Long-Term Hepatitis B Surface Antigen Profile and Seroclearance Following Antiviral Treatment: A Single-Center, Real-World Cohort Study.

Hepatitis B surface antigen (HBsAg) seroclearance, an indicator of recovery from hepatitis B virus (HBV) infection, is uncommon in long-term nucleos(t)ide analog (NUC) therapy. We compared the incidence of HBsAg seroclearance in patients with and without NUC discontinuation to identify predictors of HBsAg seroclearance. This retrospective study enrolled adult patients with a chronic HBV infection followed for ≥12 months after NUC discontinuation (finite group) and those treated with NUCs for >3 years (non-finite group). Demographic, clinical, and laboratory data were analyzed. The study cohort included 978 patients, including 509 and 469 patients in the finite and non-finite groups, respectively. Cumulative HBsAg seroclearance incidence was significantly higher in the finite group than in the non-finite group (p = 0.006). The 5- and 10-year cumulative HBsAg seroclearance incidence were 6.6% and 18.9% in the finite group and 3% and 14.6% in the non-finite group, respectively. The likelihood of HBsAg seroclearance was higher in those with end of treatment (EOT) HBsAg levels of <100 IU/mL and in those without clinical relapse (CR). The cumulative 3-year CR incidence was 16.8%. The incidence of liver decompensation and hepatocellular carcinoma were 4.1 and 0.4 per 1000 person-years, respectively. The hepatocellular carcinoma incidence did not significantly differ between the finite and non-finite groups (p = 0.941). In conclusion, higher HBsAg seroclearance incidence in patients receiving finite therapy, and the increased likelihood of HBsAg seroclearance in those with EOT HBsAg levels of <100 IU/mL and in those without CR should be considered during decision-making of treatment options.

Chronic Hepatitis B Relapse Rates after Cessation of Tenofovir Alafenamide and Entecavir Therapy.

Chronic hepatitis B (CHB) relapse occurs after the cessation of nucleos(t)ide analogues (NUC) therapy due to the waning of viral suppression. Few studies have investigated the viral relapse rate and clinical relapse rate after tenofovir alafenamide (TAF) therapy. We compared the CHB relapse rate between TAF and entecavir therapy. We enrolled patients with chronic hepatitis B who underwent TAF or entecavir therapy. NUC therapy was terminated after HBeAg loss for 1 year in HBeAg-positive patients and after undetectable serum HBV DNA on three separate tests each >6 months apart in HBeAg-negative patients. After cessation of NUC therapy, we followed alanine aminotransferase (ALT) levels at 12, 24, and 48 weeks. Serum HBV DNA levels were checked if patients showed a two-fold elevation from the upper limit of normal ALT levels (41 IU/mL). Clinical relapse (CR) was defined as a two-fold elevation in ALT levels and HBV DNA levels > 2000 IU/mL. We then investigated the CR rate of HBV after cessation of TAF and entecavir therapy at 12, 24, and 48 weeks. Of the 117 patients enrolled, 78 were in the entecavir group and 39 were in the TAF group. At 12 weeks after cessation of NUC therapy, no patients had HBV CR in the entecavir group. However, three patients (CR cumulative rate 7.9%) had CR in the TAF group. At 24 weeks, the CR cumulative rate in the entecavir and TAF groups were 1.3% and 13.2%, respectively (p < 0.05). At 48 weeks, the CR cumulative rates were 9.2% and 24.2%, respectively (p = 0.055). Patients in the TAF group had a higher cumulative rate of CR than those in the entecavir group (log-rank p = 0.023). Furthermore, patients in the TAF group had earlier CR times than those in the entecavir group, especially in the first 24 weeks after cessation of therapies (p < 0.05). The cessation of TAF therapy had significantly earlier and higher CR rates than that of entecavir therapy. Close monitoring of liver function and HBV DNA levels may be necessary, especially within 24 weeks after cessation of TAF therapy.

OmpR coordinates the expression of virulence factors of Enterohemorrhagic Escherichia coli in the alimentary tract of Caenorhabditis elegans.

Enterohemorrhagic Escherichia coli (EHEC), an enteropathogen that colonizes in the intestine, causes severe diarrhea and hemorrhagic colitis in humans by the expression of the type III secretion system (T3SS) and Shiga-like toxins (Stxs). However, how EHEC can sense and respond to the changes in the alimentary tract and coordinate the expression of these virulence genes remains elusive. The T3SS-related genes are known to be regulated by the locus of enterocyte effacement (LEE)-encoded regulators, such as Ler, as well as non-LEE-encoded regulators in response to different environmental cues. Herein, we report that OmpR, which participates in the adaptation of E. coli to osmolarity and pH alterations, is required for EHEC infection in Caenorhabditis elegans. OmpR protein was able to directly bind to the promoters of ler and stx1 (Shiga-like toxin 1) and regulate the expression of T3SS and Stx1, respectively, at the transcriptional level. Moreover, we demonstrated that the expression of ler in EHEC is in response to the intestinal environment and is regulated by OmpR in C. elegans. Taken together, we reveal that OmpR is an important regulator of EHEC which coordinates the expression of virulence factors during gastrointestinal infection in vivo.

Host CDK-1 and formin mediate microvillar effacement induced by enterohemorrhagic Escherichia coli.

Enterohemorrhagic Escherichia coli (EHEC) induces changes to the intestinal cell cytoskeleton and formation of attaching and effacing lesions, characterized by the effacement of microvilli and then formation of actin pedestals to which the bacteria are tightly attached. Here, we use a Caenorhabditis elegans model of EHEC infection to show that microvillar effacement is mediated by a signalling pathway including mitotic cyclin-dependent kinase 1 (CDK1) and diaphanous-related formin 1 (CYK1). Similar observations are also made using EHEC-infected human intestinal cells in vitro. Our results support the use of C. elegans as a host model for studying attaching and effacing lesions in vivo, and reveal that the CDK1-formin signal axis is necessary for EHEC-induced microvillar effacement.

Sorafenib-induced Acute Pancreatitis: A Case Report and Review of the Literature.

Sorafenib has been approved to increase the survival in patients with advanced hepatocellular carcinoma. Acute pancreatitis is an uncommon complication of sorafenib treatment. Only a few cases of sorafenib-induced acute pancreatitis have been reported in the English literature. We herein present the case of a 56-year-old man with hepatocellular carcinoma treated with sorafenib at 200 mg once daily. After six days of treatment, he suffered epigastric pain. Laboratory tests showed markedly elevated serum amylase and lipase levels. Imaging studies demonstrated negative findings. Sorafenib-induced acute pancreatitis was diagnosed after reviewing his history. The sorafenib treatment was discontinued, and his symptoms were resolved seven days later. To date, this case had the shortest duration and the lowest dosage of sorafenib to have induced acute pancreatitis.