Patients with CLD referred to the Outpatient Clinic of CLD at Hospital das Clinicas of the Federal University of Uberlândia, Minas Gerais State, Brazil in the period of 2011–2012 were recruited for the study. Patients of either gender had be 18 years or more and have a diagnosis of CLD by a hepatologist.

The diagnosis of chronic hepatitis B virus (HBV) infection was based on the presence of hepatitis B surface antigen for more than six months and elevated serum alanine aminotransferase levels with or without HBV DNA, detected by real-time polymerase chain reactions (PCR).20

Chronic hepatitis C virus (HCV) infection was diagnosed based on the presence of hepatitis C antibodies for more than six months assessed by ELISA III and HCV RNA by qualitative polymerase chain reaction and elevated serum alanine aminotransferase levels.21

Primary biliary cirrhosis was diagnosed based on positive anti-mitochondrial antibodies (AMA) and elevated liver enzymes with or without liver biopsy.22 Alcohol was deemed the cause of chronic liver disease if daily alcohol consumption was greater than 40g for at least 10 years with elevated γ-glutamyl transferase when controlling for other liver diseases.23

Autoimmune hepatitis diagnosis was based on simplified diagnostic criteria for routine clinical practice including age, sex, autoantibodies [smooth muscle actin (SMA), anti-nuclear antibody (ANA), AMA, liver-kidney microsomal antibodies (LKM), soluble liver/liver-pancreas antibodies (SLA/LP)], γ-globulins, immunoglobulin A, immunoglobulin G (IgG), immunoglobulin M (IgM), absence of viral hepatitis, and liver histology.24

Diagnosis of nonalcoholic fatty liver disease (NAFLD) was based in the evidence of hepatic steatosis, either by imaging or histology, controlling for other causes of secondary hepatic fat accumulation such as significant alcohol consumption, steatogenic medication, or hereditary disorders.25 Cryptogenic chronic hepatitis was diagnosed if the patient presented with persistent inflammation of the liver, unexplained by conventional clinical, laboratory, and histological methods.26

Liver cirrhosis diagnosis was based on clinical, biochemical, serologic, and radiographic parameters and ultrasonography.27 Cirrhosis without a diagnosis of the etiology was termed “other forms of cirrhosis or unspecified cirrhosis”.

Exclusion criteria were presence of malignancy, liver transplantation, co-infection with human immunodeficiency virus (HIV), psychiatric or emotional problems, cognitive or language difficulties that prevented the reliable application of the questionnaire, and a diagnosis of hepatic encephalopathy.6 The study was conducted in accordance with the Helsinki Declaration and study protocols were approved by local ethics committees. All patients provided informed consent before enrollment.

A pilot study to verify the applicability of these instruments was first conducted on 23 individuals with the same population characteristics. These patients were not included in the final sample.

The investigators informed patients about the study aims. After obtaining informed consent, participants completed a socio-demographic questionnaire and the CLDQ.

The CLDQ has recently been translated and validated for the Brazilian population.18 This instrument was developed by Yonossi et al. in 1999 to assess QoL of patients with liver diseases.6 The CLDQ is the only validated instrument for the different etiologies and degrees of severity of liver disease. It yields both domains and total scores, demonstrating both multidimensional and overall perception of QoL, emphasizing the effects of liver disease symptoms. The Brazilian version comprises 29 questions encompassing six domains: Abdominal Symptoms (AS), Fatigue (FA), Systemic Symptoms (SS), Activity (AT), Emotional Function (EM), and Worry (WR). AS and AT domains have 3 items each; FA, SS, and WR have 5 items each; whereas EM comprises 8 items. Each item is rated on a 7-point Likert scale.28 Higher score on the questionnaire is indicative of minimum symptoms and lower score indicates more pronounced symptoms. A CLDQ cut-off score was determined to evaluate HRQoL based on prior literature; mean CLDQ scores ≥5 was considered to represent high HRQoL and mean CLDQ scores <5 implied low HRQoL.29

The Model for End-Stage Liver Disease (MELD) index—a mathematical model that uses three laboratory tests (values of serum creatinine, serum total bilirubin, and international normalized ratio; INR) to determine the severity of liver disease30—was also calculated. The formula adopted by the United States (U.S.) Department of Health & Human Services was used: {0.957×loge [creatinin (mg/dL)]+0.378×loge [bilirubin (mg/dL)]+1.120×loge (INR)+0.643}*10.

For patients on dialysis more than twice a week, creatinine values were always registered at 4.0. All patients were categorized into groups, based on MELD scores: low (<15), moderate (16–25) and high (>25) risk of mortality. The MELD is used as a tool to guide liver organ allocation system for liver transplantation in the US, Europe, and Brazil.30

Data were entered into Microsoft Excel, a spreadsheet program. Frequencies of variables were crosschecked for accuracy. Subsequently, this database was transferred to Epi Info™ 7.1.0.6, through which statistical analyses were performed. Categorical variables (e.g., gender, race/ethnicity, etiology of liver disease) are presented as frequencies and percentages, whereas continuous variables (MELD and CLDQ scores) are presented as means and standard deviations. To evaluate gender differences in average CLDQ scores, a Student's t-test was used, while analysis of variance (ANOVA) was used to compare differences in average CLDQ scores for different categories, level of education, occupation, and family income (p<0.05 was considered significant). Pearson's correlation coefficient was used to verify the existence of correlation between the following variables: CLDQ scores, MELD scores, age, education, and family income.

The socio-demographic characteristics of 133 patients with chronic liver disease of different etiologies are shown in Table 1. The majority of participants in this study were male (66.2%), Caucasian (70.7%), employed (42.9%), and had a family income of US$329–US$658.2 (43.6%). Over 27% had received up to four years of schooling. The participants’ mean age was 50±13.3 years. Regarding chronic liver etiology, 75 individuals were classified as chronic HCV patients (56.4%), 25 as HBV patients (18.8%), 15 with alcoholic liver cirrhosis (11.3%), 8 with autoimmune hepatitis (6%), 4 with NAFLD (3%), 1 with cryptogenic hepatitis (0.8%), and 5 had other causes of cirrhosis (3.8%).

Table 2 shows the minimum, maximum, mean, and standard deviation CLDQ scores. Higher mean CLDQ scores were found for emotional function (39.70±12.98) while lower mean CLDQ scores were obtained for abdominal symptoms (16.00±6.25). Fifty-two patients (39.1%) obtained low (<5) overall CLDQ scores. CLDQ was evaluated according to age, gender, family income and school level. Family income was correlated to CLDQ (r=0.187, p=0.031) (Table 3).

Regarding MELD, 124 (93.2%) individuals were at low risk (≤15), seven (5.3%) were at moderate risk, and two (1.5%) were at high risk for mortality (>25). MELD indices were correlated to age (r=0.185; p=0.033; Table 3).