Hepatitis E and Acute-on-Chronic Liver Failure
2013; Elsevier BV; Volume: 3; Issue: 3 Linguagem: Inglês
10.1016/j.jceh.2013.08.013
ISSN2213-3453
AutoresAshish Kumar, Vivek A. Saraswat,
Tópico(s)Liver Disease Diagnosis and Treatment
ResumoHepatitis E virus (HEV) is the most common cause of acute viral hepatitis (AVH) globally. It causes large scale epidemics of AVH across the low- and middle income countries in Asia and Africa, and also causes sporadic cases of AVH in the same geographical region. AVH due to HEV is usually an acute, self-limiting illness, similar in clinical presentation to AVH caused by hepatitis A virus (HAV). When HEV causes AVH in patients of chronic liver disease it may worsen rapidly to a syndrome called acute-on-chronic liver failure (ACLF) leading to very high mortality. Acute deterioration of liver function in a patient with compensated chronic liver disease is the characteristic feature of ACLF. The typical disease course of patients with ACLF is the appearance of organ failure, which progresses to multi-organ failure and death. Many publications have reported HEV as one of the leading causes for ACLF from Asia and Africa, where HEV is endemic. The mortality rate of HEV-related ACLF (HEV-ACLF) ranges from 0% to 67% with a median being 34%. These patients require admission in the intensive care unit and they benefit from a team approach of clinicians with expertise in both hepatology and critical care. The goals of treatment are to prevent further deterioration in liver function, reverse precipitating factors, and support failing organs. Liver transplantation is required in selected patients to improve survival and quality of life. One preliminary report suggests that ribavirin may be an effective and safe drug for treatment of HEV-ACLF however this requires validation in large trials. Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis (AVH) globally. It causes large scale epidemics of AVH across the low- and middle income countries in Asia and Africa, and also causes sporadic cases of AVH in the same geographical region. AVH due to HEV is usually an acute, self-limiting illness, similar in clinical presentation to AVH caused by hepatitis A virus (HAV). When HEV causes AVH in patients of chronic liver disease it may worsen rapidly to a syndrome called acute-on-chronic liver failure (ACLF) leading to very high mortality. Acute deterioration of liver function in a patient with compensated chronic liver disease is the characteristic feature of ACLF. The typical disease course of patients with ACLF is the appearance of organ failure, which progresses to multi-organ failure and death. Many publications have reported HEV as one of the leading causes for ACLF from Asia and Africa, where HEV is endemic. The mortality rate of HEV-related ACLF (HEV-ACLF) ranges from 0% to 67% with a median being 34%. These patients require admission in the intensive care unit and they benefit from a team approach of clinicians with expertise in both hepatology and critical care. The goals of treatment are to prevent further deterioration in liver function, reverse precipitating factors, and support failing organs. Liver transplantation is required in selected patients to improve survival and quality of life. One preliminary report suggests that ribavirin may be an effective and safe drug for treatment of HEV-ACLF however this requires validation in large trials. Hepatitis E virus (HEV) is a small non-enveloped virus with a size of 27–34 nm, and belongs to the genus Hepevirus in the Hepeviridae family.1Panda S.K. Varma S.P. Hepatitis E: molecular virology and pathogenesis.J Clin Exp Hepatol. 2013; 3: 114-124Abstract Full Text Full Text PDF Scopus (22) Google Scholar, 2Kamar N. Bendall R. Legrand-Abravanel F. et al.Hepatitis E.Lancet. 2012; 379: 2477-2488Abstract Full Text Full Text PDF PubMed Scopus (718) Google Scholar It is primarily transmitted through the fecal–oral route, and is the most common cause of acute viral hepatitis (AVH) globally. It causes large scale epidemics of AVH across the low- and middle income countries in Asia and Africa, and also causes sporadic cases of AVH in the same geographical region.3Aggarwal R. Hepatitis E: epidemiology and natural history.J Clin Exp Hepatol. 2013; 3: 125-133Abstract Full Text Full Text PDF Scopus (27) Google Scholar, 4Kmush B. Wierzba T. Krain L. Nelson K. Labrique A.B. Epidemiology of hepatitis E in low- and middle-income countries of Asia and Africa.Semin Liver Dis. 2013; 33: 15-29Crossref PubMed Scopus (52) Google Scholar AVH due to HEV is usually an acute, self-limiting illness, similar in clinical presentation to AVH caused by hepatitis A virus (HAV). However, in two situations HEV may cause serious disease leading to high mortality: when AVH occurs in pregnant women which may rapidly worsen as acute liver failure,5Shalimar Acharya S.K. Hepatitis E and acute liver failure in pregnancy.J Clin Exp Hepatol. 2013; 3 (in this issue)Abstract Full Text Full Text PDF PubMed Google Scholar and when AVH occurs in patients of chronic liver disease which may worsen as acute-on-chronic liver failure (ACLF).The present review describes ACLF which is precipitated by HEV.Concept of acute-on-chronic liver failureACLF is an increasingly recognized entity encompassing an acute deterioration of liver function in patients with cirrhosis, which is usually associated with a precipitating event and results in the failure of one or more organs and high short-term mortality.6Jalan R. Gines P. Olson J.C. et al.Acute-on chronic liver failure.J Hepatol. 2012; 57: 1336-1348Abstract Full Text Full Text PDF PubMed Scopus (447) Google Scholar Although, there is no universally agreed definition of this entity, two consensus working definitions for this syndrome exist: one put forward by the Asia–Pacific Association for the Study of Liver (APASL)7Sarin S.K. Kumar A. Almeida J.A. et al.Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL).Hepatol Int. 2009; 3: 269-282Crossref PubMed Scopus (639) Google Scholar and the other based on an EASL-AASLD single topic symposium.8Olson J.C. Kamath P.S. Acute-on-chronic liver failure: concept, natural history, and prognosis.Curr Opin Crit Care. 2011; 17: 165-169Crossref PubMed Scopus (126) Google Scholar According to the APASL, ACLF is defined as 'Acute hepatic insult manifesting as jaundice and coagulopathy, complicated within 4 weeks by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease'.7Sarin S.K. Kumar A. Almeida J.A. et al.Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL).Hepatol Int. 2009; 3: 269-282Crossref PubMed Scopus (639) Google Scholar The EASL-AASLD defined ACLF as 'Acute deterioration of pre-existing, chronic liver disease, usually related to a precipitating event and associated with increased mortality at 3 months due to multisystem organ failure'.8Olson J.C. Kamath P.S. Acute-on-chronic liver failure: concept, natural history, and prognosis.Curr Opin Crit Care. 2011; 17: 165-169Crossref PubMed Scopus (126) Google Scholar Both these definitions address the essential feature of acute hepatic insult or acute deterioration in patients with pre-existing chronic liver disease.9Wlodzimirow K. Abu-Hanna A. Chamuleau R.A.F.M. Acute-on-chronic liver failure – its definition remains unclear.J Hepatol. 2013; 59: 190-191Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar Recently investigators from the EASL–CLIF Consortium collected data from 1343 hospitalized patients with cirrhosis and acute decompensation from 29 liver units in 8 European countries.10Moreau R. Jalan R. Gines P. et al.Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis.Gastroenterology. 2013; 144 (1437.e1–9): 1426-1437Abstract Full Text Full Text PDF PubMed Scopus (1682) Google Scholar They used the organ failure and mortality data to define ACLF grades, assess mortality, and identify differences between ACLF and acute decompensation. They also established diagnostic criteria for ACLF based on analyses of patients with organ failure (defined by the chronic liver failure–sequential organ failure assessment [CLIF-SOFA] score) and high 28-day mortality rate (>15%).10Moreau R. Jalan R. Gines P. et al.Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis.Gastroenterology. 2013; 144 (1437.e1–9): 1426-1437Abstract Full Text Full Text PDF PubMed Scopus (1682) Google ScholarACLF differs from chronic hepatic decompensation in many aspects. First, the development of liver failure and end-organ dysfunction in ACLF is much faster than in chronic hepatic decompensation. Second, in ACLF, there is still a chance of recovery of liver function (i.e. there is reversibility component in ACLF). Third, there is usually a well defined precipitating event which precedes the liver failure. And lastly, the short-term (3-month) mortality is significantly higher than expected with chronic hepatic decompensation.11Olson J.C. Kamath P.S. Acute-on-chronic liver failure: what are the implications?.Curr Gastroenterol Rep. 2012; 14: 63-66Crossref PubMed Scopus (26) Google Scholar, 12Verbeke L. Nevens F. Laleman W. Bench-to-beside review: acute-on-chronic liver failure – linking the gut, liver and systemic circulation.Crit Care Lond Engl. 2011; 15: 233Crossref PubMed Scopus (40) Google ScholarACLF is frequently accompanied by the development of severe inflammatory response syndrome associated with multi-organ failure leading to high in-hospital mortality despite costly intensive care therapy.12Verbeke L. Nevens F. Laleman W. Bench-to-beside review: acute-on-chronic liver failure – linking the gut, liver and systemic circulation.Crit Care Lond Engl. 2011; 15: 233Crossref PubMed Scopus (40) Google Scholar, 13Graziadei I.W. The clinical challenges of acute on chronic liver failure.Liver Int. 2011; 31 (Off J Int Assoc Study Liver): 24-26Crossref PubMed Scopus (33) Google Scholar Basically all organ systems can be affected, particularly circulation, brain, kidneys and liver. A key role for the interaction of innate immune dysfunction, enhanced bacterial translocation from the gut, and circulatory dysfunction has been proposed. The characteristic circulatory dysfunction includes peripheral arterial vasodilatation, reduced renal blood flow, increased portosystemic shunting and high cardiac output (hyperdynamic circulation). These phenomena are thought to be secondary to a reduction in vascular responsiveness and down regulation of receptors leading to hyporesponsive vasoconstriction. Intense renal vasoconstriction may occur which may lead to the development of a hepatorenal syndrome.13Graziadei I.W. The clinical challenges of acute on chronic liver failure.Liver Int. 2011; 31 (Off J Int Assoc Study Liver): 24-26Crossref PubMed Scopus (33) Google ScholarThe onset of ACLF depends on the severity of underlying chronic liver disease and the severity of the acute event. A minor acute insult may be enough to cause the ACLF in a patient with severe underlying chronic liver disease, and a severe acute insult may be required in a patient who has mild underlying chronic liver disease.7Sarin S.K. Kumar A. Almeida J.A. et al.Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL).Hepatol Int. 2009; 3: 269-282Crossref PubMed Scopus (639) Google Scholar, 14Duseja A. Chawla Y.K. Dhiman R.K. Kumar A. Choudhary N. Taneja S. Non-hepatic insults are common acute precipitants in patients with acute on chronic liver failure (ACLF).Dig Dis Sci. 2010; 55: 3188-3192Crossref PubMed Scopus (62) Google Scholar Both hepatic and non-hepatic insults could occur as acute precipitating events leading to the syndrome of ACLF. The 'hepatic' precipitating events, that directly exaggerate the liver injury, are alcoholic hepatitis, drug-induced liver injury, superimposed viral hepatitis, portal vein thrombosis and ischemic hepatitis. The 'non-hepatic' insults precipitating ACLF are trauma, surgery, variceal bleeding or infection. In a proportion of patients, there may be no identifiable precipitating event.6Jalan R. Gines P. Olson J.C. et al.Acute-on chronic liver failure.J Hepatol. 2012; 57: 1336-1348Abstract Full Text Full Text PDF PubMed Scopus (447) Google Scholar Superimposed viral infections with hepatotropic viruses in patients with cirrhosis can have devastating consequences by direct hepatocellular damage. Perhaps, the best examples are HEVsuperinfection15Acharya S.K. Kumar Sharma P. Singh R. et al.Hepatitis E virus (HEV) infection in patients with cirrhosis is associated with rapid decompensation and death.J Hepatol. 2007; 46: 387-394Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar and reactivation of hepatitis B virus (HBV) in patients on immunosuppression.16Shouval D. Shibolet O. Immunosuppression and HBV reactivation.Semin Liver Dis. 2013; 33: 167-177Crossref PubMed Scopus (112) Google ScholarRole of hepatitis E virus in acute-on-chronic liver failureThe first report documenting HEV superinfection in patients of chronic liver disease leading to severe liver decompensation was published from Pakistan in 2002.17Hamid S.S. Atiq M. Shehzad F. et al.Hepatitis E virus superinfection in patients with chronic liver disease.Hepatol Baltim Md. 2002; 36: 474-478Crossref PubMed Scopus (180) Google Scholar Subsequently, many publications have reported HEV as one of the leading causes for decompensation of cirrhosis from Asia and Africa, where HEV is endemic (Table 1).14Duseja A. Chawla Y.K. Dhiman R.K. Kumar A. Choudhary N. Taneja S. Non-hepatic insults are common acute precipitants in patients with acute on chronic liver failure (ACLF).Dig Dis Sci. 2010; 55: 3188-3192Crossref PubMed Scopus (62) Google Scholar, 15Acharya S.K. Kumar Sharma P. Singh R. et al.Hepatitis E virus (HEV) infection in patients with cirrhosis is associated with rapid decompensation and death.J Hepatol. 2007; 46: 387-394Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar, 17Hamid S.S. Atiq M. Shehzad F. et al.Hepatitis E virus superinfection in patients with chronic liver disease.Hepatol Baltim Md. 2002; 36: 474-478Crossref PubMed Scopus (180) Google Scholar, 18Ramachandran J. Eapen C.E. Kang G. et al.Hepatitis E superinfection produces severe decompensation in patients with chronic liver disease.J Gastroenterol Hepatol. 2004; 19: 134-138Crossref PubMed Scopus (111) Google Scholar, 19Kumar A. Aggarwal R. Naik S.R. Saraswat V. Ghoshal U.C. Naik S. Hepatitis E virus is responsible for decompensation of chronic liver disease in an endemic region.Indian J Gastroenterol. 2004; 23 (Off J Indian Soc Gastroenterol): 59-62PubMed Google Scholar, 20Monga R. Garg S. Tyagi P. Kumar N. Superimposed acute hepatitis E infection in patients with chronic liver disease.Indian J Gastroenterol. 2004; 23: 50-52PubMed Google Scholar, 21Kc S. Mishra A.K. Shrestha R. Hepatitis E virus infection in chronic liver disease causes rapid decompensation.JNMA J Nepal Med Assoc. 2006; 45: 212-215PubMed Google Scholar, 22Ke W.M. Li X.J. Yu L.N. et al.Etiological investigation of fatal liver failure during the course of chronic hepatitis B in southeast China.J Gastroenterol. 2006; 41: 347-351Crossref PubMed Scopus (25) Google Scholar, 23Kumar M. Sharma B.C. Sarin S.K. Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized asymptomatic patients with hepatitis B virus-related chronic liver disease.J Gastroenterol Hepatol. 2008; 23: 883-887Crossref PubMed Scopus (62) Google Scholar, 24Kumar A. Das K. Sharma P. Mehta V. Sharma B.C. Sarin S.K. Hemodynamic studies in acute-on-chronic liver failure.Dig Dis Sci. 2009; 54: 869-878Crossref PubMed Scopus (40) Google Scholar, 25Mahtab M.A. Rahman S. Khan M. Karim M.F. Hepatitis E virus is a leading cause of acute-on-chronic liver disease: experience from a tertiary centre in Bangladesh.Hepatobiliary Pancreat Dis Int. 2009; 8: 50-52PubMed Google Scholar, 26Radha Krishna Y. Saraswat V.A. Das K. et al.Clinical features and predictors of outcome in acute hepatitis A and hepatitis E virus hepatitis on cirrhosis.Liver Int. 2009; 29 (Off J Int Assoc Study Liver): 392-398Crossref PubMed Scopus (94) Google Scholar, 27Zhang X. Ke W. Xie J. Zhao Z. Xie D. Gao Z. Comparison of effects of hepatitis E or A viral superinfection in patients with chronic hepatitis B.Hepatol Int. 2010; 4: 615-620Crossref PubMed Scopus (41) Google Scholar, 28Lal J. Thapa B.R. Rawal P. Ratho R.K. Singh K. Predictors of outcome in acute-on-chronic liver failure in children.Hepatol Int. 2011; 5: 693-697Crossref PubMed Scopus (36) Google Scholar, 29El Sayed Zaki M. Othman W. Role of hepatitis E infection in acute on chronic liver failure in Egyptian patients.Liver Int. 2011; 31: 1001-1005Crossref PubMed Scopus (24) Google Scholar, 30Jagadisan B. Srivastava A. Yachha S.K. Poddar U. Acute on chronic liver disease in children from the developing world: recognition and prognosis.J Pediatr Gastroenterol Nutr. 2012; 54: 77-82Crossref PubMed Scopus (52) Google Scholar, 31Garg H. Kumar A. Garg V. Sharma P. Sharma B.C. Sarin S.K. Clinical profile and predictors of mortality in patients of acute-on-chronic liver failure.Dig Liver Dis. 2012; 44: 166-171Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar, 32Jha A.K. Nijhawan S. Rai R.R. Nepalia S. Jain P. Suchismita A. Etiology, clinical profile, and inhospital mortality of acute-on-chronic liver failure: a prospective study.Indian J Gastroenterol. 2013; 32: 108-114Crossref PubMed Scopus (20) Google Scholar, 33Duseja A. Choudhary N.S. Gupta S. Dhiman R.K. Chawla Y. APACHE II score is superior to SOFA, CTP and MELD in predicting the short-term mortality in patients with acute-on-chronic liver failure (ACLF).J Dig Dis. 2013; 14: 484-490Crossref PubMed Scopus (69) Google Scholar Most of these studies have used the APASL definition of ACLF and in median21% of cases (range 4–72%) of ACLF, HEV was the precipitating cause for liver decompensation. This contrasts with the Western countries where HEV is rarely the precipitating cause of acute decompensation in ACLF.Table 1Summary of important studies on ACLF from countries where HEV is endemic.AuthorsPlaceYearNumber (and %) of cases of ACLF due to HEV out of all ACLF casesShort-term mortalityHamid et al17Hamid S.S. Atiq M. Shehzad F. et al.Hepatitis E virus superinfection in patients with chronic liver disease.Hepatol Baltim Md. 2002; 36: 474-478Crossref PubMed Scopus (180) Google ScholarKarachi200241/4 (25%)Ramachandran et al18Ramachandran J. Eapen C.E. Kang G. et al.Hepatitis E superinfection produces severe decompensation in patients with chronic liver disease.J Gastroenterol Hepatol. 2004; 19: 134-138Crossref PubMed Scopus (111) Google ScholarVellore200496/9 (67%)Kumar et al19Kumar A. Aggarwal R. Naik S.R. Saraswat V. Ghoshal U.C. Naik S. Hepatitis E virus is responsible for decompensation of chronic liver disease in an endemic region.Indian J Gastroenterol. 2004; 23 (Off J Indian Soc Gastroenterol): 59-62PubMed Google ScholarLucknow200414/32 (44%)2/14 (14%)Monga et al20Monga R. Garg S. Tyagi P. Kumar N. Superimposed acute hepatitis E infection in patients with chronic liver disease.Indian J Gastroenterol. 2004; 23: 50-52PubMed Google ScholarDelhi2004103/10 (30%)Kc et al21Kc S. Mishra A.K. Shrestha R. Hepatitis E virus infection in chronic liver disease causes rapid decompensation.JNMA J Nepal Med Assoc. 2006; 45: 212-215PubMed Google ScholarKathmandu200672/7 (28%)Ke et al22Ke W.M. Li X.J. Yu L.N. et al.Etiological investigation of fatal liver failure during the course of chronic hepatitis B in southeast China.J Gastroenterol. 2006; 41: 347-351Crossref PubMed Scopus (25) Google ScholarChina200680/107 (75%)80/80 (100%)aOnly fatal cases included in the study.Acharya et al15Acharya S.K. Kumar Sharma P. Singh R. et al.Hepatitis E virus (HEV) infection in patients with cirrhosis is associated with rapid decompensation and death.J Hepatol. 2007; 46: 387-394Abstract Full Text Full Text PDF PubMed Scopus (216) Google ScholarDelhi200730/107 (28%)13/30 (43%)Kumar et al23Kumar M. Sharma B.C. Sarin S.K. Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized asymptomatic patients with hepatitis B virus-related chronic liver disease.J Gastroenterol Hepatol. 2008; 23: 883-887Crossref PubMed Scopus (62) Google ScholarDelhi20089/43 (21%)0/9 (0%)Kumar et al24Kumar A. Das K. Sharma P. Mehta V. Sharma B.C. Sarin S.K. Hemodynamic studies in acute-on-chronic liver failure.Dig Dis Sci. 2009; 54: 869-878Crossref PubMed Scopus (40) Google ScholarDelhi20097/48 (15%)–Mahtab et al25Mahtab M.A. Rahman S. Khan M. Karim M.F. Hepatitis E virus is a leading cause of acute-on-chronic liver disease: experience from a tertiary centre in Bangladesh.Hepatobiliary Pancreat Dis Int. 2009; 8: 50-52PubMed Google ScholarDhaka200915/69 (22%)2/15 (13%)bExact HEV mortality data unclear, figure derived from overall mortality.Radha Krishna et al26Radha Krishna Y. Saraswat V.A. Das K. et al.Clinical features and predictors of outcome in acute hepatitis A and hepatitis E virus hepatitis on cirrhosis.Liver Int. 2009; 29 (Off J Int Assoc Study Liver): 392-398Crossref PubMed Scopus (94) Google ScholarLucknow200980/121 (66%)35/80 (44%)Duseja et al14Duseja A. Chawla Y.K. Dhiman R.K. Kumar A. Choudhary N. Taneja S. Non-hepatic insults are common acute precipitants in patients with acute on chronic liver failure (ACLF).Dig Dis Sci. 2010; 55: 3188-3192Crossref PubMed Scopus (62) Google ScholarChandigarh20104/102 (4%)2/4 (50%)bExact HEV mortality data unclear, figure derived from overall mortality.Zhang et al27Zhang X. Ke W. Xie J. Zhao Z. Xie D. Gao Z. Comparison of effects of hepatitis E or A viral superinfection in patients with chronic hepatitis B.Hepatol Int. 2010; 4: 615-620Crossref PubMed Scopus (41) Google ScholarChina2010136/188 (72%)46/136 (34%)Lal et al28Lal J. Thapa B.R. Rawal P. Ratho R.K. Singh K. Predictors of outcome in acute-on-chronic liver failure in children.Hepatol Int. 2011; 5: 693-697Crossref PubMed Scopus (36) Google ScholarChandigarh20113/31 (10%)1/3 (33%)bExact HEV mortality data unclear, figure derived from overall mortality.El Sayed Zaki et al29El Sayed Zaki M. Othman W. Role of hepatitis E infection in acute on chronic liver failure in Egyptian patients.Liver Int. 2011; 31: 1001-1005Crossref PubMed Scopus (24) Google ScholarEgypt201113/100 (13%)3/13 (23%)Jagadisan et al30Jagadisan B. Srivastava A. Yachha S.K. Poddar U. Acute on chronic liver disease in children from the developing world: recognition and prognosis.J Pediatr Gastroenterol Nutr. 2012; 54: 77-82Crossref PubMed Scopus (52) Google ScholarLucknow201223/36 (64%)8/23 (35%)bExact HEV mortality data unclear, figure derived from overall mortality.Garg et al31Garg H. Kumar A. Garg V. Sharma P. Sharma B.C. Sarin S.K. Clinical profile and predictors of mortality in patients of acute-on-chronic liver failure.Dig Liver Dis. 2012; 44: 166-171Abstract Full Text Full Text PDF PubMed Scopus (143) Google ScholarDelhi201214/91 (15%)9/14 (64%)Jha et al32Jha A.K. Nijhawan S. Rai R.R. Nepalia S. Jain P. Suchismita A. Etiology, clinical profile, and inhospital mortality of acute-on-chronic liver failure: a prospective study.Indian J Gastroenterol. 2013; 32: 108-114Crossref PubMed Scopus (20) Google ScholarJaipur20135/52 (10%)3/5 (60%)bExact HEV mortality data unclear, figure derived from overall mortality.Duseja et al33Duseja A. Choudhary N.S. Gupta S. Dhiman R.K. Chawla Y. APACHE II score is superior to SOFA, CTP and MELD in predicting the short-term mortality in patients with acute-on-chronic liver failure (ACLF).J Dig Dis. 2013; 14: 484-490Crossref PubMed Scopus (69) Google ScholarChandigarh20138/100 (8%)4/8 (50%)bExact HEV mortality data unclear, figure derived from overall mortality.Total471 (21% median)220/464 (34% median)a Only fatal cases included in the study.b Exact HEV mortality data unclear, figure derived from overall mortality. Open table in a new tab The largest of these studies documenting HEV as the acute insult of ACLF was from China by Zhang et al published in 2010.27Zhang X. Ke W. Xie J. Zhao Z. Xie D. Gao Z. Comparison of effects of hepatitis E or A viral superinfection in patients with chronic hepatitis B.Hepatol Int. 2010; 4: 615-620Crossref PubMed Scopus (41) Google Scholar The authors compared the demographics, liver function, and prognosis of Chinese patients infected with chronic hepatitis B (CHB) and superinfected with HEV or hepatitis A virus (HAV). Among 188 patients with CHB, 136 had HEV superinfection and 52 had HAV superinfection. More patients in the HEV group had complications (94.9 vs. 61.5%, P < 0.001), and liver failure (39.7 vs. 11.5%, P = 0.002). Additionally, the mortality among the HEV group was significantly higher (33.8 vs. 1.9%, P < 0.001). The authors concluded that patients with CHB with HEV superinfection had more severe liver disease and poorer prognosis than those with HAV superinfection. The authors recommended that since there is no vaccine against HEV, patients with CHB should take appropriate precautions against superinfection with HEV, such as consumption of boiled water and well-cooked food, in regions where it is endemic.The largest study from India on this aspect was published by Radha Krishna et al from Lucknow, India in 2009.26Radha Krishna Y. Saraswat V.A. Das K. et al.Clinical features and predictors of outcome in acute hepatitis A and hepatitis E virus hepatitis on cirrhosis.Liver Int. 2009; 29 (Off J Int Assoc Study Liver): 392-398Crossref PubMed Scopus (94) Google Scholar The authors aimed to evaluate the clinical profile and predictors of 3-month mortality in patients with ACLF. In 121 cases of ACLF, the precipitating cause was HEV in 80 (61%), HAV in 33 (27%) and both in 8 (6%). The underlying liver cirrhosis had varying etiologies such as HBV, alcohol, Wilson's disease, HCV, autoimmune, Budd–Chiari syndrome, hemochromatosis and cryptogenic. The three-month mortality was 45%. Multivariate analysis revealed grades 3 and 4 hepatic encephalopathy [odds ratio (OR 32.1)], hyponatremia (OR 9.2) and renal failure (OR 16.8) as significant predictors of 3-month mortality.26Radha Krishna Y. Saraswat V.A. Das K. et al.Clinical features and predictors of outcome in acute hepatitis A and hepatitis E virus hepatitis on cirrhosis.Liver Int. 2009; 29 (Off J Int Assoc Study Liver): 392-398Crossref PubMed Scopus (94) Google ScholarClinical features and prognosis of HEV-related ACLFEven though ACLF is a heterogenous disease in term of its varying acute and chronic etiologies, there is little evidence to suggest that its clinical presentation may differ depending on the etiology. In fact ACLF is defined by APASL to present uniformly as 'Acute hepatic insult manifesting as jaundice and coagulopathy, complicated within 4 weeks by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease'.7Sarin S.K. Kumar A. Almeida J.A. et al.Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL).Hepatol Int. 2009; 3: 269-282Crossref PubMed Scopus (639) Google Scholar Thus the acute deterioration of liver function in a patient with compensated chronic liver disease mainly stable liver cirrhosis is the characteristic feature of ACLF. Multi-organ failure often ensues in the ACLF syndrome following the hepatic decompensation.34Laleman W. Verbeke L. Meersseman P. et al.Acute-on-chronic liver failure: current concepts on definition, pathogenesis, clinical manifestations and potential therapeutic interventions.Expert Rev Gastroenterol Hepatol. 2011; 5: 523-537Crossref PubMed Scopus (76) Google Scholar Liver insufficiency is typically associated with a decreased detoxification function as manifested by hyperbilirubinemia (with clinical jaundice), encephalopathy and reduction of synthetic function leading to hypoalbuminemia and a decrease in prothrombin time. In this specific setting, the lack of liver detoxification and metabolic and regulatory functions leads to life-threatening complications, which in the context of ACLF typically involve systemic hemodynamic dysfunction, renal insufficiency, cerebral failure (hepatic encephalopathy) and increased susceptibility to infections.34Laleman W. Verbeke L. Meersseman P. et al.Acute-on-chronic liver failure: current concepts on definition, pathogenesis, clinical manifestations and potential therapeutic interventions.Expert Rev Gastroenterol Hepatol. 2011; 5: 523-537Crossref PubMed Scopus (76) Google ScholarIn a large prospective study on ACLF, Garg et al have described the clinical, biochemical and etiological profiles of 91 ACLF patients.31Garg H. Kumar A. Garg V. Sharma P. Sharma B.C. Sarin S.K. Clinical profile and predictors of mortality in patients of acute-on-chronic liver failure.Dig Liver Dis. 2012; 44: 166-171Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar The median ages of these patients was 36 years and most were males. Acute onset ascites with jaundice with or without hepatic encephalopathy was the presenting symptom in 92% of cases, and rest 8% presented with only hepatic encephalopathy with jaundice but no ascites (acute liver failure like presentation). Most patients had severe jaundice with median bilirubin of 23 mg/dL. Esophageal varices were present in 83% patients; however, only 2% presented with gastrointestinal bleeding. One-third of the patients had already hepatorenal syndrome at presentation. Most patients had leukocytosis with median white blood cell count of 12 × 103 cells/mm3; however, infection could be documented in a few of these patients. Spontaneous bacterial peritonitis was present in 18% patients. Evidence of stigmata fo
Referência(s)