Objective: The aim of the study is to investigate the “new-onset jaundice” incidence, map of causes, approaching method, and risk factors for treatment failure in adult in-patients at a tertiary general hospital as Cho Ray Hospital, Ho Chi Minh City, Viet Nam. Method: Retrospective study was done on 416 jaundice patients administered over 38 continuous days. Laboratory tests investigated were total bilirubin, direct bilirubin, AST, ALT, AST/ALT ratio, GGT, AP, bilirubin and urobilinogen in urine. Jaundice was defined as total bilirubin ≥ 2.5 mg/dL, direct bilirubin jaundice defined as direct bilirubin > 2 mg/dL and D/T percentage > 60%, the severity of AST, ALT evaluated according to Common Terminology Criteria for Adverse Events, AST/ALT ratio, and bilirubin, urobilinogen in urine. Outcome of treatment were classified in two groups: failure (dead or discharge due to worse status) and success. Descriptive statistics and analytic statistics were applied, mono-variable analysis and multinomial logistic regression to find out the independent risk factors for treatment failure. Results: The incidence of “new-onset” jaundice in adult patients was 11 ± 5 person/day. The map of jaundice included 3 phases as pre-heaptic 13.7%, in-hepatic 58.2%, and post-hepatic 22.8%. Pancreatic and biliary tract diseases accounted 17.1%, then cirrhosis 16.3%, liver tumor 14.7%, hepatitis 8.9%, sepsis 8.9%, hematology diseases 7.9%, and cardiac diseases 7.5%. A guide for approaching causes of jaundice basing on 7 parameters as total bilirubin, D/T percentage, severity of ALT, AST/ALT ratio, severity of GGT, and bilirubin and urobilinogen in urine was established. The overall mortality was 7.5% (31/416), sepsis had highest death rate of 37.8% (14/37). Sepsis and AST/ALT ratio > 2 were the two independent risk factors of mortality. Conclusion: At tertiary hospital, jaundice is common sign in adult patient, diverse enormously in many clinical wards. The map of causes of jaundice completed all 3 phases: pre-hepatic, intra-hepatic and post-hepatic phase. Drug hepatitis jaundice was an important cause in hepatitis. Sepsis had highest mortality in adult jaundice patients. Combination of 7 criteria as total bilirubin, the D/T percentage, ALT severity, AST/ALT ratio, GGT, bilirubin and urobilinogen in urine gave the guide for approaching to jaundice. Sepsis and AST/ALT ratio > 2 were independent risk factors of treatment failure. The survey of jaundice in adult in-patients in a tertiary general government hospital gave the full picture for this common pathological sign.
Jaundice is a common sign in clinical settings, presenting as a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae, and other mucous membranes caused by hyperbilirubinemia [
We report the results of a retrospective study on 416 new-onset jaundice in-patients administrated over 38 consecutive days at Cho Ray Hospital, Ho Chi Minh City, Vietnam. The aims of study were to identify the incidence rate of new-onset jaundice, causes of jaundice, roles of bilirubin and liver function tests in diagnosis of jaundice, mortality and risk factors related to the treatment failure in adult jaundice in-patients.
Cho Ray Hospital is a tertiary general government hospital, located in Ho Chi Minh City, including 43 clinical departments, 11 laboratory departments, 3 medical centers; having 1800 beds and around 2000 out-patients per day.
The study was retrospective. Data were started from the source of bilirubin results of biochemistry department. Other results of liver function test, including aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase (AP), and total urinalysis were recorded if available together with bilirubin results. The list of patients with corresponding administration was sent to the Medical Planning Room for reviewing the patient medical files to record the personal characteristics (year of birth, gender, date of administration, date of hospital discharge) and the final diagnosis and results of treatment on discharge. Hyperbilirubinemia was defined as total bilirubin ≥ 2.5 mg/dl, and classified into 3 groups, based on the percentage of direct bilirubin over total bilirubin (D/T percentage) as: <20%: increased indirect bilirubin; 20% - 60%: hepatic or post-hepatic jaundice; and >60%: post-hepatic (direct bilirubin) jaundice [
Data were stored by Excel program. Statistical analysis was performed with SPSS version 18. The main statistics was descriptive with values presented as mean, median, standard deviation, range (minimum - maximum values) and percentage. Mono-variable analysis with 2 × 2 tables for relationship between risk factors with treatment outcome. Treatment outcomes were classified as 2 values: success and failure (including dead and discharge due to worse status). Multinomial logistic regression was applied to find out the independent risk factors for treatment failure. The p value < 0.05 was indicated as a significant difference.
There were 416 jaundice cases investigated, male/female as 240/176 (57.7%/42.3%). The mean age was 53.8 ± 16.9 years old (range: 16 - 93); age distributed as <20 yrs.: 1.2%; 20 - 39 yrs.: 20.5%; 40 - 59 yrs.: 41%; ≥60 yrs.: 37%). Surgery medicine included 170 cases (41.1%), internal medicine with 246 cases (58.9%). In surgery, there were 8 departments: Liver-Biliary-Pancreas 79 cases (46.5%), Liver Tumor 43 (25.3%), Open Heart Surgery 26 (15.9%); Gastro-intestinal Surgery 8 (4.7%) and 14 cases belonging 4 others (Orthopedics, Neuro-sur- gery, Burn, Vascular Surgery departments). In medicine, there were 13 departments: Gastrointestinal, Liver, Biliary, Pancreatic diseases 101 cases (41.1%), Hepatitis 32 (13%), Clinical hematology 27 (11.0%), Cardiology 14 (5.7%), Palliative care 16 (6.5%), Intensive Care Unit 15 (6.1%), Tropical Diseases 13 (5.3%), Neurology 9 (3.7%) and 19 belonged to 5 (General Medicine, Pneumology, Endocrinology, Cardiac Intervention).
The incidence of “new-onset jaundice” in in-patients calculated over 38 consecutive days was 11 ± 5 person/day (median: 11, minimum: 2, maximum: 19) (
The causes of jaundice were presented in
Pre-hepatic jaundice included hematology diseases, hematoma/hemorrhagy, and hemorrhagic stroke accounted 13.7% (57/416); in-hepatic jaundice (liver abscess, tumor, hepatitis, cirrhosis, trauma, sepsis, cardiac cirrhosis) 58.2% (242/416); post-hepatic jaundice (pancreatic and biliary tract diseases, cholangitis) 22.8% (95/416); and unclassified causes 5.3% (22/416).
Among 37 hepatitis cases, viral causes (hepatitis B virus, hepatitis C virus) accounted 18 cases (48.6%), drug induced liver injury 14 (DILI) (37.8%), alcoholic hepatitis 1, autoimmune diseases 1, and unclassified hepatitis 3. The total bilirubin values were high in DILI cases: 7 with >15 mg/dL, 4 with 7.1 - 15 mg/dL, and 3 with 3.1-7.0 mg/dL.
Hematoma/hemorrhagy were seen in 18 cases: multiple trauma 8 (44.4%), hemorrhagy 5 (27.8%), aortic dissection 4 (22.2%), and post-mitral valve replacement surgery.
Pathogen | n (%) | Pathogen | n (%) |
---|---|---|---|
Liver abscess | 5 (1.2) | Pancreatic and biliary tract diseases | 71 (17.1) |
Hematology diseases | 33 (7.9) | Choledocholithiasis | 19 |
Thalassemia | 9 | Biliary strictures | 3 |
Hemolysis | 8 | Acute pancreatitis | 3 |
Bone marrow failure | 6 | Sphincter of Oddi disorder | 2 |
Leukemia (acute, chronic) | 5 | Cholecystitis | 1 |
Phagocytosis | 3 | Bile duct lesion | 1 |
Multiple myeloma | 1 | Cholangiocarcinoma | 20 |
Hemophilia B | 1 | Pancreatic cancer | 10 |
Liver tumor | 61 (14.7) | Peri-ampulary cancer | 9 |
Hematoma/hemorrhagy | 18 (4.3) | Gallbladder cancer | 3 |
Sepsis | 37 (8.9) | Hepatitis | 37 (8.9) |
Cholangitis | 24 (5.8) | Viral hepatitis | 18 |
Cardiac diseases | 31 (7.5) | Drug induced hepatitis | 14 |
Cirrhosis | 68 (16.3) | Alcoholic hepatitis | 1 |
Liver trauma | 3 (0.7) | Autoimmune hepatitis | 1 |
Other tumors | 6 (1.4) | Unclassified hepatitis | 3 |
Hemorrhagic stroke | 6 (1.4) | Other | 28 (5.0) |
The characteristics of bilirubin were presented in
In hepatitis ALT increased >5 times over UNL (upper normal limit) accounting 59.5% (22/37). In cirrhosis, there were 22/68 cases (32.4%) having normal or low ALT. Hematology disease with jaundice often had ALT in normal range 51.5% (17/33) (
AST/ALT ratio ≥ 2 was seen mainly in cirrhosis (52/68: 76.5%), liver tumors (36/61: 59%), hematoma/he- morrhagy (11/18: 61.1%), sepsis (18/37: 48.6%). Inversely, in hepatitis AST/ALT ratio was <1 (16/37: 43.2%) (
Parameters | Results | Parameters | Results | ||
---|---|---|---|---|---|
Total bilirubin (mg/dL) | 8.1 ± 7.1 5.2 (2.5 - 42.2) | Direct bilirubin (mg/dL) | 6.0 ± 5.9 3.6 (0.4 - 32.4) | ||
Distribution of total bilirubin (mg/dL) | D/T percentage (direct Bilirubin/total bilirubin) (%) | ||||
≥2.5 - <3.0 | 69 | 16.6% | ≤20% | 19 | 4.6% |
≥3.0 - <6.0 | 165 | 39.7% | >20% - ≤40% | 26 | 6.3% |
≥6.0 - <15.0 | 124 | 29.8% | >40% - ≤60% | 54 | 13% |
≥15.0 | 58 | 13.9% | >60% | 317 | 76.2% |
Bilirubin in urine (n = 136) | Urobilinogen in urine (mg/dL) (n = 136) | ||||
Negative | 69 | 50.7% | 0.1 | 81 | 59.5% |
+ | 17 | 12.5% | 1 | 22 | 16.2% |
++ | 13 | 9.6% | 4 | 14 | 10.3% |
+++ | 37 | 27.2% | 8 | 19 | 14.0% |
Pathogen | Level of ALT (compared to upper normal limit 35 U/L) | Total | ||||
---|---|---|---|---|---|---|
≤1 | >1 - 2.5 | >2.5 - 5 | >5 - 20 | >20 | ||
Liver abscess | 1 | 2 | 2 | 0 | 0 | 5 |
Liver trauma | 0 | 2 | 0 | 1 | 0 | 3 |
Hematology diseases | 17 | 6 | 7 | 2 | 1 | 33 |
Liver tumors | 16 | 21 | 7 | 17 | 0 | 61 |
Other tumors | 1 | 2 | 2 | 1 | 0 | 6 |
Hematoma/hemorrhages | 7 | 5 | 1 | 3 | 2 | 18 |
Pancreatic and biliary tract diseases | 4 | 29 | 19 | 17 | 1 | 70 |
Sepsis | 7 | 17 | 7 | 6 | 2 | 37 |
Cholangitis | 3 | 11 | 8 | 1 | 0 | 23 |
Cardiac diseases | 11 | 6 | 3 | 6 | 5 | 31 |
Hepatitis | 3 | 8 | 4 | 11 | 11 | 37 |
Hemorrhagic stroke | 1 | 2 | 0 | 1 | 2 | 6 |
Cirrhosis | 22 | 30 | 10 | 6 | 0 | 68 |
Other | 4 | 5 | 3 | 2 | 1 | 15 |
Total | 97 | 144 | 73 | 74 | 25 | 413 |
Pathogen | AST/ALT ratio | Total | ||
---|---|---|---|---|
<1 | ≥1 - <2 | ≥2 | ||
Liver abscess | 1 | 3 | 1 | 5 |
Liver trauma | 0 | 2 | 1 | 3 |
Hematology diseases | 6 | 12 | 15 | 33 |
Liver tumors | 7 | 18 | 36 | 61 |
Other tumors | 3 | 2 | 1 | 6 |
Hematoma/hemorrhage | 1 | 6 | 11 | 18 |
Pancreatic and biliary tract diseases | 17 | 40 | 13 | 70 |
Sepsis | 2 | 17 | 18 | 37 |
Other | 2 | 5 | 8 | 15 |
Cholangitis | 6 | 8 | 9 | 23 |
Cardiac diseases | 7 | 11 | 13 | 31 |
Hepatitis | 16 | 12 | 9 | 37 |
Hemorrhagic stroke | 2 | 2 | 2 | 6 |
Cirrhosis | 3 | 13 | 52 | 68 |
Total | 73 | 151 | 189 | 412 |
The total bilirubin values were divided into 2 groups: total bilirubin > 7 mg/dL were seen in pancreatic and biliary tract diseases (47/72: 65.3%), hepatitis (23/37: 62.2%), cholangitis (13/24: 54.2%), and another group with total bilirubin ≤ 7 mg/dL including hematology diseases (27/33: 81.8%), liver tumor (46/61: 75.4%), hematoma/ hemorrhagy (16/18: 88.9%), sepsis (26/37: 70.3%), cardiac diseases (25/31: 80.6%) and cirrhosis (42/68: 61.8%).
The direct bilirubin increased, with D/T percentage > 60%, were seen in hepatitis 100% (37/37), sepsis 97.3% (36/37), cholangitis 95.8% (23/24), pancreatic and biliary diseases 95.8% (69/72), liver tumor 77.4% (48/62), cirrhosis 60.3 (41/68). Inversely, the pathologies without increase direct bilirubin (D/T < 60%) were hematology disease 63.6% (21/33), cardiac disease 54.8% (17/31), hematomas/hemorrhagy 50% (9/18). Especially, the D/T percentage ≤ 20% presented mainly in hematology diseases 57.9% (11/19). There were 3 cases diagnosed as con- genital non-hemolytic, increased indirect bilirubinemia (3/416, 0.7%).
In 71 patients with obstructive biliary jaundice, 69.2 patients (27/39 cases) had Gamma-glutamyl transferase (GGT) grade CTC2 (>2.5 UNL, UNL = 38 U/L), and 50% (12/24 cases) had Alkaline phosphatase (AP) grade CTC2 (>2.5 UNL, UNL = 148 U/L).
The percentage of successful treatment in jaundice patients was 92.5% (385/416). Sepsis was the cause with highest treatment failure as 37.8% (14/37). The failure rates were lower in cardiac diseases (9.7%, 3/31), cholangitis (8.3% 2/24), hematology diseases (6.1%, 2/33), and cirrhosis (4.4%, 3/68) (
Total bilirubin (mg/dL) | D/T*(%) | Severity ALT (35 U/L) | AST/ALT ratio | Bili/urine | Urobilinogen/urine | Severity GGT (38 U/L) | |
---|---|---|---|---|---|---|---|
Hematology diseases | ≤7 | ≤20 | ≤1 | ≥2 | − | Normal/increase | ≤1 |
Hematoma/hemorrhagy | ≤7 | ≤60 | ≤2.5 | ≥2 | − | Normal/increase | ≤2.5 |
Cardiac diseases | ≤7 | ≤60 | ≤2.5 | 1 - 2 | −/+ | Normal/increase | ≤2.5 |
Sepsis | ≤7 | >60 | ≤2.5 | ≥2 | − | Normal | >5 |
Cirrhosis | ≤7 | >60 | ≤2.5 | ≥2 | −/+ | Normal/increase | ≤5 |
Liver tumor | ≤7 | >60 | ≤2.5 | ≥2 | −/+ | Normal/increase | ≤5 |
Pancreatic and biliary tract diseases | >7 | >60 | ≤5.0 | 1 - 2 | +++ | Normal | >5 |
Cholangitis | >7 | >60 | ≤5.0 | 1 - 2 | ++ | Normal | >5 |
Hepatitis | >7 | >60 | >5 | <1 | ++ | Normal | ≤5 |
*D/T: direct bilirubin/total bilirubin (%).
Clinical diagnosis | Patient status on hospital discharge | Total | ||
---|---|---|---|---|
Failure | Success | |||
Dead | Worse illness discharging | Good progress | ||
Liver abscess | 0 | 0 | 5 | 5 |
Liver trauma | 0 | 0 | 3 | 3 |
Hematology diseases | 2 | 0 | 31 | 33 |
Liver cancer | 0 | 2 | 59 | 61 |
Other cancer | 0 | 0 | 6 | 6 |
Hematomas/hemorrhage | 0 | 1 | 17 | 18 |
Pancreatic and biliary tract diseases | 1 | 0 | 70 | 71 |
Sepsis | 11 | 3 | 23 | 37 |
Cholangitis | 2 | 0 | 22 | 24 |
Cardiac diseases | 3 | 0 | 28 | 31 |
Hepatitis | 1 | 0 | 36 | 37 |
Hemorrhagic stroke | 0 | 0 | 6 | 6 |
Cirrhosis | 3 | 0 | 65 | 68 |
Other | 1 | 1 | 14 | 16 |
Total | 24 | 7 | 385 | 416 |
Factors | Values | Treatment results | p | Factors | Values | Treatment results | p | ||
---|---|---|---|---|---|---|---|---|---|
Failure | Success | Failure | Success | ||||||
Pathogens | Sepsis | 14 | 23 | 0.000* | AST/ALT ratio | <2 | 9 | 215 | 0.003* |
Other | 17 | 362 | ≥2 | 22 | 167 | ||||
Total bilirubin (mg/dL) | ≤7 | 18 | 242 | 0.74 | GGT (38 U/L) | ≤5 UNL | 1 | 16 | 0.8 |
>7 | 13 | 143 | >5 UNL | 2 | 20 | ||||
D/T percentage (%) | ≤60 | 4 | 95 | 0.21 | Bilirubin in urine | −/+ | 6 | 80 | 1.0 |
>60 | 27 | 290 | ++/+++ | 3 | 47 | ||||
ALT (35 U/L) | ≤5 UNL | 21 | 293 | 0.36 | Urobilinogen in urine | normal | 7 | 96 | 0.9 |
>5 UNL | 10 | 89 | increased | 2 | 31 |
*Significant difference; UNL: upper normal limit.
Factors | Value | Failure (%) | Mono-variable analysis | Multinomial analysis | ||||
---|---|---|---|---|---|---|---|---|
p | OR | 95% KTC | p | OR | 95% CI | |||
Pathogen | Sepsis | 37.8 | 0.001* | 12.9 | 5.7 - 29.5 | 0.000* | 14.04 | 5.9 - 33.3 |
Other | 4.5 | |||||||
AST/ALT ratio | ≥2 | 11.6 | 0.003* | 3.1 | 1.4 - 7.0 | 0.004* | 3.5 | 1.5 - 8.4 |
<2 | 4.0 |
*Significant difference; CI: confidence interval.
The mean age of jaundice patients was 53.8 ± 16.9 years old, similar to study on 352 Chinese cases, 54.4 ± 16.0 yrs [
The important point of this study was the incidence of “new-onset jaundice” in in-patients. The incidence rate of 11 ± 5 new-onset jaundice cases per day at Cho Ray Hospital was a highest rate, compared to 121 jaundice cases detected over 7 months at 2 hospitals in South West Wale, British [
The location of jaundice patients by hospital specialty divided 2 parts: surgery accounted for 41.1% and internal medicine 58.9%. There were 170 patients located in 8 departments of surgery and 246 patients in 13 departments of internal medicine. These parameters showed the enormously distribution of jaundice patients in a big hospital at tertiary level as Cho Ray Hospital. In study of Whitehead MW 2008, 121 jaundice patients distributed in 5 departments of internal medicine and one of surgery, surgery accounted for 21% of total jaundice patients [
The map of causes of jaundice was presented in
Pre-hepatic causes were recorded as 3% in 352 cases at Sun Yat-Sen Memorial Hospital, Guangzhou, China [
We had 37 hepatitis cases in which viral causes accounted 18 (48.6%) and drug induced liver injury (DILI) 14 (37.8%). This showed that DILI was an important cause of hepatitis now in the recent decades when treatment by drugs is going to be increased. There were 7 drug jaundice cases compared to 2 viral hepatitis jaundices in 121 cases in study of Whitehead MW, 2001 [
There were 71 cases with obstructive jaundice divided as malignant causes (43, 60.6%) including cholangiocarcinoma, pancreas cancer, peri-ampulary cancer and gallbladder cancer; and benign causes of 39.4% in which choledocholithiasis was the main cause (
Liver enzyme as ALT was revealed as normal to <2.5 UNL (CTC1) in cirrhosis, hematology diseases and cardiac liver diseases, but was >5 UNL (CTC3) in hepatitis according to CTCAE, 2010 [
The total bilirubin could be divided into 2 grades by cut-point of 7 mg/dL. Hepatitis and obstructive biliary jaundice often had total bilirubin > 7 mg/dL, inversely jaundice due to other causes as hematology diseases, cirrhosis, liver tumor, sepsis, cardiac cirrhosis had total bilirubin < 7 mg/dL. Hemolysis alone rarely produce total bilirubin > 4 mg/dL, but extra-hepatic obstruction or hepatitis can cause the increase bilirubin up to 2 mg/day [
Increase direct bilirubin with D/T percentage > 60% were recorded as high as 100% in jaundice patients with hepatitis, pancreatic and biliary tract diseases, sepsis, cholangitis. The values of D/T percentage used for diagnosis as increase direct bilirubinemia were changed from 50%, 60% or 70% by different experts [
In 14 drug hepatitis cases, 1 case died due to acute drug hepatitis after using antithyroid drugs (1/14:7.1%). This result was as the same as those reported in other studies, as 0% mortality among 29 patients with DILI [
Mono-variable analysis of 8 risk factors against treatment failure in jaundice patients showed in
In conclusion, jaundice is a common sign in adult in-patients administered at the tertiary Cho Ray Hospital with the new-onset incidence rate as 11 ± 5 person per day. Jaundice patients distributed enormously in 21 diverse clinical departments. The map of causes of jaundice was completed with all 3 phases: pre-hepatic 13.7%, intra- hepatic 58.2%, and post-hepatic 22.8%. In hepatitis jaundice, drug induced liver injury (DILI) occupied as an important cause. Sepsis was the important cause of dead in adult jaundice patients. Approaching adult jaundice patients by 7 criteria as total bilirubin, the D/T percentage, ALT severity, AST/ALT ratio, GGT, bilirubin and urobilinogen in urine gave the guide for diagnosis of causes of jaundice. Finally, the independent risk factors of treatment failure in adult jaundice patients were sepsis and AST/ALT ratio > 2. The survey of jaundice in adult in-patients in a tertiary general government hospital gave the full picture for this common pathological sign.