Liver cirrhosis

Abstract

Cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury, which leads to portal hypertension and end-stage liver disease. Recent advances in the understanding of the natural history and pathophysiology of cirrhosis, and in treatment of its complications, have resulted in improved management, quality of life, and life expectancy of patients. Liver transplantation remains the only curative option for a selected group of patients, but pharmacological treatments that can halt progression to decompensated cirrhosis or even reverse cirrhosis are currently being developed. This Seminar focuses on the diagnosis, complications, and management of cirrhosis, and new clinical and scientific developments.

Targeting Liver Fibrosis

“…Thus, even advanced fibrosis and possibly cirrhosis can regress once the fibrogenic trigger is eliminated and fibrolysis prevails over fibrogenesis. [1][2][3] The complex biology of hepatic stellate cells and myofibroblasts (collectively termed HSC), the major producers of excessive ECM in liver fibrogenesis, has been covered extensively in recent reviews. 4 Other profibrogenic nonparenchymal cells act upstream of activated HSC (summarized in Table 1).…”

“…Impressive progress in our understanding of molecular mechanisms of fibrosis progression uncovered several promising molecular targets for antifibrotic treatments (Table 3) (for reviews, see Schuppan and Afdhal, 1 Friedman, 5 Bataller and Brenner, 6 and Rockey 44 ). However, transfer of these experimental treatments to clinical practice has been slow.…”

“…Ultrasonography, computerized tomography, magnetic resonance imaging (MRI), positron emission tomography (PET), and single photon emission computerized tomography (SPECT) are not able to detect fibrosis and are not even sensitive enough to diagnose cirrhosis in many patients. 1 Diffusion-weighted MRI may offer some differentiation, but will likely not be able to exactly stage fibrosis. 96 MR texture analysis and double-contrast MRI using supraparamagnetic iron and gadolinium as contrast agents may yield a better fibrosis assessment but are in their infancy.…”

“…With ongoing liver damage, fibrosis may progress to cirrhosis, which is characterized by a distortion of the liver vasculature and architecture, and which is the major determinant of morbidity and mortality in patients with liver disease, predisposing to liver failure and primary liver cancer. 1 Causal treatment, e.g., antiviral therapy for chronic hepatitis B and C, or weight loss and exercise for nonalcoholic steatohepatitis (NASH), can retard or prevent liver fibrosis progression. However, many patients either do not respond to causal treatment or are diagnosed with advanced fibrosis or cirrhosis.…”

High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation

“…Deposition of fibrillar extracellular matrix, altered hepatocyte regeneration, deranged microvascular architecture ultimately leads to cirrhosis, which is the major determinant of morbidity and mortality in patients with liver disease, predisposing to liver failure and hepatocellular carcinoma [5]. Although liver biopsy still remains the gold standard to assess hepatic fibrosis, it would be desirable to enable monitoring and prediction of the fibrotic process with non-invasive methods.…”