Impact of Metabolic Dysfunction-Associated Fatty Liver Disease of Varying Severity on Antiviral Treatment Outcomes and Clinical Prognosis in Patients with Chronic Hepatitis B: A Systematic Review and Meta-analysis

Literature Screening Process and Basic Characteristics of Included Studies

A total of 4867 articles were initially retrieved. After reviewing the titles, abstracts, and full texts, and applying the inclusion and exclusion criteria, 24 studies were finally included. Among them, 17 studies reported clinical outcome indicators [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29], including 11 cohort studies [13, 14, 16,17,18,19,20,21, 25, 26, 29], five case–control studies [22,23,24, 27, 28], and one cross-sectional study [15]. Seven studies reported antiviral efficacy indicators, all of which were cohort studies [30,31,32,33,34,35,36]. The literature screening process is shown in Fig. 1, the basic characteristics of the included studies are shown in Table 2, and the criteria for classifying MASLD severity are presented in Table 3.

Fig. 1figure 1

Literature screening flowchart

Table 2 Basic characteristics of included studiesTable 3 MASLD severity classification criteriaQuality Assessment of Included Studies

Among the 24 included studies, the cross-sectional study [15] received a score of 6 on the AHRQ scale. The remaining 23 studies [13, 14, 16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36] scored no less than 7 on the NOS scale, indicating high-quality literature, as shown in Table 2.

Meta-analysis ResultsSubgroup Analysis by MAFLD Severity: No Association Between HBV-DNA Suppression Rate or ALT Normalization Rate and MAFLD Severity

Six studies [30,31,32,33,34, 36] reported HBV-DNA suppression rates. A subgroup analysis based on MAFLD severity (mild vs. moderate-to-severe) included a total of 1325 patients—907 in the CHB combined with MAFLD group and 418 in the CHB-only group. The results are shown in Fig. 2. The pooled OR for HBV-DNA suppression rate was 0.66 (95% CI 0.44–1.00, I2 = 70%, P = 0.05), suggesting that the suppression rate in the CHB combined with MAFLD group was 0.52 times that of the CHB-only group. A random-effects model was used due to significant heterogeneity (I2 > 50%). There were no statistically significant differences between the CHB combined with mild MAFLD subgroup and CHB combined with moderate-to-severe MAFLD subgroup (P = 0.35 and P = 0.09, respectively).

Fig. 2figure 2

Subgroup analysis of HBV DNA suppression rate based on MASLD severity. CHB + FL CHB combined with MAFLD group (intervention group); CHB CHB-only group (control group)

Six studies [30,31,32,33] reported ALT normalization rates. Subgroup analysis by MAFLD severity (mild vs. moderate-to-severe) included 1305

patients—883 in the CHB combined with MAFLD group and 442 in the CHB-only group. The results are shown in Fig. 3. A random-effects model was used due to significant heterogeneity (I2 > 50%). No statistically significant differences were found between the CHB combined with mild MAFLD subgroup versus the CHB-only group (P = 0.48), or between the CHB combined with moderate-to-severe MAFLD subgroup versus the CHB-only group (P = 0.31).

Fig. 3figure 3

Subgroup analysis of ALT normalization rate based on MASLD severity. CHB + FL CHB combined with MAFLD group (intervention group), CHB CHB-only group (control group)

Subgroup Analysis by MAFLD Severity: Significantly Higher HBeAg Seroclearance Rate in CHB Combined with Moderate-to-Severe MAFLD Group

Six studies [31,32,33,34,35,36] reported HBeAg seroclearance rates. A subgroup analysis based on MAFLD severity (mild vs. moderate-to-severe) included a total of 1219 patients—805 in the CHB combined with MAFLD group and 414 in the CHB-only group. The results are shown in Fig. 4. Since a lower OR value indicates better improvement in the experimental group versus controls, the analysis revealed: CHB combined with moderate-to-severe MAFLD showed significantly superior HBeAg seroclearance (OR 0.48, 95% CI 0.34–0.66, P < 0.00001) compared to CHB combined with mild MAFLD (OR 0.66, 95% CI 0.50–0.87, P = 0.004). A random-effects model was applied due to substantial heterogeneity (I2 > 50%). The pooled analysis demonstrated that, despite moderate heterogeneity (I2 = 64%), the CHB combined with MAFLD group had a significantly higher HBeAg seroclearance rate than the CHB-only group (OR 0.57, 95% CI 0.46–0.71, P < 0.00001).

Fig. 4figure 4

Subgroup analysis of HBeAg seroclearance rate based on MASLD severity. CHB + FL CHB combined with MAFLD group (intervention group); CHB CHB-only group (control group)

Subgroup Analysis by MAFLD Severity: Significantly Higher HBsAg Seroclearance Rate in CHB Combined with Moderate-to-Severe MAFLD Group

Three studies [31, 34, 35] reported HBsAg seroclearance rates. A subgroup analysis based on MAFLD severity (mild vs. moderate-to-severe) included a total of 384 patients—216 in the CHB combined with MAFLD group and 168 in the CHB-only group. The results are shown in Fig. 5. A fixed-effect model was employed due to low heterogeneity (I2 < 50%). The HBsAg seroclearance rate in the CHB combined with moderate-to-severe MAFLD subgroup (OR 0.20, 95% CI 0.11–0.36, P < 0.00001) was significantly better than that in the CHB combined with mild MAFLD subgroup (OR 0.43, 95% CI 0.26–0.70, P = 0.0006). Overall, the CHB combined with MAFLD group exhibited a significantly higher HBsAg seroclearance rate than the CHB-only group (OR 0.31, 95% CI 0.21–0.46, P < 0.00001).

Fig. 5figure 5

Subgroup analysis of HBsAg seroclearance rate based on MASLD severity. CHB + FL CHB combined with MAFLD group (intervention group); CHB CHB-only group (control group)

Increased Risk of HCC in CHB Combined with MAFLD Group

Eleven studies [13,14,15,16,17,18, 20,21,22, 26] reported on the incidence of hepatocellular carcinoma (HCC), involving a total of 213,870 patients—70,499 in the CHB combined with MAFLD group and 143,902 in the CHB-only group. The results are shown in Fig. 6. A random-effects model was applied due to high heterogeneity (I2 = 84%). The analysis indicated that patients with CHB with MAFLD had a 1.77-fold higher risk of developing HCC compared to CHB-only patients (OR 1.77, 95% CI 1.13–2.77, P = 0.01), suggesting that MAFLD may serve as a pro-carcinogenic factor in patients with CHB, significantly increasing HCC risk.

Fig. 6figure 6

Clinical outcome—incidence of hepatocellular carcinoma (HCC). CHB + FL CHB combined with MAFLD group (intervention group); CHB CHB-only group (control group)

No Significant Increase in Mortality, Liver Fibrosis Incidence, or Liver Cirrhosis Incidence in Patients with CHB and MAFLD

Two studies [14, 18] reported mortality rates, as shown in Fig. 7. There was no significant difference in mortality between the CHB combined with MAFLD group and the CHB-only group (OR 0.98, 95% CI 0.42–2.31, P > 0.05). Six studies [22,23,24, 27,28,29] reported liver fibrosis incidence, as shown in Fig. 8, with no significant difference between the CHB combined with MAFLD group and the CHB-only group (OR 1.01, 95% CI 0.54–1.89, P > 0.05). Four studies [15, 18, 25, 26] reported liver cirrhosis incidence, as shown in Fig. 9, with no significant difference between the CHB combined with MAFLD group and the CHB-only group (OR 1.08, 95% CI 0.36–3.28, P > 0.05). In summary, the presence of MAFLD did not significantly alter mortality, liver fibrosis progression, or cirrhosis risk in patients with CHB.

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