Hepatitis B virus genotype has no impact on hepatitis B e antigen seroconversion after lamivudine treatment

AIM: To investigate the association of hepatitis B virus (HBV) genotype and HBeAg seroconversion after nucleotide analogue treatment.METHODS: Chronic hepatitis B patients receiving lamivudine followed up for at least 6 months post-treatment were studied. Consecutive treatment-naive patients who were prospectively followed up in the clinic for at least 18 months were studied as controls. HBeAg seroconversion was defined as loss of HBeAg, appearance of anti-HBe and normalization of alanine aminotransferase for at least 6 months.RESULTS: Thirty-five patients on lamivudine and 96 control patients followed up for 39 (18-49) months were studied.Lamivudine was given for 12 (10-18) months, and patients were followed up for 15 (6-34) months after drug cessation.Genotype B and C HBV were found in 43 and 88 patients and HBeAg seroconversion occurred in 12 (28 %) and 16(18 %) patients, respectively (P=0.30). There was no difference in HBeAg seroconversion between patients infected by genotype B and C HBV in the control (35 % vs 21%, P=0.25) and lamivudine-treated (14 % vs 10 %,P=1.00) groups.CONCLUSION: HBeAg seroconversion after treatment by lamivudine was not influenced by the HBV genotype.

Clinical significance of hepatic derangement in severe acute respiratory syndrome

AIM: Elevation of alanine aminotransferase (ALT) level is commonly seen among patients suffering from severe acute respiratory syndrome (SARS). We report the progression and clinical significance of liver derangement in a large cohort of SARS patient.METHODS: Serial assay of serum ALT was followed in patients who fulfilled the WHO criteria of SARS. Those with elevated ALT were compared with those with normal liver functions for clinical outcome. Serology for hepatitis B virus (HBV) infection was checked. Adverse outcomes were defined as oxygen desaturation, need of intensive care unit (ICU) and mechanical ventilation and death.RESULTS: Two hundred and ninety-four patients were included in this study. Seventy (24%) patients had elevated serum ALT on admission and 204 (69%) patients had elevated ALT during the subsequent course of illness. Using peak ALT >5×ULN as a cut-off and after adjusting for potential confounding factors, the odds ratio of peak ALT>5x ULN for oxygen desaturation was 3.24 (95%CI 1.23-8.59, P = 0.018), ICU care was 3.70 (95% CI 1.38-9.89, P = 0.009), mechanical ventilation was 6.64 (95%CI 2.22-19.81, P = 0.001) and death was 7.34(95%CI 2.28-24.89, P = 0.001). Ninety-three percent of the survived patients had ALT levels normalized or were on the improving trend during follow-up. Chronic hepatitis B was not associated with worse clinical outcomes.CONCLUSION: Reactive hepatitis is a common complication of SARS-coronavirus infection. Those patients with severe hepatitis had worse clinical outcome.

Follow up of serial urea breath test results in patients after consumption of antibiotics for non-gastric infections

AIM: The widespread use of antibacterial therapy hasbeen suggested to be the cause for the decline in theprevalence of Helicobacter pyloriinfection. This studyexamine the serial changes of urea breath test resultsin a group of hospitalized patients who were givenantibacterial therapy for non-gastric infections.METHODS: Thirty-five hospitalized patients who weregiven antibacterial therapy for clinical infections,predominantly chest and urinary infections, werestudied. Most (91%) patients were given singleantibiotic of either a penicillin or cephalosporin group.Serial 13C-urea breath tests were performed within 24hours of initiation of antibiotics, at one-week and atsix-week post-therapy. H. pylori infection wasdiagnosed when one or more urea breath tests waspositive.RESULTS: All 35 patients completed three serial ureabreath tests and 26 (74 %) were H. pylori-positive. Ten(38 %) H. pylori-infected patients had at least onenegative breath test results during the study period.The medium delta 13C values were significantly lowerat baseline (8.8) than at one-week (20.3) and six-week(24.5) post-treatment in H. pylori-positive individuals(P=0.022). Clearance of H. pyloriat six-week was onlyseen in one patient who had received anti-helicobactertherapy from another source.CONCLUSION: Our results suggested that one-third ofH. pylori-infected individuals had transient false-negative urea breath test results during treatment withantibacterial agent. However, clearance of H. pyloriinfection by regular antibiotic consumption is rare.

p53-independent pRB degradation contributes to a drug-induced apoptosis in AGS cells

The retinoblastoma (RB) tumor suppressor protein, pRB, plays an important role in the regulation of mammalian cell cycle. Furthermore, several lines of evidence suggest that pRB also involves in the regulation of apoptosis. In the present study, the degradation of pRB was observed in apoptotic gastric tumor cells treated with a new potent anti-tumor component, tripchlorolide (TC). The inhibition of pRB degradation by a general cysteine protease inhibitor IDAM resulted in the reduction of the apoptotic cells. Furthermore, the survival of the gastric tumor cells under the TC treatment was enhanced by an over-expression of exogenous pRB. These results suggest that the pRB degradation of the gastric tumor cells under the TC treatment involves in the apoptotic progression. In addition, the same extent of TC- induced pRB-degradation was detected in the gastric tumor cells containing a p53 dominant-negative construct, indicat- ing that this kind of pRB degradation is p53-independent.

Cell cycle-related kinase reprograms the liver immune microenvironment to promote cancer metastasis

The liver is an immunologically tolerant organ and a common metastatic site of multiple cancer types.Although a role for cancer cell invasion programs has been well characterized,whether and how liver-intrinsic factors drive metastatic spread is incompletely understood.Here,we show that aberrantly activated hepatocyte-intrinsic cell cycle-related kinase(CCRK)signaling in chronic liver diseases is critical for cancer metastasis by reprogramming an immunosuppressive microenvironment.Using an inducible liverspecific transgenic model,we found that CCRK overexpression dramatically increased both B16F10 melanoma and MC38 colorectal cancer(CRC)metastasis to the liver,which was highly infiltrated by polymorphonuclear-myeloid-derived suppressor cells(PMNMDSCs)and lacking natural killer T(NKT)cells.Depletion of PMN-MDSCs in CCRK transgenic mice restored NKT cell levels and their interferon gamma production and reduced liver metastasis to 2.7% and 0.7%(metastatic tumor weights)in the melanoma and CRC models,respectively.Mechanistically,CCRK activated nuclear factor-kappa B(NF-κB)signaling to increase the PMN-MDSC trafficking chemokine C-X-C motif ligand 1(CXCL1),which was positively correlated with liver-infiltrating PMN-MDSC levels in CCRK transgenic mice.Accordingly,CRC liver metastasis patients exhibited hyperaaivation of hepatic CCRK/NF-κB/CXCL1 signaling,which was associated with accumulation of PMN-MDSCs and paucity of NKT cells compared to healthy liver transplantation donors.In summary,this study demonstrates that immunosuppressive reprogramming by hepatic CCRK signaling undermines antimetastatic immunosurveillance.Our findings offer new mechanistic insights and therapeutic targets for liver metastasis intervention.