Detection of carboxyhemoglobin in patients with hepatic encephalopathy due to hepatitis B virus-related cirrhosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The heme oxygenase/carbon monoxide (HO/CO) system plays an important role in the development of hepatic fibrosis. The level of the HO/CO can be directly obtained by determining the carboxyhemoglobin (COHb) level. The aims of this study were to reveal the significance of COHb in patients with hepatitis B virus-related cirrhosis (HBC) complicated by hepatic encephalopathy (HE), and to further investigate the influence of the HO/CO pathway on the end-stage cirrhosis, hoping to find a reliable indicator to evaluate the course of HBC.</p><p><b>METHODS</b>According to the diagnostic criteria, 63 HBC inpatients with HE were enrolled in group H. Patients regaining awareness with current therapies were categorized into group P-H. Comparisons were made with a control group (group N) consisting of 20 health volunteers. The levels of COHb, partial pressure of oxygen (PaO2) and oxygen saturation (SaO2) were determined by arterial blood gas analysis method. The incidences of hepatorenal syndrome (HRS), upper gastrointestinal bleeding, esophagogastric varices and spontaneous bacterial peritonitis (SBP) in group H were recorded. COHb levels in different groups were compared, and the correlations of COHb levels with HE grades (I, II, III, and IV), PaO2, SaO2 and hypoxemia were analyzed.</p><p><b>RESULTS</b>The COHb level in group P-H ((1.672 ± 0.761)%) was significantly higher than that in group N ((0.983 ± 0.231)%) (P < 0.01), and the level in group H ((2.102 ± 1.021)%) was significantly higher than groups P-H and N (P < 0.01). A positive correlation was observed between the COHb concentration and the grade of HE (r(s) = 0.357, P = 0.004). There were no significant differences of COHb levels between HE patients with and without complications such as esophagogastric varices ((2.302 ± 1.072)% vs. (1.802 ± 1.041)%, P > 0.05) or the occurrence of SBP ((2.960 ± 0.561)% vs. (2.030 ± 1.021)%, P > 0.05). Compared with HE patients with HRS, the level of COHb was significantly higher in HE patients without HRS ((2.502 ± 1.073)% vs. (1.981 ± 1.020)%, P = 0.029). The COHb level had a negative correlation with PaO2 (r = -0.335, P = 0.007) while no statistically significant relationship was found with SaO2 (r = -0.071, P > 0.05). However, when the above two parameters met the diagnostic criteria of hypoxemia, the COHb concentration increased ((2.621 ± 0.880)% vs. (1.910 ± 0.931)%, P = 0.011).</p><p><b>CONCLUSIONS</b>COHb is a potential candidate to estimate the severity and therapeutic effect of HE. The levels of COHb may be tissue-specific in cirrhotic patients with different complications.</p>

Effects of heme oxygenase-1 on pulmonary function and structure in rats with liver cirrhosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The hepatopulmonary syndrome (HPS) is a severe vascular complication in lungs resulting in systemic hypoxemia in patients with cirrhosis and portal hypertension. The underlying structural change in HPS is intrapulmonary vasodilation, which can lead to impaired oxygenation of pulmonary venous blood. It has been demonstrated that the heme oxygenase-1/carbon monoxide (HO-1/CO) system plays an important role in the control of vascular tone. The aim of this study was to further investigate the role of HO-1 in the pathogenesis of HPS in animal model.</p><p><b>METHODS</b>Totally 35 rats were divided into liver cirrhosis, zinc protoporphyrin IX (ZnPP), cobalt protoporphyrin (CoPP) and sham groups. Biliary cirrhosis was established in the first three groups by bile duct ligation. Rats in the ZnPP and CoPP groups received once intraperitoneal injection of ZnPP and CoPP, respectively, 24 hours before sample collection. Expression of HO-1 mRNA in lung was detected by reverse-transcription polymerase chain reaction, while protein expression was determined by immunohistochemical analysis. Hematoxylin and eosin staining was performed to confirm the presence of liver cirrhosis and intrapulmonary vasodilation. Arterial blood gases, mean arterial pressure and portal vein pressure were also measured. Analysis of variance or Wilcoxon statistical methods were used to determine statistical significance.</p><p><b>RESULTS</b>Compared with the sham group, the cirrhotic group demonstrated increased expression of pulmonary HO-1 mRNA and protein (P < 0.01). The level of arterial carboxyhemoglobin (COHb), alveolar-arterial oxygen gradient (A-aPO2), mean arterial pressure, portal vein pressure (P < 0.05, respectively), and intrapulmonary vasodilation were also significantly increased. Compared with the cirrhotic group, CoPP treatment increased pulmonary HO-1 mRNA and protein expression, the level of A-aPO2 (P < 0.05 respectively), COHb (P < 0.01), and intrapulmonary vasodilation, while ZnPP treatment decreased pulmonary HO-1 mRNA and protein expression, the level of COHb (P < 0.05 respectively), and intrapulmonary vasodilation, without obvious alteration of mean arterial pressure and portal vein pressure.</p><p><b>CONCLUSION</b>Increased pulmonary HO-1 expression is an important contributor to the development of experimental HPS.</p>

Heme oxygenase-1 regulates the major route involved in formation of immune hepatic fibrosis in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Heme oxygenase (HO) plays roles in some liver diseases, but what it does in immune liver fibrosis is rarely reported. We investigated the regulation mechanisms of HO-1 in rat immune liver fibrosis to find routes for intervention.</p><p><b>METHODS</b>Male Sprague-Dawley rats were randomly divided into control group (N, n = 12), fibrosis group (F, n = 20), cobalt protoporphyrin (CoPP) inducing group (Co, n = 20) and zinc protoporphyrin (ZnPP) inhibiting group (Zn, n = 20). In groups F, Co and Zn, immune liver fibrosis was established with human serum albumin. At the attacked stage, CoPP (5 mg/kg) and ZnPP (5 mg/kg) were intraperitoneally injected in groups Co and Zn, respectively. After establishment of rat models, the numbers of rats reduced to 11, 15, 17 and 12 in groups N, F, Co and Zn respectively, because of death during the process. HO-1 in liver was detected by Western blotting and immunohistochemistry. The indexes of fibrosis were assessed by radioimmunoassay. Concentrations of serum transforming growth factor-β1 (TGF-β1), and tissue inhibitor of metalloproteinses (TIMP-1) were detected using enzyme-linked immunosorbent assay. Hepatic stellate cell (HSC) and proliferation degree of fibrosis were assessed by pathological examination. Data analysis was performed by SPSS 10.0 software.</p><p><b>RESULTS</b>The expression of HO-1 in group F was significantly higher than that in group N, but lower than that in group Co (P < 0.05); while that in group Zn was lower than in group F (P < 0.05), but still higher than that in group N (P < 0.01). Compared with group N, liver functional and liver fibrosis indicators were increased in group F (P < 0.01), while comparing to group F, they were decreased in group Co (P < 0.05) and increased in group Zn (P < 0.05). CoPP reduced the extent of hepatocellular injury and hepatic fibrosis in comparison with group F (P < 0.01), being the opposite effect of ZnPP (P < 0.01). HSC was observed using indirect method and the result showed that the number of HSC in group F increased more than that in groups N and Co, while much less than in group Zn. The concentration of TGF-β1 decreased when HO-1 expressed increasingly (group Co: (3.5 ± 1.0) ng/ml, group F: (7.8 ± 1.3) ng/ml, P < 0.01) and enhanced (group Zn: (9.6 ± 13.6) ng/ml) when HO-1 presented less (P < 0.01). The concentrations of TIMP-1 were (151.1 ± 32.0), (472.0 ± 34.8), (232.3 ± 41.3) and (533.2 ± 37.2) ng/g liver wet weight in groups N, F, Co, and Zn, respectively. It was reduced in group Co (P < 0.01) and increased in group Zn compared with group F (P < 0.05).</p><p><b>CONCLUSIONS</b>Inducing HO-1 expression appropriately may lighten hepatic fibrosis, and in contrast, inhibiting it strengthens the lesion. HO-1 interferes with the main ways to form liver fibrosis.</p>