Risk Of Liver-related Events Research Articles

Advances in the management of HIV/HCV coinfection.

HCV coinfection has emerged as a major cause of non-AIDS-related morbidity and mortality in HIV-positive patients. As a consequence of the availability of modern combined antiretroviral therapy regimens, for optimally managed HIV/HCV-coinfected patients, the rates of liver fibrosis progression and the risk of liver-related events are increasingly similar to those of HCV-monoinfected patients. Moreover, our understanding of modulators of liver disease progression has greatly improved. In addition to immune status, endocrine, metabolic, genetic and viral factors are closely interrelated and might be important determinants of liver disease progression. In the last decade, a variety of serologic and radiographic tests for noninvasive liver disease staging have been extensively validated and are commonly used in HIV/HCV-coinfected patients. Sustained virologic response prevents end-stage liver disease, hepatocellular carcinoma, and death, with an even greater effect size in HIV-positive compared to HIV-negative patients. As interferon-free regimens achieve comparable rates of sustained virologic response in HIV-negative and HIV-positive patients, HIV/HCV-coinfected patients should from now on be referred to as a special, rather than a difficult-to-treat, population. Our comprehensive review covers all relevant aspects of HIV/HCV coinfection. Beginning with the changing epidemiology, it also provides new insights into the natural history of this condition and gives an overview on non-invasive techniques for the staging of liver disease. Furthermore, it outlines current recommendations for the treatment of acute hepatitis C and summarizes the unprecedented advances in the field of chronic hepatitis C therapy.

Five Laboratory Tests Predict Patient Risk and Treatment Response in Hepatitis C: Veterans Affairs Data from 1999-2010

Background and Aims: New Hepatitis C [HCV] drugs are expensive but highly effective but have created an overwhelming ‘cash flow’ problem for payers facing a large bolus of infected patients. Health plans are developing ‘watchful waiting’ strategies to safely defer treatment for low risk patients. This study identifies five laboratory tests which predict increasing risk of liver related events and documents that delaying treatment until after an abnormal lab test diminished effectiveness of treatment with interferon alpha plus ribavirin. Methods: Patients from the Veterans Administration’s clinical registry of HCV patients [1999-2010] were screened for a detectable viral load at baseline and a recorded baseline genotype. The primary outcomes were time to death and time to time to a composite clinical event. Cox proportional hazards models were estimated with time dependent independent variables for initial treatment and first abnormal laboratory test. Results: 128,769 patients met all inclusion criteria. Abnormal values for five laboratory were associated with increased risk for the composite outcome/death: 1.35/1.84 for the AST/ALT ratio > 1; 2.35/5.01 for albumin 195 IU/L; 3.85/1.55 for platelet count 144 ng/mL. Delaying drug therapy until after an abnormal lab test significantly reduced treatment effectiveness. Discussion: Five tests predict liver complications for HCV patients which can be used to develop “watchful waiting” protocols which monitor untreated HCV patients over time and defer access to expensive new drug regimens to those patients most at risk adverse liver-related events.

Surrogate End Points and Long-Term Outcome in Patients With Chronic Hepatitis B

It is unclear whether surrogate end points reported in clinical trials correlate with long-term outcome of patients with chronic hepatitis B. Patients with chronic hepatitis B who participated in any of 4 randomized controlled trials were followed prospectively for liver-related events (hepatocellular carcinoma, ascites, spontaneous bacterial peritonitis, variceal bleeding, liver transplantation, and death). Biochemical (normal ALT levels), virologic (levels of hepatitis B virus DNA below 10,000 copies/mL), and histologic (reduction of necroinflammation grading by 2 points or more with no increase in fibrosis staging) responses were evaluated at the end of each trial. One hundred ninety-five patients with adequate pretreatment and post-treatment liver biopsies (15 mm long and 6 portal tracts) were followed for 86 months (interquartile range, 77-98). Liver-related events occurred in 12 patients (6%). The risk of liver-related events was lower in patients with biochemical (hazard ratio, 0.21; 95% confidence interval, 0.068-0.68) and histologic (hazard ratio, 0.095; 95% confidence interval, 0.012-0.74) responses. Only 1 patient with a histologic response and 1 patient with an ALT level below Prati's cutoffs (30 IU/L in men and 19 IU/L in women) developed liver-related events. Fifteen of 25 patients (60%) with cirrhosis at baseline had regression of cirrhosis, and none of these patients died or developed liver-related events. In contrast, 3 of these patients still developed liver-related events, despite an initial virologic response, and 2 had virologic breakthrough. Biochemical and histologic responses, particularly regression of cirrhosis, in patients with chronic hepatitis B are associated with decreased liver-related complications.