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Fatty liver (FL) has become a common chronic liver disease worldwide, with a prevalence of about 25%. As the incidence of obesity and diabetes increases, the prevalence of FL is likely to increase. FL is often present in patients with HBV HCV infection, and some studies have reported that FL may synergistically lead to the development of liver cancer, and some studies have shown that the risk of liver cancer in patients with chronic hepatitis B with fatty liver is reduced. Recently, Professor Li Tao's team from Qilu Hospital of Shandong University published a meta-analysis in Expert Review of Gastroenterology & Hepatology, and the results showed that:Liver biopsy confirmedflProbablyhbv/hcvAn important risk factor for the development of liver cancer in infected patients. Therefore,hbv/hcvInfected people should receive appropriate interventions to prevent the development of liver cancer or at least reduce the risk of liver cancer. 
Research Methods:
The Cochrane Library, Pubmed, MEDLINE, Embase, and Scopus were searched from inception to 10 December 2022. Inclusion criteria: (1) studies involving only people with confirmed HBV HCV infection, with or without receiving ** and with or without a sustained virologic response (SVR); (2) Confirmed FL or liver cancer by liver biopsy, imaging or reasonable records; (3) to evaluate the association between FL and liver cancer risk in patients with HBV HCV infection based on concomitant HR and 95% CI; (4) For republished articles, only the articles with the most complete data are retained.
Study characteristics
Sixteen studies published between 2011 and 2022 with 88,618 patients from six countries were included. During the follow-up period, 5,311 patients developed liver cancer. There were 14 high-quality studies and the remaining two were of moderate quality with a NOS score of 6.
Table 1: Study characteristics
Findings:
The relationship between FL and the risk of liver cancer in patients with HBV HCV infection
The pooled results suggested that FL may be a risk factor for the development of HCC in patients with HBV HCV infection. However, due to significant confounders, pooled results from multivariate analysis were not statistically significant (univariate analysis: hr = 1.).55, 95% ci = 1.24 - 1.96, i2= 88.2%;Multivariate analysis: hr = 118, 95% ci = 0.92 - 1.51, i2 = 88.9%）。There was considerable heterogeneity in these studies based on I2 and p-values. After sensitivity analysis, the robustness of the pooled results was confirmed by the one-in-one method.
Figure 1: Univariate and multivariate analysis FLAbility to develop liver cancer in patients with HBV HCV infection
The ability of FL to assess the risk of liver cancer varies between those with and from HBV infection. flProbably nothbvRisk factors for the development of liver cancer in infected patients(Univariate analysis: hr = 1.)57, 95% ci = 0.80 - 3.07;Multivariate analysis: hr = 082, 95% ci = 0.53 - 1.26；Figure 2).ButflProbablyhcvRisk factors for the development of liver cancer in infected patients(Univariate analysis: hr = 1.)64, 95% ci = 0.93 - 2.90;Multivariate analysis: hr = 185, 95% ci = 1.19 - 2.90；Figure 3).
Figure 2: Univariate and multivariate analysis FLAbility to develop liver cancer in patients with HBV infection
Figure 3: Univariate and multivariate analysis of FLThe best ability to develop liver cancer in HCV infected patients
Liver biopsy-confirmed FL may be a risk factor for the development of HCV in HCV-infected patients
According to sensitivity analysis, liver biopsy-confirmed FL (hepatic steatosis 5%) may be a risk factor for the development of liver cancer in patients with HBV HCV infection (univariate analysis: HR = 197, 95% ci = 1.22 - 3.18;Multivariate analysis: hr = 196, 95% ci = 1.19 - 3.24), and FL diagnosed by a reasonable method other than liver biopsy may not be a risk factor for the development of liver cancer (univariate analysis: HR = 0.).90, 95% ci = 0.44 - 1.81;Multivariate analysis: hr = 080, 95% ci = 0.51-1.23）。Further sensitivity analysis found that:Liver biopsy confirmedflProbablyhbvInfected(Univariate analysis: hr = 3.)13, 95% ci = 1.69 - 5.79;Multivariate analysis: hr = 342, 95% ci = 0.83 - 14.09）withhcvInfected(Univariate analysis: hr = 1.)64, 95% ci = 0.93 - 2.90;Multivariate analysis: hr = 175, 95% ci = 1.02 - 3.00）Risk factors for the development of liver cancer
In patients with HBV infection, FL is diagnosed using a reasonable method other than liver biopsyProbably notRisk factors for the development of liver cancer (univariate analysis: hr = 0.).90, 95% ci = 0.44 - 1.81;Multivariate analysis: hr = 069, 95% ci = 0.45 - 1.08）。There was only one study in which fl was diagnosed by a reasonable method other than liver biopsy in people with HCV infection, which was not representative.
Table 2: Sensitivity analysis based on diagnostic methods
Subgroup analysis
To further assess the potential for high heterogeneity affecting the ability of FL in patients with HBV HCV infection to risk HCC. The results show that:The incidence of diabetes, cirrhosis, hypertension, and dyslipidemia, as well as the proportion of males, were potentially heterogeneous in all studies**。Sample size, interval of HCC surveillance, incidence of hypertension, proportion of males, and use of antiviral** may be the potential for high heterogeneity in studies of patients with HBV infection**. Taken together, age, follow-up time, and proportion of obesity may not be potentially heterogeneous**.
Table 3: Subgroup analysis of patients with HBV HCV infection
Liver Linjun has something to sayThe effect of fatty liver on HBV infection remains controversial. Meta-analyses have shown that patients with chronic hepatitis B and fatty liver have a higher risk of developing liver cancer, and some meta-analyses have shown that patients with chronic hepatitis B and fatty liver have a significantly lower risk of liver cancer and death. In this meta-analysis, fatty liver confirmed by liver biopsy may be a risk factor for the development of liver cancer in patients with HBV HCV infection. Inconsistencies in these studies may be related to fatty liver type, patient characteristics, diagnostic approach to fatty liver, etc.
Several studies have shown that antiviral** treatment in patients with chronic hepatitis B is effective in reducing the risk of liver cancer, and interferons are superior to nucleosides. Therefore, for patients with HBV HCV infection with fatty liver, active intervention measures should be taken, on the one hand, receiving reasonable antiviral**, on the other hand, dietary intervention and appropriate exercise, so as to reduce the impact of fatty liver on the occurrence of liver cancer, and regular follow-up monitoring.
References:
han cl, tian bw, yang cc, et al. the association of fatty liver and risk of hepatocellular carcinoma in hbv or hcv infected individuals: a systematic review and meta-analysis [j]. expert rev gastroenterol hepatol, 2023, 17(2): 189-198.
Fatty liver.