Cirrhosis regression in hepatitis C patients with sustained virological response after antiviral therapy: a meta-analysis.

BACKGROUND & AIMS: Chronic hepatitis C may be associated with cirrhosis, liver failure and hepatocellular carcinoma. Studies have demonstrated improved clinical outcome in patients who achieved a sustained viral response (SVR). METHODS: A systematic literature search was performed to identify studies that assessed the association between SVR and cirrhosis regression. The main outcome studied was cirrhosis regression in patients with a SVR as compared with patients without a SVR. Six studies totalling 443 patients were included. Dichotomous outcomes were reported as risk ratios (RR) with 95% confidence intervals (CI). RESULTS: Of the 443 patients with cirrhosis, 137 achieved a SVR. Of these 137 patients who achieved an SVR, 73 (53%) patients had regression of cirrhosis. The risk ratio of cirrhosis regression was 2.69 [Confidence Interval (CI) 1.45-4.97, P < 0.01] in patients who achieved a SVR. The risk of cirrhosis regression was consistently in favour of patients who achieved a SVR regardless of the length of the biopsy or whether the biopsy was reviewed by a single or multiple pathologists. The risk ratio of cirrhosis regression was related to the duration of follow-up between biopsies. The relative risk for regression of cirrhosis in studies in which the mean or median time for the follow-up liver biopsy was greater than 36-month was 4.33 (CI 1.1-17.0, P = 0.04) as compared to a relative risk of 1.79 (CI 1.26-2.29, P < 0.01) in studies with a mean or median time between the follow-up biopsy of less than 36-month. CONCLUSIONS: Our results suggest that the majority of patients with cirrhosis who achieve a SVR develop cirrhosis regression. Time between biopsies appears to be an important determinant of the likelihood of cirrhosis regression.

Cirrhosis regression in patients with viral hepatitis B and C: a systematic review.

INTRODUCTION: Cirrhosis is a major milestone in patients with chronic liver disease because of its impact on patient morbidity and mortality. Chronic hepatitis B (CHB) and hepatitis C (CHC) are important causes of cirrhosis. This systematic review examines the relevant literature and evidence to assess whether cirrhosis can be reversible in patients with cirrhosis from viral hepatitis through long viral suppression. METHODS: A MEDLINE and Cochrane Library search was conducted to identify all articles pertinent to the subject matter. Fourteen publications were included in the final analysis: 4 hepatitis B studies and 10 hepatitis C studies. Data abstracted from individual studies included patient demographics, antiviral therapy used, length of treatment, liver biopsy scoring system, length of biopsy, and time between biopsies. RESULTS: In CHB, the 7 studies reviewed included a total of 463 cirrhotic patients. Regression of cirrhosis was noted in a median of 70% (range, 33% to 80%) of patients. In CHC, the 13 studies reviewed included a total of 58 cirrhotic patients. Regression of cirrhosis was seen in a median of 64% (range, 33% to 100%) of patients with sustained viral response. CONCLUSIONS: The results of our review suggest that viral suppression in CHB and sustained virologic response in CHC can be associated with histologic regression of cirrhosis in select patients.

Panhematin provides a therapeutic benefit in experimental pancreatitis.

BACKGROUND AND AIM: Acute pancreatitis (AP) can result in pancreatic necrosis and inflammation, with subsequent multi-organ failure. AP is associated with increased neutrophil recruitment and a rise in pro-inflammatory cytokines such as TNFα. Pretreatment with haemin, results in recruitment of haem-oxygenase-1 (HO-1)(+) macrophages and protects against experimental pancreatitis. It is not clear whether modulation of HO-1 after onset of disease has a protective role. In this study, we tested the utility of Panhematin, a water-soluble haemin formulation, in activating and inducing pancreatic HO-1, and as a therapeutic agent in treating mouse acute pancreatitis. METHODS: We defined the distribution of radiolabelled haemin, then used in vivo HO-1-luciferase bioluminescence imaging and the CO-release assay to test Panhematin-induced upregulation of HO-1 transcription and activity, respectively. Using two well-defined AP murine models, we tested the therapeutic benefit of Panhematin, and quantified cytokine release using a luminex assay. RESULTS: Intravenously administered Panhematin induces rapid recruitment of HO-1(+) cells to the pancreas within 2 h and de novo splenic HO-1 transcription by 12 h. Despite high baseline spleen HO-1 activity, the pancreas is particularly responsive to Panhematin-mediated HO-1 induction. Panhematin-treated mice, at various time points after AP induction had significant reduction in mortality, pancreatic injury, together with upregulation of HO-1 and downregulation of pro-inflammatory cytokines and CXCL1, a potent neutrophil chemoattractant. CONCLUSIONS: Despite AP-associated mortality and morbidity, no effective treatment other than supportive care exists. We demonstrate that Panhematin leads to: (i) rapid induction and activation of pancreatic HO-1 with recruitment of HO-1(+) cells to the pancreas, (ii) amelioration of AP even when given late during the course of disease, and (iii) a decrease in leucocyte infiltration and pro-inflammatory cytokines including CXCL1. The utility of Panhematin at modest doses as a therapeutic in experimental pancreatitis, coupled with its current use and safety in humans, raises the potential of its applicability to human pancreatitis.

Heme oxygenase-1 is induced in peripheral blood mononuclear cells of patients with acute pancreatitis: a potential therapeutic target.

Heme oxygenase-1 (HO-1) induction by hemin or Panhematin protects against experimental pancreatitis. As a preclinical first step toward determining whether HO-1 upregulation is a viable target in acute pancreatitis (AP) patients, we tested the hypothesis that HO-1 expression in peripheral blood mononuclear cell (PBMC) subsets of hospitalized patients with mild AP is upregulated then normalizes upon recovery and that cells from AP patients have the potential to upregulate their HO-1 ex vivo if exposed to Panhematin. PBMCs were isolated on days 1 and 3 of hospitalization from the blood of 18 AP patients, and PMBC HO-1 levels were compared with PMBCs of 15 hospitalized controls (HC) and 7 volunteer healthy controls (VC). On day 1 of hospitalization, AP patients compared with VCs had higher HO-1 expression in monocytes and neutrophils. Notably, AP monocyte HO-1 levels decreased significantly upon recovery. Panhematin induced HO-1 in ex vivo cultured AP PBMCs more readily than in HC or VC PBMCs. Furthermore, PBMCs from acutely ill AP patients on day 1 were more responsive to HO-1 induction compared with day 3 upon recovery. Similarly, mouse splenocytes had enhanced HO-1 inducibility as their pancreatitis progressed from mild to severe. In conclusion, AP leads to reversible PBMC HO-1 upregulation that is associated with clinical improvement and involves primarily monocytes. Leukocytes from AP patients or mice with AP are primed for HO-1 induction by Panhematin, which suggests that Panhematin could offer a therapeutic benefit.

The Autoimmune Protocol Diet Modifies Intestinal RNA Expression in Inflammatory Bowel Disease.

Researchers from the Scripps Clinic in La Jolla, CA recently looked at gene expression to better understand the role that diet plays in inflammatory bowel disease. Their findings suggest that diet may help modify inflammatory pathways in people with ulcerative colitis.