Delayed clearance of serum HBsAg in compensated cirrhosis B: relation to interferon alpha therapy and disease prognosis

Objective: The aim of this study was to evaluate the incidence, prognostic factors and clinical significance of delayed clearance of serum HBsAg in compensated cirrhosis B.
Methods: This was a retrospective cohort study of 309 consecutive white patients with biopsy-proved compensated cirrhosis type B.
Results: During a mean follow-up of 68 months, HBsAg loss occurred in 32 patients, including 16 (8%) of 196 untreated patients (mean annual incidence 0.8%), 8 (10%) of 82 interferon (IFN) alpha–treated patients and eight patients who had been treated with other antivirals or steroids. The 5-yr probability of HBsAg loss was 4% and 16% for untreated and IFN-treated patients, respectively (   p = 0.0001  ). Cox's regression analysis identified hepatitis B e antigen–positivity at entry as the sole independent prognostic factor for HBsAg loss. Of the 32 patients who lost HBsAg, one (3%) subsequently developed hepatocellular carcinoma (HCC) and died, whereas, among the patients who remained HBsAg-positive, 11% developed HCC and 20% had died. The probability of HCC appearance was lower (   p = 0.0137  ) and survival was longer (   p = 0.0006  ) in patients who cleared HBsAg compared with patients with HBsAg persistence.
Conclusion: The incidence of HBsAg loss is about 0.8% in cirrhosis type B. Prognostic factors for clearance of HBsAg are initial HBeAg positivity and therapy with alpha interferon. Patients with cirrhosis type B, who lose HBsAg, have a low risk for liver cancer or liver-related death.     

Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B

We studied the long-term efficacy of adefovir dipivoxil (ADV) treatment in 42 HBeAg-negative patients with chronic hepatitis B (CHB) who had developed genotypical lamivudine (LAM) resistance with virological and clinical breakthroughs under long-term LAM treatment. Patients were allocated in 2 treatment groups. In the first (n = 14), LAM was switched to ADV monotherapy whereas in the second (n = 28) ADV was added to LAM. The two groups did not differ in patients' characteristics, all of them having HBV genotype D infection with the precore stop codon mutation. Within 12 months from start of ADV treatment, serum HBV DNA became nondetectable and ALT normalized in 71% and 90% of patients, respectively, with no difference between the 2 arms. Patients with baseline HBV DNA levels less than 10(7) copies/ml experienced a significantly earlier and more frequent decline in serum HBV DNA to nondetectable levels as compared with patients with greater than 10(7) HBV DNA copies/ml at baseline (P = 0.0013) This response has hitherto been maintained (median treatment duration 40 months) in all patients with ADV added to LAM, whereas virological and biochemical breakthroughs due to development of ADV signature resistance mutations occurred in 3 of 14 patients (21%) on ADV monotherapy 15 to 18 months from start of treatment (P = 0.0174). Conclusion: Adding ADV to LAM in HBeAg-negative CHB patients with LAM resistance effectively suppresses HBV replication inmost of them and induces biochemical remission that can be maintained in all of them at least for 3 years without any evidence of development of resistance to ADV.     

Percutaneous endoscopic gastrostomy as a tool to assist pneumatic dilation in a difficult case of sigmoid esophagus

We describe a case of a long-standing, untreated achalasia with a huge sigmoid esophagus in a 58-year-old Caucasian man who declined surgery. All means of classical endoscopic approach for pneumatic dilation, including the use of an overtube, were impossible because any attempt to propel the balloon dilator made the guide wire pull back out of the stomach because of the large loops and the tortuosity of the esophagus. For this reason, we used, for the first time, a combined approach of percutaneous gastrostomy and endoscopy in order to fix the guide wire at two points, achieving a pneumatic dilation in this way. A few months later, a significant improvement in the symptoms and nutritional status of the patient were observed.     

Wireless capsule endoscopy in the investigation of patients with chronic renal failure and obscure gastrointestinal bleeding （preliminary data）

AIM: To investigate the role of wireless capsule endoscopy (WCE) in detection of small bowel (SB) pathology in patients with chronic renal failure (CRF) and obscure bleeding. METHODS: Consecutive CRF patients with obscure bleeding were prospectively studied. Patients with normal renal function and obscure bleeding, investigated during the same period with WCE, were used for the interpretation of results. RESULTS: Seventeen CRF patients (11 overt, 6 occult bleeding) and 51 patients (33 overt, 18 occult bleeding) with normal renal function were enrolled in this study. Positive SB findings were detected in 70.6% of CRF patients and in 41.2% of non-CRF patients (P < 0.05). SB angiodysplasia was identified in 47% of CRF patients and in 17.6% of non-CRF patients. Univariate logistic regression revealed CRF as a significant predictive factor for angiodysplasia (P < 0.05). Therapeutic measures were undertaken in 66% of the patients with the positive findings. CONCLUSION: According to our preliminary results, SB angiodysplasia was found in an increased prevalence among CRF patients with obscure bleeding. WCE is useful in diagnosis of gastrointestinal pathologies and in planning appropriate therapeutic intervention and, therefore, should be included in the work-up of this group of patients.     

Intracellular distribution of hepatitis B virus core protein expressed in vitro depends on the sequence of the isolate and the serologic pattern

Intracellular localization of hepatitis B core antigen (HBcAg) in vivo varies with liver cell damage. Localization of HBcAg was studied using transfection of cloned HBcAg variants. Twenty-six samples were obtained from 14 patients with liver disease; 10 were hepatitis B e antigen positive, and 16 were anti-hepatitis B e (HBe) positive. In hepatitis B e antigen (HBeAg)-positive patients, HBcAg predominantly localized in the nucleus; in anti-HBe-positive patients, it accumulated mainly in the cytoplasm. Of the 13 samples with nuclear localization, 9 were HBeAg positive; 5 of 13 had C-terminus and/or B cell epitope mutations. All but 1 of the 13 samples with predominantly cytoplasmic localization were anti-HBe positive; all 13 had mutations. Reversion of mutant sequences with cytoplasmic expression back to the wild type led to a shifting back to nuclear distribution. Thus, the pattern of HBcAg localization in vitro depends on sequence and the serologic pattern of chronic infection, paralleling the situation in vivo.     

Spinal interleukin-1beta in a mouse model of arthritis and joint pain

OBJECTIVE: Pain from arthritis has been associated with peripheral sensitization of primary sensory afferents and the development of inflammation at the dorsal horns. This study was undertaken to determine whether the role of spinal interleukin-1beta (IL-1beta) in central processing of pain is important in the development of arthritis. METHODS: Col1-IL-1betaXAT mice and GFAP-IL-1betaXAT mice were injected with the feline immunodeficiency virus (FIV) (Cre) vector in the right and left temporomandibular joints (TMJs), or in the cisterna magna, respectively, to induce IL-1beta expression in the dorsal horns of the spinal horn. To inhibit intrathecal IL-1 receptor type I (IL-1RI) signaling, FIV(IL-1Ra) vector was injected into the cisterna magna of Col1-IL-1betaXAT mice. The effects of IL-1RI receptor inhibition in GFAP-IL-1betaXAT mice were studied in the GFAP-IL-1betaXAT-IL-1RI(-/-) compound mouse model. Neuroinflammatory, sensory, and behavioral changes were evaluated in conjunction with arthritic changes in the TMJ, assessed by histopathologic and immunohistochemical analyses. RESULTS: Induction of an osteoarthritis-like condition in the TMJ in the Col1-IL-1betaXAT mouse model resulted in up-regulation of murine IL-1beta at the dorsal horns. Moreover, intrathecal inhibition of IL-1RI in Col1-IL-1betaXAT mice with arthritis led to amelioration of joint pathology and attenuation of the attendant joint pain. Overexpression of spinal IL-1beta in the recently developed GFAP-IL-1betaXAT somatic mosaic model of neuroinflammation led to development of arthritis-like pathology accompanied by increased pain-like behavior. CONCLUSION: Our results indicate that joint pathology and pain are dependent on spinal IL-1beta, and suggest the presence of a bidirectional central nervous system-peripheral joints crosstalk that may contribute to the development, expansion, and exacerbation of arthritis.     

Further evidence for treatment of recalcitrant neuropathy of the upper limb with autologous vein wrapping

ABSTRACT: The treatment of entrapment neuropathy in the upper extremity with surgical decompression has generally provided good results. Recurrence of symptoms, however, is not uncommon, and its management is both challenging and difficult. Autologous vein graft wrapping is an alternative technique, and it is recommended for the treatment of recalcitrant upper limb nerve compression in which 2 or more previous surgical procedures have failed to resolve the problem. Each patient underwent both subjective and objective evaluation. To our knowledge, this is the largest reported single series of vein wrapping cases in the upper limb outside the United States and the first to report results using the well-validated patient evaluation measure.     

Effect of time interval on tissue concentrations of cephalosporins after tourniquet inflation: Highest levels achieved by administration 20 minutes before inflation

We studied the effect of different time intervals between antibiotic administration and tourniquet inflation in 62 patients undergoing reconstructive surgery in the lower extremities. The in vivo concentrations in soft tissue and bone of 3 cephalosporins (ceftazidime, ceftriaxone and ceforanide) were determined. Our findings suggest that the highest tissue concentrations were achieved by administration 20 min before tourniquet inflation.