Risk of secondary osteoporosis due to lobular cholestasis in non-cirrhotic primary biliary cholangitis.

BACKGROUND AND AIM: It remains unclear whether primary biliary cholangitis (PBC) represents a risk factor for secondary osteoporosis. METHODS: A case-control study was conducted to examine bone mineral density and bone turnover markers in middle-aged postmenopausal PBC patients without liver cirrhosis. We compared the incidence of low bone mineral density between propensity-score matched subgroups of PBC patients and healthy controls and investigated the mechanisms underlying unbalanced bone turnover in terms of the associations between bone turnover markers and PBC-specific histological findings. RESULT: Our analysis included 128 consecutive PBC patients, all postmenopausal women aged in their 50s or 60s, without liver cirrhosis or fragility fracture at the time of PBC diagnosis. The prevalence of osteoporosis was significantly higher in the PBC group than in the control group (26% vs 10%, P = 0.015, the Fisher exact probability test). In most PBC patients (95%), the level of bone-specific alkaline phosphatase was above the normal range, indicating increased bone formation. On the other hand, the urine type I collagen-cross-linked N-telopeptide showed variable levels among our PBC patients, indicating unbalanced bone resorption. Advanced fibrosis was associated with low bone turnover. Lobular cholestasis, evaluated as aberrant keratin 7 expression in hepatocytes, showed significant negative correlations with bone formation and resorption, indicating low bone turnover. CONCLUSION: Our results show that, compared with healthy controls, even non-cirrhotic PBC patients have significantly higher risk of osteoporosis. Moreover, lobular cholestasis was associated with low bone turnover, suggesting this feature of PBC may itself cause secondary osteoporosis in PBC patients.

Detection of hepatitis B virus DNA in the liver and serum of patients with hepatitis B surface antigen and hepatitis C virus antibody negative chronic liver disease.

To elucidate the positive frequency of hepatitis B virus (HBV) DNA in patients with hepatitis B surface antigen (HBsAg) and antibody to hepatitis C virus (HCVAb) negative (NBNC) chronic liver disease, we detected serum HBV-DNA using the real-time detection polymerase chain reaction method (RTD-PCR) in comparison with HBsAg and HCVAb negative individuals with normal alanine aminotransferase (ALT). We also revealed the nucleotide sequence of the X-pre-C gene-coding region of intrahepatic HBV-DNA. Serum HBV-DNA was detected in 12 of 36 NBNC patients (five of 22 chronic hepatitis, three of eight liver cirrhosis and four of six hepatocellular carcinoma), whereas none of 31 control individuals were positive for serum HBV-DNA (P<0.01). Serum antibody to hepatitis B core antigen (HBcAb) was positive in nine of 36 in patients with NBNC patients and was positive in nine of 31 in control individuals (n.s). Five of six NBNC patients with serum HBV-DNA positive by RTD-PCR were also positive for intrahepatic HBV-DNA. Analysis of the nucleotide sequence of the X-pre-C coding region of HBV-DNA in the liver showed similar mutation sites of 1677, 1679, 1709, 1753, 1762, 1764. These findings suggested that serum HBV-DNA was more frequently detected in NBNC patients than normal individuals and the presence of low levels of serum HBV-DNA was correlated to the 1677--1764 X-pre-C mutations.