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Alcoholic hepatitis [keywords]
- Serum lactonase and arylesterase activities in alcoholic hepatitis and hepatitis B. [JOURNAL ARTICLE]
- Indian J Gastroenterol 2013 May 23.
BACKGROUND:PON1 is an HDL-associated enzyme having antioxidant activity. PON1 is synthesized in the liver, and there is decreased synthesis of PON1 with increased lipid peroxidation. The study was carried with the aim of establishing whether chronic liver disease (CLD) produced any significant changes in serum arylesterase (AE) and lactonase activities of PON. The second objective was to determine whether there was any correlation between serum AE and lactonase activities and the various routine liver function tests. The usefulness of adding serum lactonase and AE activity to standard liver function tests was analyzed by multiple logistic regression analysis. Finally, the diagnostic efficacy or analytical performance of AE and lactonase in assessing patients with CLD was determined using 'receiver operating characteristic' (ROC) plot.
METHODS:The study group consisted of 120 subjects; 60 were patients with liver disease out of which 40 were having chronic alcoholic liver disease and 20, acute viral hepatitis B, and 60 were healthy controls. Serum PON1 lactonase activity was measured manually using dihydrocoumarin, and AE activity was measured using phenylacetate as substrate. Liver function tests (bilirubin, albumin, AST, ALT, alkaline phosphatise) were done by standard technique.
RESULT:The serum lactonase and AE activities were decreased significantly in patients with chronic alcoholic liver disease (p < 0.001, p < 0.001) and acute viral hepatitis B (p < 0.001, p < 0.001). Both measurements showed higher efficiency in testing liver dysfunction in multivariate regression analysis. Model 1 consisted of bilirubin, albumin, AST, ALT, and alkaline phosphatase, R2 = 0.912. Model 2 consisted of model 1+arylesterase having higher R2 = 0.0.954, and model 3 consisted of model 1+lactonase having R2 = 0.962. ROC plots demonstrated a high diagnostic accuracy for serum PON1 lactonase (area under ROC curve = 0.982) and serum PON1 arylesterase (area under ROC curve = 0.986).
CONCLUSION:Low PON1 lactonase and AE activity were found in acute viral hepatitis B and in chronic alcoholic hepatitis.
- Intra-operative hypercoagulability during liver transplantation as demonstrated by thromboelastography. [JOURNAL ARTICLE]
- Liver Transpl 2013 May 21.
Thrombotic complications are more common in liver disease than might be expected given the coagulopathy described by conventional coagulation tests. Some of these complications may be life-threatening. The phenomenon of hypercoagulation is associated with complications in many populations, but the incidence in liver transplant recipients is unclear. A retrospective database review of intra-operative thromboelastography (TEG) for 124 liver transplant recipients. We assessed the prevalence of hypercoagulation in this group, and investigated the relative frequency of both shortened TEG r-time and increased G value. These findings were correlated with thrombotic complications. At baseline, the prevalence of high G values was 15.5% on native TEG and shortened r-times 6% on heparinase TEG. Cholestatic pathologies had a particularly high incidence of hypercoagulation; 43% (PBC) and 85% (PSC), but it was also common in fulminant hepatic failure and non-alcoholic steato-hepatitis (50% and 37.5%). There was poor correlation between TEG r-time and INR, with 30% of TEGs demonstrating a short r-time having an INR >2. 6 of the patients developed early hepatic artery thrombosis (5%), of whom 3 had TEG evidence of high G value, (p=0.25) and 4 had short r-times (NS). Intra-operative thromboelastographic evidence of high G values and short r-times is relatively common in liver transplantation. It is unclear what bearing this condition has on thrombotic complications. Conventional coagulation tests have no ability to diagnose this condition. It is conceivable that such patients may come to harm if hypercoagulability is unrecognised and therefore inappropriately managed. Liver Transpl, 2013. © 2013 AASLD.
- The effect of hepatitis B virus infection on hepcidin expression in hepatitis B patients. [Journal Article]
- Ann Clin Lab Sci 2013; 43(2):126-34.
Background Hepcidin is a central regulator of iron metabolism. As hepcidin is produced mainly by hepatocytes, pathologic changes in the liver may affect hepcidin production. Abnormal hepcidin expression has been reported following liver injury, including liver cirrhosis, alcoholic liver disease, and chronic hepatitis B and hepatitis C. However, it is unclear whether there is a dose-dependent relationship between hepcidin expression and hepatitis B virus load. The aim of this study was to characterize hepcidin levels in patients with different hepatitis B virus (HBV) DNA levels. Methods We investigated serum hepcidin levels in 71 patients with different HBV DNA loads, 10 patients with hepatocelluar carcinoma (HCC), and 13 healthy individuals. The relationships between hepcidin expression and hematological/liver functional parameters, iron, and inflammatory indicators were also analyzed. Results Serum IL-6, ferritin, and hepcidin levels were significantly higher in patients with hepatitis B and in HCC patients than in controls (P<0.05), and strong positive correlations were found between hepcidin and ferritin, AST, ALT, GGT, ALP, TBIL, IBIL, and AFU, as well as between log [hepcidin] and log [HBV], respectively. There were no significant differences in hematological parameters, including WBC, Hb, and platelets among hepatitis B patients, nor was a correlation found between hepcidin and any hematological parameters. Conclusion Our results indicate that hepcidin expression is regulated by iron and inflammatory factors in hepatitis B infection patients, and that the virus load can affect hepcidin production.
- 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). [JOURNAL ARTICLE]
- J Dig Dis 2013 May 21.
OBJECTIVE:The aim of the study was to assess the performance of various prognostic scores including acute physiology and chronic health evaluation (APACHE II), sequential organ failure assessment (SOFA), Child-Turcotte-Pugh (CTP) and model for end stage liver disease (MELD) in predicting the short-term mortality in patients with acute-on-chronic liver failure (ACLF).
METHODS:One hundred consecutive patients with ACLF were evaluated prospectively. The diagnosis of ACLF was based on the Asian-Pacific Association for the Study of the Liver criteria except for the inclusion of non-hepatic insults as acute events. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for predicting short-term mortality was calculated for APACHE II, SOFA, CTP and MELD in all patients and Maddrey's discriminant function (DF) and Glasgow alcoholic hepatitis scores (GAHS) for patients with alcoholic hepatitis only.
RESULTS:A majority of patients had alcohol-related cirrhosis and alcoholic hepatitis as the acute insults for ACLF. Fifty-three patients either died or left hospital in very sick status and were confirmed to be dead the same day after leaving the hospital. Overall, the area under the receiver operating characteristic curve (AUROC) of APACHE II was higher than those of MELD, SOFA and CTP scores for predicting short-term mortality. Even for patients with alcoholic hepatitis, APACHE II performed better than DF and GAHS.
CONCLUSION:The short-term mortality is high in patients with ACLF, and APACHE II scoring system is superior to other prognostic scores in predicting its short-term mortality.
- Viral genotypes and associated risk factors of hepatocellular carcinoma in India. [Journal Article]
- Cancer Biol Med 2012 Sep; 9(3):172-81.
This study aims to investigate the etiological relationship among hepatitis B virus (HBV), hepatitis C virus (HCV), and alcohol as risk factors in a cohort of hepatocellular carcinoma (HCC) patients from India. The clinical and biochemical profiles and tumor characteristics in the HCC cases were also evaluated.A total of 357 consecutive cases of HCC fulfilling the diagnostic criteria from the Barcelona-2000 EASL conference were included in the study. The blood samples were evaluated for serological evidence of HBV and HCV infection, viral load, and genotypes using serological tests, reverse transcription-polymerase chain reaction, and restriction fragment length polymorphism.The male/female ratio for the HCC cases was 5.87:1. Majority of the HCC patients (33.9%) were 50 to 59 years of age, with a mean age of 4±13.23 years. More than half the cases (60.8%) had underlying cirrhosis at presentation. Among the HCC patients, 68.9% were HBV related, 21.3% were HCV related, 18.8% were alcoholic, and 18.2% were of cryptogenic origin. The presence of any marker positive for HBV increased the risk for developing HCC by almost 27 times [OR: 27.33; (12.87-60.0)]. An increased risk of 10.6 times was observed for HCC development for cases positive for any HCV marker [OR: 10.55; (3.13-42.73)]. Heavy alcohol consumption along with HCV RNA positivity in cirrhotic patients was found to be a risk for developing HCC by 3 folds [OR: 3.17; (0.37-70.71)].Patients of chronic HBV infection followed by chronic HCV infection were at higher risk of developing HCC in India. Chronic alcohol consumption was found to be a risk factor in cirrhotic cases only when it was associated with HCV RNA positivity. Most of the patients had a large tumor size (>5 cm) with multiple liver nodules, indicating an advanced stage of the disease thus making curative therapies difficult.
- Prevalence of Hepatitis C Virus Infection in Alcoholic Patients: Cohort Study and Systematic Review. [JOURNAL ARTICLE]
- Alcohol Alcohol 2013 May 19.
AIMS:Prevalence of chronic hepatitis C virus (HCV) infection among alcoholics is thought to be higher than in the general population, although prevalence rates reported are quite variable. Our study is aimed to analyze HCV prevalence in a cohort of alcoholics and to perform a systematic review on this topic.
PATIENTS AND METHODS:A total of 396 alcoholic patients consecutively referred to our Alcoholism Unit were included. HCV infection status and other clinical variables were recorded for each patient. Variables associated with HCV infection were analyzed by means of logistic regression. Additionally, we performed a systematic review focused on previous studies on this topic.
RESULTS:Among our alcoholic patients, 14 of them (3.53%) had chronic HCV infection. Variables independently associated with HCV infection were female gender, injection drug use (IDU) and the presence of alcoholic liver disease (ALD). Twenty-four studies analyzing HCV prevalence in alcoholic patients were included in our systematic review, showing prevalence rates of HCV infection ranging from 2.1 to 51% and an average weighted prevalence of 16.32%.
CONCLUSION:In our series, the prevalence rate of chronic HCV infection among alcoholic patients is lower than previously reported, which is probably explained by the relatively low number of patients with ALD or IDU in our sample. Prevalence rates previously published are quite different and the presence of ALD and/or IDU can act as confounding factors for HCV prevalence among alcoholics.
- Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma. [Journal Article]
- World J Gastroenterol 2013 Apr 28; 19(16):2449-55.
Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5' and 3' flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the data in the literature on the genetic association between the -174 G/C polymorphism and some specific liver diseases characterized by different etiologies are still controversial. In particular, most of the studies are quite unanimous in describing a correlation between the presence of the high-producer genotype and a worse evolution of the chronic liver disease. This is valid for patients with hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis and hepatocellular carcinoma (HCC) whatever the etiology. Studies in hepatitis B virus-related chronic liver diseases are not conclusive, while specific populations like non alcoholic fatty liver disease/non-alcoholic steatohepatitis, autoimmune and human immunodeficiency virus/HCV co-infected patients show a higher prevalence of the low-producer genotype, probably due to the complexity of these clinical pictures. In this direction, a systematic revision of these data should shed more light on the role of this polymorphism in chronic liver diseases and HCC.
- Semisynthesis, cytotoxicity, antiviral activity, and drug interaction liability of 7-O-methylated analogues of flavonolignans from milk thistle. [JOURNAL ARTICLE]
- Bioorg Med Chem 2013 Apr 16.
Silymarin, an extract of the seeds of milk thistle (Silybum marianum), is used as an herbal remedy, particularly for hepatoprotection. The main chemical constituents in silymarin are seven flavonolignans. Recent studies explored the non-selective methylation of one flavonolignan, silybin B, and then tested those analogues for cytotoxicity and inhibition of both cytochrome P450 (CYP) 2C9 activity in human liver microsomes and hepatitis C virus infection in a human hepatoma (Huh7.5.1) cell line. In general, enhanced bioactivity was observed with the analogues. To further probe the biological consequences of methylation of the seven major flavonolignans, a series of 7-O-methylflavonolignans were generated. Optimization of the reaction conditions permitted selective methylation at the phenol in the 7-position in the presence of each metabolite's 4-5 other phenolic and/or alcoholic positions without the use of protecting groups. These 7-O-methylated analogues, in parallel with the corresponding parent compounds, were evaluated for cytotoxicity against Huh7.5.1 cells; in all cases the monomethylated analogues were more cytotoxic than the parent compounds. Moreover, parent compounds that were relatively non-toxic and inactive or weak inhibitors of hepatitis C virus infection had enhanced cytotoxicity and anti-HCV activity upon 7-O-methylation. Also, the compounds were tested for inhibition of major drug metabolizing enzymes (CYP2C9, CYP3A4/5, UDP-glucuronsyltransferases) in pooled human liver or intestinal microsomes. Methylation of flavonolignans differentially modified inhibitory potency, with compounds demonstrating both increased and decreased potency depending upon the compound tested and the enzyme system investigated. In total, these data indicated that monomethylation modulates the cytotoxic, antiviral, and drug interaction potential of silymarin flavonolignans.
- Management practices of hepatitis C virus infected alcoholic hepatitis patients: A survey of physicians. [Journal Article]
- World J Gastrointest Pharmacol Ther 2013 May 6; 4(2):16-22.
To survey gastroenterologists and hepatologists regarding their current views on treating hepatitis C virus (HCV) infected alcoholic hepatitis (AH) patients.A sixteen item questionnaire was electronically mailed to gastroenterologists and hepatologists. A reminder was sent after 2 mo to increase the response rate. Participation of respondents was confidential. Accessing secured web site to respond to the questionnaire was considered as informed consent. Responses received on the secured website were downloaded in an excel sheet for data analysis.Analyzing 416 responses to 1556 (27% response rate) emails, 57% respondents (56% gastroenterologists) reported HCV prevalence > 20% amongst AH patients. Sixty nine percent often treated AH and 46% preferred corticosteroids (CS). Proportion of respondents with consensus (75% or more respondents agreeing on question) on specific management of HCV infected AH were: routine HCV testing (94%), HCV not changing response to CS (80%) or pentoxifylline (91%), no change in approach to treating HCV infected AH (75%). None of respondent variables: age, specialty, annual number of patients seen, and HCV prevalence could predict respondent to be in consensus on any of or all 4 questions. Further, only 4% would choose CS for treating HCV infected AH as opposed to 47% while treating HCV negative AH.Gastroenterologists and hepatologists believe that AH patients be routinely checked for HCV. However, there is lack of consensus on choice of drug for treatment and outcome of HCV positive AH patients. Studies are needed to develop guidelines for management of HCV infected AH patients.
- Liver progenitor cells and therapeutic potential of stem cells in human chronic liver diseases. [Journal Article]
- Acta Gastroenterol Belg 2013 Mar; 76(1):3-9.
Liver progenitor cells, thought to reside in the terminal bile ductules (canals of Hering) at the interface between portal tracts and liver lobule, proliferate during severe hepatic injury. They may contribute to hepatocyte regeneration, or even take over this role if the liver injury is severe and associated with an impairment of hepatocyte proliferation. They represent promising targets in an attempt to stimulate liver regeneration in chronic diseases. Recent studies on liver progenitor cell recruitment in response to injury in chronic viral hepatitis B, hepatitis C, alcoholic and non-alcoholic liver diseases are presented in this review, as well as clinical trials in which stem cells are administered as a therapeutic intervention to promote liver regeneration. Liver progenitor cell expansion is part of the disease process itself and may contribute to disease severity, mainly related to fibrosis. As the majority of these progenitor cells tend to acquire a biliary phenotype, their role in liver repair and improvement in liver function remains to be addressed. Present data on stem cell therapy are heterogeneous in terms of methods and endpoints; thus, results need to be carefully examined prior to drawing a conclusion on possible benefits.