Etiology Of Chronic Liver Disease Research Articles

Etiology of chronic liver disease and HCC biomarkers

Etiology of chronic liver disease and HCC biomarkers

Nonalcoholic Fatty Liver Disease: Key Considerations Before and After Liver Transplantation.

Nonalcoholic fatty liver disease (NAFLD) is the most common etiology of chronic liver disease in developed countries and is on trajectory to become the leading indication for liver transplantation in the USA and much of the world. Patients with NAFLD cirrhosis awaiting liver transplant face unique challenges and increased risk for waiting list stagnation and dropout due to burdensome comorbidities including obesity, diabetes, cardiovascular disease, and kidney disease. Thus far, patients transplanted for NAFLD cirrhosis have excellent mid- and long-term patient and graft survival, but concerns regarding short-term morbidity and mortality continue to exist. Post-liver transplantation, NAFLD occurs as both a recurrent and de novo manifestation, each with unique outcomes. NAFLD in the donor population is of concern given the growing demand for liver transplantation and mounting pressure to expand the donor pool. This review addresses key issues surrounding NAFLD as an indication for transplantation, including its increasing prevalence, unique patient demographics, outcomes related to liver transplantation, development of post-liver transplantation NAFLD, and NAFLD in the liver donor population. It also highlights exciting areas where further research is needed, such as the role of bariatric surgery and preconditioning of marginal donor grafts.

Etiology of chronic liver diseases in the Northwest of Italy, 1998 through 2014.

AIMTo assess the etiology of chronic liver diseases (CLD) from 1998 to 2014 at the outpatient clinic of Gastroenterology of the main hospital in Northwest of Italy among those dedicated to hepatology.METHODSA random sample of charts of patients referred to for increased liver enzymes between January 1998 and December 2006, and between January 2012 and December 2014 were reviewed. Etiology search included testing for hepatitis B virus (HBV), hepatitis C virus (HCV), autoimmune hepatitis, primary biliary cirrhosis, Wilson’s disease and hereditary hemocromatosis. A risky alcohol consumption was also considered. Non-alcoholic fatty liver disease (NAFLD) was diagnosed in patients with histological and/or ultrasound evidence of steatosis/steatohepatitis, and without other causes of CLD.RESULTSThe number of patients included was 1163. Of them, 528 (45%) had positivity for HCV and 85 (7%) for HBV. Among the virus-free patients, 417 (36%) had metabolic disorders whereas the remaining had history of alcohol abuse, less prevalent causes of CLD or concomitant conditions. In comparison to 1998-2000 (41%), a reduction of HCV alone-related cases was detected during the periods 2001-2003 (35%, OR = 0.75, 95%CI: 0.53-1.06), 2004-2006 (33%, OR = 0.70, 95%CI: 0.50-0.97) and 2012-2014 (31%, OR = 0.64, 95%CI: 0.46-0.91). On the contrary, in comparison to 1998-2000 (31%), metabolic-alone disorders increased in the period 2004-2006 (39%, OR = 1.37, 95%CI: 0.99-1.91) and 2012-2014 (41%, OR = 1.53, 95%CI: 1.09-2.16). The other etiologies remained stable. The increase of incidence of metabolic-alone etiology during the period 2004-2006 and 2012-2014 tended to be higher in older patients (≥ 50 years) compared to younger (P = 0.058).CONCLUSIONIn the Northwest of Italy, during this study period, the prevalence of HCV infection decreased notably whereas that of NAFLD increased.

Nonalcoholic Fatty Liver Disease: Epidemiology, Pathogenesis, Natural History, Diagnosis, and Current Treatment Options.

Nonalcoholic fatty liver disease (NAFLD) is on the rise and has become a major etiology for chronic liver disease. It is frequently associated with obesity, insulin resistance, hypertension, and dyslipidemia and is considered the hepatic manifestation of metabolic syndrome. In this review, we present a summary of the epidemiology and pathogenesis of NAFLD, and discuss the clinical evaluation and stratification of NAFLD patients into low, intermediate, and high risk with respect to liver-related outcomes. While diet and exercise are the cornerstone of treatment in all patients, the low rate of adherence and inadequacy of these recommendations necessitate pharmacologic intervention, especially in intermediate- and high-risk patients. We discuss vitamin E and pioglitazone which are often used as first-line therapy by many practitioners, with pentoxifylline and liraglutide as backup agents. Several drugs are in advanced-phase clinical trials and will likely change the landscape for management of NAFLD in the very near future.

Can paracetamol (acetaminophen) be administered to patients with liver impairment?

Although 60 years have passed since it became widely available on the therapeutic market, paracetamol dosage in patients with liver disease remains a controversial subject. Fulminant hepatic failure has been a well documented consequence of paracetamol overdose since its introduction, while short and long term use have both been associated with elevation of liver transaminases, a surrogate marker for acute liver injury. From these reports it has been assumed that paracetamol use should be restricted or the dosage reduced in patients with chronic liver disease. We review the factors that have been purported to increase risk of hepatocellular injury from paracetamol and the pharmacokinetic alterations in different pathologies of chronic liver disease which may affect this risk. We postulate that inadvertent under-dosing may result in concentrations too low to enable efficacy. Specific research to improve the evidence base for prescribing paracetamol in patients with different aetiologies of chronic liver disease is needed.

Combined use of AFP, PIVKA-II, and AFP-L3 as tumor markers enhances diagnostic accuracy for hepatocellular carcinoma in cirrhotic patients

Objective: As data on the effectiveness of tumor markers in detecting hepatocellular carcinoma (HCC) in cirrhotic patients are limited, we investigated the diagnostic accuracy of alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-II (PIVKA-II), and Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3). Material and methods: This retrospective study enrolled 361 cirrhotic patients with HCC, and 276 cirrhotic patients without HCC occurrence. Results: Most patients were men (n = 431, 67.7%); the median age was 57.0 years. The main etiology of chronic liver disease was chronic hepatitis B (n = 467, 73.3%). The sensitivity and specificity of combined three biomarkers was 87.0 and 60.1% in overall HCC, and 75.7 and 60.1% in early HCC, respectively (cutoff: 20 ng/mL for AFP, 40 mAU/mL for PIVKA-II, and 5% for AFP-L3). The area under the receiver operating characteristic curve (AUROC) for HCC diagnosis was 0.765 (95% confidence interval [CI], 0.728–0.801) for AFP; 0.823 (95% CI, 0.791–0.854) for PIVKA-II; and 0.755 (95% CI, 0.718–0.792) for AFP-L3. The AUROC for early HCC diagnosis was 0.754 (95% CI, 0.691–0.816) for AFP, 0.701 (95% CI, 0.630–0.771) for PIVKA-II, and 0.670 (95% CI, 0.596–0.744) for AFP-L3. Combining the three tumor markers increased the AUROC to 0.877 (95% CI, 0.851–0.903) for HCC diagnosis, and 0.773 (95% CI, 0.704–0.841) for early HCC diagnosis. Conclusion: Diagnostic accuracy improved upon combining the AFP, PIVKA-II, and AFP-L3 tumor markers compared to each marker alone in detecting HCC and early HCC in cirrhotic patients.

ER stress induces NLRP3 inflammasome activation and hepatocyte death.

The incidence of chronic liver disease is constantly increasing, owing to the obesity epidemic. However, the causes and mechanisms of inflammation-mediated liver damage remain poorly understood. Endoplasmic reticulum (ER) stress is an initiator of cell death and inflammatory mechanisms. Although obesity induces ER stress, the interplay between hepatic ER stress, NLRP3 inflammasome activation and hepatocyte death signaling has not yet been explored during the etiology of chronic liver diseases. Steatosis is a common disorder affecting obese patients; moreover, 25% of these patients develop steatohepatitis with an inherent risk for progression to hepatocarcinoma. Increased plasma LPS levels have been detected in the serum of patients with steatohepatitis. We hypothesized that, as a consequence of increased plasma LPS, ER stress could be induced and lead to NLRP3 inflammasome activation and hepatocyte death associated with steatohepatitis progression. In livers from obese mice, administration of LPS or tunicamycin results in IRE1α and PERK activation, leading to the overexpression of CHOP. This, in turn, activates the NLRP3 inflammasome, subsequently initiating hepatocyte pyroptosis (caspase-1, -11, interleukin-1β secretion) and apoptosis (caspase-3, BH3-only proteins). In contrast, the LPS challenge is blocked by the ER stress inhibitor TUDCA, resulting in: CHOP downregulation, reduced caspase-1, caspase-11, caspase-3 activities, lowered interleukin-1β secretion and rescue from cell death. The central role of CHOP in mediating the activation of proinflammatory caspases and cell death was characterized by performing knockdown experiments in primary mouse hepatocytes. Finally, the analysis of human steatohepatitis liver biopsies showed a correlation between the upregulation of inflammasome and ER stress markers, as well as liver injury. We demonstrate here that ER stress leads to hepatic NLRP3 inflammasome pyroptotic death, thus contributing as a novel mechanism of inflammation-mediated liver injury in chronic liver diseases. Inhibition of ER-dependent inflammasome activation and cell death pathways may represent a potential therapeutic approach in chronic liver diseases.

Integrative Review of Co-Occurring Symptoms Across Etiologies of Chronic Liver Disease and Implications for Symptom Management Research and Practice.

Chronic liver disease affects over 30 million people worldwide, and despite advances in medical management that have increased survival, a majority of these individuals report multiple symptoms that severely impair function and quality of life. The purpose of this integrative review was to examine and summarize the current literature focused on self-reported symptoms in individuals with chronic liver disease in order to inform the development and delivery of symptom management strategies in clinical practice. Combinations of search terms related to the symptom experience were used to search three electronic databases. Inclusion criteria were empirical studies that measured self-reported symptoms in populations with chronic liver disease published in English between 2003 and 2014. The literature search initially yielded 112 results; 26 quantitative studies met the inclusion criteria. The symptom of fatigue was commonly reported across chronic liver disease populations and was often found to co-occur with other distressing symptoms, including depression, sleep disturbance, pain, cognitive impairment, and dizziness associated with autonomic dysfunction. Due to the high prevalence and persistence of these "core" symptoms, the use of core symptom measures integrated longitudinally across populations would inform the development and delivery of symptom management interventions as well as enhance the ability of nurses to incorporate population-level symptom management programs. Nurses play an important role in symptom assessment and may use the findings from the integrative review to incorporate core symptom measures across chronic liver disease populations and advance the development and delivery of symptom management interventions.

PWE-124 Role of acoustic radiation force impulse (arfi) elastography in non-invasive assessment of liver fibrosis in iron overload: a single centre experience

Introduction The predictive accuracy of ARFI elastography (virtual touch quantification, VTq ™) for the non-invasive assessment of liver fibrosis is increasingly recognised, particularly in viral hepatitis. There is less information on its role in other aetiologies of chronic liver disease. We report the results of a preliminary study examining liver stiffness (LS) measurements by ARFI in patients with iron overload. Method Forty-nine measurements of LS in 43 patients were performed to investigate possible iron overload. LS estimation by ARFI was performed using a standard validated protocol with a Siemens Acuson S2000 + 4C1 probe. Biopsies were performed in 19 (39%) from the same region of liver, immediately after LS measurement. Clinical, biochemical, ultrasonic and histopathological data were collated retrospectively. Predictive accuracy variables were determined for fibrosis stage, using both standard published and local 1 calibrations. Results Aetiologies of iron overload in the biopsy cohort were: genetic haemochromatosis (n = 4); hyperferritinaemia with NAFLD or alcohol excess (8); hyperferritinaemia of unknown cause (3); transfusion-dependent thalassaemia (2); C282Y/H63D compound heterozygote (1); and high ferritin from renal cell carcinoma (1). Validation criteria for ARFI technical quality (SD/mean 1 ; b) the exclusion of ≥F2 fibrosis were 0.80, 0.78, 0.80 and 0.78, respectively, with both calibrations. No correlation was seen between LS and either a) necro-inflammation, histological grade of siderosis or scan technical quality; or b) serum ferritin levels. Conclusion ARFI elastography may prove a useful non-invasive technique for excluding F2 fibrosis and identifying F4 cirrhosis secondary to iron overload. The high incidence of dual pathology, particularly NAFLD and alcohol-related, may have influenced predictive accuracy in this small “real world” cohort. The degree of hepatic iron overload did not correlate with LS. Further biopsy-controlled studies are needed to validate the role of ARFI in this patient group. Disclosure of interest None Declared. Reference Sherman D, et al . J Hepatol. 2014;60(1):S413

Noninvasive Testing for NASH and NASH with Advanced Fibrosis: Are We There Yet?

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent etiology of chronic liver disease in America. NAFLD can be broadly classified in two subtypes: nonalcoholic fatty liver (NAFL), which is generally considered a benign condition with negligible risk of progression to cirrhosis, and nonalcoholic steatohepatitis (NASH), which is generally considered to be progressive with substantial risk of progression to cirrhosis. Additionally, recent studies suggest the odds of liver mortality increases amongst NASH patients with advanced fibrosis (bridging fibrosis ± cirrhosis). Liver biopsy examination is the current gold standard to accurately discriminate between NAFL vs. NASH as well as diagnose advanced fibrosis. However, due to its invasive nature, risk of bleeding (and even rarely death), prohibitive cost, and sampling error, liver biopsies are imperfect for diagnosis and monitoring of NAFLD. As a result, noninvasive biomarkers that can accurately detect NASH and advanced fibrosis without biopsy are needed. This article will discuss the most novel noninvasive biomarkers in diagnosing NASH and advanced fibrosis.

Occult hepatitis B infection in children with chronic liver disease.

Occult hepatitis B infection (OBI) may adversely affect the outcome of patients with chronic liver disease (CLD). There are no data on OBI and CLD in children. This study determined the prevalence and effect of OBI in HBsAg-negative CLD children. CLD children were prospectively evaluated with a demographic, clinical, and investigative proforma. All HBsAg-negative CLD cases were tested for exposure to hepatitis B (total anti-HBc, anti-HBs). Serum hepatitis B virus DNA was measured in exposed (total anti-HBc positive) patients. A total of 115 HBsAg-negative CLD children (59 boys, age 9.0±3.6 years) were enrolled. The etiology of CLD was known in 94 cases and 21 children had cryptogenic CLD. Of these, 45 (39.1%) had evidence of HBV exposure (23 total anti-HBc positive, 17 total anti-HBc and anti-HBs positive, five only anti-HBs positive without previous vaccination). The anti-HBc-positive children had a higher Child's score than the anti-HBc-negative children [11 (5-13) vs. 7 (5-13); P=0.00]. A total of 4/45 children had seropositive OBI with serum HBV DNA of 8, 36, 133, and 156 IU/ml, respectively. The proportion of total anti-HBc positivity (8/21 vs. 32/94; P=0.8) and OBI (2/21 vs. 2/94; P=0.1) was similar in cryptogenic CLD and known cause CLD. Seropositive OBI is infrequent in Indian children with CLD. The prevalence is similar in cryptogenic and CLD of known etiology.

Long-term outcomes after hospitalization with spontaneous bacterial peritonitis.

To assess the determinants of long-term outcome in patients with spontaneous bacterial peritonitis (SBP). This study was conducted retrospectively. Kaplan-Meier (KM) and Cox proportional hazards survival analyses were performed. Altogether, 93 patients with SBP were identified, with their mean age of 57.9 ± 12.9 years, Child-Pugh score 10.4 ± 1.9 and model for end-stage liver disease (MELD) score 20.2 ± 6.8. The etiology of chronic liver disease (CLD) was alcohol-related liver disease (ARLD) (n = 58) and viral hepatitis/non-alcoholic steatohepatitis (n = 28). SBP was the index presentation of cirrhosis in 26 (28.0%) patients. Overall mortality was 80.6%; among them 81.3% were liver-related, and 33 (35.5%) died during index hospitalization. In total, 70.0% of patients who survived index hospitalization died during follow-up, with a median survival of 12.5 months. Estimated survival at 3 months, 1 year and 5 years was 54.8%, 34.4% and 15.2%, respectively. Non-ARLD etiology for CLD was an independent predictor of overall mortality (HR 3.484, 95% CI 1.802-6.757, P < 0.001) and mortality in those surviving hospitalization (HR 2.319, 95% CI 1.210-4.444, P = 0.011). Hepatorenal syndrome did not predict outcomes. Two (3.3%) patients surviving hospitalization underwent liver transplantation (LT). One-year survival after hospitalization with SBP remains poor (34.4%) with unacceptably low LT rates. Non-ARLD etiology for CLD is an independent predictor of both overall mortality and mortality after discharge. In view of the projected increase in non-alcoholic steatohepatitis-related CLD, screening strategies for timely CLD diagnosis are warranted.

Using serum α-fetoprotein for prognostic prediction in patients with hepatocellular carcinoma: what is the most optimal cutoff?

Background and AimsThe prognostic ability of α-fetoprotein (AFP) for patients with hepatocellular carcinoma (HCC) was examined by using different cutoff values. The optimal AFP cutoff level is still unclear.MethodsA total of 2579 HCC patients were consecutively enrolled in Taiwan, where hepatitis B is the major etiology of chronic liver disease. Four frequently used AFP cutoff levels, 20, 200, 400, 1000 ng/mL, were investigated. One-to-one matched pairs between patients having AFP higher and lower than the cutoffs were selected by using the propensity model. The adjusted hazard ratios of survival difference were calculated with Cox proportional hazards model.ResultsPatients with a higher AFP level were associated with more severe cirrhosis, more frequent vascular invasion, higher tumor burden and poorer performance status (all p<0.0001). In the propensity model, 4 groups of paired patients were selected, and there was no difference found in the comparison of baseline characteristics (all p>0.05). Patients with AFP <20 ng/mL had significantly better long-term survival than patients with AFP ≧20 ng/mL (p<0.0001), and patients with AFP <400 ng/mL had significantly better overall outcome than patients with AFP ≧400 ng/mL (p = 0.0186). There was no difference of long-term survival between patients divided by AFP levels of 200 and 1000 ng/mL. The adjusted hazard ratios of AFP ≧20 ng/mL and AFP ≧400 ng/mL were 1.545 and 1.471 (95% confidence interval: 1.3–1.838 and 1.178–1.837), respectively.ConclusionsThis study shows the independently predictive ability of baseline serum AFP level in HCC patients. AFP levels of 20 and 400 ng/mL are considered feasible cutoffs to predict long-term outcome in unselected HCC patients.

Utility of Platelet Count for Predicting Cirrhosis in Alcoholic Liver Disease: Model for Identifying Cirrhosis in a US Population.

Thrombocytopenia has been shown to be the single most useful laboratory investigation for identifying subclinical cirrhosis of varying etiologies. However, alcohol per se can result in thrombocytopenia, and hence it is unclear whether platelet count can identify cirrhosis in patients who are alcoholic. To characterize the utility of clinical predictors, especially platelet count, for identifying the presence of cirrhosis in alcoholics. To develop a simple, objective model for identifying cirrhosis in alcoholics. Retrospective cohort study. A total of 2,471 consecutive hospitalized patients with abnormal liver enzyme levels were screened, from which 272 patients with a history of recent and ongoing alcohol intake, negative diagnostic studies for alternative etiologies of chronic liver disease, and recent liver imaging with ultrasound or CT scan were included. Results of liver imaging and admission laboratory studies including liver enzymes, coagulation studies, and blood counts. One hundred twenty-nine patients (47%) had cirrhosis based on imaging; 143 patients (53%) had no cirrhosis. A pre-sobriety platelet count (during ongoing alcohol intake) of less than 70*10(3) cells/mm(3) was effective for ruling in cirrhosis (positive likelihood ratio [LR] 6.8, 95% CI: 3.4, 14); platelet count greater than 200*10(3) was useful for ruling out cirrhosis in alcoholics (negative LR 0.18, 95% CI: 0.10, 0.35). Multivariate logistic regression analysis identified international normalized ratio (INR) (p < 0.01) and pre-sobriety platelet count (p < 0.01) as independent predictors of cirrhosis. A Model for identifying Cirrhosis in Alcoholic Liver Disease (MCALD) was developed using the INR and pre-sobriety platelet count; it had an area under the receiver operating characteristic curve of 0.89 and Hosmer-Lemeshow goodness of fit chi(2) (p value) of 8.9 (0.35) for predicting cirrhosis in alcoholics. A MCALD score > 5.5 corresponded to an increased likelihood of cirrhosis (LR: 6.5, 95% CI: 4.3, 11.0) and a MCALD score < 5.5 corresponded to decreased likelihood of cirrhosis in alcoholics (LR: 0.25, 95% CI: 0.19, 0.36). Sobriety platelet count (after alcohol abstinence) at a cutoff of 160*10(3) had positive LR of 7.9 (95% CI: 4.4, 14) and negative LR of 0.42 (95% CI: 0.34, 0.52) for predicting cirrhosis in alcoholics. A simple model of platelet count and INR has good diagnostic accuracy for identifying cirrhosis in alcoholics.

Covering the Cover

Covering the Cover

An overview of effective therapies and recent advances in biomarkers for chronic liver diseases and associated liver cancer.

Chronic liver diseases (CLDs) such as hepatitis, alcoholic liver disease, nonalcoholic fatty liver, and their downstream effect cancer affect more than a billion of people around the world both symptomatically and asymptomatically. The major limitation for early detection and suitable medical management of CLDs and liver cancer is either the absent of symptoms or their similar manifestations as other diseases. This detection impediment has led to a steady increase in the number of people suffering from CLDs with an ultimate outcome of liver failure and undergoing transplantation. A better understanding of CLD pathogenesis has helped us to develop novel therapies for patients who are at greatest risk for CLD progression to the most serious disease cancer. With the discovery of aberrant molecular pathways in CLDs, it is now possible to delineate a road map for selecting targeted therapies for CLDs. Technological advances in imaging as well as the availability of several stable, sensitive, early, noninvasive biomarkers for distinguishing different stages of CLDs and cancer have greatly facilitated both drug target identification and real-time monitoring of response to therapy. Biomarkers are the most useful in clinical practice for liver diseases like hepatocellular carcinoma (HCC), which is associated with secretion of various tumor-related proteins or nucleotides in peripheral circulation. The need for the identification of CLD biomarkers remains high. This article reviews the etiologies of CLDs, the results of recent clinical trials of treatments for CLDs, and development of noninvasive methodologies for detecting CLDs and monitoring their progression toward HCC.

Growth rate of early-stage hepatocellular carcinoma in patients with chronic liver disease.

Background/AimsThe goal of this study was to estimate the growth rate of hepatocellular carcinoma (HCC) and identify the host factors that significantly affect this rate.MethodsPatients with early-stage HCC (n=175) who underwent two or more serial dynamic imaging studies without any anticancer treatment at two tertiary care hospitals in Korea were identified. For each patient, the tumor volume doubling time (TVDT) of HCC was calculated by comparing tumor volumes between serial imaging studies. Clinical and laboratory data were obtained from the medical records of the patients.ResultsThe median TVDT was 85.7 days, with a range of 11 to 851.2 days. Multiple linear regression revealed that the initial tumor diameter (a tumor factor) and the etiology of chronic liver disease (a host factor) were significantly associated with the TVDT. The TVDT was shorter when the initial tumor diameter was smaller, and was shorter in HCC related to hepatitis B virus (HBV) infection than in HCC related to hepatitis C virus (HCV) infection (median, 76.8 days vs. 137.2 days; P=0.0234).ConclusionsThe etiology of chronic liver disease is a host factor that may significantly affect the growth rate of early-stage HCC, since HBV-associated HCC grows faster than HCV-associated HCC.

Advances in hepatocellular carcinoma: Nonalcoholic steatohepatitis-related hepatocellular carcinoma.

An increase in the prevalence of obesity and diabetes mellitus has been associated with the rise in nonalcoholic fatty liver disease (NAFLD). Two-thirds of the obese and diabetic populations are estimated to develop NAFLD. Currently, NAFLD is the most common etiology for chronic liver disease globally. The clinical spectrum of NAFLD ranges from simple steatosis, an accumulation of fat greater than 5% of liver weight, to nonalcoholic steatohepatitis (NASH), a more aggressive form with necroinflammation and fibrosis. Among the patients who develop NASH, up to 20% may advance to cirrhosis and are at risk for complications of end-stage liver disease. One of the major complications observed in patients with NASH-related cirrhosis is hepatocellular carcinoma (HCC), which has emerged as the sixth most common cancer and second leading etiology of cancer-related deaths worldwide. The incidence of HCC in the United States alone has tripled over the last three decades. In addition, emerging data are suggesting that a small proportion of patients with NAFLD may be at higher risk for HCC in the absence of cirrhosis - implicating obesity and diabetes mellitus as potential risk factors for HCC.

Study on assessment of renal function in chronic liver disease.

Renal dysfunction is common in chronic liver disease. The cause of this renal dysfunction is either multi-organ involvement in acute conditions or secondary to advanced liver disease. The study was undertaken to assess the renal function in chronic liver diseases and find out the association of alteration of renal function with gradation of liver disease. (assessed by child-pugh criteria) and to find out the association of alteration of renal function among the cases of chronic liver disease of different aetiology. This cross-sectional, observational study was undertaken in Department of General Medicine, Calcutta National Medical College & Hospital, Kolkata during March 2012 to July 2013 with 50 admitted patients of chronic liver disease after considering the exclusion criteria. The patients were interviewed with a pre-designed and pre-tested schedule, examined clinically, followed by some laboratory investigations relevant to diagnose the aetiology of chronic liver disease, and to assess the severity of liver and renal dysfunction. Data was analysed by standard statistical method. Eighty six percent of the patients were male and the mean age of study population was 43.58 y, 68% patients suffered from alcoholic liver disease, followed by 14% patients had chronic Hepatitis-B, 10% patients developed acute kidney injury, 20% had hepato renal syndrome and 14% had IgA deposition. The distribution of serum urea and creatinine across the categories of Child Pugh classification tested by Mann-Whitney test and the distribution was statistically significant. The present study has found significant association between severity of liver dysfunction and certain parameters of renal dysfunction.

Gender, Age, Etiology, and Complications in Liver Transplant Candidates.

Liver cirrhosis is the end stage of chronic liver disease (CLD), which is characterized by the appearance of fibrosis and regenerated nodules. It can be caused by different etiological factors. The only therapeutic modality is liver transplantation. The objective of this study was to describe the basic demographic characteristics, etiology, and complications of CLD in liver transplant candidates in patients of both genders. Autoimmune chronic disease was significantly more frequent in females (p = .022), whereas alcoholic liver disease was more frequent in males (p = .038). There was no difference between gender in other causes of CLD. Ascites was significantly higher in males (p = .041), whereas for other complications there was no difference between genders. Candidates for liver transplantation of different genders are different in the frequency of autoimmune and alcoholic liver disease, and the frequency of ascites. Frequency of other etiologies and complications does not relate to gender.