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ORIGINAL ARTICLE
Year : 2022 | Volume
: 21
| Issue : 4 | Page : 316-321
The evaluation of serum lipid profile in chronic Hepatitis B patients at a Tertiary Care Centre in Western India: A cross-sectional study
Durga Shankar Meena1, Deepak Kumar1, Mahendra Kumar Garg1, Mahadev Meena1, Bharat Seju1, Gopal Krishana Bohra1, Naresh Kumar Midha1, Mithu Banerjee2
1 Department of Internal Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
2 Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
Correspondence Address:
Deepak Kumar
Department of Internal Medicine, All India Institute of Medical Sciences, Jodhpur - 342 005, Rajasthan
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/aam.aam_35_21
Abstract
Introduction: Hepatitis B virus (HBV) is known as a metabolovirus due to its impact on lipid and glucose metabolism in the liver. Previous literature showed a trend of hypolipidemia and reduced risk of metabolic syndrome in hepatitis B surface antigen-positive patients. However, data from the Indian population are lacking. We evaluate the relation of lipid profile with HBV infection and severity of liver disease. Materials and Methods: This was an observational cross-sectional study in which 50 patients with chronic hepatitis B and 43 anthropometrically matched seronegative controls were enrolled. Demographical, clinical, and laboratory data including lipid profile (high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides, and total cholesterol [TC]) were collected. Seropositive patients were categorized based on prognostic models (model for end-stage liver disease [MELD] and Child-Pugh score) for further analysis. Results: Our study revealed significant low levels of serum TC, HDL, and LDL cholesterol in hepatitis B patients compared to seronegative controls (133.06 vs. 162.39, 35.56 vs. 43.65, and 76.62 vs. 99.95 mg/dl respectively, P < 0.05). The patients with high MELD and Child-Pugh score were associated with hypolipidemia. Significant low levels of LDL and TC were observed in Child-Pugh class C in comparison to class A (94.8 vs. 149.2 and 50.6 vs. 87.9 mg/dl respectively, P < 0.05). Conclusions: A significant reduction in various lipid parameters was seen with chronic hepatitis B. Furthermore, prognostic score (high MELD and Child-Pugh score) were associated with hypolipidemia.
Abstract in French Résumé
Introduction: Le virus de l'hépatite B (VHB) est connu comme un métabolovirus en raison de son impact sur le métabolisme des lipides et du glucose dans le foie. Précédent la littérature a montré une tendance à l'hypolipidémie et à une réduction du risque de syndrome métabolique chez les patients positifs à l'antigène de surface de l'hépatite B. Cependant, les données de la population indienne font défaut. Nous évaluons la relation entre le profil lipidique et l'infection par le VHB et la gravité de la maladie hépatique. Matériels et méthodes: Il s'agissait d'une étude transversale observationnelle dans laquelle 50 patients atteints d'hépatite B chronique et 43 des témoins séronégatifs appariés ont été recrutés. Données démographiques, cliniques et de laboratoire, y compris le profil lipidique (lipoprotéines de haute densité [HDL], lipoprotéines de basse densité [LDL], triglycérides et cholestérol total [TC]) ont été collectés. Les patients séropositifs ont été classés en fonction de modèles pronostiques (modèle pour l'hépatopathie terminale [MELD] et score de Child-Pugh) pour une analyse plus approfondie. Résultats: Notre étude a révélé des taux sériques bas significatifs de cholestérol TC, HDL et LDL chez les patients atteints d'hépatite B par rapport aux témoins séronégatifs (133,06 contre 162,39, 35,56 vs 43,65 et 76,62 vs 99,95 mg/dl respectivement, P < 0,05). Les patients avec un MELD et un score de Child-Pugh élevés étaient associés à hypolipidémie. Des niveaux significativement faibles de LDL et de TC ont été observés dans la classe C de Child-Pugh par rapport à la classe A (94,8 vs. 149,2 et 50,6 vs 87,9 mg/dl respectivement, P < 0,05). Conclusions: Une réduction significative de divers paramètres lipidiques a été observée avec l'hépatite chronique B. De plus, le score pronostique (MELD élevé et score de Child-Pugh) était associé à une hypolipidémie.
Mots-clés: Cholestérol, maladie hépatique chronique, hépatite B, hypolipidémie, métabolisme lipidique
Keywords: Cholesterol, chronic liver disease, hepatitis B, hypolipidemia, lipid metabolism
Introduction 
Hepatitis B Virus (HBV) infection is a major public health burden with more than 250 million people infected with this virus worldwide.[1] A large proportion of these patients are from India (about 50 million), causing significant morbidity and mortality in the form of liver cirrhosis and hepatocellular carcinoma.[2] The liver plays an important role in glucose, apoprotein, lipoprotein, and lipid metabolism. Hepatocytes receive fatty acids which are either derived from lipolysis of adipose tissue or hydrolysis of fatty tissues in triglycerides (TG) (transported by gut chylomicron).[3],[4] These fatty acids further oxidized to form ATP and acetyl-CoA, and TG synthesis. Similarly, the liver plays an important role in cholesterol and phospholipids metabolism. Apoprotein A5 (ApoA5) and Apoprotein C3 (ApoC3) are an important component of lipoproteins which are expressed in liver and present in high-density lipoprotein cholesterol, chylomicrons, and very low-density lipoproteins (VLDL).[5],[6] There are reports showing the inverse relation of ApoA5 and ApoC3 with hepatitis B replication.[7],[8],[9] However, there is a dearth of data from India highlighting the relation of various lipids with HBV infection.[10] We undertook this study to compare the lipid profile of chronic hepatitis B patients with healthy seronegative control.
Materials and Methods Study design and patient selection
This was an observational cross-sectional study which was carried out in the department of internal medicine at a tertiary care center in western India. The study was conducted after the approval from the institutional ethical committee and performed according to the Declaration of Helsinki with an objective to find out the possible association between lipid profile and chronic hepatitis B infection. All patients with a diagnosis of chronic hepatitis B for at least 6 months and age group of 18–62 years, who were admitted or attended the clinic to the department of medicine, were included. Patients with a history of alcohol intake, obesity, diabetes mellitus, metabolic syndrome, hypertension, and already diagnosed case of dyslipidemia or/and on antilipidemic drugs, pregnancy were excluded from the study. A total of 50 patients were recruited for analysis after the exclusion of 24 participants (denied consent, clinical history was not available). All study participants were given a questionnaire with a clinical history and anthropometric variables, drug history, and demographic variables. Forty-three anthropometrically matched seronegative healthy controls were also enrolled. Written, informed consent was taken from all participants.
Measurements and laboratory analysis
All study participants were subjected to detailed clinical history, physical examination, and anthropometric measurements. The height and weight were measured, and body mass index was calculated for comparison with controls. The determination of hepatitis B surface antigen (HBsAg) was based on ELISA sandwich method (Merilisa, Meril Diagnostics). Anti-Hbs conjugated with peroxidase is added to the microplate wells and react with antigen-antibody complex. After the addition of enzyme-substrate, the solution yielded blue color which is proportionate of HbsAg concentration.
All patients underwent complete blood counts, liver function test including prothrombin time and international normalized ratio (INR), kidney function test including urine analysis and ultrasound of abdomen for liver details, spleen size, portal hypertension, and ascites. Overnight fasting venous blood samples (5 ml) were collected using antecubital venepuncture under aseptic conditions for serum lipid profile. The samples were collected in sterile tubes and labeled with a patient identification number. The serum separated after centrifugation was stored for further biochemical analysis. Serum lipid profile, including high-density lipoprotein (HDL), total cholesterol (TC), low-density lipoprotein (LDL), and TG were determined using an AU2700/5400 Beckman Coulter Analyzers. TC was determined by cholesterol oxidase/hydrogen peroxide (CHO-POD) method. The enzyme cholesterol oxidase oxidized cholesterol into cholest-4-en-3 one and hydrogen peroxide in the presence of oxygen. Hydrogen peroxide oxidized phenol and 4-aminoantipyrine to produce red color that was measured spectrophotometrically, the intensity of color is proportional to cholesterol concentration in serum. GPO/POD (glycerol phosphate dehydrogenase/peroxidase) method was used to determine TG level. TG was hydrolyzed by lipase into glycerol and free fatty acids. Phosphorylation of glycerol first formed glycerol-3 phosphate, which was converted into hydrogen peroxide by GPO. The intensity of color produced by peroxidase reaction is proportional to TG concentration. LDL and HDL were measured by CHO-POD with immune inhibition method. The final LDL and HDL were released after reaction with cholesterol esterase, cholesterol oxidase to yield a blue color complex, which was measured biochromatically at 540/660 nm and 600/700 nm, respectively. VLDL-C levels were estimated by using the Friedewald equation.[11]
Prognostication of patients was done with Child–Turcotte–Pugh (CTP) score and model for end-stage liver disease (MELD) score. Child-Pugh score (CTP) was calculated by using serum albumin, bilirubin, INR levels, and the presence of hepatic encephalopathy and ascites. Patients were subclassified into 3 groups (CTP class A, B, and C) for further comparison between each group. MELD score was calculated using serum creatinine, bilirubin, and INR levels and categorized into 3 groups (MELD <10, 10–18, and >18).[12]
Statistical analysis
The data were analyzed using SPSS (version 20.0, Armonk, NY, USA: IBM Corp). Numerical data were expressed as mean values ± standard deviation, and categorical data were expressed in percentage. Student's t- test was performed for analyzing the significance between different variables. Analysis of variance test was used for analyzing the significant difference between prognostic groups (based on MELD and CTP scores) of chronic hepatitis B. P < 0.05 was considered statistically significant.
Results In this study, a total of 50 patients with chronic hepatitis B infection were enrolled who were compared with 43 seronegative healthy controls. [Table 1] shows the demographic, clinical, and liver function parameters of hepatitis B patients and seronegative controls. Among 50 patients of chronic hepatitis B, 39 were male (78%). The mean duration of HBV infection was 18.2 months (time interval since the first diagnosis to study enrolment). Comparison of serum lipid profile (HDL, LDL, TG, and TC) was shown in [Table 2]. This study revealed significant low levels of serum TC, HDL, and LDL cholesterol in chronic hepatitis B patients compared to seronegative controls (133.06 vs. 162.39, 35.56 vs. 35.56, and 76.62 vs. 99.95 mg/dl respectively). [Table 3] shows the comparison of lipid profile between chronic hepatitis B with abnormal alanine aminotransferase (ALT) (≥36 U/L), chronic hepatitis B with normal ALT (<36 U/L), and healthy controls. Both groups (chronic hepatitis B with abnormal ALT and normal ALT) showed significantly low HDL, LDL, and low cholesterol in comparison to controls. We also compared the lipid parameters on chronic hepatitis B patients based on the severity of Child-Pugh class. The patients with Child-Pugh class B and C were having significantly low levels of TC and LDL compared to Child-Pugh class A [Table 4], which showed the association of severity of liver disease with hypolipidemia (cholesterol and LDL). There was no significant difference found between Child-Pugh class and TG in this study. [Table 5] shows the comparison of lipid profile of patients based on MELD score. This report showed significant low HDL and LDL levels in patients with increased MELD score.
Table 2: Serum lipid profile of the study population compared with healthy control
Table 3: Serum lipid profile of inactive hepatitis B (alanine transaminase ≤36 U/L) compared with active infection (alanine transaminase >36 U/L) and healthy control
Table 4: Comparison of lipid profile in chronic hepatitis B patients according to Child-Pugh class
Table 5: Comparison of lipid profile in chronic hepatitis B patients according to Model for End-Stage Liver Disease score Discussion The present study was aimed to explore the effect of chronic hepatitis B infection on the lipid profile. The liver plays an integral part in lipid metabolism. The mechanism of steatosis in various liver diseases is well-established; however, little is known about how chronic hepatitis B affects different lipids and lipoproteins.[13] There are studies showing conflicting reports about the relation of HBV and the prevalence of metabolic syndrome and lipid profile.[14],[15],[16] Data from the Indian population are also lacking in this regard with only one study from New Delhi reported the relation of lipid profile with HBV infection.[10] Results from the present study showed the trend of hypolipidemia in patients with chronic hepatitis B infection. Significant low levels of HDL, TC, and LDL were observed in CHB patients compared to healthy controls. These findings were consistent with other studies.[17],[18] However, in the present report, the level of TG was not found to be significantly different in both groups. This result was in agreement with findings described by Liu et al. (Mean TG levels: 126 vs. 131 mg/dl, HBV patients vs. control) and few other reports.[15],[16],[19],[20],[21] Conversely, a meta-analysis performed by Li Y et al. showed a strong negative effect of Hepatitis B virus on TG (odds ratio [OR] =0.62, 95% confidence interval [CI], 0.59–0.64).[22]
In the present study, significant hypolipidemia was seen in patients with chronic HBV infection, while no significant difference in lipid profile was observed between patients with abnormal ALT and normal ALT. This result was in contrast to other reports described by Su et al. and Agbecha et al., which highlighted rising ALT as an indicator for hypolipidemia.[16],[23] The duration of hepatitis B infection, viral load and effect of antiviral therapy in these patients may be the other factors which could have impacted the outcome of lipid levels.
We also evaluate the lipid profile of HBV patients in relation to the severity of the liver disease. The Child-Pugh classification and MELD score were the commonly used prognostic model for this purpose.[24] The results from our study showed the inverse relation of Child-Pugh score and various lipid components. Those with Child-Pugh class C were associated with significantly low levels of TC and LDL. These findings were consistent with previous reports,[25],[26] Bassani et al. described the hypocholesterolemia and low LDL (TC <100 mg/dl and LDL <70 mg/dl in 47.1% and 70.6% of the HBV patients with Child-Pugh class C, respectively). The correlation of TG with Child-Pugh score was weak, which was also highlighted by Ghadir et al.[26] Another study discussed the role of hypocholesterolemia in predicting the survival in severe liver disease, reported the survival of only 17 months in patients with TC <100 mg/dl and Child-Pugh class C.[27] Similar observations were found in our report when HBV patients were categorized based on MELD score with significant low LDL and HDL were seen with higher MELD score. The inverse relation between liver disease prognostic scores (Child-Pugh and MELD) and cholesterol showed that it can be used as an alternate prognostic index for prediction of survival in HBV patients.[21]
The mechanism of hypolipidemia in hepatitis B infection is still not clearly understood. Hepatitis B virus is also described as “metabolovirus” due to its ability to regulate the hepatic metabolic genes which can shape important metabolic events in the liver.[28],[29] A report by Oehler et al. described the role of HBV replication in alteration of cholesterol metabolism as a result of impaired bile acid uptake through binding of pre-S1 domain to its cellular receptor NTCP (sodium-taurocholate cotransporting polypetide).[30] In addition, repression of farnesoid X receptor and upregulation of cholesterol 7-alpha-hydroxylase (CYP7A1) by HBV infection also results in decreased cholesterol synthesis. Cholesterol synthesis is also reduced due to the decreased expression of the ACAT enzyme (acyl-CoA: Cholesterol acyltransferase) and decreased esterification.[31] Another possible theory was an increased level of adiponectin which was positively correlated with HBV replication.[32] The activation of peroxisome proliferator-activated receptor γ due to hepatitis B virus leads to increase adiponectin. Adiponectin causes decrease VLDL and TG synthesis by inducing their catabolism. The secretion of LDL and VLDL from the liver is dependent on the synthesis of apolipoprotein in the liver. According to in vitro models, the HBx protein has shown to increase the GnT-III (N-acetylglucosaminyltransferase III) expression and repression of apo B and related lipids.[33]
To the best of our knowledge, this is the second study from India to investigate the relationship between hepatitis B infection and lipid profile. The majority of previous reports were cohort studies lacking a control group for comparison. In addition, all possible confounding factors responsible for the alteration of lipid metabolism were excluded. However, there are still some limitations of our study. Our sample size was relatively small given the high prevalence of hepatitis B in India. We did not include prospective data to highlight the impact of Hbs Ag over a period of time in changing lipid parameters. In addition, there may be a selection bias due to the lack of severe hepatitis B cases in the study population. The impact of antiviral therapy on lipid profile in these patients was also unclear.
Conclusions Our study highlighted a significant association of hypolipidemia with Hepatitis B-positive patients. Furthermore, the severity of liver disease was also in parallel with decreased lipid parameters. There is a need for future studies involving a larger population with prospective data, which can also help in better understanding of the impact of Hepatitis B virus on lipid metabolism.
Ethical standards
This work was approved by Institutional Ethical Committee (AIIMS, Jodhpur, reference no-AIIMS/IEC/2020/3111).
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References 
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