Characteristics of Drug-induced Liver Injury in Chronic Liver Disease: Results from the Thai Association for the Study of the Liver (THASL) DILI Registry

Background and AimsThe impact of drug-induced liver injury (DILI) on patients with chronic liver disease (CLD) is unclear. There are few reports comparing DILI in CLD and non-CLD patients. In this study, we aimed to determine the incidence and outcomes of DILI in patients with and without CLD.MethodsWe collected data on eligible individuals with suspected DILI between 2018 and 2020 who were evaluated systematically for other etiologies, causes, and the severity of DILI. We compared the causative agents, clinical features, and outcomes of DILI among subjects with and without CLD who were enrolled in the Thai Association for the Study of the Liver DILI registry. Subjects with definite, or highly likely DILI were included in the analysis.ResultsA total of 200 subjects diagnosed with DILI were found in the registry. Of those, 41 had CLD and 159 had no evidence of CLD in their background. Complementary and alternative medicine (CAM) products were identified as the most common class of DILI agents. Approximately 59% of DILI in the CLD and 40% in non-CLD group were associated with CAM use. Individuals with pre-existing CLD had similar severity including mortality. Twelve patients (6%) developed adverse outcomes related to DILI including seven (3.5%) deaths and five (2.5%) with liver failure. Mortality was 4.88% in CLD and 3.14% in non-CLD subjects over median periods of 58 (8–106) days and 22 (1–65) days, respectively.ConclusionsIn this liver disease registry, the causes, clinical presentation, and outcomes of DILI in subjects with CLD and without CLD patients were not different. Further study is required to confirm our findings.     

Factors predisposing to peptic ulcer disease in asymptomatic cirrhotic patients

BACKGROUND: There is a high prevalence of peptic ulcer in cirrhotic patients, but the pathogenesis of peptic ulcer in cirrhosis remains inconclusive. AIM: To investigate factors associated with peptic ulcer and to evaluate peptic ulcer prevalence in asymptomatic cirrhotic patients. METHODS: A total of 130 cirrhotics were recruited into the study for endoscopic screening. Data were collected and biochemical tests were done. Doppler ultrasound was used to assess the portal vein velocity and size. Patients underwent endoscopy for the presence of varices and peptic ulcer. Helicobacter pylori infection was confirmed by urease test, histology and 14C-urea breath test. Statistical analysis was performed. RESULTS: Peptic ulcer was detected in 50 (39%) cases. Between peptic ulcer and non-peptic ulcer groups, there were no significant differences in age, sex, alcoholic drinking, smoking, non-steroidal anti-inflammatory drug use, portal vein velocity and size, except for H. pylori infection (P = 0.006), serum albumin (P = 0.02) and Child-Pugh score (P = 0.03). By multivariate analysis, H. pylori infection (OR: 3.26; 95% CI: 1.49-7.13; P = 0.003), Child-Pugh classes B (OR: 2.48; 95% CI: 1.04-5.91; P = 0.04) and C (OR: 3.26; 95% CI: 1.2-8.81; P = 0.02) were independently associated with peptic ulcer. CONCLUSION: H. pylori infection and advanced cirrhosis are important factors associated with active peptic ulcer.     

A prophylactic approach for bone marrow transplantation from a hepatitis B surface antigen-positive donor

It has been accepted that bone marrow transplantation (BMT)is the only curative therapeutic option for certain hematologic malignancies.The southeast Asia region is an endemic area of hepatitis B virus(HBV)infection;thus,BMT using a hepatitis B surface antigen(HBsAg)-positive donor is occasionally unavoidable.Organ transplantation using a HBsAg-positive donor can lead to post-transplantation de novo HBV infection and severe HBV-related hepatitis if no effective prophylactic measures are taken prior to and after transplantation.In this report,a four-level approach was designed for a patient with chronic myeloid leukemia,beginning with a booster HBV vaccination before performing BMT with a HBsAg-positive donor.Prior to BMT,the HBV viral load of the donor was reduced to an undetectable level by antiviral therapy.After BMT,hepatitis B immunoglobulin was administered intramuscularly for 1 wk together with a long-term antiviral drug,lamivudine.One year after discontinuation of lamivudine,the patient is still free of HBV infection.     

Budd-Chiari-like presentation of hepatic adenoma

Hepatic adenoma is a benign tumor characterized by its hypervascularity. Hepatic adenoma tends to occur more frequently in women and is related to the use of contraceptive hormones, androgenic/anabolic steroids, pregnancy, glycogen storage diseases and hemochromatosis. Hepatic venous obstruction, or Budd-Chiari syndrome, is a condition of hepatic vein occlusion that has many causes. A 35-year-old woman presented shortly after pregnancy with a huge cystic lesion in the liver. The lesion compressed the hepatic vein and created an early stage of Budd-Chiari syndrome. Tumor resection was carried out successfully. The final diagnosis of this case was multiple hepatic adenomas.     

Nutritional assessment in various stages of liver cirrhosis

OBJECTIVES: The aims of this study were to determine the prevalence of protein-calorie malnutrition, characteristics, and clinical importance of nutrition disorders in patients with liver cirrhosis according to severity of disease. METHODS: Nutrition assessments such as subjective global assessment, anthropometric and biochemical measurements, immunocompentency, thiamin and riboflavin status in 60 patients with cirrhosis (33 male and 27 female) were recorded between June 1999 and December 1999 at an outpatient clinic at Ramathibodi Hospital, Bangkok, Thailand. The origin of liver disease was alcohol related in 50% of patients. Child-Pugh criteria were used to establish the severity of liver disease. RESULTS: In terms of energy malnutrition, 13.3% of patients had ideal body weights below 90% and 11.7% had body mass indexes below 18.5 kg/m(2). Protein malnutrition (low albumin) and immunoincompetence (abnormal response to skin tests) were found much more frequently (45% and 22%) than energy malnutrition. Patients with alcoholic cirrhosis had ascites (P < 0.05) and hepatic encephalopathy (P < 0.001) more frequently and less triceps skinfold thickness than those with non-alcoholic cirrhosis. Subjective global assessment and serum proteins correlated with the degree of liver-function impairment, but immunologic tests correlated inversely in cirrhosis patients. Mean values for creatinine-height index, hemoglobin, cholesterol, and complement C4 showed significant decreases in severe liver failure (Child-Pugh class C) only in patients with alcoholic cirrhosis (P < 0.05). Malnutrition was correlated with the clinical severity of liver disease. CONCLUSIONS: The study showed that protein-energy malnutrition is a common complication of liver cirrhosis. Nutritional disorders appeared to be related to the degree of liver injury and the etiology of nutritional disorders. Nutritional disorders were more severe with alcoholic cirrhosis than with non-alcoholic cirrhosis.     

Improving quality of colonoscopy by adding simethicone to sodium phosphate bowel preparation

AIM： To evaluate the effectiveness of simethicone in enhancing visibility and efficacy during colonoscopy.
METHODS： A prospective, double-blind, randomized, placebo-controlled study was conducted. One hundred and twenty-four patients were allocated to receive 2 doses of sodium phosphate plus 240 mg of tablet simethicone or placebo as bowel preparation. Visibility was blindly assessed for the amount of air bubbles and adequacy of colon preparation. Total colonoscopic time, side effects of the medication, endoscopist and patient satisfaction were also compared.
RESULTS： Sodium phosphate plus simethicone, compared to sodium phosphate plus placebo, improved visibility by diminishing air bubbles （100.00% vs 42.37%, P 〈 0.0002） but simethicone failed to demonstrate improvement in adequacy of colon preparation （90.16% vs 81.36%, P = 0.17）. Endoscopist and patient satisfaction were increased significantly in the simethicone group. However, there was no difference in the total duration of colonoscopy and side effects of the medication.
CONCLUSION： The addition of simethicone is of benefit for colonoscopic bowel preparation by diminishing air bubbles, which results in enhanced visibility. Endoscopist and patient satisfaction is also increased.     

Visceral fat and insulin resistance as predictors of non-alcoholic steatohepatitis

AIM： To examine whether visceral fat is associated with non-alcoholic steatohepatitis （NASH）, to assess for parameters associated with visceral adiposity and to investigate for factors associated with fibrotic severity in NASH. METHODS： Thirty NASH and 30 control subjects underwent biochemical tests, anthropometric assessment, bioelectrical impedance, dual energy X-ray absorptiometry and abdominal fat study by CT scan. Liver biopsies were graded according to the Brunt criteria. RESULTS： NASH subjects had elevated blood pressure, body mass index, waist circumference and waist-to-hip ratio. A greater number of diabetes rnellitus, impaired glucose tolerance test and HOMA-IR 〉 3.5 were found in NASH patients. HOMA-IR 〉 2.8 （OR 20.98, 95% CI 3.22-136.62; P 〈 0.001） and visceral fat area 〉 158 cm^2 （OR 18.55, 95% CI 1.60-214.67; P = 0.019） were independent predictors for NASH. Advanced stage of NASH was found in 15 （50%） patients. HOMA-IR 〉 3.5 （OR 23.12, 95% CI 2.00-266.23; P = 0.012） and grading of portal inflammation （OR 7.15, 95% CI 1.63-31.20; P = 0.009） were determined as independent risk factors for advanced stage of NASH. CONCLUSION： Obesity （especially central obesity） and metabolic syndrome are common in Thai NASH. Insulin resistance and elevated visceral fat are risk factors for the presence of NASH. The advanced stage of thedisease is related to insulin resistance.     

Factors influencing health-related quality of life in chronic liver disease

INTRODUCTION In 1947, the World Health Organization expanded the definition of health to include in addition to the absence of disease, a complete state of physical, mental and social well-being[1]. Health-related quality of life (HRQL) emerges as a tool …     

Chronic liver disease questionnaire： Translation and validation in Thais

AIM: Quality of life (QOL) is a concept that incorporates many aspects of life beyond “health“ The chronic liver disease questionnaire (CLDQ) was developed to evaluate the impact of chronic liver diseases (CLD) on QOL. The objectives of this study were to translate and validate a liver specific questionnaire, the CLDQ.METHODS: The CLDQ was formally translated from the original version to Thai language with permission. The translation process included forward translation, back translation, cross-cultural adaptation and a pretest. Reliability and validity of the translated version was examined in CLD patients. Enrolled subjects included CLD and normal subjects with age- and sex-matched. Collected data were demography,physical findings and biochemical tests. All subjects were asked to complete the translated versions of CLDQ and SF36, which was previously validated. Cronbach‘s alpha and test-retest were performed for reliability analysis. One-way Anova or non-parametric method was used to determine discriminant validity. Spearman‘s rank correlation was used to assess convergent validity. P-value &lt;0.05 was considered statistically significant.RESULTS: A total of 200 subjects were recruited into the study, with 150 CLD and 50 normal subjects. Mean ages(SD) were 47.3(11.7) and 49.1(8.5) years, respectively. The number of chronic hepatitis: cirrhosis was 76:74, and the ratio of cirrhotic patients classified as Child A:B:C was 37(50%): 26(35%): 11(15%). Cronbach‘s alpha of the overall CLDQ scores was 0.96 and of all domains were higher than 0.93. Item-total correlation was&gt;0.45. Test-retest reliability done at 1 to 4 wk apart was 0.88 for the average CLDQ score and from 0.68 to 0.90 for domain scores. The CLDQ was found to have discriminant validity. The highest scores of CLDQ domains were in the normal group, scores were lower in the compensated group and lowest in the decompensated group. The significant correlation between domains of the CLDQ and SF-36 was found. The average CLDQ score was strongly correlated with the general health domain of SF-36. (P=0.69: P=0.01).CONCLUSION: The translated CLDQ is valid and applicable in Thais with CLD. CLDQ reveals that QOL in these patients is lower than that in normal population. QOL is more impaired in advanced stage of CLD.