Chronic hepatitis B-associated liver disease in the context of human immunodeficiency virus co-infection and underlying metabolic syndrome

Table 1 Metabolic syndrome―definition, diagnostic criteria and association with chronic liver disease

Definition of MetS
A clustering of metabolic disorders that include hypertension, central obesity, impaired glucose metabolism including insulin resistance and abnormal cholesterol or triglyceride levels. MetS increases the risk of morbidity and mortality from cardiovascular disease, stroke, type 2 diabetes, chronic kidney disease and chronic liver disease
Diagnostic criteria1
NCEP/ATP III[27]	AHA/NHLBI[28]	IDF[29]	JIS[30]	WHO[31]
Presence of ≥ 3 of the following:	Presence of ≥ 3 of the following:	Central obesity; ethnicity-specific waist circumference values2 or BMI > 30 kg/m2 plus any 2 of the following:	Presence of ≥ 3 of the following:	Glucose intolerance, impaired glucose tolerance or diabetes mellitus and/or insulin resistance and any 2 of the following:
Abdominal obesity; > 102 cm in males and > 88 cm in females	Elevated waist circumference; ≥ 102 cm in males and ≥ 88 cm in females	Raised triglycerides; ≥ 150 mg/dL (1.7 mmol/L) or specific treatment for this lipid abnormality	Elevated waist circumference; population- and country-specific definitions2	Raised arterial pressure; ≥ 160/90 mmHg
Elevated triglycerides; ≥ 150 mg/dL or treatment for elevated triglycerides	Elevated triglycerides; ≥ 150 mg/dL (1.7 mmol/L) or treatment for elevated triglycerides	Reduced HDL cholesterol; < 40 mg/dL (1.03 mmol/L) in males and < 50 mg/dL (1.29 mmol/L) in females, or specific treatment for this lipid abnormality	Elevated triglycerides; ≥ 150 mg/dL (1.7 mmol/L) or treatment for elevated triglycerides	Raised plasma triglyceride; ≥ 150 mg/dL, and/or low HDL cholesterol; < 35 mg/dL in males and < 39 mg/dL in females
Reduced HDL cholesterol; < 40 mg/dL in males and < 50 mg/dL in females	Reduced HDL cholesterol; < 40 mg/dL (1.03 mmol/L) in males and < 50 mg/dL (1.3 mmol/L) in females or treatment for reduced HDL cholesterol	Raised blood pressure; ≥ 130/≥ 85 mmHg, or treatment of previously diagnosed hypertension	Reduced HDL cholesterol; < 40 mg/dL (1.0 mmol/L) in males and < 50 mg/dL (1.3 mmol/L) in females, or treatment for reduced HDL cholesterol	Central obesity; waist/hip ratio > 0.90 in males and > 0.85 in females and/or BMI > 30 kg/m2
Elevated blood pressure; ≥ 130/≥ 85 mmHg or treatment for elevated blood pressure	Elevated blood pressure; ≥ 130/≥ 85 mmHg or antihypertensive treatment	Raised fasting plasma glucose; ≥ 100 mg/dL (5.6 mmol/L), or previously diagnosed type 2 diabetes	Elevated blood pressure; ≥ 130/≥ 85 mmHg or anti-hypertensive treatment	Microalbuminuria; urinary albumin excretion rate ≥ 20 μg/min or albumin/creatinine ratio ≥ 20 μg/mg
Elevated fasting glucose; ≥ 110 mg/dL or treatment for elevated glucose	Elevated fasting glucose; ≥ 100 mg/dL or treatment for elevated glucose		Elevated fasting glucose; ≥ 100 mg/dL, or treatment of elevated glucose
MetS and chronic liver disease
The association between MetS and chronic liver disease involves a complexity of risk factors which are yet to be fully understood. NAFLD which covers a spectrum of fatty liver disorders including NASH, is the most common cause of abnormal liver function among individuals with MetS. MetS components like insulin resistance may increase fatty acids in the liver, leading to fat or triglyceride accumulation in hepatocytes. NASH, which is an advanced form of NAFLD, is associated with liver inflammation and liver damage, leading to the development of liver cirrhosis and progression to advanced liver fibrosis. In addition, type 2 diabetes and obesity may increase the risk of HCC. The presence of MetS may have worse outcomes in individuals with other causes of chronic liver disease, such as viral hepatitis.

¹NCEP/ATP III: National Cholesterol Education Program/Adult Treatment Panel III; AHA/NHLBI: American Heart Association/National Heart, Lung and Blood Institute; IDF: International Diabetes Federation; JIS: Joint Interim Statement; WHO: World Health Organization.

²Currently, ethnicity-specific waist circumference values have not been defined for populations from sub-Saharan Africa. BMI: Body mass index; HCC: Hepatocellular carcinoma; HDL: High-density lipoprotein; MetS: Metabolic syndrome; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis.

Table 2 Prevalence of metabolic syndrome among people living with human immunodeficiency virus in sub-Saharan Africa from selected studies

Ref.	Country	Study design	Sample size, n	MetS diagnostic criteria	Prevalence of MetS	Independent risk factors1
Adébayo et al[53]	Benin	Cross-sectional	244	IDF	18.4%	-
Ayodele et al[54]	Nigeria	Cross-sectional	291	NCEP/ATP III; IDF; JIS	12.7%; 17.2%; 21.0%	-
Berhane et al[55]	Ethiopia	Cross-sectional	313	NCEP/ATP III	21.1%	HAART > 12 mo, female sex
Bosho et al[56]	Ethiopia	Cross-sectional	286	NCEP/ATP III; IDF; JIS	23.5%; 20.5%; 27.6%	BMI ≥ 25 kg/m2, formal education
Dimodi et al[57]	Cameroon	Cross-sectional	463	IDF; NCEP/ATP III	32.8%; 30.7%	-
Guira et al[58]	Burkina Faso	Cross-sectional	300	IDF	18.0%	-
Hirigo et al[59]	Ethiopia	Cross-sectional	185	IDF; NCEP/ATP III	24.3%; 17.8%	BMI ≥ 25 kg/m2, female sex, age > 40 yr
Mbunkah et al[60]	Cameroon	Cross-sectional	173	NCEP/ATP III	15.6%	-
Muhammad et al[61]	Nigeria	Cross-sectional	200	NCEP/ATP III	15.0%	-
Muyanja et al[62]	Uganda	Cross-sectional	250	AHA/NHLBI	58.0%	Female sex, age > 40 yr
Ngatchou et al[63]	Cameroon	Cross-sectional	108	AHA/NHLBI	47.0%	-
Nguyen et al[64]	South Africa	Cross-sectional	748	JIS; IDF; NCEP/ATP III	28.2%; 26.5%; 24.1%	-
Obirikorang et al[65]	Ghana	Cross-sectional	433	NCEP/ATP III; WHO; IDF	48.3%; 24.5%; 42.3%	-
Sobieszczyk et al[66]	South Africa	Longitudinal	160	NCEP/ATP III	19.2%	Older age, time post HIV infection, family history of diabetes, human leukocyte antigen B 81:01 allele
Tesfaye et al[67]	Ethiopia	Cross-sectional	374	IDF; NCEP/ATP III	25.0%; 16.8%	Female sex, older age, BMI ≥ 25 kg/m2, total cholesterol ≥ 200 mg/dL

¹Based on multivariate analysis in the individual studies. AHA/NHLBI: American Heart Association/National Heart, Lung and Blood Institute; BMI: Body mass index; HAART: Highly active antiretroviral therapy; IDF: International Diabetes Federation; JIS: Joint Interim Statement; MetS: Metabolic syndrome; NCEP/ATP III: National Cholesterol Education Program/Adult Treatment Panel III; WHO: World Health Organization.