Whether primary biliary cirrhosis (PBC)—autoimmune hepatitis (AIH) overlap syndrome requires immunosuppressive therapy in addition to ursodeoxycholic acid (UDCA) is a controversial issue.
Seventeen ...patients with simultaneous form of strictly defined overlap were followed for 7.5 years. First-line treatment was UDCA alone (UDCA) in 11 and combination of immunosuppressors and UDCA (UDCA+IS) in 6.
Characteristics at presentation were not significantly different between the 2 groups. In the UDCA+IS group (f-up 7.3 years), biochemical response in terms of AIH features (ALT<2ULN and IgG<16g/L) was achieved in 4/6 and fibrosis did not progress. In the UDCA group, biochemical response was observed in three patients together with stable or decreased fibrosis (f-up 4.5 years) whereas the eight others were non-responders with increased fibrosis in four (f-up 1.6 years). Seven of these eight patients subsequently received combined therapy for 3 years. Biochemical response was obtained in 6/7 and no further increase of fibrosis was demonstrated. Overall, fibrosis progression in non-cirrhotic patients occurred more frequently under UDCA monotherapy (4/8) than under combined therapy (0/6) (P=0.04).
Combination of UDCA and immunosuppressors appears to be the best therapeutic option for strictly defined PBC-AIH overlap syndrome.
Patients with obstructive sleep apnea (OSA) are at risk for the development of fatty liver as a result of being overweight. Several data suggest that OSA per se could be a risk factor of liver ...injury; ischemic hepatitis during OSA has been reported, and OSA is an independent risk factor for insulin resistance. Therefore, we investigated liver damage and potential mechanisms in 163 consecutive nondrinking patients with nocturnal polysomnographic recording for clinical suspicion of OSA. Serum levels of liver enzymes were measured in all patients. Liver biopsy was offered to patients with elevated liver enzymes. Intrahepatic hypoxia was assessed by the expression of vascular endothelial growth factor (VEGF) on liver biopsy specimens. Severe OSA (apnea-hypopnea index AHI > 50/hr) was seen in 27% of patients; 52% had moderate OSA (AHI 10-50/hr), and 21% had no OSA. Overall, 20% had elevated liver enzymes. Independent parameters associated with elevated liver enzymes were body mass index (BMI) (OR: 1.13; CI: 1.03-1.2) and severe OSA (OR: 5.9; CI: 1.2-29). Liver biopsy was performed in 18 of 32 patients with elevated liver enzymes and showed steatohepatitis in 12 cases, associated with fibrosis in 7 cases. Patients with severe OSA were more insulin-resistant according to homeostasis model assessment, had higher percentage of steatosis as well as scores of necrosis and fibrosis, despite similar BMI. Hepatic immunostaining used as an indirect marker of hypoxia was not different between patients with or without severe OSA. In conclusion, severe OSA is a risk factor for elevated liver enzymes and steatohepatitis independent of body weight. Promotion of insulin resistance is probably involved. Further studies are needed to determine whether hypoxia contributes directly to liver injury.
Bile acids (BAs) retention in the liver is a potent determinant of liver failure risk inchronic cholestatic diseases. Schematically, these diseasesinclude « inherited » forms resulting from ABCB11, ...ATPB8, ABCB4, CFTR, JAGGED1 gene defects and acquired mmune mediated-pathologies such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).
AIM： To investigate the phenotype of inflammatory bowel disease associated with primary sclerosing cholangitis （PSC-IBD）.
METHODS： Data from 75 PSC-IBD patients evaluated in our tertiary center ...between 1963 and 2006 were collected and compared to 150 IBD patients without PSC, matched for sex, birth date, IBD diagnosis date and initial disease location regarding ileal, different colonic segments, and rectum, respectively.
RESULTS： While PSC-IBD patients received more 5-aminosalicylates （8.7 years/patient vs 2.9 years/ patient, P 〈 0.001）, they required less immuno-suppressors （24% vs 46% at 10 years; P 〈 0.001） and less intestinal resection （10% vs 44% at 10 years, P 〈 0.001）. The 25-year cumulative rate of colectomy was 25.1% in PSC-IBD and 37.3% in controls （P = 0.004）. The 25-year cumulative rate of colorectal cancer was 23.4% in PSC-IBD vs 0% in controls （P = 0.002）. PSC was the only independent risk factor for the development of colorectal cancer （OR = 10.8; 95% CI, 3.7-31.3）. Overall survival rate without liver transplantation was reduced in PSC-IBD patients （67% vs 91% in controls at 25 years, P = 0.001）.
CONCLUSION： This study confirms that patients with PSC-IBD have a particular disease phenotype independent of the initial disease location. Although their disease is less active and they use more 5-aminosalicylates, they present a higher risk of colorectal cancer.
Aims: The aim of this study was to determine whether serum levels of adipokines, including the ratio of serum adiponectin to leptin (A/L) levels could predict the severity of liver injury in patients ...with non‐alcoholic fatty liver disease (NAFLD).
Patients and methods: Fifty‐seven patients with biopsy‐proven non‐alcoholic steatohepatitis (NASH) (mean age 51±12, sex ratio 1), 17 with simple steatosis (mean age 47±12, sex ratio 1.4) and 10 controls without steatosis (mean age 51±11, sex ratio 4) were investigated. In all subjects, serum concentrations of triglycerides, ultrasensitive C reactive protein, leptin, adiponectin, soluble tumour necrosis factor receptor 1, interleukin (IL)‐6 and Homeostasis Model Assessment Method (HOMA) were measured. Hepatic expression of adiponectin and its two receptors was assessed by quantitative reverse transcriptase polymerase chain reaction.
Results: Body mass index (BMI) and HOMA were correlated positively with leptin levels (r=0.44 and 0.28 respectively) and negatively with the A/L ratio (r=0.51 and 0.41 respectively). Independent parameters associated with NASH vs steatosis were HOMA>3 odds ratio (OR)=6.9 and A/L ratio <1.4 103 (OR=5.2). The combination of HOMA with A/L ratio showed an area under the receiver operating characteristic curve of 0.82 for distinguishing between NASH and steatosis. Extensive portal fibrosis was present in 17 (23%) patients with NAFLD. Three independent parameters were associated with fibrosis: age (OR=1.1), BMI (OR=1.3) and high IL‐6 levels (OR=1.6). The hepatic expression of adiponectin receptor 2 was significantly higher in patients with NASH compared with controls and was related with necroinflammatory injury.
Conclusions: This study shows that in patients with NAFLD, the combination of HOMA with A/L ratio may be a useful non‐invasive approach to appreciate the severity of liver damage.
Ursodeoxycholic acid (UDCA) slows the progression of primary biliary cirrhosis (PBC). However, some UDCA-treated patients escape and progress toward cirrhosis and end-stage disease. This study aimed ...to assess the incidence of cirrhosis in UDCA-treated patients with PBC and to determine the predictive factors of cirrhosis development under this treatment.
A Markov model was used to describe the progression toward cirrhosis in 183 UDCA-treated patients with PBC. A total of 254 pairs of liver biopsy specimens collected during 655 patient-years were studied.
The incidence of cirrhosis after 5 years of UDCA treatment was 4%, 12%, and 59% among patients followed-up from stages I, II, and III, respectively. At 10 years, the incidence was 17%, 27%, and 76%, respectively. The median time for developing cirrhosis from stages I, II, and III was 25 years, 20 years, and 4 years, respectively. The independent predictive factors of cirrhosis development were serum bilirubin greater than 17 μmol/L, serum albumin less than 38 g/L, and moderate to severe lymphocytic piecemeal necrosis.
This study provides new data about the time course of PBC under UDCA and constitutes a rationale for the design and evaluation of clinical trials aimed to assess the efficacy of drugs associated with UDCA.
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