Introduction

Nonalcoholic fatty liver disease (NAFLD) is a commonly occurring chronic liver disease with a global prevalence1. This syndrome primarily affects individuals with diabetes and obesity2. NAFLD encompasses a continuum of pathological manifestations, beginning with hepatic lipid accumulation and progressing to nonalcoholic steatohepatitis, characterized by varying degrees of necrotic inflammation, cirrhosis, and fibrosis3. NAFLD is associated with an increased vulnerability to hepatocellular carcinoma, cardiovascular disorders, and problems related to type 2 diabetes, such as neuropathy and nephropathy4,5,6. The global prevalence of NAFLD affects around 15–20% of women and 30–40% of men worldwide7. The prevalence is even higher among individuals with type-2 diabetes, with up to 70% of them being affected8. The increasing cases of NAFLD coincide with the rise of obesity in Asia9, where it is estimated to affect 29.6% of the population, potentially surpassing Western countries. This is likely due to age, urbanization, growing economies, a sedentary lifestyle, insulin resistance (type-2 diabetes), and poor health awareness10. Because of more significant visceral fat deposition, Asians are more prone to obesity-related problems. Despite having a BMI of less than 25 kg/m2, Asians exhibit a notable prevalence of type-2 diabetes and cardiovascular risk factors11,12.

In Pakistan, the prevalence of NAFLD has been increasing over recent years. This is mostly because of changed lifestyles, urbanization, and changes in diet that lead to a more calorie-dense diet and a less active lifestyle. The high prevalence of type-2 diabetes13,14,15,16, obesity17, and metabolic syndrome18 in the population contributes to the increasing burden of NAFLD. Several regional studies have been published on the prevalence of NAFLD in Pakistan, but there is no nationwide data or survey on the prevalence of NAFLD in Pakistan. Therefore, the main purpose of this study is to systematically collect, summarize, synthesize, and quantify the pool prevalence of NAFLD in Pakistan.

Method

The preferred reporting items for systematic reviews and meta-analyses guidelines were followed in this work19. The study protocol was registered in the PROSPERO database with the registration number CRD42022356607.

Search strategy

From inception to March 30, 2024, two investigators (F.H. and S.A.) independently performed an electronic literature search in MEDLINE (via PubMed), Web of Science, Embase (via Ovid), Scopus and local databases by using a combination of MeSh terms related to NAFLD in Pakistan. We searched (“NAFLD”, “nonalcoholic fatty liver disease”, “non-alcoholic fatty liver disease” OR “fatty liver” OR “fatty liver*” OR “nonalcoholic steatohepatitis*” OR “steatohepatitis*” OR “liver steatosis*”) AND (“Pakistan” OR “Pakistani”) AND (“prevalence” OR “incidence” OR “epidemiology” OR “frequency”). Furthermore, we carefully examined the reference lists of all relevant original and review papers to find potential new data sources.

Inclusion and exclusion

For inclusion, studies had to meet the following criteria: (1) the studies should be cross-sectional or longitudinal in nature and reflect the prevalence of NAFLD, or the prevalence can be calculated using the data provided. (2) Only studies that reported the prevalence of NAFLD in Pakistan were included. We excluded articles if (1) they were focused mainly on individuals younger than 18 years; (2) research was conducted on a Pakistani population but outside of Pakistan; (3) they were case reports, letters to editors, perspectives, communications, reviews, or reports of studies; (4) there were duplicate studies found within and across the databases; and (5) studies lacked sufficient data.

Data extraction

Two authors (F.H. and S.A.) independently extracted the data from individual studies, with disagreements being resolved by discussion and mutual consensus between the two investigators. A standardized data extraction form using Microsoft Excel was used to collect information on the first author’s surname, geographical location, publication year, survey period, study design, setting (urban vs rural), data collection timing, median or mean age of the participants, and proportion of females, as well as the number of participants with NAFLD.

Data analysis

To account the expected between-study heterogeneity, the prevalence of NAFLD was combined across studies, systematically using models with random effects. We generated pooled proportions using DerSimonian and Laird random effects models and stabilized the variances of the raw proportions before combining the data20. The findings of the meta-analyses are displayed in forest plots, which illustrate the prevalence proportions together with their corresponding 95% confidence intervals for each individual study as well as the overall random-effects pooled estimate. Statistical software R (ver. 4.3.3) with two packages (‘meta’ and ‘metafor’) was used to conduct the analysis. In pooled studies, we utilized the I2 index to measure between-study heterogeneity21. We investigated publication bias visually with funnel plots and statistically with Begg-Mazumdar22 and Egger linear regression23 tests. To evaluate the probable sources of heterogeneity, subgroup analysis, and univariable meta-regression were performed. We did not create a multivariable meta-regression model due to the limited number of observations. The R2 statistic was employed to quantitatively assess the extent to which factors in meta-regression models accounted for the overall between-study heterogeneity. To investigate the influence of individual studies on the overall effect size, sensitivity analyses were conducted by systematically removing each study in a sequential manner24. Using the Cohen kappa coefficient, we evaluated inter-rater agreement for article inclusion and methodological quality25.

Results

Our database searches yielded 468 potentially relevant articles. 196 study titles and abstracts were evaluated after removing duplicates Fig. 1. We evaluated 63 full-text papers for eligibility criteria, 29 were removed from the meta-analysis. Screening titles and abstracts (Kappa = 0.81) and entire texts (Kappa = 0.83) had strong inter-rater reliability.

Figure 1
figure 1

PRISMA flow chart of the prevalence of NAFLD in Pakistan.

Full size image

Study characteristics

The study characteristics and quality rating of all 34 selected studies26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59 are presented in (Table 1). In total, 12995 participants were included. The selected articles were published between 2008 and 2024, with the majority (89%) being published within the last decade. The study encompassed a range of sample sizes, from 51 to 2007 participants. The median sample size was 202 participants, with an interquartile range of 132–202 participants. The age range of participants was documented in a total of 33 studies, with the reported average ages spanning from 23 to 58 years. A total of 17 studies33,34,35,36,37,38,39,40,41,42,43,44,45,46,55,56,57 (50%) were conducted in Punjab province, 8 studies47,48,49,50,51,52,53,54 (24%) in Sindh, and 726,27,28,29,30,31,58 (21%) in Khyber Pakhtunkhwa while one59 study was conducted in Baluchistan. In addition, one32 study was conducted nationwide. 1326,33,35,36,41,42,43,44,46,49,55,58,59 of the total number of studies reviewed were determined to have a low risk of bias, while 2127,28,29,30,31,32,34,37,38,39,40,45,47,48,50,51,52,53,54,56,57 were determined to have a moderate risk. There was no high risk of bias in any of the studies.

Table 1 Study characteristics and quality of the included articles.
Full size table

NAFLD prevalence in the general population

The NAFLD prevalence in the general population was assessed in 13 studies, encompassing a total of 8461 participants (Table 2). The NAFLD prevalence ranged from 13.73% (95% CI 8.70–20.21%) to 60.84% (95% CI 58.00–63.64%). The pooled NAFLD prevalence in the general population was 29.82% (95% CI 21.39–39.01%; prediction interval: 2.98–68.92%) with significant heterogeneity (I2 = 98.9%, p < 0.001) Fig. 2. The Egger linear regression test (t = 0.65, p-value = 0.65), Begg-Mazumdar test (z = 1.29, p-value = 0.1970), and the visual evaluation of the funnel plot Fig. 3 collectively indicate the absence of publication bias in the conducted meta-analysis. The findings of the sensitivity analysis demonstrated that the pooled NAFLD prevalence ranged from 27.33% (95% CI 19.87–35.50%) to 31.40% (95% CI 22.63–40.89%) when each study was systematically excluded (Supplementary file S1). The results revealed no significant impact on the pooled outcome when any individual study was excluded systematically. This suggests that our meta-analysis is statistically robust and stable.

Table 2 Overall and subgroup analysis of the prevalence of NAFLD in Pakistan.
Full size table
Figure 2
figure 2

Forest plot of the prevalence of NAFLD in general population in Pakistan.

Full size image
Figure 3
figure 3

Funnel plot of the prevalence of NAFLD in general population in Pakistan.

Full size image

When the data were stratified into different publication years, the pooled NAFLD prevalence estimates were found to be 23.83 (95% CI 14.49–36.65%) for the period between 2008 and 2014, and 35.30% (95% CI 22.61–49.14%) for the period between 2015 and 2024. When the data was stratified by gender, the pooled prevalence estimates were found to be (26.68%; 95% CI 15.63–39.41%) in the female group and 27.82% (95% CI 14.13–43.98%) in the male group. Regarding the geographical distribution, the pooled prevalence estimates were found to be 25.38% (95% CI 18.07–33.46%) in the Khyber Pakhtunkhwa province, 30.26% (95% CI 11.87–52.74%) in Sindh, and 34.03 (95% CI 21.33–48.02%) in the Punjab.

The meta-regression analysis indicated that there was no significant association in the prevalence estimations based on the year of publication (slope = 0.0052; 95% CI −0.0165–0.0270; p-value = 0.6392), baseline survey year (slope = 0.0053; 95% CI −0.0328–0.0222; p-value = 0.7065), average age (slope = 0.0056, 95% CI −0.0072–0.0185; p-value = 0.3900), and methodological quality (slope = −0.0006, 95% CI −0.0250–00.0238; p-value = 0.9640).

NAFLD prevalence in individuals with metabolic disorders

The prevalence of NAFLD in individuals with diabetes was assessed in 23 studies, encompassing a total of 4534 patients. The NAFLD prevalence in patients with diabetes ranged from 40.84% (95% CI 34.83–47.06%) to 78.74% (95% CI 70.60–85.50%). The pooled NAFLD prevalence in the individuals with diabetes was 58.47% (95% CI 54.23–62.64%; prediction interval: 38.17–77.40%) with significant heterogeneity (I2 = 88.0%, p < 0.01) Fig. 4. Egger linear regression test (t = 0.98, p-value = 0.34), Begg-Mazumdar (0.50, p-value = 0.58) and the visual evaluation of the funnel plot collectively Fig. 5 indicate the absence of publication bias in the conducted meta-analysis. The findings of the sensitivity analysis demonstrated that the pooled NAFLD prevalence ranged from 57.54% (95% CI 52.84–62.16%) to 59.32% (95% CI 55.24–63.34%) when each study was systematically excluded. The sensitivity analysis findings indicate that the inclusion or exclusion of any individual study did not have a significant impact on the overall effect seen in our meta-analysis (see Supplementary file S2). This suggests that our meta-analysis is statistically robust and stable. Furthermore, the NAFLD prevalence in obese people was 74.08% (95% CI 60.50–85.70%; prediction interval: 12.73–100.00%) while the NAFLD prevalence in hypertensive patients was (47.43; 95% CI 30.49–64.66; prediction interval: 1.20–97.20%).

Figure 4
figure 4

Forest plot the prevalence of the NAFLD in patients with diabetes in Pakistan.

Full size image
Figure 5
figure 5

Funnel plot of the prevalence of NAFLD in diabetes patients.

Full size image

According to subgroup meta-analysis, the prevalence of NAFLD among patients with diabetes was found to be 56.54% (95% CI 48.08–64.82%) between 2008 and 2018, and 59.74% (95% CI 55.23–64.17%) between 2019 and 2024. When looking at gender differences, the prevalence was 63.17% (95% CI 49.98–75.45%) among females and 53.90% (95% CI 47.39–60.36%) among males. Geographically, the prevalence varied with 54.80% (95% CI 50.10–60.83%) in Khyber Pakhtunkhwa, 55.30% (95% CI 46.73–63.72%) in Baluchistan, 59.97% (95% CI 53.51–66.27%) in Punjab, and 60.20% (95% CI:53.51–66.27%) in Sindh.

The meta-regression analysis indicated that there was no significant association in the prevalence estimations based on the year of publication (slope = 0.0035; 95% CI −0.0089–0.0159; p-value = 0.5810), baseline survey year (slope = 0.0008; 95% CI 0.0036–0.0053; p-value = 0.7169), average age (slope = 0.0026, 95% CI 0.0060–0.0113; p-value = 0.5494), and methodological quality (slope = 0.0676, 95% CI −0.0375–0.1728; p-value = 0.2075).

Discussion

NAFLD is an increasingly important cause of morbidity, disability, and mortality worldwide. Addressing the root cause of NAFLD is imperative to alleviate the burden of diseases associated with excessive caloric intake and metabolic dysfunction from a societal perspective7,8. The rise in obesity and its associated comorbidities, such as NAFLD, in Pakistan can be attributed to significant shifts in the lifestyle patterns of the Pakistani population. The primary objective of this research was to collect information about the prevalence of NAFLD and the risk factors that are associated with NAFLD in Pakistan. This meta-analysis is expected to contribute to the mitigation of NAFLD and its associated problems by providing valuable information that can support public health initiatives. The pooled NAFLD prevalence in general (low risk) population was 29.82%, which is comparable with the similar meta-analysis conducted on South Asia60 (26.9%) and global level61 (30.01%). The prevalence of NAFLD in patients with metabolic disease (high-risk population) is significantly higher than the general population. The NAFLD pooled prevalence in patients with diabetes was found to be 61.22%. The results are in line with the recent meta-analysis60 (59.69%) and the neighboring country India62 (57%). The pooled prevalence of NAFLD in patients with diabetes higher than the recent meta-analysis on South Asian (54.1%)60.

The data stratification revealed interesting patterns. The prevalence of NAFLD appeared to increase over time, with estimates of 23.83% for the period between 2008 and 2014, and 35.30% for the period between 2015 and 2024. This increasing trend might reflect changes in lifestyle factors, diagnostic criteria, or increased awareness of NAFLD over the years. Furthermore, there were also notable disparities in gender and geographic factors. The prevalence estimates obtained from pooling the data were slightly higher in males (27.82%) than in females (26.68%). Geographically, there were noticeable differences in prevalence rates among different provinces. The highest prevalence was seen in Punjab (34.03%), followed by Sindh (30.27%) and Khyber Pakhtunkhwa (25.38%).

The subgroup analyses revealed that the prevalence of NAFLD in patients with metabolic disease was highest in obese population 74.08% (95% CI 60.50–85.70%), followed by patients with diabetes 58.47% (95% CI 54.23–62.64%) and hypertension patients 47.43% (95% CI 30.49–64.66%). The patients with diabetes are twice as likely to get fatty liver as compared to the general Pakistani population. This is because elevated glucose levels in individuals with diabetes or prediabetes contribute to an increased availability of substrates for triglyceride synthesis58. Furthermore, the diminished secretion of very low-density lipoprotein, a condition often associated with insulin resistance, exacerbates the buildup of fat in the liver63.

There are several limitations to our meta-analyses that should be considered when interpreting the findings. Firstly, the meta-analytical component of this investigation was constrained by substantial heterogeneity observed among the studies, which could not be investigated or elucidated through subgroup analysis or meta-regression. However, this is a recognized characteristic of meta-analyses concerning prevalence rates64. Secondly, most of the studies did not have a nationally representative sample, as they were based in a single center. As such, larger studies across multiple centers are needed to investigate true prevalence. The low number of included studies set in the low and high-risk populations is also a limitation of this study as we were unable to use multivariable meta-regression models to check the significance of risk factors combined. In addition, it is important to note that our analysis solely relied on published reports, so excluding the potential insights that could have been derived from the unpublished grey literature. This omission may have implications for the overall findings and conclusions of our study. Nevertheless, despite these limitations, this is the first meta-analysis to provide pooled prevalence of NAFLD in Pakistan. Prior to commencing the study, we published a protocol delineating our technique and methodology, and we utilized scientific and statistical methodologies to gather and aggregate data. We conducted subgroup studies and random effect meta-regression analyses to assess several factors that could influence our estimate.

Conclusion

The prevalence of NAFLD in Pakistan from 2008 to 2024 is thoroughly described in this study. This study suggests that while the pooled NAFLD prevalence in the general population was 29.02%, the prevalence among patients with diabetes is almost double, at 58.70%. With the rising prevalence of NAFLD in Pakistan, the government should implement diabetes management initiatives nationwide. The Pakistani government should develop a comprehensive plan and strategy to enhance knowledge about fatty liver, as well as to improve its control, prevention, and treatment, thereby reducing the prevalence of the disease in the country.