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Patients with stage 3 compared to stage 4 liver fibrosis have lower frequency of and longer time to liver disease complications.

ABSTRACT: BACKGROUND AND AIMS:Advanced liver fibrosis is an important predictor of liver disease progression and mortality, and current guidelines recommend screening for complications of cirrhosis once patients develop F3 fibrosis. Our study compared liver disease progression and survival in patients with stage 3 (F3) and stage 4 (F4) fibrosis on liver biopsy. METHODS:Retrospective study of patients with F3 or F4 on liver biopsy followed for development of liver disease complications (variceal bleeding, ascites, and hepatic encephalopathy); hepatocellular carcinoma, and survival (overall and transplant free survival). RESULTS:Of 2488 patients receiving liver biopsy between 01/02 and 12/12, a total of 294 (171 F3) were analyzed. Over a median follow up period of 3 years, patients with F4 (mean age 53 years, 63% male) compared to F3 (mean age 49 years, 43% male) had higher five year cumulative probability of any decompensation (38% vs. 14%, p<0.0001), including variceal bleed (10% vs. 4%, p = 0.014), ascites (21% vs. 9%, p = 0.0014), and hepatic encephalopathy (14% vs. 5%, p = 0.003). F4 patients also had lower overall 5-year survival (80% vs. 93%, p = 0.003) and transplant free survival (80% vs. 93%, p = 0.002). Probability of hepatocellular carcinoma in 5 years after biopsy was similar between F3 and F4 (1.2% vs. 2%, p = 0.54). CONCLUSIONS:Compared to F4 stage, patients with F3 fibrosis have decreased risk for development of liver disease complications and better survival. Prospective well designed studies are suggested with large sample size and overcoming the limitations identified in this study, to confirm and validate these findings, as basis for modifying guidelines and recommendations on follow up of patients with advanced fibrosis and stage 3 liver fibrosis.

SUBMITTER: Axley P

PROVIDER: S-EPMC5944985 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Accurate staging of liver fibrosis is crucial to guide therapeutic decisions for patients with nonalcoholic fatty liver disease (NAFLD). Digital image analysis has emerged as a promising tool for quantitative assessment of fibrosis in chronic liver diseases. We sought to determine the relationship of histologic fibrosis stage with fiber amounts quantified in liver biopsy specimens for the better understanding of NAFLD progression. We measured area ratios of collagen and elastin fibers in Elastica van Gieson-stained biopsy tissues from 289 patients with NAFLD from four hospitals using an automated computational method and examined their correlations with Brunt's fibrosis stage. As a secondary analysis, we performed multivariable logistic regression analysis to assess the associations of the combined area ratios of collagen and elastin with noninvasive fibrosis markers. The combined fiber area ratios correlated strongly with Brunt's stage (Spearman correlation coefficient, 0.78; P < 0.0001), but this relationship was nonlinear (P = 0.007) with striking differences between stage 4 (median area ratios, 12.3%) and stages 0-3 (2.1%, 2.8%, 4.3%, and 4.8%, respectively). Elastin accumulation was common in areas of thick bridging fibrosis and thickened venous walls but not in areas of perisinusoidal fibrosis. The highest tertile of the combined fiber area ratios was associated with the fibrosis-4 index and serum type IV collagen 7s domain (7s collagen) levels, whereas the upper two tertiles of the fiber amounts significantly associated with body mass index, aspartate aminotransferase, and 7s collagen in the multivariable analysis. Conclusion: Quantitative fibrosis assessment reveals a nonlinear relationship between fibrosis stage and fiber amount, with a marked difference between stage 4 and stage 3 and much smaller differences among stages 0-3, suggesting a heterogeneity in disease severity within NAFLD-related cirrhosis. (Hepatology Communications 2018;2:58-68).

Project description:IntroductionRelative risks (RRs) for coronary heart disease (CHD) by cigarettes/day exhibit a concave pattern, implying the RR increase with each additional cigarette/day consumed decreases with greater intensity. Interpreting this pattern faces limitations, since cigarettes/day alone does not fully characterize smoking-related exposure. A more complete understanding of smoking and CHD risk requires a more comprehensive representation of smoking.MethodsUsing Poisson regression, we applied a RR model in pack-years and cigarettes/day to analyze two diverse cohorts, the US Agricultural Health Study, with 4396 CHD events and 1 425 976 person-years of follow-up, and the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, with 5979 CHD events and 486 643 person-years.ResultsIn both cohorts, the concave RR pattern with cigarettes/day was consistent with cigarettes/day modifying a linear RR association for CHD by pack-years within categories of cigarettes/day, indicating that strength of the pack-years association depended on cigarettes/day (p < .01). For example, at 50 pack-years (365 000 total cigarettes), estimated RRs of CHD were 2.1 for accrual at 20 cigarettes/day and 1.5 for accrual at 50 cigarettes/day.ConclusionsRRs for CHD increased with pack-years with smoking intensities affecting the strength of association. For equal pack-years, smoking fewer cigarettes/day for longer duration was more deleterious than smoking more cigarettes/day for shorter duration. We have now observed inverse smoking intensity effects in multiple cohorts with differing smoking patterns and other characteristics, suggesting a common underlying phenomenon.ImplicationsRisk of CHD increases with pack-years of smoking, but accrual intensity strongly influences the strength of the association, such that smoking fewer cigarettes/day for longer duration is more deleterious than smoking more cigarettes/day for shorter duration. This observation offers clues to better understanding biological mechanisms, and reinforces the importance of cessation rather than smoking less to reduce CHD risk.

Project description:Liver fibrosis is the most important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Quantitative risk of mortality by fibrosis stage has not been systematically evaluated. We aimed to quantify the fibrosis stage-specific risk of all-cause and liver-related mortality in NAFLD. Through a systematic review and meta-analysis, we identified five adult NAFLD cohort studies reporting fibrosis stage-specific mortality (0-4). Using fibrosis stage 0 as a reference population, fibrosis stage-specific mortality rate ratios (MRRs) with 95% confidence intervals (CIs) for all-cause and liver-related mortality were estimated. The study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Included were 1,495 NAFLD patients with 17,452 patient years of follow-up. Compared to NAFLD patients with no fibrosis (stage 0), NAFLD patients with fibrosis were at an increased risk for all-cause mortality, and this risk increased with increases in the stage of fibrosis: stage 1, MRR = 1.58 (95% CI 1.19-2.11); stage 2, MRR = 2.52 (95% CI 1.85-3.42); stage 3, MRR = 3.48 (95% CI 2.51-4.83); and stage 4, MRR = 6.40 (95% CI 4.11-9.95). The results were more pronounced as the risk of liver-related mortality increased exponentially with each increase in the stage of fibrosis: stage 1, MRR = 1.41 (95% CI 0.17-11.95); stage 2, MRR = 9.57 (95% CI 1.67-54.93); stage 3, MRR = 16.69 (95% CI 2.92-95.36); and stage 4, MRR = 42.30 (95% CI 3.51-510.34). Limitations of the study include an inability to adjust for comorbid conditions or demographics known to impact fibrosis progression in NAFLD and the inclusion of patients with simple steatosis and nonalcoholic steatohepatitis without fibrosis in the reference comparison group.ConclusionThe risk of liver-related mortality increases exponentially with increase in fibrosis stage; these data have important implications in assessing the utility of each stage and benefits of regression of fibrosis from one stage to another. (Hepatology 2017;65:1557-1565).

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Patients with stage 3 compared to stage 4 liver fibrosis have lower frequency of and longer time to liver disease complications.

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