- Email: [email protected]
Hepatitis E Virus Infection is Associated with Better Survival in Acute Liver Failure
ABSTRACTS
Department of Medicine, Maulana Azad Medical College, New Delhi, India
ALF and ACLF
Introduction: Cell death markers, caspase-cleaved [CK18 (M30)] and total cytokeratin [CK-18 (M65)] indicate the extent and relative proportions of apoptotic and necrotic cell death in acute liver failure (ALF) patients. Serum levels of apoptotic biomarkers [CK 18 (M30 and M 65)] are expected to be elevated in ALF compared to controls and these biomarkers may be linked to outcome. Aims and Objectives: To assess whether the circulating apoptotic markers [CK 18 (M30 and M 65)] are altered in ALF and its correlation with disease outcome. Methodology: 40 cases of acute liver failure and 30 age and sex matched healthy controls were included in the study. The study population was divided into spontaneous survival and mortality groups. The serum levels of M30 and M65 were measured using commercially available ELISA kits as described by the manufacturer's instructions. The serum levels between the survival, mortality and healthy control groups were compared by ANOVA analysis (with post hoc Tukey's analysis) using SPSS (version 20). Results: 29 patients died and 11 patients survived. Serum levels of apoptotic biomarkers [CK 18 (M30 and M 65)] were significantly elevated in ALF compared to controls [7000 U/L vs 30 U/L; P < 0.001 for CK18 (M30) and 6000 U/L vs 40 U/L; P < 0.05 for CK 18 (M65)]. The levels of total CK18 (M65) are significantly higher in non-survivors compared to survivors (10000 U/L vs. 4000 U/L; P < 0.05) and the levels of cleaved CK 18 (M30) are significantly higher in non-survivors compared to the survivor group (8700 U/L vs. 3000; P < 0.05) suggesting increased caspase activation and cell death. The findings from this study indicate the role ofM30 and M65 as predictive markers in ALF. Conclusion: The findings from this study establish the role of serum apoptosis markers M30 and M65 as prognostic markers in patients with acute liver failure which can be used as a guide for management of the patients in the near future. Corresponding author: Premashis Kar. Email: [email protected]
POLYMORPHISM AND EXPRESSION OF HSP70 GENE IN ACUTE VIRAL HEPATITIS AND FULMINANT HEPATIC FAILURE AND ITS CLINICAL RELEVANCE Premashis Kar*, Ujjwal Sonika*, Rajib Hazam*, Bhudev C. Dasy
S2
22ND ANNUAL CONFERENCE–2014
*
Department of Medicine, Maulana Azad Medical College, New Delhi, India and †Department of Biotechnology , Dr. B R Ambedkar Center for Biomedical Research, New Delhi, India
Background and Aims: To study the Polymorphism and expression of HSP70 gene in patients of fulminant hepatic failure (FHF) and acute viral hepatitis (AVH); and to evaluate whether quantification of HSP70 protein at admission could predict the outcome of disease. Methods: 43 patients with FHF and 45 patients with AVH were included in the study. HSP70 expression was measured at admission by quantification of HSP70 protein using ELISA and gene polymorphism was studied by PCR RFLP method. Results: The mean HSP70 protein levels were significantly higher (47.17 26.34) in FHF as compared to AVH (19.74 8.50) and Controls (8.31 5.30); P < 0.01. The b1b1 genotype of HSP70-1 was found significantly less commonly in AVH and b1b2 more frequently in FHF compared to controls (P < 0.05). Genotype b2b2 was decreased in FHF as compared to AVH (P < 0.05). The b2 allele of HSP70-1 was found significantly increased in AVH (P < 0.05). Genotype AA and BB of HSP70-2 were found respectively less and more commonly in AVH group (P < 0.05). AB genotype was increased in FHF as compared to AVH group. Allele B of HSP70-2was associated with increased risk of AVH.AA, AB and BB genotypes of HSP70-hom gene did not show significant difference among various groups. Allele B of HSP70-homgene was associated with less severe liver injury in patients with hepatitis (OR 0.2, 95% CL 0.040.77). Conclusion: HSP70 gene expression and polymorphism may play an important role in susceptibility to AVH and FHF and may also predict the severity of disease. Corresponding author: Premashis Kar. Email: [email protected]
HEPATITIS E VIRUS INFECTION IS ASSOCIATED WITH BETTER SURVIVAL IN ACUTE LIVER FAILURE Subrat K. Acharya, S. Shalimar, Hanish Sharma, Sreejith Vasudevan, Saurabh Kedia, Praneeth Moka, Ujjwal Sonika Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India Background and Aims: Acute Liver Failure (ALF) is associated with a high mortality. The difference in outcomes
© 2014, INASL
CLIF-SOFA SCORE PREDICTS MORTALITY IN PATIENTS WITH ACUTE ON CHRONIC LIVER FAILURE
with active alcoholism present in 55.9% of patients. Sepsis (66%) was the most common cause of acute decompensation. ACLF patients were younger and had significantly higher INR, serum creatinine, Child-Pugh score, MELD, CLIF SOFA and APACHE II scores (P < 0.05). The 28-day mortality in patients with no ACLF (n = 12), ACLF grade 1 (n = 11), ACLF grade 2 (n = 14) and ACLF grade 3 (n = 13) were 8.3%, 18.2%, 42.9% and 76.9% (c2 for trend, P = 0.002) and 90-day mortality were 16.7%, 27.3%, 78.6% and 100% (c2 for trend, P < 0.0001) respectively. Nonsurvivors at 28 days irrespective of ACLF grade had significantly higher incidence of cerebral and renal failure, higher INR, Child-Pugh score, MELD, CLIF SOFA and APACHE II scores as compared to survivors (P < 0.05). Patients with prior decompensation had similar 28-day and 90-day mortality (39.3% and 53.6%) as patients without prior decompensation (36.4% and 63.6%) (P=NS). Area under curve for 28-day mortality was 0.795, 0.787, 0.739 and 0.710 for CLIF-SOFA, APACHE-II, Child-Pugh and MELD scores respectively. On multivariate analysis of these scores, CLIF-SOFA was the only significant independent predictor of mortality with an odds ratio 1.538 (95% CI: 1.078-2.194). Conclusion: Presence of organ failure predicts mortality in patients with cirrhosis with acute decompensation. With increasing grades of ACLF, there is increasing 28and 90-day mortality among various groups of ACLF. CLIF-SOFA score was the best predictor of mortality at 28 days. Patients with and without prior decompensation had similar 28-day and 90-day mortality.
Tarana Gupta, Swastik Agrawal, Ajay Duseja, Yogesh Chawla, Radha K. Dhiman
Corresponding author: Radha K. Dhiman. Email: [email protected]
between different etiologies is not clear. We analysed the outcomes of consecutive ALF patients admitted at a single tertiary-care centre over a period of 25 years. Methods: An analysis of the prospectively maintained database of ALF patients was performed to assess the effect of etiology on the outcome. Results: A total of 1347 patients were evaluated. Out of these 755 (56.1%) were females and 592 (43.9%) were males. The mean age SD was 28.4 11.7 years. Hepatitis A (1.2%), acute Hepatitis B (7.6%), Hepatitis E (29.0%), Non -A, Non-E (38.3%), dual infection (4.9%) and anti-tubercular therapy (4.8%) comprised different etiologies of ALF. Among 10.2% of patients only chronic markers were positive and no etiological data was available in 4% of patients. A total of 797 (59.2%) patients died. The survival among different etiologies was HAV (62.5%), acute HBV (32%), HEV (53.6%), Non-A, Non-E (37.9%), dual infection (30.3%), ATT (32.3%) and 32.1% in those with chronic markers (P < 0.001). Conclusions: HEV is an important cause of ALF and, among the different viral etiologies it is associated with a better survival rate. Corresponding author: Subrat K. Acharya. Email: [email protected]
Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India Background and Aims: Acute on chronic liver failure (ACLF) is a new entity which pertains to acute deterioration of underlying chronic liver disease by an inciting cause. Here, we aimed to study organ failure in patients of acute decompensation of cirrhosis and mortality of patients diagnosed as ACLF versus non ACLF groups. Methods: Consecutive patients of cirrhosis presenting in acute decompensation were prospectively studied. Based on CANONIC study criteria, patients were grouped into ACLF and no ACLF groups and grading of ACLF was done according to number and type of organ failure (Gastroenterology 2013; 144:1426-37). Mortality rates among various grades of ACLF were determined and various prognostic scores for mortality were compared. Results: Out of 50 patients with cirrhosis of liver and acute decompensation, 38 (76%) had ACLF and 12 (24%) had no ACLF. Males (86%) were predominant and alcoholic liver disease (68%) was the most common etiology of cirrhosis
COMPARISON OF CLIF-SOFA WITH OTHER PROGNOSTIC SCORES IN DETERMINING THE IN-HOSPITAL MORTALITY IN PATIENTS WITH ACUTE ON CHRONIC LIVER FAILURE Ajay Duseja, Swastik Agrawal, Tarana Gupta, Radha Krishan Dhiman, Yogesh Chawla Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India Background and Aims: Recently the CANONIC study proposed the CLIF-SOFA score to grade patients by organ failure and increasing mortality in acute decompensation of cirrhosis. We compared the CLIF-SOFA score with established scores for predicting the in-hospital mortality in patients with ACLF diagnosed as per the APASL criteria. Patients and Methods: Eighty consecutive patients of ACLF were included prospectively over a period of two years (2012–2013). The diagnosis of ACLF was based on
Journal of Clinical and Experimental Hepatology | March 2014 | Vol. 4 | No. S2 | S1–S5
S3
ALF and ACLF
JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY
Department of Medicine, Maulana Azad Medical College, New Delhi, India
ALF and ACLF
Introduction: Cell death markers, caspase-cleaved [CK18 (M30)] and total cytokeratin [CK-18 (M65)] indicate the extent and relative proportions of apoptotic and necrotic cell death in acute liver failure (ALF) patients. Serum levels of apoptotic biomarkers [CK 18 (M30 and M 65)] are expected to be elevated in ALF compared to controls and these biomarkers may be linked to outcome. Aims and Objectives: To assess whether the circulating apoptotic markers [CK 18 (M30 and M 65)] are altered in ALF and its correlation with disease outcome. Methodology: 40 cases of acute liver failure and 30 age and sex matched healthy controls were included in the study. The study population was divided into spontaneous survival and mortality groups. The serum levels of M30 and M65 were measured using commercially available ELISA kits as described by the manufacturer's instructions. The serum levels between the survival, mortality and healthy control groups were compared by ANOVA analysis (with post hoc Tukey's analysis) using SPSS (version 20). Results: 29 patients died and 11 patients survived. Serum levels of apoptotic biomarkers [CK 18 (M30 and M 65)] were significantly elevated in ALF compared to controls [7000 U/L vs 30 U/L; P < 0.001 for CK18 (M30) and 6000 U/L vs 40 U/L; P < 0.05 for CK 18 (M65)]. The levels of total CK18 (M65) are significantly higher in non-survivors compared to survivors (10000 U/L vs. 4000 U/L; P < 0.05) and the levels of cleaved CK 18 (M30) are significantly higher in non-survivors compared to the survivor group (8700 U/L vs. 3000; P < 0.05) suggesting increased caspase activation and cell death. The findings from this study indicate the role ofM30 and M65 as predictive markers in ALF. Conclusion: The findings from this study establish the role of serum apoptosis markers M30 and M65 as prognostic markers in patients with acute liver failure which can be used as a guide for management of the patients in the near future. Corresponding author: Premashis Kar. Email: [email protected]
POLYMORPHISM AND EXPRESSION OF HSP70 GENE IN ACUTE VIRAL HEPATITIS AND FULMINANT HEPATIC FAILURE AND ITS CLINICAL RELEVANCE Premashis Kar*, Ujjwal Sonika*, Rajib Hazam*, Bhudev C. Dasy
S2
22ND ANNUAL CONFERENCE–2014
*
Department of Medicine, Maulana Azad Medical College, New Delhi, India and †Department of Biotechnology , Dr. B R Ambedkar Center for Biomedical Research, New Delhi, India
Background and Aims: To study the Polymorphism and expression of HSP70 gene in patients of fulminant hepatic failure (FHF) and acute viral hepatitis (AVH); and to evaluate whether quantification of HSP70 protein at admission could predict the outcome of disease. Methods: 43 patients with FHF and 45 patients with AVH were included in the study. HSP70 expression was measured at admission by quantification of HSP70 protein using ELISA and gene polymorphism was studied by PCR RFLP method. Results: The mean HSP70 protein levels were significantly higher (47.17 26.34) in FHF as compared to AVH (19.74 8.50) and Controls (8.31 5.30); P < 0.01. The b1b1 genotype of HSP70-1 was found significantly less commonly in AVH and b1b2 more frequently in FHF compared to controls (P < 0.05). Genotype b2b2 was decreased in FHF as compared to AVH (P < 0.05). The b2 allele of HSP70-1 was found significantly increased in AVH (P < 0.05). Genotype AA and BB of HSP70-2 were found respectively less and more commonly in AVH group (P < 0.05). AB genotype was increased in FHF as compared to AVH group. Allele B of HSP70-2was associated with increased risk of AVH.AA, AB and BB genotypes of HSP70-hom gene did not show significant difference among various groups. Allele B of HSP70-homgene was associated with less severe liver injury in patients with hepatitis (OR 0.2, 95% CL 0.040.77). Conclusion: HSP70 gene expression and polymorphism may play an important role in susceptibility to AVH and FHF and may also predict the severity of disease. Corresponding author: Premashis Kar. Email: [email protected]
HEPATITIS E VIRUS INFECTION IS ASSOCIATED WITH BETTER SURVIVAL IN ACUTE LIVER FAILURE Subrat K. Acharya, S. Shalimar, Hanish Sharma, Sreejith Vasudevan, Saurabh Kedia, Praneeth Moka, Ujjwal Sonika Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India Background and Aims: Acute Liver Failure (ALF) is associated with a high mortality. The difference in outcomes
© 2014, INASL
CLIF-SOFA SCORE PREDICTS MORTALITY IN PATIENTS WITH ACUTE ON CHRONIC LIVER FAILURE
with active alcoholism present in 55.9% of patients. Sepsis (66%) was the most common cause of acute decompensation. ACLF patients were younger and had significantly higher INR, serum creatinine, Child-Pugh score, MELD, CLIF SOFA and APACHE II scores (P < 0.05). The 28-day mortality in patients with no ACLF (n = 12), ACLF grade 1 (n = 11), ACLF grade 2 (n = 14) and ACLF grade 3 (n = 13) were 8.3%, 18.2%, 42.9% and 76.9% (c2 for trend, P = 0.002) and 90-day mortality were 16.7%, 27.3%, 78.6% and 100% (c2 for trend, P < 0.0001) respectively. Nonsurvivors at 28 days irrespective of ACLF grade had significantly higher incidence of cerebral and renal failure, higher INR, Child-Pugh score, MELD, CLIF SOFA and APACHE II scores as compared to survivors (P < 0.05). Patients with prior decompensation had similar 28-day and 90-day mortality (39.3% and 53.6%) as patients without prior decompensation (36.4% and 63.6%) (P=NS). Area under curve for 28-day mortality was 0.795, 0.787, 0.739 and 0.710 for CLIF-SOFA, APACHE-II, Child-Pugh and MELD scores respectively. On multivariate analysis of these scores, CLIF-SOFA was the only significant independent predictor of mortality with an odds ratio 1.538 (95% CI: 1.078-2.194). Conclusion: Presence of organ failure predicts mortality in patients with cirrhosis with acute decompensation. With increasing grades of ACLF, there is increasing 28and 90-day mortality among various groups of ACLF. CLIF-SOFA score was the best predictor of mortality at 28 days. Patients with and without prior decompensation had similar 28-day and 90-day mortality.
Tarana Gupta, Swastik Agrawal, Ajay Duseja, Yogesh Chawla, Radha K. Dhiman
Corresponding author: Radha K. Dhiman. Email: [email protected]
between different etiologies is not clear. We analysed the outcomes of consecutive ALF patients admitted at a single tertiary-care centre over a period of 25 years. Methods: An analysis of the prospectively maintained database of ALF patients was performed to assess the effect of etiology on the outcome. Results: A total of 1347 patients were evaluated. Out of these 755 (56.1%) were females and 592 (43.9%) were males. The mean age SD was 28.4 11.7 years. Hepatitis A (1.2%), acute Hepatitis B (7.6%), Hepatitis E (29.0%), Non -A, Non-E (38.3%), dual infection (4.9%) and anti-tubercular therapy (4.8%) comprised different etiologies of ALF. Among 10.2% of patients only chronic markers were positive and no etiological data was available in 4% of patients. A total of 797 (59.2%) patients died. The survival among different etiologies was HAV (62.5%), acute HBV (32%), HEV (53.6%), Non-A, Non-E (37.9%), dual infection (30.3%), ATT (32.3%) and 32.1% in those with chronic markers (P < 0.001). Conclusions: HEV is an important cause of ALF and, among the different viral etiologies it is associated with a better survival rate. Corresponding author: Subrat K. Acharya. Email: [email protected]
Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India Background and Aims: Acute on chronic liver failure (ACLF) is a new entity which pertains to acute deterioration of underlying chronic liver disease by an inciting cause. Here, we aimed to study organ failure in patients of acute decompensation of cirrhosis and mortality of patients diagnosed as ACLF versus non ACLF groups. Methods: Consecutive patients of cirrhosis presenting in acute decompensation were prospectively studied. Based on CANONIC study criteria, patients were grouped into ACLF and no ACLF groups and grading of ACLF was done according to number and type of organ failure (Gastroenterology 2013; 144:1426-37). Mortality rates among various grades of ACLF were determined and various prognostic scores for mortality were compared. Results: Out of 50 patients with cirrhosis of liver and acute decompensation, 38 (76%) had ACLF and 12 (24%) had no ACLF. Males (86%) were predominant and alcoholic liver disease (68%) was the most common etiology of cirrhosis
COMPARISON OF CLIF-SOFA WITH OTHER PROGNOSTIC SCORES IN DETERMINING THE IN-HOSPITAL MORTALITY IN PATIENTS WITH ACUTE ON CHRONIC LIVER FAILURE Ajay Duseja, Swastik Agrawal, Tarana Gupta, Radha Krishan Dhiman, Yogesh Chawla Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India Background and Aims: Recently the CANONIC study proposed the CLIF-SOFA score to grade patients by organ failure and increasing mortality in acute decompensation of cirrhosis. We compared the CLIF-SOFA score with established scores for predicting the in-hospital mortality in patients with ACLF diagnosed as per the APASL criteria. Patients and Methods: Eighty consecutive patients of ACLF were included prospectively over a period of two years (2012–2013). The diagnosis of ACLF was based on
Journal of Clinical and Experimental Hepatology | March 2014 | Vol. 4 | No. S2 | S1–S5
S3
ALF and ACLF
JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY