Overweight and obesity, hepatic steatosis, and progression of chronic hepatitis C: a retrospective study on a large cohort of patients in the United States

doi:10.1016/S0168-8278(03)00479-3

Journal of Hepatology

Volume 40, Issue 1, January 2004, Pages 147-154

https://doi.org/10.1016/S0168-8278(03)00479-3 Get rights and content

Abstract

Background: Hepatic steatosis has been associated with chronic hepatitis C (CHC), but its prevalence, risk factors, and clinical significance remain to be determined.

Aims: The present study determined the frequency of, and risk factors for hepatic steatosis and its association with activity and progression of CHC in a large cohort of U.S. patients.

Methods: This is a retrospective study that utilized systematic chart review and statistical analyzes to investigate 324 U.S. patients with CHC from a university medical center and a regional VA medical center.

Results: The frequency of hepatic steatosis was 66.0%. We demonstrated that not only being obese, but also overweight (i.e. body mass index ≥25 kg/m²) was independently associated with hepatic steatosis. In our cohort of patients with CHC, hepatic steatosis, especially grade II/III steatosis, was significantly associated with elevated aspartate aminotransferase at entry, persistently elevated alanine aminotransferase, and stage III/IV fibrosis. Grade II/III steatosis, was significantly associated with a higher histology activity index as well. Multivariate analysis indicated that steatosis, especially grade II/III steatosis, was independently associated with stage III/IV fibrosis.

Conclusions: Being overweight/obese serves as an independent risk factor for hepatic steatosis in U.S. patients with CHC. Steatosis accelerates activity and progression of CHC, and is independently associated with stage III/IV hepatic fibrosis in these patients.

Introduction

Chronic hepatitis C virus (HCV) infection affects 170 million people worldwide, including 2.7 million of U.S. individuals [1], [2], [3]. Although a great deal of progress has been made [3], [4], [5], [6], [7], factors affecting disease progression and development of cirrhosis in these patients remain incompletely defined.

Hepatic steatosis is a well-documented histological feature during HCV infection [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18]. Most studies [8], [10], [11], [12], [13], [14], [15], [19] have suggested that obesity is associated with steatosis in patients with chronic hepatitis C (CHC). However, a general threshold of body mass index (BMI) for steatosis and association of BMI with grade of steatosis remain to be determined.

Besides obesity, type 2 diabetes mellitus (DM) and hypertriglyceridemia have also been associated with hepatic steatosis in patients with non-alcoholic fatty liver disease [20], [21], [22], [23], [24]. Increased frequency of type 2 DM has been reported in patients with CHC [25], [26]. A recent study included 7.7% patients with DM, but could not directly associate DM with hepatic steatosis [19]. In addition, the effect of hypertriglyceridemia on hepatic steatosis in HCV-infected patients has not been systematically examined. Therefore, it is important to determine whether DM and/or hypertriglyceridemia alone, or in combination with obesity, contribute to development of hepatic steatosis in these patients.

Expression of HCV proteins has been associated with hepatic steatosis in transgenic mice [27], [28]. These results were further supported by findings that HCV genotype 3a (HCV-3a) is associated with both higher prevalence and grade of hepatic steatosis in patients with CHC [9], [14], [15], [19], [29], [30], [31]. However, this association remains to be further defined [16].

Several studies have reported an association of steatosis with advanced hepatic fibrosis in patients with CHC [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19]. However, it remains unknown whether a higher grade of steatosis is more associated with a higher stage of hepatic fibrosis. In addition, it remains controversial whether BMI affects progression of fibrosis directly [8]. A few studies have reported that hepatic steatosis is associated with higher levels of alanine aminotransferase (ALT) and histological activity index (HAI) [8], [9], [19], but these findings were not supported by other studies [11], [12], [16]. Thus, it is necessary to re-examine these issues in a large cohort of HCV-infected patients.

The aims of this retrospective study were to determine the prevalence of and the risk factors for hepatic steatosis and to assess the association of being overweight/obese and steatosis with activity and progression of CHC in U.S. patients.

Section snippets

Patient population

The present study retrospectively included 324 consecutive patients from two Liver Clinics at Loma Linda VA Medical Center (n=112) and Loma Linda University Medical Center (n=212) between July 1999 and April 2002. The study protocol was approved and informed consent was exempted by the institutional review boards from both medical centers. Inclusion criteria were: (1) positive HCV RNA reverse transcription polymerase chain reaction (RT-PCR) for at least 6 months; (2) a liver biopsy to stage

Baseline demographic findings

The baseline demographic data are summarized in Table 1. Of the 307 patients with recorded BMI, the mean BMI was 28.5±5.3 (17–47) kg/m². Overweight was seen in 122/307 (39.7%) cases, and obesity was seen in 116/307 (37.8%) patients. Overall, 238/307 (77.5%) patients were overweight or obese. In 250 patients with documented information of drinking, 69.6% reported a past history of alcohol use. In 189 patients with recorded duration of sobriety, 32.8% have been sobered for 6–12 months and 67.2%

Discussion

The present study investigated a large cohort of US patients with CHC and demonstrated that the frequency of steatosis was as high as 66.0% in these patients. Hourigan et al. reported that 20.0% of Australian patients with CHC have grade II/III steatosis [6]. Using the same scoring system, grade II/III steatosis was seen in 30.0% of our patients with CHC. Therefore, hepatic steatosis, especially a higher grade of steatosis, is a very common presentation in U.S. patients with CHC.

Although it is

Acknowledgements

The authors are indebted to Dr. Pramil N. Singh for his invaluable comments on statistical analysis. Part of this work was published as an abstract in Hepatology 2002; 36: 349A and presented in 53 AASLD annual meeting in November 2002 in Boston. This work was supported by a grant from the Division of Gastroenterology and Hepatology, Loma Linda University School of Medicine (K-Q. H.).

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Overweight and obesity, hepatic steatosis, and progression of chronic hepatitis C: a retrospective study on a large cohort of patients in the United States

Abstract

Introduction

Section snippets

Patient population

Baseline demographic findings

Discussion

Acknowledgements

Lancet Infect Dis

Gastroenterology

Hepatology

J Hepatol

J Hepatol

Hepatology

Hepatology

Hepatology

Hepatology

Gastroenterology

Gastroenterology

J Hepatol

Hepatology

Am J Gastroenterol

J Hepatol

Prevalence of hepatitis C virus infection in the United States

N Engl J Med

Management of Hepatitis C: 2002-June 10–12, 2002

Hepatology

Natural history of hepatitis C

Hepatology

Natural history of hepatitis C: its impact on clinical management

Hepatology

The long-term outcomes of patients with compensated hepatitis C virus-related cirrhosis and history of parenteral exposure in the United States

Hepatology