Exploration of Medicine

Table 2. HCV and obesity

Author, year [Ref.]	Method	Findings	Conclusion
Adinolfi et al., 2001 [76]	Cross-sectional study of 180 consecutive patients with biopsy-proven CHC	The grade of steatosis was associated with BMI in HCV genotype 1 infection (r = 0.689; P < 0.001) and with levels of HCV RNA in HCV genotype 3a infection (r = 0.786; P < 0.001). Visceral fat distribution, rather than BMI, was associated with steatosis (P < 0.001).	Visceral obesity and genotype 3a play a role in the development of steatosis.
Monto et al., 2002 [77]	Cross-sectional study of 297 consecutive patients with HCV	At LRA BMI (P = 0.0002) and genotype 3a infection (P = 0.02) independently predicted steatosis. After exclusion of subjects with risk factors for NASH, genotype 3a infection remained the only independent predictor of steatosis. Steatosis (P = 0.04) and inflammation (P < 0.0001) scores on liver biopsy were the only independent predictors of fibrosis.	Steatosis in HCV infection is associated with risk factors for NASH, particularly obesity, rather than alcohol consumption.
Ortiz et al., 2002 [78]	114 prospectively recruited subjects who tested positive for HCV-RNA. Rapid disease progression was defined as a rate greater than 0.2 U/year.	At LRA the following variables were associated with progression: advanced age at infection (P = 0.0001), BMI ≥ 25 kg/m² (P = 0.01), and ALT > 1.5 times ULN (P = 0.01). Among patients with ALT > 1.5 times ULN, these predictors were: age at infection, BMI ≥ 25 kg/m², diabetes, and transferrin saturation > 45%. Among those with normal ALT levels, only BMI ≥ 30 kg/m² predicted progression.	Obesity, advanced age at infection, and elevated ALT levels predict rapid fibrosis progression in HCV infection.
Friedenberg et al., 2003 [79]	Analysis of 264 consecutive CHC patients	The degree of steatosis and fibrosis both tended to increase with increasing BMI (rho = 0.47, P < 0.001 and rho = 0.13, P = 0.03, respectively).	BMI is an independent predictor of both fibrosis and steatosis in HCV patients.
Younossi et al., 2004 [80]	Cross-sectional analysis of 120 CHC subjects who had available liver biopsies	Patients with superimposed NASH had more evidence of obesity (BMI: 30.64 ± 5.23 vs. 29.90 ± 5.35 vs. 27.33 ± 4.07, P = 0.008; W/H: 0.97 ± 0.06 vs. 0.91 ± 0.08 vs. 0.87 ± 0.07, P < 0.001), were more commonly infected with HCV genotype 3 (14% vs. 12% vs. 0%, P = 0.036), and had more advanced fibrosis (95.5% vs. 75.5% vs. 42.9%, P < 0.001).	The extent of steatosis and the type of SLD are associated with BMI, W/H, and HCV genotype 3a. Severe steatosis and superimposed NASH are both associated with advanced hepatic fibrosis.
Walsh et al., 2006 [81]	A cohort of 145 individuals with CHC was analyzed to determine host factors associated with non-response to antiviral therapy with either IFN-α or PEG-IFN-α, alone or in combination with ribavirin.	Factors independently associated with NR were viral genotype 1/4 (P < 0.001), cirrhosis on pretreatment biopsy (P = 0.025), and BMI ≥ 30 kg/m² (P = 0.010). At LRA, SOCS-3 mRNA expression remained independently associated with obesity (P = 0.023). SOCS-3 immunoreactivity was significantly increased in obesity (P = 0.013) and in non-responders compared with responders (P = 0.014).	Obesity reduces the response rate to IFN-alpha via increased expression of inhibitors of interferon signaling in CHC owing to HCV genotype 1.
Nishikawa et al., 2013 [82]	233 patients with HCV-related HCC who underwent curative SR were recruited. 60 patients (25.8%) were in the obesity group with a BMI greater than 25 kg/m², while 173 controls had a BMI less than 25 kg/m².	No differences were found between the obesity group and the control group regarding 1-, 3-, and 5-year cumulative OS (P = 0.818), RFS rates (P = 0.124), nor as regards blood loss during surgery (P = 0.899) and surgery-related serious adverse events (P = 0.813).	Obesity does not affect survival in patients with HCV-related HCC after curative SR.
Aguilar et al., 2016 [83]	Analysis of 43,478 new LT waitlist registrants with chronic HCV (21.0% with HCC, 79% without HCC) included in the 2003–2013 UNOS database.	Compared to non-obese patients, those with obesity had lower probability of receiving LT (OR: 0.91; 95% CI: 0.85 to 0.97; P < 0.01) and a lower probability of waitlist mortality (OR: 0.80; 95% CI: 0.72 to 0.89; P < 0.001).	Although it does not affect waitlist survival, obesity is associated with reduced odds of receiving LT.
Rao et al., 2017 [84]	Prospective study of two cohorts of HCV patients recruited from the US (n = 1,000) and China (n = 957)	Compared to subjects from China, more US patients had cirrhosis (38.2% vs. 16.0%) and HCC (14.1% vs. 2.7%). AT LRA, significant predictors of advanced disease were age, visceral obesity, diabetes, and prior HCV treatment.	The finding that the US had more advanced liver disease than those from China probably mirrors underlying SLD being a major contributor to this difference.
Tsao et al., 2017 [85]	Retrospective cross-sectional analysis of 1,267 medical records	After adjustment for confounders, body fat percentage, FFM/BW and MM/BW were the independent determinants of visceral obesity in HCV-free individuals (P < 0.001) although the trend, still statistically significant (P < 0.05), was not such obvious among HCV-infected individuals with HCV infection and less significant in HCV-infected men.	HCV affects the host’s lipid homeostasis and body fat distribution, with sex differences.
Turner et al., 2019 [86]	Analysis of a multiethnic cohort of 748 HCV-infected individuals, with 53% non-Hispanic black, 26% non-Hispanic white, and 22% Hispanic, of whom 23% had advanced liver disease defined as a FIB-4 index score above 3.25.	Among those with obesity (BMI ≥ 30 kg/m²) with a diagnosis of diabetes, the adjusted OR of advanced liver disease for Hispanics vs non-Hispanic black was 7.89 (95% CI: 3.66 to 17.01) and adjusted OR: 12.49 (95% CI: 3.24 to 48.18) for Hispanic vs non-Hispanic white patients (both P < 0.001).	The presence of obesity and diabetes among HCV-infected Hispanics is associated with a far higher risk for advanced liver disease than other ethnic groups.
Minami et al., 2021 [87]	Analysis of 2,055 HCV-infected individuals (840 in the IFN group and 1,215 in the DAA group)	At LRA, age, serum albumin, platelet count, AFP, and normal lipidemia, BMI ≥ 25 kg/m², and alcohol consumption ≥ 60 g/day independently predicted incident HCC, AHR 2.53 (95% CI: 1.51 to 4.25) and 2.56 (95% CI: 1.14 to 5.75), respectively.	Obesity and heavy alcohol consumption are associated with the risk of developing HCC after SVR.

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AFP: alpha-fetoprotein; AHR: adjusted hazard ratio; ALT: alanine transaminase; BMI: body mass index; BW: body weight; CHC: chronic hepatitis C; DAA: direct-acting antivirals; FFM: fat-free mass; FIB-4: fibrosis 4; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; IFN: interferon; LRA: logistic regression analysis; LT: liver transplantation; MM: muscle mass; NASH: nonalcoholic steatohepatitis; OR: odds ratio; OS: overall survival; PEG: pegylated; RFS: recurrence-free survival; SLD: steatotic liver disease; SR: surgical resection; SOCS-3: suppressors of insulin signaling 3; SVR: sustained virological response; ULN: upper limit of normal; UNOS: United Network for Organ Sharing; US: United States

Supplementary materials

The supplementary material for this article is available at: https://www.explorationpub.com/uploads/Article/file/1001334_sup_1.pdf.

Declarations

Acknowledgments

The graphical abstract was generated using Servier Medical Art, provided by Servier. The authors would like to express their gratitude to Sabine Weiskirchen from the University Hospital Aachen for preparing Figure 2 of this review. Additionally, we would like to extend our sincere thanks to the World Obesity Federation for assisting and granting permission to publish Figure 1B and the Supplementary material.

AI and AI-assisted Technologies: The authors of this article used the Large Language Model RWTHgpt by RWTH Aachen University exclusively for minor translations and grammatical corrections in this work. All sentences revised by RWTHgpt were reviewed and verified by the authors.

Author contributions

AL and RW: Conceptualization, Writing—original draft, Writing—review & editing. Both authors read and approved the submitted version.

Conflicts of interest

Amedeo Lonardo who is the Associate Editor of Exploration of Medicine had no involvement in the decision-making or the review process of this manuscript. Another author declares that there are no conflicts of interest.

Ethical approval

Not applicable.

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