Janczura J, Brzdęk M, Flisiak R, Dobrowolska K, Brzdęk K, Rzymski P, Zarębska-Michaluk D. Steatotic liver disease in patients with chronic hepatitis C. World J Hepatol 2025; 17(12): 113639 [DOI: 10.4254/wjh.v17.i12.113639]
Corresponding Author of This Article
Michał Brzdęk, Collegium Medicum, Jan Kochanowski University, aleja IX Wieków Kielc 19A, Kielce 25-516, Poland. michal.brzdek@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Observational Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Author contributions: Janczura J, Flisiak R, and Zarębska-Michaluk D conceived the study design; Janczura J, Dobrowolska K, and Zarębska-Michaluk D acquired the final version of the manuscript; Brzdęk M and Brzdęk K prepared tables and figures; Brzdęk M performed the statistical analysis, prepared manuscript for the submission; all authors contributed to analyzed and interpreted the data, drafted the manuscript, and approved the final version of the manuscript.
Institutional review board statement: This observational, single-center study was conducted following the approval of the Bioethics Committee of Jan Kochanowski University in Kielce (approval No. 57/2024, dated July 25, 2024).
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement:
Dataset available upon reasonable request to the corresponding author.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Michał Brzdęk, Collegium Medicum, Jan Kochanowski University, aleja IX Wieków Kielc 19A, Kielce 25-516, Poland. michal.brzdek@gmail.com
Received: August 31, 2025 Revised: September 9, 2025 Accepted: November 20, 2025 Published online: December 27, 2025 Processing time: 118 Days and 2.8 Hours
Abstract
BACKGROUND
Steatotic liver disease (SLD) including metabolic dysfunction-associated SLD is the most prevalent chronic liver disease worldwide and is strongly associated with metabolic dysfunction as well as chronic hepatitis C (CHC).
AIM
To compare the characteristics of patients with CHC virus infection and the treatment with direct-acting antivirals (DAAs), considering the presence of SLD comorbidity.
METHODS
The study included all consecutive hepatitis C virus-infected patients treated with pangenotypic DAA regimens at a single tertiary hepatology center in 2018-2024. SLD was diagnosed via abdominal ultrasound.
RESULTS
Among 688 patients included in the study, 290 (42.2%) had comorbid SLD. The highest prevalence (62.3%) was observed in patients infected with genotype 3. The SLD group was predominantly male (62.8%), in contrast to the non-SLD group, where women predominated. Patients with SLD were significantly older (P = 0.0007), had a higher body mass index (P < 0.0001), and more frequently presented with diabetes (P = 0.01), obesity (P < 0.0001), hyperlipidemia (P = 0.004), and a history of alcohol abuse (P < 0.0001). They also had more advanced liver disease as indicated by a higher rate of cirrhosis (35.5% vs 12% in the non-SLD group, P < 0.0001), elevated aminotransferase activity (P < 0.0001), bilirubin concentration (P < 0.0001), and international normalized ratio values (P = 0.0001), and lower albumin concentration (P = 0.0028). While most patients in both groups completed treatment as planned, adverse events, including severe events and deaths, were more frequent in the SLD group. A sustained virologic response was achieved in 97.6% of the overall population but was significantly lower among patients with SLD compared to the non-SLD group (95.6% vs 99.0%, P = 0.0081). However, logistic regression analysis did not identify SLD as an independent predictor of treatment failure.
CONCLUSION
Comorbid SLD was common among CHC patients treated with DAAs and was associated with adverse baseline characteristics, including older age, higher body mass index, greater comorbidity burden, and more advanced liver disease. Although SLD patients achieved slightly lower rates of sustained virologic response, SLD itself was not an independent predictor of treatment failure. These findings suggest that poorer treatment outcomes in this subgroup are largely attributable to coexisting risk factors rather than SLD per se, highlighting the need for comprehensive management of metabolic and liver-related comorbidities to optimize antiviral therapy outcomes.
Core Tip: Steatotic liver disease (SLD) is common in patients with chronic hepatitis C and shapes their overall health and treatment journey. In our real-world study, SLD patients were older, had higher body mass index, and carried more metabolic and liver-related risks, leading to lower response rates to antiviral therapy. Yet, SLD itself was not the culprit - other comorbidities were. This highlights that successful treatment depends not only on antivirals but also on managing the broader metabolic and lifestyle factors that impact liver health.
Citation: Janczura J, Brzdęk M, Flisiak R, Dobrowolska K, Brzdęk K, Rzymski P, Zarębska-Michaluk D. Steatotic liver disease in patients with chronic hepatitis C. World J Hepatol 2025; 17(12): 113639
Steatotic liver disease (SLD) is a recently redefined umbrella term encompassing a spectrum of liver conditions characterized by hepatocellular fat accumulation[1]. The term includes liver damage attributable to metabolic dysfunction, monogenic disorders, certain medications, and alcohol abuse. In 2023, the Delphi consensus led to a shift in terminology, replacing the previously used “nonalcoholic fatty liver disease” with SLD, and reflecting a broader recognition of the metabolic determinants of SLD and its strong associations with systemic comorbidities such as obesity, type 2 diabetes mellitus, dyslipidemia, and arterial hypertension[2,3]. This terminological change also underscores the clinical need to consider SLD as a heterogeneous but highly prevalent condition that interacts with a wide range of chronic diseases.
Notably, chronic hepatitis C (CHC) is increasingly associated with the presence of SLD. Epidemiological studies indicate that hepatic steatosis occurs in approximately 50% of individuals with CHC, a prevalence significantly higher than that observed in the general population[3]. In hepatitis C virus (HCV)-related SLD, multiple risk factors contribute to the development of hepatic steatosis, including both host-related and virus-related mechanisms[4]. Host-related factors largely mirror those seen in the general population, particularly components of metabolic syndrome, such as obesity and type 2 diabetes mellitus. These factors are especially prevalent in Western countries, where the burden of metabolic disorders is high[4]. However, in contrast to hepatitis B virus-related SLD, HCV infection also involves virus-specific mechanisms, most notably associated with HCV genotype 3 (GT3)[5,6]. This GT is strongly linked to the development of hepatic steatosis due to its direct interference with lipid metabolism, particularly through impaired very-low-density lipoprotein secretion[5]. As a result, steatosis occurs with significantly higher prevalence in individuals infected with GT3 compared to those infected with non-GT3 viral variants.
HCV infection continues to represent a significant global concern. According to the World Health Organization, an estimated 50 million individuals are currently living with CHC, with approximately 1 million new infections occurring annually[7]. In 2022 alone, HCV infection was associated with an estimated 242000 deaths worldwide[7]. HCV infection is a well-recognized contributor to severe liver disease, with cirrhosis and hepatocellular carcinoma (HCC) representing its most severe and life-threatening complications[8]. Currently, SLD is considered the most prevalent chronic liver disease globally[9]. The coexistence of SLD and HCV therefore represents a major clinical challenge, not only because both conditions independently contribute to liver disease progression, but also because their interaction may amplify the risk of fibrosis, cirrhosis, and HCC. Although direct-acting antivirals (DAAs) have revolutionized the treatment of HCV, leading to cure rates exceeding 95% in most populations, real-world evidence on treatment outcomes in patients with comorbid SLD remains valuable yet sometimes inconsistent[10,11]. To address this issue, we designed an observational, single-center real-world study, comparing patients with and without SLD who were treated for chronic HCV infection using pangenotypic DAAs regimens.
MATERIALS AND METHODS
Study population
A real-world, observational study was conducted at a single tertiary hepatology center - the Department of Infectious Diseases in Kielce, Poland. The analysis included all consecutive patients with CHC treated with pangenotypic DAAs under the reimbursed National Health Fund program. The patients started antiviral therapy from the beginning of the availability of pangenotypic regimens in Poland, i.e., from July 2018 to December 2024. Data were collected from patients’ medical records and included laboratory results, virological profiles, and relevant clinical parameters.
Data collection
Observational data were collected at the start of antiviral therapy and during drug program-required follow-up visits. Records at the start of therapy included demographic and clinical information, including comorbidities and medications used, history of prior antiviral treatment and hepatitis B virus or human immunodeficiency virus co-infection, data on current and past drug or alcohol abuse, diagnosis of HCC, and information regarding liver transplantation. Virological status, including GT and viral load, was assessed by polymerase chain reaction with a lower detection limit of 15 IU/mL. Laboratory parameters included complete blood count, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, creatinine, albumin, and bilirubin concentration, and international normalized ratio. The effectiveness of DAA therapy was assessed 12 weeks after its completion by evaluating HCV RNA. During treatment and the 12-week post-therapy period, the safety of treatment was assessed based on its course, the occurrence of adverse events, including severe ones, and deaths.
Liver disease
The stage of liver disease was assessed using non-invasive methods, by shear wave elastography with Aixplorer (SuperSonic Imagine, Aix-en-Provence, France). Liver stiffness evaluation was complemented by calculation of serum-based indices such as fibrosis-4 index (FIB-4) or aspartate aminotransferase to platelet ratio index (APRI)[12]. In addition, in all patients who were diagnosed with cirrhosis, data were collected regarding the decompensation of liver function in the past and at the start of therapy, the presence of oesophageal varices, and the baseline Child-Pugh score was calculated. The diagnosis of SLD was based on the detection of hepatic steatosis, identified through imaging by abdominal ultrasound, which was performed in all patients during the baseline visit.
Ethical considerations
This observational, single-center study was conducted following the approval of the Bioethics Committee of Jan Kochanowski University in Kielce (approval No. 57/2024, dated July 25, 2024). Access to medical records and the use of patient treatment data were granted with the prior consent of the hospital’s management. All patients were informed about the purpose of the study, and their inclusion was contingent upon providing informed consent.
Statistical analysis
Categorical variables were expressed as absolute numbers and percentages. Continuous variables were presented as medians along with interquartile ranges. The normality of distribution for continuous data was assessed using the Shapiro-Wilk test. Comparisons of continuous variables between groups were performed using the Mann-Whitney U test. Differences in categorical data, such as event frequencies between patients with and without SLD, were assessed using Pearson’s χ2 test, or Fisher’s exact test when appropriate. Based on univariate analyses identifying factors associated with achieving or not achieving sustained virologic response (SVR) at 12 weeks post-treatment, multivariate logistic regression models were constructed to estimate the odds of treatment failure. P < 0.05 was considered statistically significant. All analyses were carried out using Statistica version 13 (Dell Inc., Round Rock, TX, United States).
RESULTS
Characteristics of the study population
Of the 688 consecutive Caucasian patients treated with pangenotypic DAAs for CHC, 290 individuals (42.2%) were diagnosed with SLD. The median age of patients in the SLD group was significantly higher compared to those without SLD (P = 0.0007) with higher proportion of individuals aged over 50 years (54.5% vs 41.7%) (Table 1). The SLD population was predominantly male, whereas the non-SLD group consisted mainly of women (59%). Patients with SLD had a significantly higher median of body mass index (BMI) compared to those without SLD (26.5 vs 24.6, respectively, P < 0.0001). Importantly, 62.4% of individuals in the SLD group had a BMI exceeding 25, indicating a high prevalence of overweight or obesity within this population (Table 1). The distribution of BMI values across both groups is illustrated in Figure 1A. The SLD group was more burdened with comorbidities (P = 0.0014), with statistically significant differences observed for diabetes, hyperlipidemia, and obesity (Table 1). While the overall prevalence of hypertension did not differ significantly between groups, patients with this diagnosis were significantly less likely to have SLD, 45.2% (P = 0.0354) (Table 2). A significantly higher percentage of patients in the SLD group reported a history of alcohol abuse (defined as alcohol intake exceeding 20 g/day for females and 30 g/day for males) compared to the non-SLD group (23.1% vs 3.8%, respectively). Of the 82 people who reported a history of alcohol abuse, the majority, 67 (81.7%, P < 0.0001), belonged to the SLD group (Table 2). Since qualifying for and during antiviral therapy, all patients declared abstinence (Table 1).
Figure 1 Comparison chart of the steatotic liver disease group and the non-steatotic liver disease group.
A: Distribution of body mass index categories; B: Distribution of genotypes; C: Liver disease severity based on elastography; D: Distribution of aspartate aminotransferase to platelet ratio index categories; E: Distribution of fibrosis-4 index categories; F: Effectiveness of direct-acting antiviral therapy. SLD: Steatotic liver disease; F: Fibrosis; ITT: Intention-to-treat; PP: Per-protocol.
Table 1 Baseline characteristics in the steatotic liver disease and non-steatotic liver disease groups, n (%).
The median baseline HCV RNA viral load was comparable between the SLD and non-SLD groups (Table 3). Patients with SLD demonstrated significantly higher median aminotransferase activity, with elevated levels of both alanine aminotransferase and aspartate aminotransferase (P < 0.0001 for both) (Table 3). Other liver function parameters also differed significantly between the groups: Patients with SLD exhibited higher gamma-glutamyltransferase and bilirubin levels, lower albumin concentrations and platelet counts, and increased international normalized ratio values (Table 3). A significantly lower proportion of patients in the SLD group were treatment-naive compared to those without SLD (Table 4). Notably, previous non-response to both interferon-based regimens and DAA therapy was more frequently documented among patients with SLD (Table 4). Throughout the study, the most frequently used therapy in the SLD group was sofosbuvir/velpatasvir with or without ribavirin, accounting for 54.5% of treatments, whereas the glecaprevir/pibrentasvir regimen predominated in the non-SLD group (61.6%) (Table 4).
Table 3 Baseline laboratory parameters in the steatotic liver disease and non-steatotic liver disease groups, median (Q1-Q3).
Clinical indicators of advanced liver disease were more prevalent in the SLD population. A significantly higher proportion of patients with SLD had a documented history of hepatic decompensation, including ascites and/or hepatic encephalopathy (8.6% vs 2.0%, respectively, P = 0.0001). Similarly, the presence of documented oesophageal varices was significantly more frequent in the SLD group (P < 0.0001). This pattern persisted at baseline evaluation, where patients with SLD continued to show a higher prevalence of ascites and/or encephalopathy compared to the non-SLD subpopulation (7.9% vs 2.3%, P = 0.0005). Patients with SLD had a significantly higher prevalence of GT3 infection compared to the non-SLD group (24.5% vs 10.8%) (Table 4, Figure 1B). Among the 114 patients infected with HCV GT3, nearly one-third had SLD (P = 0.0002) (Table 2). Nevertheless, GT 1b predominates, so this GT remained the most prevalent in both groups (Figure 1B). Fibrosis staging revealed a significantly greater proportion of patients with fibrosis stage 4 (F4) in the SLD group compared to the non-SLD group (35.8% vs 12.0%, P < 0.0001) (Figure 1C). Additionally, the proportion of patients classified as Child-Pugh B or C among those with F4 fibrosis was higher in the SLD group (29.1%) than in the non-SLD group (25.0%) (Table 4). Consistently, the SLD subpopulation demonstrated a higher proportion of patients with an APRI score ≥ 1 compared to the non-SLD group (46.6% vs 19.1%, respectively) (Figure 1D). Similarly, FIB-4 scores were significantly higher in the SLD group, with the largest subgroup consisting of patients with FIB-4 > 2.67, accounting for 43.5% of the SLD group, in contrast to 19.1% in the non-SLD population (Figure 1E). Furthermore, HCC was more frequently diagnosed in patients with SLD than in those without (3.4% vs 1.0%, P = 0.0299) (Table 4).
Treatment safety and outcomes
The effectiveness of DAA therapy differed significantly between the SLD and non-SLD groups in both the intention-to-treat (ITT) and per-protocol (PP) analyses. In the ITT analysis, 91.0% of patients in the SLD group achieved SVR, compared to 98.2% in the non-SLD group (P < 0.0001) (Figure 1F). Similarly, in the PP analysis, the SVR rate was 95.6% in the SLD group to 99.0% in the non-SLD group (P = 0.0025) (Figure 1F). Patients in the SLD subgroup were more likely to experience serious adverse events during treatment (P = 0.0054), mainly non-liver related. Adverse events of special interest, ascites and encephalopathy, were also significantly more frequent in patients with SLD (Tables 4 and 5). The mortality rate was significantly higher among patients with SLD compared to the non-SLD group (3.8% vs 1.0%, P = 0.0168). Across both study groups, 13 patients failed to achieve SVR. The majority of non-responders were male (92.3%) and were characterized by significantly higher BMI and poorer laboratory parameters compared to responders (Table 6). Among non-responders, 53.8% were infected with HCV GT3. Clinical indicators of advanced liver disease were more prevalent among non-responders as compared to responders, 5 out of 13 patients (38.5%) presented with hepatic encephalopathy and/or ascites (P < 0.0001), and 69.2% had cirrhosis (P = 0.0002) (Table 6). Multivariate analysis documented that GT3 infection and cirrhosis appeared to be independent predictors of SLD in patients with CHC, P = 0.0234 and P = 0.0046, respectively (Table 7).
Table 5 Safety of direct-acting antiviral therapy in the steatotic liver disease and non-steatotic liver disease groups, n (%).
The prevalence of SLD among individuals with chronic HCV infection varies widely according to available data, with estimates ranging from 27% to 79%[3,13-15]. The values obtained in our analysis fall within this range, as SLD was confirmed in 42.2% of the study population. Discrepancies in the prevalence of steatosis in patients with HCV infection reported in different studies may be due to differences in the characteristics of the populations analyzed, including the percentage of patients infected with GT3, the severity of liver fibrosis, the burden of cardiometabolic risk factors, and geographical regions[13]. The influence of geographical region was demonstrated in the latest meta-analysis conducted by Li et al[3], covering 321 eligible studies on SLD in HCV-infected individuals. This paper reported a pooled prevalence of 49%, which aligns closely with our findings, with the highest frequency of 52% observed in the World Health Organization Region of the Americas. However, the majority of studies included in the meta-analysis by Li et al[3], used liver biopsy as the diagnostic gold standard, which may contribute to a higher reported prevalence due to the ability to detect even mild degrees of steatosis[16,17]. Therefore, the method used to diagnose hepatic steatosis also appears to influence the results obtained[18].
Despite its undoubted advantages, liver biopsy as a diagnostic method has largely become obsolete in recent decades and has been replaced by noninvasive examinations[19]. Currently, shear-wave or transient elastography or even serum markers such as APRI or FIB-4 are used to assess liver fibrosis. Using transient elastography with controlled attenuation parameter assessment, it is also possible to assess liver steatosis. This method was used in the analysis of a population of 328 Spanish patients with HCV monoinfection, among whom 45% had coexisting SLD, which is also very similar to our results[20]. However, due to the cost and limited availability of this examination, ultrasound, which does not have these limitations, is the most commonly used method for diagnosing SLD[21].
The population-based study conducted from 2007 to 2020, which covered a population of nearly 300000 Egyptian patients infected with HCV, was based on the diagnosis of liver steatosis using ultrasound, the same approach as in our study[22]. The researchers documented a 41.9% prevalence of SLD, which is almost identical to the value found in our analysis. A very similar result was obtained in a study from Taiwan, which included nearly 6000 patients, with an SLD rate of 36.8% and ultrasound as the predominant diagnostic method[23].
With an overall prevalence of 42% in our study, we documented a significantly higher prevalence in patients infected with GT3, reaching as high as 62.3%. GT3 is a well-established virus-related risk factor for hepatic steatosis and has been consistently associated with a significantly greater prevalence of SLD compared to non-GT3 GTs[6,24]. Our findings align closely with those reported by Rubbia-Brandt et al[25], who reported a steatosis prevalence of 61.2% among GT3-infected patients. A retrospective RWE study involving 98 Swedish patients infected with HCV showed that steatosis assessed by the liver biopsy was significantly more common in individuals infected with the GT3, and this association appeared to be independent of the host-related risk factors, suggesting a GT-specific, virus-induced mechanism of fat accumulation in the liver[26].
When comparing HCV-infected patients according to the presence of hepatic steatosis, we documented a significantly higher age (P = 0.0007) and a clear predominance of men (< 0.0001) in the SLD population. Our results regarding the higher incidence of SLD in men are consistent with the results of a study conducted in an Italian cohort of 400 patients infected with HCV[27]. This analysis also showed a significantly higher prevalence of cardiometabolic risk factors associated with SLD in men. Both sex and age are well-known non-modifiable risk factors for SLD, regardless of the presence of HCV infection. In the general population, the incidence of SLD is higher in men than in women, partly due to the influence of sex hormones, with estrogen acting as a protective factor and testosterone increasing the risk of SLD[28,29]. In a large follow-up Japanese study investigating the relationship between age, menopause, and SLD incidence, premenopausal women were found to have the lowest SLD prevalence out of the analyzed group, followed by post-menopausal women (15%), and men (24%)[30]. Interestingly, age was found to be an independent risk factor for hepatic steatosis only in premenopausal women[30]. The results of the Eurostat report released in July 2024 note an increasing percentage of overweight people with age in several European countries. In Poland, the percentage increases steadily from 40.9% for the 25-34 years group to 72.8% for those aged 65-74 years[31]. The increasing incidence of hepatic steatosis in an ageing European population may be due to the increasing burden of comorbidities, including metabolic disorders[32]. In a large prospective Chinese study performed from 2021 to 2022, age ≥ 60 years was associated with a higher prevalence of SLD[33].
Past alcohol abuse was another parameter that we documented as significantly more common in patients with SLD (P < 0.0001). Since alcohol-related liver disease is a separate category of SLD, our findings are not surprising[2]. The development of SLD is also undeniably linked to the presence of other modifiable conditions, such as diabetes, obesity and dyslipidaemia, which are elements of metabolic syndrome[5,34]. This is reflected in our study, as individual cardiometabolic risk factors such as obesity (25.9% vs 10.6%, P < 0.0001), hyperlipidaemia (17.2% vs 9.8%, P = 0.0041), diabetes (14.1% vs 8%, P = 0.0103) and hypertension (37.2% vs 32.9%, P = 0.2392) were significantly more common in the SLD population as compared to non-SLD patients. These observations are consistent with the results obtained by many other researchers[5,15,22,23].
The number of metabolic syndrome components is important to factor in, as the presence of multiple metabolic disorders can be associated with the progression of liver disease, development of liver fibrosis or even cirrhosis, and a higher risk of HCC[5,35]. Each component of metabolic syndrome increases the risk of liver-related mortality[36]. We demonstrated a significantly higher occurrence of cirrhosis and advanced liver fibrosis in patients with SLD compared to the non-SLD group, accompanied by significantly increased noninvasive markers such as APRI and FIB-4 (35.8% vs 12% and 12.1% vs 6.3%, P < 0.0001 for cirrhosis and F3 fibrosis in SLD and non-SLD groups, respectively). According to data available in the literature, the documented progression of liver disease in HCV infection in the case of coexisting steatosis may result not only from its presence per se, but also from risk factors leading to the development of SLD[37,38].
Another important element of our analysis was the assessment of whether the co-occurrence of SLD in HCV-infected patients affects the effect of antiviral therapy. We assessed the use of pangenotypic regimens to include patients infected with various GTs, including GT3, in the analyzed population because in the interferon era, hepatic steatosis was a well-documented negative predictor of SVR, especially in patients infected with GT3[39]. In our study, despite all patients receiving modern pangenotypic DAA regimens, SVR rates remained significantly lower in the SLD group compared to the non-SLD group in both ITT and PP analyses. However, it is noteworthy that findings from other real-world studies have been inconsistent regarding the role of SLD in treatment outcomes. For instance, data from the German Hepatitis C-Registry - a national multicenter real-world cohort - showed that no significant differences were observed in SVR between those with and without steatosis[40]. Similarly, another large-scale study involving 14,346 patients treated with interferon-free regimens found no significant difference in SVR rates between patients with or without hepatic steatosis[5]. In our cohort, although SVR was lower in the SLD group, multivariate analysis did not confirm SLD as an independent risk factor for non-response. We hypothesize that the observed poorer treatment outcomes in this population may be attributed to a higher prevalence of advanced liver disease, more frequent GT3 infection, and a predominance of male sex - all of which are recognized independent predictors of treatment failure, as demonstrated in previous research[41,42].
In our study, not only effectiveness but also safety differed between patients with and without SLD. Patients with liver steatosis experienced a higher overall rate of adverse events during DAA treatment, which appears to be primarily related to their more advanced liver disease and greater burden of comorbidities, rather than to steatosis itself. Both hepatic (e.g., ascites, hepatic encephalopathy) and extrahepatic complications occurred more frequently in the SLD group. Although serious liver-related adverse events and liver-related deaths were also more common among patients with SLD, these differences did not reach statistical significance. These findings underscore the need for careful monitoring of patients with advanced liver disease and multiple comorbidities.
Our study has limitations, which we are aware of. These arise from the real-world nature and observational design of the analysis, with possible bias and data gaps. There is potential for unmeasured confounding factors, such as dietary habits, levels of physical activity, and other lifestyle variables, that could not be fully accounted for in our analysis. We assessed the presence of liver steatosis based on ultrasound examination, which is a widely available and inexpensive method, but has low diagnostic efficiency in mild SLD and people with a BMI > 40 kg/m2. It may have underestimated the actual prevalence of SLD in the analyzed population. The single-center nature of the study prevents drawing general conclusions about the prevalence of SLD among the HCV-infected population throughout the country, which is also a limitation. Furthermore, our study lacks follow-up data on SLD status after achieving SVR. Consequently, we are unable to determine whether hepatic steatosis resolved or whether associated metabolic factors improve, which are key considerations for the long-term management of this patient population. Finally, it should be remembered that the diagnosis of liver steatosis based on ultrasound examination is reliable when the process involves 20%-30% of hepatocytes; moreover, in individuals with a BMI > 40, this test is less accurate, and these factors should be taken into account when interpreting the result[21]. At the same time, however, the single-center nature of the study is its strength, as all patients analyzed were treated according to the same principles by the same team of doctors, and all tests were performed in the same laboratory. Ultrasound examination and elastography were also performed by the same researchers using the same equipment.
CONCLUSION
We documented a 42% rate of SLD comorbidity in a real-world population of HCV-infected patients treated with DAAs. Patients with liver steatosis were older, had a higher BMI, a higher burden of comorbidities, more frequent GT3 infection, and more advanced liver disease compared to those without SLD. Due to these negative predictors, the effectiveness of DAA treatment was significantly lower than in patients without SLD. These findings underscore the importance of systematically assessing SLD in HCV-infected individuals, not only as a comorbidity but also as a clinically relevant modifier of treatment response and prognosis. Integrating non-invasive tools for steatosis evaluation into routine HCV management could help identify high-risk patients, guide closer monitoring, and inform adjunctive interventions aimed at reducing metabolic risk factors. Given the ageing population and the rising prevalence of obesity and metabolic disorders, SLD is likely to play an increasingly important role in determining long-term liver health in those with past or ongoing HCV infection. Addressing this challenge will require both improved clinical pathways for risk stratification and broader public health strategies to mitigate the growing burden of metabolic disease.
Footnotes
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: Poland
Peer-review report’s classification
Scientific Quality: Grade B
Novelty: Grade B
Creativity or Innovation: Grade B
Scientific Significance: Grade B
P-Reviewer: Giangregorio F, Assistant Professor, Chief Physician, Director, Italy S-Editor: Hu XY L-Editor: A P-Editor: Zhang YL
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