Clinical-biochemical profile and etiology of acute viral hepatitis in hospitalized young adults at tertiary care center.

BACKGROUND: Acute viral hepatitis (AVH) is a major health concern in developing nations like India in regard to morbidity and mortality.
OBJECTIVE: To identify incidence, clinical presentation, laboratory abnormalities, severity, and complication of AVH in young adults.
MATERIALS AND METHODS: A prospective study was conducted from August 2016 to August 2018 among 70 young adult patients of AVH at Civil Hospital, Ahmedabad. Data on clinical presentation, laboratory values, complication, and severity were obtained, and analysis was performed.
RESULTS: Hepatitis E viral (HEV) infection was seen in 70% case and was more common in age group of 21-30 years followed by Hepatitis B and Hepatitis A, 15.8% and 12.8% case respectively. Most common presenting symptom was jaundice in 80-85% of patients followed by anorexia 65.7% and nausea and vomiting 57.1% of patients. Most common clinical sign was icterus followed by hepatomegaly. Total serum bilirubin and serum SGOT elevated in all cases. Acute liver failure was seen in seven cases. Six cases were due to hepatitis E and one case was due to hepatitis A. Acute kidney injury was present in seven cases. Coagulopathy was found to be major complication in 25.7% cases.
CONCLUSION: HEV is the major etiological agent of AVH in young adults. It is not possible to differentiate viral hepatitis based on clinical features and biochemical parameters. However, cholestasis is found to be significantly associated with hepatitis-E infection. Copyright:

Introduction

Acute viral hepatitis (AVH) is a major health concern in developing nations in regard to morbidity and mortality, although AVH is prevalence worldwide. AVH is caused by viral agents such as A, B, C, D, E and G. However, most frequent viral agents of AVH with major health burden in India are hepatitis A and hepatitis E.[123] Hepatitis E virus (HEV) causes sporadic cases and major epidemic of viral hepatitis and fulminant hepatic failure in developing countries.[45] Hepatitis A and hepatitis E (HEV) are transmitted mainly by feco-oral route while hepatitis B (HBV), C (HCV), and D (HDV) through parenteral route. Earlier seroprevalence studies of anti-HAV reveal high seroprevalence in India. However, there is increased incidence of HAV infection in the adult and adolescent population compare to children in India.[1] Hepatitis B and hepatitis C are major global health problem. It can cause chronic infection which progress to cirrhosis, hepatic decompensation, and hepatocellular carcinoma.[67] Primary care integration of viral hepatitis testing, vaccination, other prevention, care, and treatment can increase access and improve health outcomes for at-risk patients and patients with chronic infection. The aim of the study was to identify the clinical and laboratory parameters, severity, and complication of AVH in young adults.

Method

Ethics: This study was approved by Institutional Ethics Committee. Date of approval: 30th November, 2018.

The present prospective study included 70 young adult patients of AVH, admitted in tertiary care hospital during August 2016 to December 2018.

Inclusion criteria for cases

All patients with age 18–40 years

Patient with recent onset of jaundice, conjugated hyperbilirubinemia or mixed hyperbilirubinemia, positive serum report of immunoglobulin M

[IgM] HAV, IgM HEV, hepatitis B surface antigen [HBsAg], and IgM HCV, HBc IgM.

Exclusion criteria for cases:

All patient with age <18 year and >40 year.

Patient with underlying chronic liver disease, negative serological test, USG suggestive of cirrhosis of liver.

Patient with drug-induced hepatitis, alcoholic hepatitis, and cholestatic hepatitis of pregnancy.

Patient with hepatitis due to metabolic disease and sepsis-induced multiorgan failure.

Acute hepatitis case was defined as acute illness with discrete onset of clinical symptoms (e.g. fever, headache, malaise, nausea, vomiting, loss of appetite, dark urine, and abdominal pain) with jaundice or serum (ALT) levels >200 IU/L or at least twice upper limit of normal without having an history of chronic liver disease.[8]

Complete medical history and all relevant clinical information were obtained for each patient. Past history was taken with the special reference to contact with a jaundiced patient (e.g. surgical/dental procedure, blood transfusion, vaccination, and other medical procedures involving injections). Drug history was taken to rule out drug-induced liver injury.

We used SPSS Ver. 10.0 for the statistical analysis.

Results

Study was carried out on 70 patients of AVH, 37 (52.8%) were male and 33 (47.2%) were female. Male–female ratio was 1.12:1 [Figure 1].

Figure 1

Sex-wise distribution of cases according to etiological pattern

In this study we found HAV in 9 (12.8%), HEV in 49 (70%), HBV in 11 (15.8%), and HCV in 1 (1.4%) adults [Table 1].

Table 1

Age-wise distribution of cases according to etiological pattern

Age (in yr.)	HAV(%) n (9)	HEV(%) n (49)	HBV(%) n (11)	HCV(%) n (1)	Total no. of patients n (70)
18-20	5 (55.5%)	7 (14.3%)	1 (9.1%)	0	13 (18.6%)
21-30	4 (44.5%)	27 (55.1%)	5 (45.5%)	0	36 (51.4%)
31-40	0	15 (30.6%)	5 (45.5%)	1 (100%)	21 (30%)

Most common presenting symptoms were found to be yellowish discoloration of urine in 59 (84.3%) cases followed by yellowish discoloration of sclera in 57 (81.4%). Most common was found to be icterus in 63 (90%) followed by hepatomegaly 22 (31.4%) [Table 2].

Table 2

Clinical symptoms and sign in young adult with AVH

Symptom and sign	HAV(%) n (9)	HEV(%) n (49)	HBV(%) n (11)	HCV(%) n (1)	Total (%) n (70)
Yellowish Discolouration of Sclera	7 (77.7%)	40 (81.6%)	10 (90.9%)	0	57 (81.4%)
Yellowish Discolouration of Urine	7 (77.7%)	41 (83.7%)	10 (90.9%)	1 (100%)	59 (84.3%)
Nausea & Vomiting	2 (22.2%)	34 (69.4%)	3 (27.2%)	0	39 (55.7%)
Loss of Appetite	7 (77.7%)	32 (65.3%)	6 (54.5%)	1 (100%)	46 (65.7%)
Abdominal Pain	4 (44.4%)	27 (55.1%)	6 (54.5%)	0	37 (52.9%)
Fever	4 (44.4%)	29 (59.1%)	4 (36.4%)	0	37 (52.9%)
Weakness (Malaise)	03 (33.3%	22 (44.9%)	5 (45.5%)	01 (100%)	31 (44.3%)
Itching	1 (11.1%)	06 (12.2%)	0	0	07 (10%)
Altered Sensorium	00	06 (12.2%)	01 (9.0%)	00	07 (10%)
Icterus	09 (100%)	43 (87.7%)	10 (90.9%)	01 (100%)	63 (90%)
Pallor	02 (22.2%)	14 (28.5%)	03 (6.12%)	01 (100%)	20 (28.5%)
Hepatomegaly	01 (11.1%)	18 (36.7%)	03 (6.12%)	00	22 (31.4%)
Splenomegaly	00	03 (6.12%)	01 (100%)	00	04 (5.7%)
Pedal Edema	01 (11.1%)	02 (4.08%)	00	00	03 (4.2%)
Ascitis	01 (11.1%)	03 (6.12%)	00	00	04 (5.7%)
Acute Liver Failure	00	06 (12.24%)	01 (100%)	00	07 (10%)

Hb level (<10 gm%) seen in 27 (38.6%) patients. Mean Hb level was 10.99 gm%. WBC count was raised in 23 (32.8%) patients and mean WBC count was 10112.74 per μL. Low platelet was found in 14 (20%) patients and mean platelet count was 2.48 (×104/mm3) [Table 3].

Table 3

Frequency of hematological changes in young adult patients with acute viral hepatitis

Investigation		HAV(%) n (9 )	HEV(%) n (49 )	HBV(%) n (11)	HCV(%) n (1 )	TOTAL n (70)
Hemoglobin (gm%)	>10	06 (66.6%)	30 (61.2%)	07 (63.6%)	00	43 (61.4%)
	8-10	01 (11.1%)	12 (24.4%)	02 (18.1%)	00	15 (21.4%)
	<8	02 (22.2%)	07 (14.2%)	02 (18.1%)	01 (100%)	12 (17.2%)
Total Leucocyte count (TLC) (µL)	>11000	01 (11.1%)	17((34.6%)	04 (36.3%)	01 (100%)	23 (32.8%)
	4000-11000	08 (88.8%)	32((65.3%)	05 (45.4%)	00	45 (64.2%)
	<4000	00	00	02 (18.1%)	00	02 (3%)
Platelets Count (×104/mm3)	<150000	01 (11.1%)	08 (16.3%)	05 (45.4%)	00	14 (20%)
	>150000	08 (88.8%)	41 (83.6%)	06 (54.5%)	01 (100%)	56 (80%)

Total serum bilirubin was raised in all cases of hepatitis. Mean bilirubin was 7.99 mg/dl. Anicteric hepatitis with bilirubin <3 mg/dl seen in 11 (15.71%) cases. Direct hyperbilirubinemia was seen in 97% of patients [Table 4].

Table 4

Serum bilirubin in young adult with AVH

Bilirubin mg/dl	HAV(%) n (9)	HEV(%) n (49)	HBV(%) n (11)	HCV(%) n (1)	Total(%) n (70)
1.3-3	00	10 (20.4%)	01 (9.1%)	00	11 (15.7%)
3.1-10	06 (66.7%)	16 (32.6%)	03 (27.3%)	01 (100%)	26 (37.14%)
10.1-20	03 (33.3%)	17 (34.7%)	05 (45.4%)	00	25 (35.71%)
20.1-30	00	04 (8.16%)	02 (18.2%)	00	06 (8.57%)
>30	00	02 (4.1%)	00	00	02 (2.85%)

SGOT was raised in 69 (98.5%) cases. SGPT was raised in all cases of AVH A and hepatitis E. Serum level of SGPT was high in 98.5% patients of our study groups but highest in case of hepatitis E followed by hepatitis B and hepatitis A. Mean SGPT level was 1036.62 IU/L. Serum SGOT was raised in all cases. SGOT was highest in hepatitis E followed by hepatitis A and hepatitis B. Mean SGOT level was 776.7 IU/L [Table 5].

Table 5

SGPT and SGOT in young adults with AVH

Parameter	HAV(%) n (9)	HEV(%) n (49)	HBV(%) n (11)	HCV(%) n (1)	Total(%) n (70)
SGPT (IU/L)
1-40	00	00	01 (9.1%)	00	01 (1.4%)
41-1000	02 (22.2%)	15 (30.6%)	03 (27.3%)	01 (100%)	21 (30%)
1001-2000	02 (22.2%)	10 (20.4%)	02 (15.2%)	00	14 (20%)
2001-3000	00	01 (1.04%)	00	00	01 (1.42%)
>3000	00	02 (4.08%)	00	00	02 (2.85%)
SGOT (IU/L)
1-40	00	00	00	00	00
41-1000	06 (66.6%)	32 (65.3%)	09 (81.8%)	01 (100%)	48 (68.5%)
1001-2000	02 (22.2%)	14 (28.5%)	02 (18.1%)	00	18 (25.7%)
2001-3000	01	01 (2.0%)	00	00	02 (2.8%)
>3000	00	02 (4.0%)	00	00	02 (2.8%)

In this study, alkaline phosphate seen high as >500 IU/dl in 2 (22.2.%); 9 (18.3%) and 4 (36.3%) cases of hepatitis A; E and B respectively. In this study seven cases of cholestatic jaundice were noted: six from hepatitis E and one from hepatitis A. In all seven cases alkaline phosphate was raised to >500 [Table 6].

Table 6

Biochemical parameter in young adult with AVH

Parameters	HAV(%) n (9)	HEV(%) n (49)	HBV(%) n (11)	HCV(%) n (1)	Total(%) n (70)
Alkaline phosphatase (IU/dl)
25-90	00	05 (10.2%)	00	01 (100%)	06 (8.57%)
91-500	07 (77.7%)	35 (71.4%)	07 (63.6%)	00	49 (70.0%)
>500	02 (22.2%)	09 (18.3%)	04 (36.3%)	00	15 (21.42%)
Serum Protein (gm%)
6-8.3 (gm%)	08 (88.8%)	34 (69.3%)	09 (81.8%)	00	51 (72.8%)
<6 (gm%)	01 (11.1%)	15 (30.6%)	02((18.1%)	01 (100%)	19 (27.2%)
Serum Albumin (gm%)
3.2-5(gm%)	08 (88.8%)	37 (75.5%)	10 (90.9%)	00	55 (78.6%)
<3.2(gm%)	01 (11.1%)	12 (24.4%)	01 (9.1%)	01 (100%)	15 (21.4%)
Serum Globulin (gm%)
2.8-3.3(gm%)	07 (77.7%)	40 (81.6%)	11 (100%)	00	58 (82.8%)
>3.3(gm%)	02 (22.2%)	09 (18.3%)	00	01 (100%)	12 (17.1%)
Prothrombin time (sec)
<15 sec	05 (55.5%)	38 (77.5%)	08 (72.7%)	01 (100%)	52 (74.28%)
>15 sec	04 (44.5%)	11 (22.5%)	03 (22.5%)	00	18 (25.71%)

Hepatic coagulopathy was the commonest complication found in study. Coagulopathy was observed in all cases of acute liver failure. In this study, seven cases of renal failure was present and among them six cases were due to hepatitis E and one case was due to hepatitis A. Severe anemia was documented in 12 (17.1%) patients [Figure 2].

Figure 2

Complication wise distribution of cases

Discussion

AVH is a major health concern affecting in young productive population. In this study, among 70 AVH patients, majority were hepatitis E (70%), followed by hepatitis B (15.8%), hepatitis A (12.8%), and hepatitis C (1.4%). Similarly other study done by Dabadghao et al. found among 40 hepatitis cases, majority were hepatitis E (45%).[9] Study done by Nishar Ahmed Shah et al. also found that hepatitis E was most common cause of AVH accounting for 50% of patients in their study group.[10] From this study it can be concluded that HEV is the major etiological agents of AVH in young adults. Important fact noted in the present study was the frequency of HAV among adults. In the present study 12.8% patients suffering from hepatitis A. Seroprevalence studies reveal that 90–100% of the population acquires anti-HAV antibody and becomes immune by adolescence.[11] A study conducted by Behera MR et al. found that hepatitis A infection is more common among children which accounting for 62.5%.[12] India is thought to be endemic for HAV and by age of 15 most of the population are observed to be protected against HAV due to subclinical exposure to HAV in childhood.[13] This observation indicate that in India, due to developmental progress, certain population are not exposed to HAV. In childhood and adult population involvement could be due to developmental progress.[1213]

In the present study, AVH was commonly seen in the age group of 21–30 years with a mean age of 27.25 years among them hepatitis E were majority accounting for 55.1%. In this study, mean age of presentation was 27.25±9.5 years which was slightly lower with other studies Nishar Ahmed et al. 30±12.4 years and Birajdar SV et al. 36.2±3.5 years [Table 7].[610] Study done by Varsha Dabadghao et al. and study by Birajdar SV et al. found that maximum number of patients were young adults.[914] Male were affected slightly more than female.

Table 7

Comparison of mean age with other studies

	In Present Study (n=70)	Nishar Ahmad Shah et al.[6] (n=56)	Birajdar SV et al.[10] (n=106)
Mean age (years)	27.25±9.5	30±12.4	36.2±3.5

A study done by Nishar Ahmed Shah et al., most common symptoms observed were jaundice (86.10%) followed by anorexia (76.50%), dark-colored urine (73%), fever with chills (66.1%), and abdominal pain in (36.3%).[10] Another study done by Zhang et al. also observed that the common clinical symptoms were jaundice, fatigue, and anorexia.[15] In the present study, the most common presenting symptoms was yellowish discoloration of urine (84.2%) followed by yellowish discoloration of sclera (81.2%). Next common symptoms were anorexia (65.7%), nausea and vomiting (40%), abdominal pain (38%), and fever (37%).

In the present study, anemia was seen in 27 (38.6%) patients and mean hemoglobin was 10.99 gm%. TLC was raised in all cases except two (18.1%) cases of acute hepatitis B. Study done by Ali SJ, et al. also observed increase TLC in HBV patients.[16] Mean TLC was 10115.74 cu/mm. Low platelet count was found in 14 (20%). Study done by Rahman MM et al, low platelet count was observed in 36 cases of HEV patients.[17] Anemia was observed in 24% of patients in Perseghin P et al. is not unusual in AVH.[18] This is attributed to a temporary bone marrow suppression and autoimmune hemolytic anemia, which may accompany viral hepatitis.[19] Dilutional anemia is another possible explanation for this observation, as plasma volume is frequently increased in active hepatic disease.[20] Study done by Changgeng Yi Xue Za Zhi Zhi et al. found that leukocytosis and leucopenia in 10.8% and 7.4% respectively.[21] This is attributed to a virus interfering with leucopoiesis supports the more frequent finding of leucopenia rather than leukocytosis.[22] In contrast, study done by Ahmad AE et. al found that there were no significant changes in TLC, RBC count, Platelet count in patients with CHB, where as this study was strictly focus on AVH.[23]

In the present study, total serum bilirubin (mg/dl) was raised in all cases and SGPT was raised in 98.5% patients. Raised SGOT was observed in all cases of hepatitis A and E. In this study, raised alkaline phosphatase was observed in 2 (22.2%); 20 (40.8%) and 5 (45.5%) cases of hepatitis A, E, and B respectively. In this study we noted seven cases of cholestatic jaundice among six of them were hepatitis E and one case from hepatitis A. In other study done by Varsha Dabadghao et al., Nandi et al. raised alkaline phosphatase was observed 10% and 88.5% respectively.[924] In this study, low serum albumin was observed in 15 (21.4%) cases. Similar results observed in study done by Birajdar SV et al. in 17.9% cases and by Varsha Dabadghao et al. in 37.5% cases of AVH.[914] PT/INR was found deranged in 4 (44.5%), 11 (22.5%), 3 (22.5%) cases of hepatitis A, E, B respectively. Birajdar SV et al. also observed deranged PT >15 sec in hepatitis A, B, C.[9] Varsha Dabadghao et al. found that altered PT/INR >15 sec was present in 30% cases of AVH.[14] In present study, altered coagulation profile was present in all cases of acute liver failure. Coagulation failure during the course of AVH is regarded as of prognostic importance.

In the present study, mortality was 7.2%. Five patients were expired due to acute fulminant hepatic failure. High TLC count was present in four expired cases. This indicates that leukocytosis is often associated with fulminant viral hepatitis and higher mortality.

In disease endemic areas, viral hepatitis E is usually diagnosed based on the detection of IgM antibodies to the hepatitis E virus and over the past years rapid tests are available for field use. Primary care integration of viral hepatitis testing, vaccination, other prevention, care, and treatment can increase access and improve health outcomes for at-risk patients.

Conclusion

Viral hepatitis E has been found to be the commonest cause of AVH in young adults, although AVH A is known as an infection of childhood, this infection can be seen in adolescents and adults. Improvement in hygiene and socioeconomic conditions, routine immunization has resulted in a decrease in the immunity of the population. This is reflected in the increasing incidence of hepatitis A among adults. From the present study, it can be concluded that HEV is the major etiological agents of AVH in young adults. It is not possible to differentiate viral hepatitis based on clinical features, biochemical parameters, and severity of illness. Serological markers are essential for correct etiological diagnosis. However, cholestasis is found to be significantly associated with hepatitis-E infection.

Contribution: H.D conceived the idea, collected data, analyzed, and prepared the initial draft of the paper. D.M and A.A supervised the data collection and provided support, encouragement, and administrative help to carry out this study. D.J and J.G helped in analysis and drafting the manuscript.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.