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©2014 Baishideng Publishing Group Inc.
World J Gastroenterol. Jun 21, 2014; 20(23): 7089-7103
Published online Jun 21, 2014. doi: 10.3748/wjg.v20.i23.7089
Published online Jun 21, 2014. doi: 10.3748/wjg.v20.i23.7089
Table 1 Steatosis is associated with fibrosis
Method and findings | Conclusion | Ref. |
98 CHC patients who had undergone repeat liver biopsies before antiviral treatment (median follow-up 5.8 yr) | In HCV patients with genotype 3 infection, steatosis was a risk factor for fibrosis progression | [68] |
297 consecutive patients with HCV | Steatosis and inflammation scores were the only parameters independently predicting fibrosis | [70] |
96 non-cirrhotic treatment-naive CHC patients | In untreated CHC patients fibrosis progression was strongly associated with worsening of steatosis | [71] |
1428 CHC treatment-naïve patients included in a French therapeutic trial | The variables independently associated with steatosis were genotype 3 , higher age, triglycerides and body mass index (BMI) values and septal fibrosis | [72] |
131 biopsy-proven CHC individuals | Hepatic steatosis was related to genotype, fibrosis degree, and serum leptin level | [73] |
160 CHC patients | Irrespective of viral genotype, patients who had steatosis showed significantly more fibrosis than non-steatosic | [74] |
Cross sectional study evaluating: 233 hepatic biopsies from 219 CHC patients and hepatectomy specimens from 65 patients transplanted for HCV-related cirrhosis. Longitudinal study: 41 patients with two biopsies and 10 patients with three biopsies performed over 2-8 yr | Steatosis was associated with fibrosis independently of necroinflammation, but declined in cirrhosis | [75] |
Retrospective study conducted on 324 US patients with CHC from a university medical center and a regional VA medical center | Steatosis was independently associated with advanced fibrosis stage | [76] |
135 treatment-naive CHC patients who had undergone repeat liver biopsies after a median interval of 61 months after the baseline biopsy | Irrespective of HCV genotype, steatosis was a chief contributor to fibrosis progression in mild CHC and the probability of such a fibrosis worsening is directly dependent on the proportion of steatotic hepatocytes | [77] |
116 CHC patients undergoing liver biopsy | The MTHFR C677T polymorphism, responsible for hyperhomocysteinemia, contributed to increasing steatogenesis and steatosis which in its turn, hastened hepatic fibrosis progression | [78] |
Meta-analysis on individual data from 3068 patients with biopsy- proven CHC recruited from 10 centers in Europe, Australia, and United States | Steatosis was significantly and independently associated with fibrosis in CHC. Hepatic inflammation may mediate fibrogenesis in patients with liver steatosis | [79] |
180 patients infected with genotype 1b HCV | At multivariate analysis, fibrosis was significantly related to age, alanine transaminase, diabetes, hepatitis B core antibody, steatohepatitis and grading | [80] |
Overall, 600 consecutive individuals: 500 with CHC; and 100 with CHB | IR, was associated with 1 and 4 HCV genotypes and high viral load. The association of significant fibrosis with IR occurs independent of steatosis | [81] |
153 chronic hepatitis C patients enrolled in the Swiss hepatitis c cohort study and for whom a liver biopsy and plasma samples were available | By multiple regression analysis, CTGF levels were independently associated with steatosis, a past history of alcohol abuse, plasma leptin and HCV RNA levels; when only patients with genotypes non-3 were considered, CTGF levels were independently associated with a past history of alcohol abuse, plasma leptin levels and steatosis | [82] |
107 consecutive CHC patients | Multiple regression analysis revealed that, HOMA-IR, fibrosis and oxidative stress were independently associated with steatosis, whereas steatosis was independently associated with oxidative stress and HOMA-IR. Steatosis and HAI were also independent predictors of fibrosis | [83] |
143 AA and 157 CA adults with untreated chronic HCV genotype 1 infection | In 3-variable models including race and biopsy adequacy, the factors significantly associated with fibrosis progression were age when infected, steatosis, ALT level, and necroinflammatory score | [84] |
228 HCV treatment-naive patients who met the inclusion/exclusion criteria | Genotype 1 and presence of steatosis were found to be associated significantly with MS. After adjusting for confounding variables, MS remained independently associated with a lack of SVR | [85] |
346 untreated, nondiabetic patients solely infected with either genotype 1 or 3 | HOMA-IR rather than steatosis was independently associated with fibrosis for both HCV genotype 1 and genotype 3. Exclusion of cirrhotic subjects did not alter the findings with respect to the greater contribution of IR compared to hepatic steatosis, as a predictor of fibrosis | [86] |
Retrospective study of 460 patients with CHC | Elevated AST, alpha fetoprotein, and presence of grade 2 and 3 steatosis are independent parameters associated with stage 3 and 4 fibrosis in patients with CHC | [87] |
112 HCV RNA positive subjects who had two liver biopsies performed | On multivariate analysis, only baseline steatosis was significantly associated with fibrosis. Kaplan-Meier analysis demonstrated that steatosis impacted on time to progression to both significant fibrosis and cirrhosis | [88] |
Of 253 HCV RNA-positive persons who underwent at least one liver biopsy | The presence of T2D, steatosis and duration of HCV infection were independent predictors of advanced fibrosis | [89] |
Metanalysis of 12 published studies, including 1989 HIV/HCV co-infected patients | In co-infected patients, HS was associated with higher body mass index, diabetes mellitus, elevated alanine aminotransferase, necroinflammatory activity and fibrosis | [90] |
Liver biopsy samples were collected from 59 patients with HCV without a sustained virologic response (SVR) or cirrhosis | There were no associations between fibrosis progression and histologic features including inflammation, fibrosis, or steatosis | [91] |
170 genotype 1 CHC patients | At multivariate analysis Severe (F3-F4 fibrosis), , was independently associated with older age, IR, steatosis > 10%, and moderate-severe necroinflammatory activity in CHC patients | [92] |
92 untreated consecutive adults with chronic HCV infection admitted for liver biopsy | In multivariate analyses, fibrosis was associated with high AST level, age ≥ 40 yr, and steatosis | [93] |
152 LT recipients with HCV were followed up with repeated liver biopsies for a median of 2.09 yr after index biopsy | In the multivariate analysis, steatosis at 1 yr was an independent predictor of subsequent F2 to F4 fibrosis. Steatosis was a stronger predictor of fibrosis in the setting of sirolimus use | [94] |
755 consecutive chronic hepatitis C patients (178 with genotype 3), admitted to three referral hospitals in Switzerland | Fibrosis was associated with steatosis in genotype 3 infected individuals alone | [95] |
574 CHC patients with chronic hepatitis C from a single United States center | In CHC owing to genotype 1 infection HCV, fibrosis was associated with steatosis severity | [96] |
Clinical data and liver histology findings in 510 HCV patients were analysed | Age at liver biopsy, BMI and duration of HCV were independent risk factors for increased fibrosis in HCV patients. Steatosis as a risk factor for fibrosis is evident in HCV genotype-1 | [97] |
60 HCV patients compared to 41 NASH patients and 18 CHB individuals | Compared to patients who had mild steatosis, those CHC individuals with moderate steatosis exhibited higher fibrosis stages | [98] |
251 CHC women | Severity of fibrosis was associated with a longer duration of infection, a higher BMI, advanced steatosis and the menopause | [99] |
Ninety HCV infected patients undergoing liver biopsy | Steatosis was not found to be independently associated with fibrosis | [100] |
Liver biopsies from 66 out of 306 HCV/HIV non-cirrhotic patients without cirrhosis at baseline who underwent a second biopsy were case-matched with a control group selected from a cohort of 233 HCV mono-infected patients | Progression of fibrosis was similar in HIV/HCV-co-infected compared to HCV mono-infected individuals and no clinical or laboratory predictor of worsening liver disease was identified | [101] |
Table 2 Steatosis is associated with poor treatment outcome
Method and findings | Conclusion | Ref. |
574 patients with chronic hepatitis C | Steatosis reduces the likelihood of achieving early and SVR in genotype 1 infected patients | [96] |
HCV genotype 2 and 3 patients | Steatosis is the independent predictor of relapse | [102] |
148 consecutive adults with HCV admitted for liver biopsy | Steatosis in chronic hepatitis C is not a negative prognostic factor of response to combined antiviral therapy | [103] |
932 patients infected with HCV genotype 2 or 3 | Steatosis was associated with significantly higher rates of relapse, irrespective of viral load, in patients infected with HCV genotype 3 who had an RVR | [104] |
A total of 116 patients [HCV-G4 85 (73.3%); HCV-G1 31 (26.7%)] were included | The NAS steatosis score correlates with response to antiviral therapy | [105] |
885 HCV patients | Steatosis did not influence the efficacy of treatment in our study population. Baseline viral load is a confounding factor, particularly in patients infected with genotype 3 and once baseline viral load was accounted for, the association between steatosis and SVR was not relevant | [106] |
250 patients with genotype 4 chronic hepatitis C, treated with different regimens of combined interferon | Among genotype 4 chronic hepatitis C patients, severe fibrosis, severe steatosis, treatment with standard interferon and a high serum AFP level were all negatively associated with SVR | [107] |
207 HCV patients | Features of the metabolic syndrome are associated with hepatic steatosis in most of these patients. Steatosis is significantly more common in genotype 3 compared with other genotypes, and in these patients, an SVR is associated with steatosis clearance | [108] |
357 HCV-infected US veterans | Steatosis is independently associated with stage III-IV fibrosis. However, only HCV genotype, and not steatosis, obesity, or stage III-IV fibrosis, was associated with SVR to interferon alpha-2b and ribavirin treatment | [109] |
80 Japanese patients with CHC. treated with IFN alpha-2b and ribavirin for 24 wk evaluated retrospectively | HS is an important predictor of poor response to therapy of IFN-alpha-2b and ribavirin in patients with CHC | [110] |
Liver specimens with both CHC and significant steatosis (> 33%) or SH were categorized as group 1 (84 specimens). A control group (group 2) of 231 CHC patients without evidence of steatosis > 33% or SH | Overall SVR for patients with HCV and significant steatosis or SH is considerably lower than for HCV and steatosis less than 33% and no SH | [111] |
Table 3 Steatosis is associated with increased hepatocellular carcinoma risk
Method and findings | Conclusion | Ref. |
1818 patients with histologically proven CHC treated with IFN Cumulative incidence and HCC risk were analyzed over a mean follow-up period of 6.1 yr HCC developed in 179 study subjects | Severe steatosis, is an independent factor significantly associated with HCC | [112] |
The 5-yr occurrence rate of HCC in 353 consecutive patients with histologically proven HCV cirrhosis and persistent viral replication prospectively followed and screened for HCC was 34% in genotype 3 and 17% in non-3 genotype group | For patients with HCV cirrhosis and ongoing infection, infection with genotype 3 (a potent steatogenic virus) is independently associated with an increased risk of HCC development | [113] |
The steatohepatitis-HCC variant was found in 35.5% of 62 HCC cases In 14 of the 22 cases (63.6%) of SH-HCC, the non-neoplastic liver showed changes of NAFLD/NASH superimposed on otherwise typical features of HCV-C | This study suggests a possible NAFLD/NASH pathway leading to SH-HCC in the setting of HCV-C | [114] |
This retrospective study investigated the features of 5 patients who developed HCC after 10 yr of achieving SVR | In 3 patients, liver tissues were obtained at the treatment of HCC. These tissues showed marked improvement in both activities and fibroses, but severe steatosis in 1 patient | [115] |
Two-hundred and sixty-six patients, who achieved SVR, were enrolled in this retrospective study | Age, hepatic fibrosis, and hepatic steatosis at pre-interferon treatment might be risk factors for developing HCC after SVR | [116] |
A retrospective study was conducted in 88 patients undergoing curative resection of HCV-associated HCC | Hepatic steatosis is a useful predictor of postoperative recurrence of HCV-related HCC | [117] |
94 consecutive patients with cirrhosis due to HCV who underwent liver transplantation and had pathology available for review were retrospectively identified | In patients with HCV-related cirrhosis, the presence of hepatic steatosis is independently associated with the development of HCC | [118] |
The histological severity of steatosis in the index liver biopsies of 25 patients with chronic hepatitis C who subsequently developed HCC was compared with matched controls who did not. As determined by percentage area of biopsy core occupied by steatosis on computer assisted morphometric evaluation, and graded semiquantitatively, steatosis was comparable among cases and controls | The odds of developing HCC among those with steatosis grades 1 and 2 did not differ significantly from those without steatosis. There was no association between increasing morphometric percentage area occupied by steatosis and the subsequent development of HCC. Neither steatosis grade or percent area of steatosis on biopsy were selected in multivariate regression analysis as independent predictors for the development of HCC | [119] |
161 patients with chronic HCV infection | At multivariate analysis hepatic steatosis, (together with aging, cirrhosis, and no IFN treatment) was an independent, significant risk factor for HCC | [120] |
Table 4 Prevalence of steatohepatitis associated with hepatitis C virus infection n (%)
Series | Steatohepatitis | Ref. |
297 patients | 17 (6) | [70] |
170 patients | 17 (10) | [124] |
1458 liver biopsies | 80 (5.5) | [125] |
95 patients | 4 (4) | [126] |
296 liver biopsies | 24 (9) | [127] |
2316 biopsies/patients | 142 (6,13) | Cumulative |
- Citation: Lonardo A, Adinolfi LE, Restivo L, Ballestri S, Romagnoli D, Baldelli E, Nascimbeni F, Loria P. Pathogenesis and significance of hepatitis C virus steatosis: An update on survival strategy of a successful pathogen. World J Gastroenterol 2014; 20(23): 7089-7103
- URL: https://www.wjgnet.com/1007-9327/full/v20/i23/7089.htm
- DOI: https://dx.doi.org/10.3748/wjg.v20.i23.7089