Chronic liver disease in HIV patients

Determinants and clinical manifestations

Abstract

Background and Aim: 

Chronic liver disease (CLD) is a common cause of morbidity and mortality in medical wards of tertiary hospitals in Nigeria, and the etiology varies from viral hepatitis B and C, retroviral disease, alcoholic and non-alcoholic fatty liver disease, drug toxicity to several other causes. Liver diseases have also been recognized as a leading cause of death among HIV-infected persons. We aim to elucidate the pattern of clinical presentation of CLD in non-hepatitis B virus/hepatitis C virus patients who are HIV-seropositive with minimal alcohol consumption as well as to identify the prevalence and risk factors for CLD in the subjects.

Materials and Methods: 

This was a retrospectively analyzed case–control study of 170 HIV-seropositive patients with age- and sex-matched controls seen at the medical outpatient department and wards of the University of Port Harcourt Teaching Hospital. Sociodemographic, anthropometric, clinical, and laboratory characteristics were extracted and were analyzed with SPSS version 21.

Results: 

Sixty-three (37.1%) HIV patients had clinical manifestations of CLD with fatigue (51, 30%) and hepatomegaly (14, 8.2%) as the commonest symptom and sign, respectively. Chronic use of medications including highly active antiretroviral therapy (5.1 ± 1.6 years, P = 0.000) and herbal preparations (n = 20, 11.8%, P = 0.000) were the most significant determinants of CLD. Hypoalbuminemia and low CD4 counts were observed.

Conclusion: 

CLD is common in HIV patients without viral hepatitis B and C. Early identification of risk factors and proper clinical evaluation can aid in its mitigation.

INTRODUCTION

Chronic liver disease (CLD) is a progressive deterioration of liver function including its synthetic, metabolic, and excretory functions lasting more than 6 months. Globally, CLD and its consequence has affected an estimated 1.5 billion persons.[¹]

CLD is one of the frequent causes of death, especially in the developing world. In Africa, liver cirrhosis is responsible for 53,000–103,000 deaths per year,[²] and CLD secondary to viral hepatitis is a leading cause of morbidity and mortality in the African and Asia-Pacific regions.[³] CLD is a common cause of morbidity and mortality in many general medical wards of the tertiary hospitals in Nigeria, and the etiology varies from viral hepatitis B and C, retroviral disease, alcoholic and non-alcoholic fatty liver disease (NAFLD), drug toxicity to several other causes.

According to Agada et al.,[⁴] there is a paucity of information and gaps in the prevalence of CLD data due to lack of computerized documentation of patients with CLD information and lack of a national program and guideline for the prevention, detection, and treatment of CLD in Nigeria. A 2018 WHO publication states that “liver disease deaths in Nigeria reached 60,044 or 3.10% of the total deaths making Nigeria the second in the world with age adjusted death rate of 64.44 per 100,000 of population.”[⁴⁵]

Despite the worldwide changing paradigm of CLD, which results from the emergence of and implementation of vaccination program for hepatitis B virus, increased screening, and early implementation of relatively safer antivirals for hepatitis B and C,[³] newer factors in the incidence of CLD are playing a key role including NAFLD—the most common cause of CLD[⁶]—and HIV-related liver disease—which is the most common non-AIDS-related cause of mortality in HIV-infected patients.[⁷] Liver disease has thus been documented as a leading cause of death among HIV-infected persons.[⁸]

Nigeria has the world’s second highest burden of HIV/AIDS, with 190,950 HIV/AIDS infections per year, and the second highest rate in the world.[⁹]

MATERIALS AND METHODS

Study setting and participants

This was a retrospectively analyzed case–control study of 170 HIV-seropositive patients with age- and sex-matched controls seen at the medical outpatient department and wards of the University of Port Harcourt Teaching Hospital (UPTH), a tertiary health facility located in the South-South region of Nigeria.

Participants older than 18 years of age with confirmed HIV infection using the ELISA-based double rapid test kit (Determine and Stat Pak) were included in the study. Those excluded from the study were participants less than 18 years of age, pregnant women as determined by a positive urine beta-human chorionic gonadotropin test, those with a significant history of alcohol ingestion in excess of >20 g/day, diabetic patients and/or fasting blood glucose >7.1 mmol/L (>126 mg/dL), and hepatitis B surface antigen (HbsAg)-positive or hepatitis C virus (HCV) antibody-positive individuals.

CLD was defined as the presence of one or more clinical features of decompensated liver disease and the presence of hepatic parenchymal heterogeneity on ultrasound scan.

Study design and methods

Sociodemographic data including age and sex, were extracted from the records. The data of the study participants were assessed for potential risk factors of CLD including their alcohol consumption level. Information on their clinical examination as well as standard laboratory assessments such as liver function test, serum albumin, and complete blood count were recorded. Radiological findings of the ultrasound scan of the abdomen were evaluated, and the diagnosis of CLD is based on the presence of an abnormal liver parenchymal heterogeneity.[¹⁰]

Ethical considerations

Ethical clearance for the study was obtained from the UPTH Ethical Committee before commencement of the study with approval number UPTH/ADM90/S.11/VOLX/90. Ethical issues and processes were addressed regarding data collection, storage, sharing and ownership of data, and necessary safeguards for the protection of data and participants.

Statistical analysis

The results were analyzed using SPSS version 21 (Statistical Package for Social Sciences, version 21). The results have been expressed using mean ± standard deviations, percentages, tables, and pie charts, and the confidence interval was set at 95% and all tests were considered to be statistically significant at the P-value less than 0.05.

RESULTS

Age and sex distribution of the study population

The mean age of the cases with HIV infection was 36.8 ± 10.1 years with a range of 18–64, whereas that of the control population was 35.6 ± 9.6 years with a range of 24–66. The most common age group was the 31–40 years, both among the patients and the controls. There was no statistical difference in age distribution between the two groups (P = 0.271).

There were predominantly more females in the study population with a female-to-male ratio of 2.2:1 [117 (68.8%): 53 (31.2%)] among the patients and a female-to-male ratio of 1.6:1 [107 (62.9%): 63 (37.0)]. There was no statistical difference in sex distribution between the two groups (P = 0.751).

Pattern of clinical presentation of study population

Clinical symptoms

Most of the HIV patients were asymptomatic [107 (62.9%)], whereas 63 (37.1%) HIV patients presented with symptoms. Twelve (7.05%) of the controls also presented with symptoms. The most common symptom in the study population was fatigue, which was present in 51 (30%) patients and 10 (5.8%) controls. Other symptoms elicited in the HIV-positive population were pruritus [26 (15.3%)], right upper quadrant discomfort [18 (10.6%)], and leg swelling [9 (5.3%)] [Figure 1]. In 11.8%[¹¹] of the patients, there was a combination of fatigue and pruritus, whereas 15 (8.8%) had experienced both fatigue and right upper quadrant discomfort at the time of recruitment.

Figure 1: Distribution of symptoms among the HIV patients

Physical signs

Physical signs were elicited in 26 (15.3%) patients, and the commonest sign was hepatomegaly which was present in 14 (8.2%) patients, though absent in the controls. Furthermore, 12 (7.1%) patients had fluffy hair, whereas bilateral leg edema was present in 9 (5.3%) patients. Other observed signs include parotid swelling (5, 2.9%), gynecomastia (3, 1.8%), and distended anterior abdominal wall veins in 1 (0.6%) patient [Figure 2]. No clinical signs were elicited in the controls.

Figure 2: Distribution of signs among the HIV patients

Risk factors for chronic liver disease in the study population [Table 1]

1. 1. Chronic use of medications
• Herbal medications: This was observed in 20 (11.8%) patients and none of the controls. This difference was statistically significant (P = 0.000).
• Duration of highly active antiretroviral therapy (HAART) use: The mean duration of HAART use was also higher among the HIV patients with clinical manifestation of CLD (5.1 ± 1.6 vs. 3.7 ± 2.2 years) and this was statistically significant (P = 0.000).
• Oral contraceptives: Two patients (1.18%) were on routine oral contraceptives.
2. History of blood transfusion: This was elicited in 23 (13.5%) patients compared with none of the controls.
3. Past history of jaundice: Seven (4.1%) patients had a history of jaundice in the past though no such history was elicited from the controls.
4. History of intravenous recreational drug use: Nine (5.3%) patients and none of the controls had a history of intravenous drug use.
5. Presence of scarification marks: Scarification marks were found on 25 (14.7%) patients and 15 (8.8%) controls. This difference was statistically significant (P = 0.007).
6. Number of sexual partners: 102 patients (60%) and 10 (5.9%) controls admitted to a history of multiple sexual partner.

Table 1: Risk factors for chronic liver disease in the study populations

Serum albumin levels were significantly lower in the cases ranging from 14 to 55 g/L compared with the controls ranging from 36 to 48 g/L. Hypoalbuminemia was noted in 65 (38.2%) patients compared with 15 (8.8%) controls, and this was statistically significant (P < 0.001). The reference range for serum albumin was 36–50 g/L. Thirty-nine (22.9%) of our patients’ population had very low CD4 levels of ≤200 cells/L, which signifies advanced HIV disease with a CD4 range of 32–984 cells/L and a mean value of 344.9 ± 241.6 cells/L. Reference range was 500–1000 cells/µL.

DISCUSSION

The study population had a slight female preponderance of 117 (68.8%). A similar higher female preponderance was also observed by other authors.[¹¹¹²] This is possibly because females utilize healthcare services more than males and may partly account for the female preponderance in this hospital-based study. Also, there are more HIV-positive women than men in sub-Saharan Africa.[¹³] A similar finding was observed in another study in northern Nigeria in which more women with HIV were hospitalized.[¹⁴]

In this study, there were 63 (37.1%) HIV-monoinfected patients with clinical manifestation of CLD. This is comparable to the findings of systematic reports of the prevalence and epidemiology of CLD in Nigeria,[⁴¹⁵] although these were focussed on different populations. Huang et al.[¹⁶] observed an overall increase in the incidence of liver damage in their cohort of HIV-monoinfected patients on HAART. Furthermore, Oluremi et al.[¹⁷] noticed a high prevalence of HIV of 18.2% among liver disease patients admitted in a tertiary center in south-western Nigerian state.

The most common symptom in our study population was fatigue, which was present in 51 (30%) patients, compared with 10 (5.8%) controls. McGovern[¹⁸] in her work on hepatic safety and HAART observed that early symptoms and signs of liver disease range from asymptomatic to general symptoms such as fatigue, abdominal pain, and loss of appetite.

In our study, we observed that chronic use of medications including HAART (5.1 ± 1.6 years, P = 0.000) and herbal preparations (n = 20, 11.8%, P = 0.000) were the most significant determinants of CLD. Amadi and Orisakwe[¹⁹] and Nwokediuko et al.[²⁰] reported a significant association between herbal medication use and liver disease and accounted for 45.5% of liver-related medical admissions.[²⁰] Additionally, multiple studies[^21222324] have linked the treatment of HIV with HAART, with an increase in the incidence of liver diseases in people living with HIV/AIDS, and the duration of HAART therapy has been reported as a major risk factor for the development of liver disease.[²¹²²]

CONCLUSION

CLD is common in HIV patients without viral hepatitis B and C, and chronic use of medications such as HAART and herbal preparations were the most significant determinants of its occurrence. Risk stratification and proper clinical evaluation can aid in its mitigation. Recreational drug use (including intravenous drug abuse) has been found to heighten the risk of liver disease in HIV patients, especially those already experiencing HAART-associated liver damage[²⁵] and a similar relationship was noticed in our study.

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.