Hepatobiliary Quiz-6 (2013)
2013; Elsevier BV; Volume: 3; Issue: 2 Linguagem: Inglês
10.1016/j.jceh.2013.05.006
ISSN2213-3453
AutoresSwastik Agrawal, Radha K. Dhiman,
Tópico(s)Liver Disease Diagnosis and Treatment
ResumoUp to 20% of the patients receiving isoniazid either in single or combination therapy develop transient asymptomatic elevation in liver enzymes, which settle with continued use of the drug.1Mitchell J.R. Zimmerman H.J. Ishak K.G. et al.Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis.Ann Intern Med. 1976; 84: 181-192Crossref PubMed Scopus (378) Google Scholar Manifestation of the anti-tubercular therapy (ATT) induced hepatotoxicity can vary from asymptomatic elevations in the liver enzymes, generally in hepatocellular pattern, to fulminant liver failure.2Ramappa V. Aithal G.P. Hepatotoxicity related to anti-tuberculosis drugs: mechanisms and management.J Clin Exp Hepatol. 2013; 3: 37-49Abstract Full Text Full Text PDF PubMed Scopus (208) Google Scholar ATT induced fulminant liver failure appears to have worse outcome when compared with that related to acute viral hepatitis. Case fatality rate varies between 0.042 and 0.07 per 1000 persons at any given time during therapy.3Ostapowicz G. Fontana R.J. Schiodt F.V. et al.Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States.Ann Intern Med. 2002; 137: 947-954Crossref PubMed Scopus (1582) Google Scholar, 4Kumar R. Bhatia V. Khanal S. et al.Antituberculosis therapy-induced acute liver failure: magnitude, profile, prognosis, and predictors of outcome.Hepatology. 2010; 51: 1665-1674Crossref PubMed Scopus (110) Google Scholar, 5Acharya S.K. Dasarathy S. Kumer T.L. et al.Fulminant hepatitis in a tropical population: clinical course, cause, and early predictors of outcome.Hepatology. 1996; 23: 1448-1455Crossref PubMed Google Scholar Combination therapy increases the risk of hepatotoxicity. Incidence of isoniazid hepatotoxicity when used as monotherapy is in the range of 0.1%-0.56.2Ramappa V. Aithal G.P. Hepatotoxicity related to anti-tuberculosis drugs: mechanisms and management.J Clin Exp Hepatol. 2013; 3: 37-49Abstract Full Text Full Text PDF PubMed Scopus (208) Google Scholar Isoniazid was more likely to be associated with hepatotoxicity (odds ratio (OR) 1.6) even in the absence of rifampicin, but the combination of these two drugs was associated with higher rate of hepatotoxicity (OR 2.6) when compared to each drug on its own.6Steele M.A. Burk R.F. DesPrez R.M. Toxic hepatitis with isoniazid and rifampin. A meta-analysis.Chest. 1991; 99: 465-471Crossref PubMed Scopus (409) Google Scholar Daily dosing regimens have not been shown to increase the risk compared to thrice weekly regimens.7Chang K.C. Leung C.C. Yew W.W. et al.Standard anti-tuberculosis treatment and hepatotoxicity: do dosing schedules matter?.Eur Respir J. 2007; 29: 347-351Crossref PubMed Scopus (28) Google Scholar Isoniazid is metabolised by N-acetyltransferase 2 (NAT2) to the non-toxic diacetyl hydrazine which is the major pathway or by direct hydrolysis to the toxic isoniazid hydrazine which is the minor pathway. In the presence of polymorphisms of NAT 2 gene that decrease NAT 2 activity (slow acetylators) the minor pathway increases tenfold.2Ramappa V. Aithal G.P. Hepatotoxicity related to anti-tuberculosis drugs: mechanisms and management.J Clin Exp Hepatol. 2013; 3: 37-49Abstract Full Text Full Text PDF PubMed Scopus (208) Google Scholar Slow acetylators have 4.6 times higher risk of developing hepatotoxicity. They also have more severe liver injury.8Wang P.Y. Xie S.Y. Hao Q. et al.NAT2 polymorphisms and susceptibility to anti tuberculosis drug-induced liver injury: a meta-analysis.Int J Tuberc Lung Dis. 2012; 16: 589-595Crossref PubMed Scopus (14) Google Scholar Rifampicin is a potent inducer of cytochrome P450 (CYP3A4) system via the hepatocyte xeno sensing pregnane X receptor (PXR). This activation of the CYP3A4 leads to increased metabolism of isoniazid yielding toxic metabolites explaining the potentiating effect of rifampicin in isoniazid induced hepatotoxicity. Rifampicin also induces isoniazid hydrolases, leading to increased hydrazine production especially in slow acetylators thus increasing the toxicity when used in combination with isoniazid.9Sarma G.R. Immanuel C. Kailasam S. et al.Rifampin-induced release of hydrazine from isoniazid. A possible cause of hepatitis during treatment of tuberculosis with regimens containing isoniazid and rifampin.Am Rev Respir Dis. 1986; 133: 1072-1075PubMed Google Scholar Rifampicin rarely causes unconjugated hyperbilirubinemia by interfering with bilirubin uptake without concomitant hepatocyte damage. However more commonly, it causes conjugated hyperbilirubinemia by interfering with bilirubin excretion by inhibiting the bile salt exporter pump.10Capelle P. Dhumeaux D. MoraM et al.Effect of rifampicin on liver function in man.Gut. 1972; 13: 366-371Crossref PubMed Scopus (77) Google Scholar, 11Grosset J. Leventis S. Adverse effects of rifampin.Rev Infect Dis. 1983; 5: S440-S450Crossref PubMed Scopus (139) Google Scholar Pyrazinamide has dose dependent hepatotoxicity with high doses of 40-50 mg/kg having higher frequency of hepatotoxicity then conventionally used dose of 25-35 mg/kg. Concomitant use of xanthine oxidase inhibitors like allopurinol inhibit metabolism of pyrazinamide and may increase its toxicity.2Ramappa V. Aithal G.P. Hepatotoxicity related to anti-tuberculosis drugs: mechanisms and management.J Clin Exp Hepatol. 2013; 3: 37-49Abstract Full Text Full Text PDF PubMed Scopus (208) Google Scholar Women are more susceptible to ATT induced hepatotoxicity with a 4-fold higher risk, possibly because of higher activity of CYP3A.12Lee A.M. Mennone J.Z. Jones R.C. et al.Risk factors for hepatotoxicity associated with rifampin and pyrazinamide for the treatment of latent tuberculosis infection: experience from three public health tuberculosis clinics.Int J Tuberc Lung Dis. 2002; 6: 995-1000PubMed Google Scholar, 13Hunt C.M. Westerkam W.R. Stave G.M. Effect of age and gender on the activity of human hepatic CYP3A.Biochem Pharmacol. 1992; 44: 275-283Crossref PubMed Scopus (345) Google Scholar Since 2002, model for end stage liver disease (MELD) score using 3 objective variables (serum bilirubin, serum creatinine, and international normalized ratio) has been used worldwide for listing and transplanting patients with end-stage liver disease, thus allowing transplanting sicker patients first irrespective of the wait time on the list. It was initially developed in the Mayo Clinic to predict survival following transjugular intrahepatic shunt, but was found to be a good predictor of mortality while awaiting liver transplantation for end stage liver disease. At the time of adoption by the United Network for Organ Sharing, some changes were made to the MELD score including capping serum creatinine at 4 mg/dl, capping the score at 40, and setting the lower limit for each component of the score to 1 in order to avoid negative scores.14Singal A.K. Kamath P.S. Model for End-stage Liver Disease.J Clin Exp Hepatol. 2013; 3: 50-60Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Further, etiology of the liver disease as a factor was removed from the model as it did not affect the mortality in end stage liver disease.15Brandsaeter B. Friman S. Broome U. et al.Outcome following liver transplantation for primary sclerosing cholangitis in the Nordic countries.Scand J Gastroenterol. 2003; 38: 1176-1183Crossref PubMed Scopus (56) Google Scholar Similarly, complications of cirrhosis or portal hypertension like ascites, hepatic encephalopathy or variceal bleeding do not add to the predictive ability of the MELD score.16Botta F. Giannini E. Romagnoli P. et al.MELD scoring system is useful for predicting prognosis in patients with liver cirrhosis and is correlated with residual liver function: a European study.Gut. 2003; 52: 134-139Crossref PubMed Scopus (263) Google Scholar There is also an association of pre-transplant MELD score with the hospital resource utilization such as operative time, use of red blood cell transfusions, duration of stay in the intensive care unit and total hospital stay and charges. MELD score of more than 23 predicted a higher morbidity and prolonged ICU stay.17Oberkofler C.E. Dutkowski P. Stocker R. et al.Model of end stage liver disease (MELD) score greater than 23 predicts length of stay in the ICU but not mortality in liver transplant recipients.Crit Care. 2010; 14: R117Crossref PubMed Scopus (49) Google Scholar To balance waitlist mortality and post operative risk combination of other recipient and donor criteria to MELD has been used. A combination of 3 extended donor criteria (EDC): age, steatosis >30% and cold ischemia time with MELD >28 predicted graft failure.18Briceno J. Ciria R. de la Mata M. Rufian S. Lopez-Cillero P. Prediction of graft dysfunction based on extended criteria donors in the model for end-stage liver disease score era.Transplantation. 2010; 90: 530-539Crossref PubMed Scopus (68) Google Scholar Worsening MELD score or delta-MELD (current MELD-maximum score in the last 3 months) has been shown to impact post-transplant outcome, and one should avoid graft with >1 EDC for such patients.19Silberhumer G.R. Pokorny H. Hetz H. et al.Combination of extended donor criteria and changes in the model for end-stage liver disease score predict patient survival and primary dysfunction in liver transplantation: a retrospective analysis.Transplantation. 2007; 83: 588-592Crossref PubMed Scopus (65) Google Scholar A product of age and delta-MELD less than 1600 may be predictive of optimal post-transplant outcomes.20Halldorson J.B. Bakthavatsalam R. Fix O. Reyes J.D. Perkins J.D. D-MELD, a simple predictor of post liver transplant mortality for optimization of donor/recipient matching.Am J Transplant. 2009; 9: 318-326Crossref PubMed Scopus (199) Google Scholar In hospitalised patients with higher MELD score there is a high risk of infections. In a retrospective analysis on 256 Albanian patients with cirrhosis, MELD score was a predictor for occurrence of SBP and mortality.21Kraja B. Sina M. Mone I. et al.Predictive value of the model of end-stage liver disease in cirrhotic patients with and without spontaneous bacterial peritonitis.Gastroenterol Res Pract. 2012; 2012: 539059Crossref PubMed Scopus (9) Google Scholar In another study on 111 hospitalized cirrhotics MELD was a predictor for SBP, increasing risk by about 11% for every increase in MELD score with 9.7 times higher odds for developing SBP at a MELD cut-off of 15.22Obstein K.L. Campbell M.S. Reddy K.R. Yang Y.X. Association between model for end-stage liver disease and spontaneous bacterial peritonitis.Am J Gastroenterol. 2007; 102: 2732-2736Crossref PubMed Scopus (58) Google Scholar Poor outcome after surgery in patients of cirrhosis is well known. Earlier, the risk used to be gauged using the Child stage with 10%, 30%, and 82% postoperative mortality amongst patients with CTP stages A, B, and C respectively.14Singal A.K. Kamath P.S. Model for End-stage Liver Disease.J Clin Exp Hepatol. 2013; 3: 50-60Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Studies have confirmed MELD score to be predictive of outcome following surgery other than liver transplant.23Causey M.W. Steele S.R. Farris Z. Lyle D.S. Beitler A.L. An assessment of different scoring systems in cirrhotic patients undergoing nontransplant surgery.Am J Surg. 2012; 203: 589-593Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar MELD score is an important variable in predicting outcome after surgery. Addition of 5.5 MELD points for American Society of Anesthesiologists (ASA) class IV and 3 MELD points for age more than 70 years improved accuracy of MELD score.24Teh S.H. Nagorney D.M. Stevens S.R. et al.Risk factors for mortality after surgery in patients with cirrhosis.Gastroenterology. 2007; 132: 1261-1269Abstract Full Text Full Text PDF PubMed Scopus (361) Google Scholar Patients with MELD score 15 should avoid an elective surgery.14Singal A.K. Kamath P.S. Model for End-stage Liver Disease.J Clin Exp Hepatol. 2013; 3: 50-60Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar In hepatic resection for hepatocellular carcinoma, MELD predicts hepatic failure as well as death. Incidence of hepatic failure after hepatic resection was 0% with MELD score of 10.25Rahbari N.N. Garden O.J. Padbury R. et al.Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS).Surgery. 2011; 149: 713-724Abstract Full Text Full Text PDF PubMed Scopus (1061) Google Scholar Similarly, mortality after liver resection is higher for MELD score >8 compared to lower MELD (4% vs.0.6%;P = 0.004) in one study, while in another it was 19% at MELD >8 vs. 0% for lower MELD.26Hsu K.Y. Chau G.Y. Lui W.Y. Tsay S.H. King K.L. Wu C.W. Predicting morbidity and mortality after hepatic resection in patients with hepatocellular carcinoma: the role of model for end-stage liver disease score.World J Surg. 2009; 33: 2412-2419Crossref PubMed Scopus (56) Google Scholar, 27Delis S.G. Bakoyiannis A. Biliatis I. Athanassiou K. Tassopoulos N. Dervenis C. Model for end-stage liver disease (MELD) score, as a prognostic factor for post-operative morbidity and mortality in cirrhotic patients, undergoing hepatectomy for hepatocellular carcinoma.HPB. 2009; 11: 351-357Abstract Full Text Full Text PDF Scopus (51) Google Scholar MELD score is also an accurate predictor of outcome after variceal hemorrhage. MELD >18 is a predictor of rebleeding within first 5 days and overall mortality at 6 weeks.28Bambha K. Kim W.R. Pedersen R. Bida J.P. Kremers W.K. Kamath P.S. Predictors of early re-bleeding and mortality after acute variceal haemorrhage in patients with cirrhosis.Gut. 2008; 57: 814-820Crossref PubMed Scopus (173) Google Scholar MELD score is also a powerful predictor for mortality at 6 weeks for patients who develop early rebleeding after endoscopic variceal ligation.29Chen W.T. Lin C.Y. Sheen I.S. et al.MELD score can predict early mortality in patients with rebleeding after band ligation for variceal bleeding.World J Gastroenterol. 2011; 17: 2120-2125Crossref PubMed Scopus (24) Google Scholar The incidence of non-alcoholic fatty liver disease (NAFLD) in those transplanted for cryptogenic cirrhosis is up to 100% after five years30Contos M.J. Cales W. Sterling R.K. et al.Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis.Liver Transpl. 2001; 7: 363-373Crossref PubMed Scopus (331) Google Scholar whereas upto 40% of patients transplanted for non-NAFLD related disease develop steatosis and 13% develop steatohepatitis after a mean follow up of 44±4 months.31Lim L.G. Cheng C.L. Wee A. et al.Prevalence and clinical associations of posttransplant fatty liver disease.Liver Int. 2007; 27: 76-80Crossref PubMed Scopus (63) Google Scholar Recurrence of NAFLD is an insidious process. Approximately 25% of patients develop steatosis within one year, and nearly 50% develop it by four years post-transplant.30Contos M.J. Cales W. Sterling R.K. et al.Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis.Liver Transpl. 2001; 7: 363-373Crossref PubMed Scopus (331) Google Scholar, 31Lim L.G. Cheng C.L. Wee A. et al.Prevalence and clinical associations of posttransplant fatty liver disease.Liver Int. 2007; 27: 76-80Crossref PubMed Scopus (63) Google Scholar De-novo NAFLD also has been documented only late, at 16 months or more post-transplant in one study32Seo S. Maganti K. Khehra M. et al.De novo nonalcoholic fatty liver disease after liver transplantation.Liver Transpl. 2007; 13: 844-847Crossref PubMed Scopus (131) Google Scholar and after six months in another study.30Contos M.J. Cales W. Sterling R.K. et al.Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis.Liver Transpl. 2001; 7: 363-373Crossref PubMed Scopus (331) Google Scholar Risk factors for recurrent or de novo NAFLD include post-transplant weight gain, diabetes mellitus/insulin resistance, decreased HDL-cholesterol, elevated total cholesterol, and hypertension, with the use of corticosteroids and calcineurin inhibitors contributing to their development.30Contos M.J. Cales W. Sterling R.K. et al.Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis.Liver Transpl. 2001; 7: 363-373Crossref PubMed Scopus (331) Google Scholar, 33Angulo P. Nonalcoholic fatty liver disease and liver transplantation.Liver Transpl. 2006; 12: 523-534Crossref PubMed Scopus (115) Google Scholar Odds ratio for development of de-novo NAFLD is as high as 19 if the increase in body mass index is greater than 10 after transplant.32Seo S. Maganti K. Khehra M. et al.De novo nonalcoholic fatty liver disease after liver transplantation.Liver Transpl. 2007; 13: 844-847Crossref PubMed Scopus (131) Google Scholar There are no published studies on therapy in patients with post-transplant de novo or recurrent NAFLD and no recommendations are available other than general recommendations to avoid excessive gains in body weight and control hypertension and diabetes.34Lucey M.R. Terrault N. Ojo L. et al.Long-term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation.Liver Transpl. 2013; 19: 3-26Crossref PubMed Scopus (271) Google Scholar There is a case report of use of metformin and pioglitazone with biochemical improvement over five months of therapy.35Cuschieri J.R. John B.K. Miick R. Ortiz J.A. Hashemi N. Successful treatment of rapid onset, symptomatic de novo non-alcoholic steatohepatitis following liver transplantation: a case report.J Clin Exp Hepatol. 2013; 3: 70-74Abstract Full Text Full Text PDF Scopus (3) Google Scholar The hepatitis C virus (HCV) prevalence rate in the general population in India is 1.85%36Chawla N.S. Sajiv C.T. Pawar G. Pawar G. Hepatitis B and C virus infections associated with renal replacement therapy in patients with end stage renal disease in a tertiary care hospital in India-prevalence, risk factors and outcome.Indian J Nephrol. 2005; 15: 205-213Google Scholar compared to 4.3% to 46% in end stage renal disease (ESRD) patients on hemodialysis.37Mittal G. Gupta P. Thakuria B. Mukhiya G.K. Mittal M. Profile of hepatitis B virus, hepatitis C virus, hepatitis D virus and human immunodeficiency virus infections in hemodialysis patients of a tertiary care hospital in Uttarakhand.J Clin Exp Hepatol. 2013; 3: 24-28Abstract Full Text Full Text PDF Scopus (12) Google Scholar History of blood transfusions, duration of hemodialysis, dialyzer reuse and dialysis at multiple centers are important risk factors for anti-HCV positivity.37Mittal G. Gupta P. Thakuria B. Mukhiya G.K. Mittal M. Profile of hepatitis B virus, hepatitis C virus, hepatitis D virus and human immunodeficiency virus infections in hemodialysis patients of a tertiary care hospital in Uttarakhand.J Clin Exp Hepatol. 2013; 3: 24-28Abstract Full Text Full Text PDF Scopus (12) Google Scholar Center for Disease Control and Prevention in the United States does not recommend dedicated machines, patient isolation, or a ban on reuse of dialyzer in patients with HCV infection as strict adherence to universal precautions, careful attention to hygiene, and strict sterilization of dialysis machines have been shown to prevent transmission of infection.38Jadoul M. Cornu C. Van Yperselle De Strihou C. The Universities Clinques St Luc (UCL) collaborative Group. Universal precautions prevent hepatitis C virus transmission: 54 month follow up of the Belgian multicenter study.Kidney Int. 1998; 53: 1022-1025Crossref PubMed Scopus (162) Google Scholar However, a study from India has shown that isolation decreases HCV transmission.39Agarwal S.K. Dash S.C. Gupta S. Pandey R.M. Hepatitis C virus infection in haemodialysis: the 'no-isolation' policy should not be generalized.Nephron Clin Pract. 2009; 111: c133-c140Crossref PubMed Scopus (35) Google Scholar After baseline screening for HCV infection, hemodialysis patients should be tested monthly for alanine aminotransferase levels and 6-monthly for anti-HCV antibodies. Re-testing for HCV RNA should be done if these parameters raise suspicion of a new infection.40Kidney disease: improving global outcomes (KDIGO).Kidney Int Suppl. 2008; : S1-S99Google Scholar This is important as ESRD patients infected with HCV have a higher mortality rate than non-infected ESRD patients, and patients with HCV infection who undergo kidney transplantation have reduced graft and patient survival rates.41Nakayama E. Akiba T. Marumo F. Sato C. Prognosis of anti-hepatitis C virus antibody-positive patients on regular hemodialysis therapy.J Am Soc Nephrol. 2000; 11: 1896-1902PubMed Google Scholar, 42Lee W.C. Shu K.H. Cheng C.H. Wu M.J. Chen C.H. Lian J.C. Long-term impact of hepatitis B, C virus infection on renal transplantation.Am J Nephrol. 2001; 21: 300-330Crossref PubMed Scopus (82) Google Scholar Gastric varices are present in 18-70% of patients with portal hypertension43Sarin S.K. Kumar A. Gastric varices: profile, classification, and management.Am J Gastroenterol. 1989; 84: 1244-1249PubMed Google Scholar, 44Watanabe K. Kimura K. Matsutani S. Ohto M. Okuda K. Portal hemodynamics in patients with gastric varices. A study in 230 patients with esophageal and/or gastric varices using portal vein catheterization.Gastroenterology. 1988; 95: 434-440Abstract PubMed Google Scholar and are the source of 5%-10% of all upper digestive bleeding in patients with portal hypertension.45D'Amico G. de Franchis R. Upper digestive bleeding in cirrhosis. Post-therapeutic outcome and prognostic indicators.Hepatology. 2003; 38: 599-612Crossref PubMed Scopus (647) Google Scholar Unlike esophageal varices bleeding from gastric varices does not correlate with portosystemic pressures because of the high frequency of spontaneous gastro-renal shunts.46Stanley A.J. Jalan R. Ireland H.M. Redhead D.N. Bouchier I.A. Hayes P.C. A comparison between gastric and oesophageal variceal haemorrhage treated with transjugular intrahepatic portosystemic stent shunt (TIPSS).Aliment Pharmacol Ther. 1997; 11: 171-176Crossref PubMed Scopus (57) Google Scholar Compared to patients with cirrhosis, patients with extra hepatic portal vein obstruction (EHPVO) are more like to have isolated gastric varices (IGV). In one study, gastroesophageal varices (GOV)1 was present in 14% of cirrhotics as compared to 7% of EHPVO patients. GOV2 was present in 80% of cirrhotics as compared to 53% of EHPVO patients while IGV1 was seen in only 4% cirrhotics compared to 40% of patients with EHPVO.47Sharma B.C. Banka A.K. Rawat A. Srivastava S. Gastric varices in cirrhosis versus extrahepatic portal venous obstruction and response to endoscopic N-Butyl-2-cyanoacrylate injection.J Clin Exp Hepatol. 2013; 3: 19-23Abstract Full Text Full Text PDF Scopus (3) Google Scholar Endoscopic glue injection and transjugular intrahepatic portosystemic shunts (TIPS) are equivalent in the control of acute bleeding, with a similar rate of rebleeding but compared with glue but TIPS is associated with higher morbidity because of an increased incidence of encephalopathy. Glue injection is also significantly cheaper and available at many more centres than TIPS.48Seewald S. Ang T.L. Imazu H. et al.A standardized injection technique and regimen ensures success and safety of N-butyl-2-cyanoacrylate injection for the treatment of gastric fundal varices (with videos).Gastrointest Endosc. 2008; 68: 447-454Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar, 49Mahadeva S. Bellamy M.C. Kessel D. et al.Cost-effectiveness of N-butyl-2-cyanoacrylate (histoacryl) glue injections versus transjugular intrahepatic portosystemic shunt in the management of acute gastric variceal bleeding.Am J Gastroenterol. 2003; 98: 2688-2693Crossref PubMed Scopus (93) Google Scholar, 50Lo G.H. Liang H.L. Chen W.C. et al.A prospective, randomized controlled trial of transjugular intrahepatic portosystemic shunt versus cyanoacrylate injection in the prevention of gastric variceal rebleeding.Endoscopy. 2007; 39: 679-685Crossref PubMed Scopus (221) Google Scholar Balloon occluded retrograde transvenous obliteration has been used successfully for gastric variceal obliteration, but is unsuitable for acute gastric variceal bleeding and requires the presence of a spontaneous gastro-renal shunt.51Matsumoto A. Hamamoto N. Nomura T. et al.Balloon-occluded retrograde transvenous obliteration of high risk gastric fundal varices.Am J Gastroenterol. 1999; 94: 643-649Crossref PubMed Google Scholar There is no relation to the amount of steatosis and degree of inflammation, and all patients with steatosis do not progress to develop steatohepatitis. Hepatic accumulation of triglycerides as such is not toxic to the liver and may in fact be protective by acting as a buffer for FFA.52Choi S.S. Diehl A.M. Hepatic triglyceride synthesis and nonalcoholic fatty liver disease.Curr Opin Lipidol. 2008; 19: 295-300Crossref PubMed Scopus (186) Google Scholar If hepatic TG synthesis is inhibited it leads to accumulation of FFA that are ultimately oxidised leading to increased oxidative stress and liver injury despite reduction in steatosis.53Yamaguchi K. Yang L. McCall S. et al.Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis.Hepatology. 2007; 45: 1366-1374Crossref PubMed Scopus (681) Google Scholar Free fatty acids are toxic by two mechanisms. One is the direct cytotoxicity of intracellular fatty acids on the hepatocytes (lipotoxicity) mainly by the apoptosis pathway (lipoapoptosis), other being cytotoxic effects of lipid peroxidation of fatty acids.54Feldstein A.E. Werneburg N.W. Canbay A. et al.Free fatty acids promote hepatic lipotoxicity by stimulating TNF expression via a lysosomal pathway.Hepatology. 2004; 40: 185-194Crossref PubMed Scopus (619) Google Scholar, 55George J. Pera N. Phung N. et al.Lipid peroxidation, stellate cell activation and hepatic fibrogenesis in a rat model of chronic steatohepatitis.J Hepatol. 2003; 39: 756-764Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar The increased load of fatty acids in the hepatocytes increases β-oxidation and increase in cytochrome P450 enzymes, leading to increase in reactive oxygen species. Levels of malondialdehyde and superoxide dismutase are higher in patients of non-alcoholic steatohepatitis (NASH) compared to chronic viral hepatitis patients.56Kumar A. Sharma A. Duseja A. et al.Patients with nonalcoholic fatty liver disease (NAFLD)have higher oxidative stress in comparison to chronic viral hepatitis.J Clin Exp Hepatol. 2013; 3: 12-18Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar CYP2E1 activity is also significantly increased in NASH patients.57Weltman M.D. Farrell G.C. Hall P. Ingelman-Sundberg M. Liddle C. Hepatic cytochrome P450 2E1 is increased in patients with nonalcoholic steatohepatitis.Hepatology. 1998; 27: 128-133Crossref PubMed Scopus (534) Google Scholar These processes lead to inflammation within the liver. Patients with NASH have generally significantly higher levels of serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, soluble TNF receptor 1 and soluble IL-6 receptor than patients with simple steatosis. The levels are higher in those patients with more severe NASH.58Abiru S. Migita K. Maeda Y. et al.Serum cytokine and soluble cytokine receptor levels in patients with non-alcoholic steatohepatitis.Liver Int. 2006; 26: 39-45Crossref PubMed Scopus (165) Google Scholar, 59Bahcecioglu I.H. Yalniz M. Ataseven H. et al.Levels of serum hyaluronic acid, TNF-alpha and IL-8 in patients with nonalcoholic steatohepatitis.Hepatogastroenterology. 2005; 52: 1549-1553PubMed Google Scholar Studies from the west have shown increased hepatic iron levels in NASH with some studies also showing high prevalence of hemochromatosis (HFE) gene mutations. However, in studies from the East, including India, Japan and Australia, NASH patients did not have significant serum iron abnormalities or HFE gene mutations suggesting that iron abnormalities do not play much role in the pathogenesis of NAFLD.60Agrawal S. Duseja A.K. Non-alcoholic fatty liver disease: East versus West.J Clin Exp Hepatol. 2012; 2: 122-134Abstract Full Text PDF Scopus (25) Google Scholar Anti-mitochondrial antibodies (AMA) are detected in more than 90% of patients of primary biliary cirrhosis (PBC) with a specificity of more than 95%. Non-specific anti-nuclear antibodies (ANA) are seen 30% of patients of PBC sera. However, ANA directed against nuclear body or envelope proteins such as anti-Sp100 and anti-gp210 have high specificity for PBC (>95%) and can be used as markers of PBC when AMA are absent. Their sensitivity, however, is low.61European Association for the Study of the Liver EASL clinical practice guidelines: management of cholestatic liver diseases.J Hepatol. 2009; 51: 237-267Abstract Full Text Full Text PDF PubMed Scopus (1209) Google Scholar Ursodeoxycholic acid (UDCA) 13-15 mg/kg/d improves histology and survival in PBC. Patients who have good response to UDCA defined by the Barcelona criteria (decrease in alkaline phosphatase [ALP] by more than 40% of baseline at 1 year) or the Paris criteria (serum bilirubin ≤1 mg/dL, ALP <3 times upper limit of normal, and aspartate aminotransferase [AST] <2 times upper limit of normal) have transplant free survival of 90-95% on 10-14 years follow-up.62Pares A. Caballeria L. Rodes J. Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic acid.Gastroenterology. 2006; 130: 715-720Abstract Full Text Full Text PDF PubMed Scopus (487) Google Scholar, 63Corpechot C. Abenavoli L. Rabahi N. et al.Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis.Hepatology. 2008; 48: 871-877Crossref PubMed Scopus (403) Google Scholar Although the role of UDCA in primary sclerosing cholangitis (PSC) is controversial, high doses from 20-30 mg/kg/d have been shown to improve histology and survival in some studies.64Mitchell S.A. Bansi D.S. Hunt N. Von Bergmann K. Fleming K.A. Chapman R.W. A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis.Gastroenterology. 2001; 121: 900-907Abstract Full Text Full Text PDF PubMed Scopus (295) Google Scholar, 65Cullen S.N. Rust C. Fleming K. Edwards C. Beuers U. Chapman R. High dose ursodeoxycholic acid for the treatment of primary sclerosig cholangitis is safe and effective.J Hepatol. 2008; 48: 792-800Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar UDCA also decreases risk of colonic neoplasia in PSC patients.66Wolf J.M. Rybicki L.A. Lashner B.A. The impact of ursodeoxy-cholic acid on cancer, dysplasia and mortality in ulcerative colitis patients with primary sclerosing cholangitis.Aliment Pharmacol Ther. 2005; 22: 783-788Crossref PubMed Scopus (102) Google Scholar, 67Pardi D.S. Loftus Jr., E.V. Kremers W.K. Keach J. Lindor K.D. Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis.Gastroenterology. 2003; 124: 889-893Abstract Full Text Full Text PDF PubMed Scopus (487) Google Scholar Liver transplantation is the only therapy of late-stage PSC with 1 and 10-year survival of 90% and 80%. Recurrence of disease is common. Colectomy prior to liver transplantation for advanced colitis or colon dysplasia or absence of inflammatory bowel disease (IBD) protects against PSC recurrence.68Cholongitas E. Shusang V. Papatheodoridis G.V. et al.Risk factors for recurrence of primary sclerosing cholangitis after liver transplantation.Liver Transpl. 2008; 14: 138-143Crossref PubMed Scopus (140) Google Scholar Immunoglobulin G4-associated cholangitis (IAC) has biochemical and imaging features like that of PSC but occurs in older individuals (mean age 60 years), is not associated with IBD, is characterised by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in bile ducts and liver tissue. Steroids have a marked effect on inflammatory activity of IAC, and complete long-term remission after three months of treatment has been reported.61European Association for the Study of the Liver EASL clinical practice guidelines: management of cholestatic liver diseases.J Hepatol. 2009; 51: 237-267Abstract Full Text Full Text PDF PubMed Scopus (1209) Google Scholar Bacterial growth occurs in only about 50% of patients with ascitic fluid polymorphonuclear leukocyte count greater than or equal to 250cells/mm3Ostapowicz G. Fontana R.J. Schiodt F.V. et al.Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States.Ann Intern Med. 2002; 137: 947-954Crossref PubMed Scopus (1582) Google Scholar if it is sent in syringe or tube of fluid to the laboratory, as compared to approximately 80% if the fluid is inoculated into blood culture bottles at the bedside prior to administration of antibiotics. A single dose of an effective antibiotic usually leads to a negative bacterial culture.69Runyon B.A. Canawati H.N. Akriviadis E.A. Optimization of ascitic fluid culture technique.Gastroenterology. 1988; 95: 1351-1355Abstract PubMed Google Scholar, 70Runyon B.A. Antillon M.R. Akriviadis E.A. McHutchison J.G. Bedside inoculation of blood culture bottles is superior to delayed inoculation in the detection of spontaneous bacterial peritonitis.J Clin Microbiol. 1990; 28: 2811-2812PubMed Google Scholar For malignant cytology 50 mL of fresh warm ascitic fluid should be hand-carried to the laboratory for immediate processing. The sensitivity of cytology in detecting peritoneal carcinomatosis increases to 96.7% if 3 samples (from different paracentesis procedures) are sent and processed promptly; the first sample is positive in only 82.8% and at least 1 of 2 samples is positive in 93.3%.71Runyon B.A. Hoefs J.C. Morgan T.R. Ascitic fluid analysis in malignancy-related ascites.Hepatology. 1988; 8: 1104-1109Crossref PubMed Scopus (260) Google Scholar CA 125 for suspected ovarian malignancy as cause of ascites should not be tested for in patients with ascites as it is elevated in essentially all patients including men with ascites or pleural fluid of any cause and decreases after control of ascites.72Runyon B.A. Malignancy-related ascites and ascitic fluid ''humoral tests of malignancy.J Clin Gastroenterol. 1994; 18: 94-98Crossref PubMed Scopus (39) Google Scholar, 73Zuckerman E. Lanir A. Sabo E. et al.Cancer antigen 125: a sensitive marker of ascites in patients with cirrhosis.Am J Gastroenterol. 1999; 94: 1613-1618Crossref PubMed Scopus (71) Google Scholar The serum-ascites albumin gradient (SAAG) is better in categorizing ascites than the total-protein-based exudate/transudate concept. If the SAAG is ≥1.1 g/dL (11 g/L), it predicts for portal hypertension with 97% accuracy.74Runyon B.A. Montano A.A. Akriviadis E.A. Antillon M.R. Irving M.A. McHutchison J.G. The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites.Ann Intern Med. 1992; 117: 215-220Crossref PubMed Scopus (427) Google Scholar It retains accuracy despite fluid infusion and diuretic use and also in patients who have portal hypertension plus a second cause for ascites formation (mixed ascites).75Dykes P.W. Jones J.H. Albumin exchange between plasma and ascitic fluid.Clin Sci. 1968; 34: 185-197PubMed Google Scholar Blood concentration of brain natriuretic peptide or pro-brain natriuretic peptide can distinguish ascites due to cirrhosis from ascites due to heart failure. The median pro-brain natriuretic peptide is 6100 pg/ml heart failure compared to 166 pg/ml in cirrhosis.76Sheer T.A. Joo E. Runyon B.A. Usefulness of serum pro-brain-type natriuretic peptide in distinguishing ascites due to cirrhosis from ascites due to heart failure.J Clin Gastroenterol. 2010; 44: e23-e26Crossref PubMed Scopus (10) Google Scholar
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