The long-term impact of acute self-limited hepatitis B on the liver is unknown. Fourteen patients were recalled at a median of 4.2 years (range, 1.8-9.5 years) after the onset of acute hepatitis B. All showed clinical and serologic recovery with circulating hepatitis B surface antigen (HBsAg) clearance. Antibody to HBsAg (anti-HBs) had developed in 12 patients. Nine underwent liver biopsies at a median of 7.2 years, and histologic findings were evaluated using Ishak scores. Serum samples and frozen liver tissue were subjected to real-time detection polymerase chain reaction (PCR) to quantify the surface and X regions of the hepatitis B virus (HBV) genome and qualitative PCR to detect the covalently closed circular (ccc) HBV DNA replicative intermediate. Three patients had low levels of circulating HBV DNA up to 8.9 years after the onset, whereas both HBV DNA surface and X regions were found in the liver of all 9 patients examined, including 7 negative for serum HBV DNA. Liver viral loads assessed by the 2 regions showed a significant correlation (r ‫؍‬ 0.946; P ‫؍‬ .008), and all patients tested positive for ccc HBV DNA. Liver fibrosis and mild inflammation persisted in 8 patients. The fibrosis stage had relation to peak serum HBV DNA in the acute phase (P ‫؍‬ .046) but not to liver viral loads in the late convalescent phase. T he clearance of circulating hepatitis B surface antigen (HBsAg) and appearance of antibody to HBsAg (anti-HBs) with normalization of liver function have been generally accepted as evidence of clinical and serologic recovery from acute hepatitis B. However, in chronic HBsAg carriers, there is growing evidence that hepatitis B virus (HBV) DNA sequences persist in the liver for years after seroclearance of HBsAg and seroconversion to anti-HBs. 1-3 Although the clinical and pathologic implications of occult HBV infection in the liver are unknown, viral eradication is unlikely to be achieved once chronic HBV infection has been established. The cytotoxic T-lymphocyte (CTL) response is weak or undetectable in chronic HBV infection. In contrast, a vigorous, polyclonal, and HBV-specific CTL response against multiple HBV epitopes is readily detectable during acute self-limited HBV infection. 4-7 HBV-specific CTLs further persist in the blood for several decades after recovery from acute hepatitis B. 7,8 In the face of an enhanced immune response leading to disease resolution, the virologic outcomes of acute self-limited hepatitis B may differ from those of HBsAg seroclearance and anti-HBs seroconversion in the course of chronic HBV infection.At present, the long-term histologic and virologic impact of acute self-limited hepatitis B on the liver is unexplored. Studies using polymerase chain reaction (PCR) to detect HBV DNA sequences have shown that low levels of circulating HBV DNA can persist after clinical and serologic recovery from acute hepatitis B but tend to disappear after long-term follow-up. 9,10 Peripheral blood mononuclear cells are known as the site of persistent HBV infection long afte...

It is generally believed that bryophytes are the earliest land plants. However, the phylogenetic relationships among bryophytes, including mosses, liverworts and hornworts, are not clearly resolved. To obtain more information on the earliest land plants, we determined the complete nucleotide sequence of the chloroplast genome from the hornwort Anthoceros formosae. The circular double-stranded DNA of 161 162 bp is the largest genome ever reported among land plant chloroplasts. It contains 76 protein, 32 tRNA and 4 rRNA genes and 10 open reading frames (ORFs), which are identical with the chloroplast genome of the other green plants analyzed. The major difference is a larger inverted repeat than that of the liverwort Marchantia, Anthoceros contains an excess of ndhB and rps7 genes and the 3' exon of rps12. The genes matK and rps15, commonly found in the chloroplast genomes of land plants, are pseudogenes. The intron of rrn23 is the first finding in the known chloroplast genomes of land plants. A striking feature of the hornwort chloroplast is that more than half of the protein-coding genes have nonsense codons, which are converted into sense codons by RNA editing. Maximum-likelihood (ML) analysis, based on 11 518 amino acid sites of 52 proteins encoded in the chloroplast genomes of the green plants, placed liverworts as the sister to all other land plants.

In Japan, bezafibrate (BF) is a second‐line agent for primary biliary cholangitis (PBC) that is refractory to ursodeoxycholic acid (UDCA) treatment. From a retrospective cohort (n = 873) from the Japan PBC Study Group, we enrolled 118 patients who had received UDCA monotherapy for at least 1 year followed by combination therapy with UDCA+BF for at least 1 year. GLOBE and UK‐PBC scores after UDCA monotherapy (i.e., immediately before UDCA+BF combination therapy) were compared with those after 1 year of UDCA+BF combination therapy. The real outcomes of enrolled patients estimated by Kaplan–Meier analysis were compared with the predicted outcomes calculated using GLOBE and UK‐PBC scores. In addition, the hazard ratio of BF treatment was calculated using propensity score analysis. The mean GLOBE score before the combination therapy was 0.504 ± 0.080, which improved significantly to 0.115 ± 0.085 (P < 0.0001) after 1 year of combination therapy. The real liver transplant‐free survival of enrolled patients was significantly better than that predicted by GLOBE score before introducing BF. Combination therapy did not significantly improve the real rates of liver transplantation or liver‐related death compared with those predicted by UK‐PBC risk score before introducing BF, but the predicted risk was significantly reduced by the addition of BF (P < 0.0001). Cox regression analysis with inverse probability of treatment weighting showed that the addition of BF significantly reduced the hazard of liver transplant or liver‐related death in patients who, after 1 year of UDCA monotherapy, had normal serum bilirubin (adjusted hazard ratio 0.09, 95% confidence interval 0.01‐0.60, P = 0.013). Conclusion: Addition of BF to UDCA monotherapy improves not only GLOBE and UK‐PBC scores but also the long‐term prognosis of PBC patients, especially those with early‐stage PBC.

Tolvaptan at 7.5 mg/day was considered the optimal dose in liver cirrhosis patients with hepatic edema who showed inadequate response to conventional diuretics.

Tolvaptan dose-dependently decreased body weight and abdominal circumference and improved ascites and edema beginning from 15 mg, demonstrating a potent aquaretic effect.