Brief communication: the relationship of regression of cirrhosis to outcome in chronic hepatitis C.
ABSTRACT The effect of regression of cirrhosis in chronic hepatitis C is unknown.
To evaluate the relation between regression of cirrhosis and clinical outcome in patients with chronic hepatitis C after antiviral therapy.
A cohort of patients with cirrhosis treated between 1988 and 2001.
Hepatology unit of a tertiary care center in France.
96 patients with chronic hepatitis C and biopsy-proven cirrhosis (METAVIR score F4) who were treated with an interferon-based regimen and had at least 1 posttreatment liver biopsy. Patients were followed until November 2006.
Occurrence of a combined end point of liver-related events (ascites, hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, hepatocellular carcinoma, or liver transplantation) and death in patients with regression of cirrhosis (defined as a decrease from 4 to <or=2 METAVIR units on posttherapy liver biopsy).
The median follow-up was 118 months (interquartile range, 86 to 138 months). Eighteen patients had regression of cirrhosis. The incidence of the combined end point per 100 patient-years was 0 in patients with regression of cirrhosis and 4 in patients without regression of cirrhosis (P = 0.002, log-rank test). The transplantation-free survival rate at 10 years was 100% in patients with regression of cirrhosis and 74.2% in patients without regression of cirrhosis (P = 0.025).
Selection of patients was retrospective; selection and survival biases may have influenced the estimates of the overall rate of regression of cirrhosis. The low number of patients who experienced regression of cirrhosis precludes analysis of factors that could predict regression of cirrhosis.
Regression of cirrhosis occurs after antiviral therapy in some patients with chronic hepatitis C. Regression is associated with decreased disease-related morbidity and improved survival.
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ABSTRACT: Persistent hepatitis E virus (HEV) infections have been described in various transplant cohorts. However, the frequency and the course of HEV infection in lung transplant recipients (Lu-Tr) are not well defined. We retrospectively analyzed serum from 95 Lu-Tr for HEV RNA and anti-HEV immunoglobulin-G (IgG) (with the MP assay). Anti-HEV seroprevalence was compared to that of 537 healthy individuals. Prospective HEV screening was subsequently initiated in Lu-Tr. Elevated liver enzymes were observed in 44/95 (46.3%) patients. Anti-HEV IgG was present in 5/95 patients (5.3%), revealing a slightly higher prevalence compared to controls (2%, 11/537; P = 0.07). Chronic HEV infection with detectable viral replication was confirmed by polymerase chain reaction in 3 (3.2%) patients, all of whom demonstrated clinical and biochemical features of active liver disease (maximum alanine aminotransferase [ALTmax ] 89, 215, and 270 IU/L, respectively). One patient had died from multi-organ failure in combination with liver cirrhosis before HEV diagnosis. Two additional patients with chronic hepatitis E were identified during prospective screening (ALTmax 359 and 318 IU/L). All patients still alive commenced ribavirin therapy for 5 months, with dose adjustment (400-600 mg/day) according to renal function and hemoglobin level. Sustained resolution of HEV infection occurred in 2 patients. One patient is still under treatment, and the fourth died from graft failure considered unrelated to ribavirin therapy. Chronic hepatitis E should be considered in the differential diagnosis of elevated liver enzymes, which are commonly seen in Lu-Tr. We observed 1 case of end-stage liver cirrhosis and death in an HEV-infected subject, who was not treated with ribavirin. Given this potentially devastating consequence, ribavirin therapy of persistent HEV infection appears to be acceptably safe and effective in Lu-Tr. However, larger prospective studies are warranted.Transplant Infectious Disease 01/2014; · 1.98 Impact Factor
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ABSTRACT: Hepatic fibrosis is a wound-healing response to various chronic stimuli, including viral hepatitis B or C infection. Activated myofibroblasts, predominantly derived from the hepatic stellate cells (HSCs), regulate the balance between matrix metalloproteinases and their tissue inhibitors to maintain extracellular matrix homeostasis. Transforming growth factor-β and platelet-derived growth factor are classic profibrogenic signals that activate HSC proliferation. In addition, proinflammatory cytokines and chemokines coordinate macrophages, T cells, NK/NKT cells, and liver sinusoidal endothelial cells in complex fibrogenic and regression processes. In addition, fibrogenesis involves angiogenesis, metabolic reprogramming, autophagy, microRNA, and epigenetic regulations. Hepatic inflammation is the driving force behind liver fibrosis; however, host single nucleotide polymorphisms and viral factors, including the genotype, viral load, viral mutation, and viral proteins, have been associated with fibrosis progression. Eliminating the underlying etiology is the most crucial antifibrotic therapy. Growing evidence has indicated that persistent viral suppression with antiviral therapy can result in fibrosis regression, reduced liver disease progression, decreased hepatocellular carcinoma, and improved chances of survival. Preclinical studies and clinical trials are currently examining several investigational agents that target key fibrogenic pathways; the results are promising and shed light on this debilitating illness.International Journal of Molecular Sciences 01/2014; 15(6):10578-10604. · 2.46 Impact Factor
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ABSTRACT: New nucleos(t)ide analogues (NAs) with high genetic barrier to hepatitis B virus (HBV) resistance (such as entecavir, tenofovir) have improved the prognosis of patients with HBV decompensated cirrhosis and have prevented HBV recurrence after liver transplantation (LT). NAs are considered the most proper approach for HBV infection in patients under renal replacement therapy but their doses should be adjusted according to the patient's creatinine clearance. In addition, physicians should be aware of the potential nephrotoxicity. However, patients with chronic hepatitis C and decompensated cirrhosis can receive only one therapeutic option before LT, as well as for Hepatitis C virus (HCV) recurrence after LT, which is the combination of subcutaneous Peg-IFN and ribavirin. Generally, therapy for HCV after renal transplantation should be avoided. Although the optimal antiviral therapy for HCV infection has not been established, attention has turned to a new, oral direct acting antiviral treatment which marks a promising strategy in prognosis and in amelioration of these diseases.World journal of hepatology. 05/2014; 6(5):315-325.