly.Preoperative and admitting laboratories are listed in Table2.Serologic testing for viral and autoimmune hepatitis was negative.She did not drink alcohol.An abdominal CT scan demonstrated hepatosplenomegaly without ascites.There was massive steatosis and mildfibro-sis on a transjugular liver biopsy(Figure2).The right atrial-wedged hepatic vein gradient was elevated to25mm Hg.The patient showed clinical and biochemical improvement with med-ical management including lactulose,volume repletion,and ini-tiation of nasoenteral feedings and metronidazole(Table2).Patient3.A54-year-old woman with a history of non-insulin-dependent diabetes and hypertension and a BMI of 49kg/m2had a RNY-GBP with an extended Roux limb.She presented7months later with jaundice,hepatic encephalopathy, ascites,renal insufficiency,muscle wasting,and profound weak-ness.Her history was notable for a35-kg weight loss(25%of body weight).She was achieving very limited oral intake prior to her boratory data are listed in Table3.Tests for viral and autoimmune hepatitis were negative.She had no history of excessive alcohol use.A transjugular liver biopsy showed severe steatosis with steatohepatitis and cirrhosis(Figures3a and3b).The right atrial-wedged hepatic vein gradient was elevated to30mm Hg.The encephalopathy improved with lactulose and treatment of an in-fection.Nasoenteral feedings and metronidazole were started. The patient’s clinical status and laboratories improved transiently (Table3).She then presented with worsening ascites and renal failure.Cytologic evaluation of the ascitesfluid showed atypical cells consistent with adenocarcinoma.The patient deteriorated rapidly and died.Gastric carcinoma infiltrating the gastric rem-nant with peritoneal metastases was identified on postmortem examination.DISCUSSIONThe identification of three patients who developed hep-atic decompensation after long limb RNY-GBP surgery is alarming.All three were severely obese before the opera-tion,with BMIs ranging from49to86kg/m2.Preopera-tive liver histology was not available for review,although none of the patients was noted to be grossly cirrhotic at the time of surgery.All three patients experienced precipitous weight loss and were achieving only limited oral intake prior to their presentation.They were weak and appeared malnourished,with muscle wasting.An extended,225-cm Roux limb was constructed in all cases.Gastric cancer ap-pears to have precipitated clinical deterioration in patient 3,who had biopsy proven cirrhosis and documented por-tal hypertension.Gastric cancer has been reported rarely after gastric bypass surgery for obesity(15–17).The patients reported here might have been at increased risk for progressive hepatic dysfunction after RNY-GBP due to preexisting NAFLD.In particular,it seems un-likely that patients1and3developed cirrhosis only7to 17months after surgery in the absence of preexisting liver pathology.Studies of liver biopsy specimens obtained at the time of bariatric surgery showed steatohepatitis in2 to35%of cases and bridgingfibrosis or cirrhosis in1to 12%of cases(9–12,18).The appearance of the liver at the time of surgery was not found to be predictive of the presence of nonalcoholic steatohepatitis(18).In one re-port,improvements in hepatic steatosis andfibrosis were observed with weight loss after RNY-GBP(19).How-ever,another study showed that steatohepatitis worsened in some patients with rapid weight loss after gastric re-striction procedures(20).Based on ourfindings and the available literature,we recommend that bariatric surgery candidates,who are known to have a high prevalence of NAFLD(9–12,18), should have a thorough evaluation for liver disease.A survey detailing outcomes in91patients found to be cir-rhotic at the time of bariatric surgery reported a periop-erative mortality rate of4%,a late death rate due to liver disease of7%,and that11%of patients were alive with progressive hepatic dysfunction(8).Another series de-tailed30patients who underwent RNY-GBP and were felt to have cirrhosis on gross inspection of the liver,al-though histologic features of cirrhosis were present in only 13(43%)cases(21).No liver-related deaths occurred,but complications including acute tubular necrosis,prolonged intubation,and need for blood transfusion were observed (21).Patients with relative thrombocytopenia suggesting the possibility of portal hypertension should be consid-ered for a preoperative liver biopsy.An intraoperative liver biopsy with evaluation of a frozen section might be con-sidered in other cases.Due to the increased risk of ce-liotomy in patients with cirrhosis and the potential for1564Digestive Diseases and Sciences,Vol.49,No.10(October2004)HEPATIC DECOMPENSATION AFTER GASTRIC BYPASSFig1.(A)A medium-power view of a liver core from patient1displays cirrhosis with extensive mixed micro-and macrovesicular steatosis involving more than50%of liver parenchyma.(Hemotoxylin and eosin stain;original magnification,×100.)(B)A high-power view of the biopsy from patient1shows microvesicularand macrovesicular steatosis with steatohepatitis(black arrow),ballooning degeneration,and Mallory hyaline(white arrow).(Hemotoxylin and eosin stain;original magnification,×400.)Digestive Diseases and Sciences,Vol.49,No.10(October2004)1565COTLER ET AL.T ABLE 2.L ABORATORY D ATA FOR P ATIENT 2Total bilirubin Direct bilirubin Total Protein Albumin BUN Creatinine Platelets Ammonia (mg/dl)(mg/dl)(g/dl)(g/dl)INR AST (U/L)ALT (U/L)(mg/dl)(mg/dl)(×103/mm 3)(µg/dl)Preoperative0.41824396Admission 13.38.15.81.5 1.91377043.11122103mo later1.62.51.56521Note.Normal ranges:total bilirubin (0–1.2mg/dl),direct bilirubin (0–0.2mg/dl),total protein (6.0–8.0g/dl),albumin (3.6–5.0g/dl),INR (0.9–1.2),AST (10–40U/L),ALT (10–50U/L),BUN (6–20mg/dl),creatinine (0.4–1.2mg/dl),platelets (150–400×103/mm 3),ammonia (<56µg/dl).progression of liver injury after RNY-GBP,we favor non-operative management of obesity in patients with precir-rhosis or cirrhosis.As demonstrated by patient 2,hepatic decompensation can also occur after RNY-GBP in the absence of cirrhosis.It is possible that the severity of steatosis or steatohepati-tis,or the use of an extended Roux limb,might predispose to progressive hepatic dysfunction after gastric bypass.We plan to use a shorter Roux limb in patients with mod-erate to severe NAFLD until prospective dataregarding Fig 2.A low-power view of a liver core from patient 2displays severe diffuse macrovesicular steatosis involving up to 95%of the liver parenchyma with focal mild fibrosis.There is no significant steatohepatitis.(Hemotoxylin and eosin stain;original magnification,×40.)risk factors for hepatic complications after RNY-GBP are available.Protein malnutrition and bacterial overgrowth have been implicated in the pathogenesis of liver disease af-ter jejunoileal bypass (22–24).Both of these factors could have contributed to the development of hepatic decompen-sation in our series.All three patients had considerable weight loss and muscle wasting and appeared malnour-ished at the time of presentation.Patients 2and 3showed substantial clinical improvement with enteral feeding and1566Digestive Diseases and Sciences,Vol.49,No.10(October 2004)HEPATIC DECOMPENSATION AFTER GASTRIC BYPASST ABLE3.L ABORATORY V ALUES FOR P ATIENT3Total bilirubin Direct bilirubin Total Protein Albumin BUN Creatinine Platelets Ammonia (mg/dl)(mg/dl)(g/dl)(g/dl)INR AST(U/L)ALT(U/L)(mg/dl)(mg/dl)(×103/mm3)(µg/dl) Admission11.7 6.9 5.9 2.7 2.0502610 1.91361112mo later0.90.47.5 1.8 1.1402727 1.13044mo later 2.70.97.9 1.9 1.5544095 4.1392Note.Normal ranges:total bilirubin(0–1.2mg/dl),direct bilirubin(0–0.2mg/dl),total protein(6.0–8.0g/dl),albumin(3.6–5.0g/dl),INR(0.9–1.2), AST(10–40U/L),ALT(10–50U/L),BUN(6–20mg/dl),creatinine(0.4–1.2mg/dl),platelets(150–400×103/mm3),ammonia(<56µg/dl).No liver enzymes were available from before the time of bariatric surgery.The preoperative platelet count was270×103/mm3.Fig3.(A)A low-power view of the liver biopsy from patient3shows cirrhosis withmacrovesicular fat replacement in up to85%of hepatic parenchyma.(Hemotoxylinand eosin stain;original magnification,×40.)(B)High-power view of liver histologyfrom patient3displays extensive mixed vesicular steatosis with ballooning degener-ation(white arrow)and steatohepatitis(black arrow).(Hemotoxylin and eosin stain;original magnification,×400.)Digestive Diseases and Sciences,Vol.49,No.10(October2004)1567COTLER ET AL.metronidazole therapy.The fact that all three patients had an extended Roux limb raises the possibility that this pro-cedure may increase the likelihood of malnutrition and bacterial overgrowth in patients undergoing RNY-GBP. Patients who develop hepatic decompensation after obesity surgery present a difficult management problem. In one report,22%of patients who underwent reversal of jejuno-ileal bypass for cirrhosis died in the perioperative period(4).Consequently,we have followed a conserva-tive management strategy in our patients consisting of en-teral feeding and empiric antibiotic therapy for bacterial overgrowth.Patient1remains on the liver transplant wait-ing list.We do not plan to reverse the RNY-GBP unless graft dysfunction develops posttransplant,based on the experience with liver transplantation for cirrhosis due to jejuno-ileal bypass(5).In conclusion,the cases presented here demonstrate that hepatic decompensation can occur after RNY-GBP.A careful assessment for liver disease is indicated in can-didates for gastric bypass,based on the high prevalence of NAFLD including cirrhosis in this population.Ourfind-ings raise the possibility that creation of a225-cm ex-tended Roux limb might place a subset of patients under-going RNY-GBP at risk for developing progressive hep-atic dysfunction.Further studies are needed to evaluate whether factors such as the length of the Roux limb and the severity of NAFLD are associated with the develop-ment of hepatic complications after bariatric surgery.REFERENCES1.Mokdad A,Bowman B,Ford E,Vinicor F,Marks J,Koplan J:Thecontinuing epidemics of obesity and diabetes in the United States.JAMA286:1195–1200,20012.Mokdad AH,Serdula MK,Dietz WH,Bowman BA,Marks JS,Koplan JP:The spread of the obesity epidemic in the United States, 1991–1998.JAMA282:1519–1522,19993.Griffen WO,Bivens BA,Bell RM:The decline and fall of the je-junoileal bypass.Surg Gynecol Obstet157:301–308,19834.Requarth JA,Burchard KW,Colacchio TA,Stukel TA,Mott LA,Greenberg ER,Weismann RE:Long-term morbidity following je-junoileal bypass:The continuing potential need for surgical reversal.Arch Surg130:318–325,19955.Lowell JA,Shenoy S,Ghalib R,Caldwell C,White FV,Peters M,Howard TK:Liver transplantation after jejunoileal bypass for mor-bid obesity.J Am Coll Surg185:123–127,19976.Hocking MP,Davis GL,Franzini DA,Woodward ER:Long-termconsequences after jejunoileal bypass for morbid obesity.Dig Dis Sci43:2493–2499,19987.Sjostrom CD,Lissner L,Wedel H,Sjostrom L:Reduction in inci-dence of diabetes,hypertension and lipid disturbances after inten-tional weight loss induced by bariatric surgery:the SOS Intervention Study.Obes Res7:477–484,19998.Brolin RE,Bradley LJ,Taliwal RV:Unsuspected cirrhosis discov-ered during elective obesity operations.Arch Surg133:84–88,1998 9.Del Gaudio A,Boschi L,Del Gaudio GA,Mastrangelo L,Munari D:Liver damage in obese patients.Obes Surg12:802–804,2002 10.Gholam PM,Kotler DP,Flancbaum LJ:Liver pathology in morbidlyobese patients undergoing roux-en-Y gastric bypass surgery.Obes Surg12:49–51,200211.Moretto M,Kupski C,Mottin CC,Repetto G,Toneto MG,Rizzolli J,Berleze D,de Souza Brito CL,Casagrande D,Colossi F:Hepatic steatosis in patients undergoing bariatric surgery and its relationship to body mass index and co-morbidities.Obes Surg13:622–624,2003 12.Beymer C,Kowdley KV,Larson A,Edmonson P,Dellinger EP,Flum DR:Prevalence and predictors of asymptomatic liver disease in patients undergoing gastric bypass surgery.Arch Surg138:1240–1244,200313.Murr MM,Balsiger BM,Kennedy FP,Mai JL,Starr MG:Malab-sorptive procedures for severe obesity:comparison of pancreatobil-iary bypass and very very long limb Roux-en-Y gastric bypass.J Gastrointest Surg3:607–612,199914.Freeman JB,Kotlarewsky M,Phoenix C:Weight loss after extendedgastric bypass.Obes Surg7:337–344,199715.Khitin L,Roses RE,Birkett DH:Cancer in the gastric remnant aftergastric bypass:a case report.Curr Surg60:521–523,200316.Lord RV,Edwards PD,Coleman MJ:Gastric cancer in the bypassedsegment after operation for morbid obesity.Aust NZ J Surg67:580–582,199717.Raijman I,Strother SV,Donegan WL:Gastric cancer after gastricbypass for obesity.Case Report.J Clin Gastroenterol13:191–194, 199118.Shalhab S,Parsee A,Gallagher SF,Haines KL,Willkomm C,Brantley SG,Pinkas H,Saff-Koche L,Murr MM:The importance of routine liver biopsy in diagnosing nonalcoholic steatohepatitis in bariatric patients.Obes Surg14:54–59,200419.Silverman EM,Sapala JA,Appelman HD:Regression of hepaticsteatosis in morbidly obese persons after gastric bypass.Am J Clin Pathol104:23–31,199520.Luyckx FH,Desaive C,Thiry A,Dewe W,Scheen AJ,Gielen JE,Lefebvre PJ:Liver abnormalities in severely obese subjects:Effect of drastic weight loss after gastroplasty.Int J Obes22:222–226,2004 21.Dallal RM,Mattar SG,Lord JL,Watson AR,Cottam DR,Eid GM,Hamad GM,Rabinovitz M,Schauer PR:Results of laparoscopic gastric bypass in patients with cirrhosis.Obes Surg14:47–53,2004 22.Moxley RE3,Lockwood DH:Protein nutrition and liver disease afterjejunoileal bypass for morbid obesity.N Engl J Med290:921–926, 197423.Drenick EJ,Fisler J,Johnson D:Hepatic steatosis after intestinalbypass–prevention and reversal by metronidazole,irrespective of protein-calorie malnutrition.Gastroenterology82:535–548,1982 24.Lichtman SN,Sartor RB,Keku J,Schwab JH:Hepatic inflamma-tion in rats with experimental small intestinal bacterial overgrowth.Gastroenterology98:414–423,19901568Digestive Diseases and Sciences,Vol.49,No.10(October2004)。