[Impact of adaptive positive end expiratory pressure and mechanical ventilation on hemodynamics and oxygen kinetics in post-liver transplantation patients].

OBJECTIVE: To determine the impact of adaptive positive end expiratory pressure (PEEP) and mechanical ventilation on hemodynamics and oxygen kinetics in post-liver transplantation patients. METHODS: The study included 11 patients who accepted mechanical ventilation after piggyback liver transplantation. Swan-Ganz catheter and radial artery catheter were used to monitor the cardiac output (CO), mean pulmonary arterial pressure (MPAP), mean arterial blood pressure (MABP) and central venous pressure (CVP) and airway pressure. After transplantation, PEEP of 0, 5, 10 and 15 cm H(2)O (1 cm H(2)O=0.098 kPa) was instituted to support the ventilation alternately. After 30 minutes, pressure regulated volume controlled ventilation (PRVCV) and pressure controlled synchronized intermittent mandatory ventilation+pressure support ventilation (PC-SIMV+PSV) were used to support the ventilation alternately and the indexes of hemodynamics and oxygen kinetics were analyzed. RESULTS: The data showed that differences existed in peak airway pressure, mean airway pressure, CVP and MPAP when different levels of PEEP were used. These indexes were significantly higher in PEEP of 15 and 10 cm H(2)O than those in PEEP of 0 and 5 cm H(2)O.There were no differences in pH, partial pressure of carbon dioxide in arterial blood (PaCO(2)), pressure of oxygen in arterial blood (PaO(2)), arterial oxygen saturation (SaO(2)), oxygen delivery (DO(2)), oxygen consumption (VO(2)) and oxygen extraction rate (O(2)ER) at different levels of PEEP. The airway pressure was significantly lower under PRVCV pattern than those under PC-SIMV+PSV pattern [(8.78+/-1.53) cm H(2)O vs. (11.64+/-3.30) cm H(2)O, P<0.05]. There were no differences in other indexes between these two mechanical ventilation patterns. CONCLUSION: These date suggested that a low level of PEEP (5 cm H(2)O) during mechanical ventilation should be used in post-liver transplantation patients in order to decrease the influence of PEEP on systemic circulation and hepatic regurgitation. PRVCV could be a more suitable mechanical ventilation pattern for patient after liver transplantation.

Clinical and virological characteristics of hepatitis B virus subgenotypes Ba, C1, and C2 in China.

Hepatitis B virus (HBV) subgenotypes Ba, C1 (Cs), and C2 (Ce) are the most prevalent HBV variants in China. To investigate the virological characteristics of these subgenotypes and their clinical implications, we enrolled a cohort of 211 patients in the Guangdong Province of China, including 132 with chronic hepatitis B virus infection (CH), 32 with liver cirrhosis (LC), and 47 with hepatocellular carcinoma (HCC) according to clinical examination, liver function test, and ultrasonograph results. Overall, HBV Ba was found in 51.2% (108/211), HBV C1 in 33.6% (71/211), and HBV C2 in 15.2% (32/211) of the cases. The distribution of HBV genotype C was greater among patients in the LC and HCC groups than among patients in the CH group, while the distribution of HBV genotype B was greater among the CH patients than among the LC and HCC patients. No significant differences in clinical features were found among patients with HBV Ba, C1, and C2. Virologically, HBV C1 had the strongest association with the A1762T G1764A double mutation, while the mutation at position 1896 resulting in A (1896A) was uncommon. In contrast, HBV Ba had the highest frequency of 1896A but the lowest of A1762T G1764A, and HBV C2 had intermediate frequencies of these mutations. Mutations of 1653T and 1753V were specifically associated with HBV C2 and C1, respectively. Multivariate analyses showed that the 1653T, 1753V, and A1762T G1764A mutations and patient age significantly increased the risk of HCC development. In conclusion, HBV Ba, C1, and C2 have different mutation patterns in the enhancer II/core promoter/precore region. Therefore, genotyping and detecting the 1653T and 1753V mutations, in addition to the A1762T G1764A double mutation, might have important clinical implications as predictive risk factors for hepatocarcinogenesis.

A new intertype recombinant between genotypes C and D of hepatitis B virus identified in China.

Hepatitis B virus (HBV) genotypes have a characteristic geographical distribution. More than 90% of chronic HBV patients in China are infected with genotypes B or C. Here, eight HBV isolates that were initially classified as genotype D by PCR-restriction fragment length polymorphism analysis were analysed in detail. The complete HBV genome was sequenced and compared with 32 sequences retrieved from GenBank, representing HBV genotypes A-G. Phylogenetic analysis of the S gene (nt 10-800) classified all eight isolates as genotype D. However, phylogenetic analyses of nt 800-10 and the open reading frames (ORFs) of the precore/core and X genes classified all eight isolates as genotype C. This discordance between phylogenetic trees reconstructed on different ORFs suggested that intertype recombination has occurred in all eight isolates. By using the simplot program, the site of recombination with genotype D was located in the preS2/S region, spanning nt 10-799 in seven of eight isolates and nt 10-1499 in the other isolate. These results demonstrate that intertype recombination should be considered as a type of variation that increases the genetic diversity of HBV. Hybrids of different HBV genotypes might exhibit specific virological properties and their significance in the diagnosis and management of chronic hepatitis B deserves further investigation.

Clinical and virological characteristics of lamivudine resistance in chronic hepatitis B patients: a single center experience.

We have investigated the characteristics of lamivudine-resistant strains in patients with chronic hepatitis B in Guangdong, China, where the predominant genotypes are B and C. Two hundred forty-seven patients treated with lamivudine in Nanfang Hospital were followed-up. Patients with hepatitis B e antigen (HBeAg) positive and hepatitis B virus (HBV)-DNA levels over 7.5 x 10(6) copies/ml at baseline had a shorter time to the selection of YMDD mutant (P = 0.02 and 0.00, respectively). The detection of YMDD mutant precedes HBV-DNA breakthrough and alanine transaminase (ALT) flare in about 2 and 3 months, respectively. The ALT flare after the appearance of YMDD mutants was more evident in HBeAg positive patients than HBeAg negative patients (P = 0.02). After emergence of YMDD mutant, the HBV-DNA level was significantly higher in genotype C patients compared with genotype B patients (P = 0.02). No significant difference of YMDD mutant pattern was found between patients with genotype B and C. Four kinds of new mutants were found in over two patients including rtL80I, rtG172E, rtG174C, and rtG172E/rtG174C. In vitro transfection and real-time analysis showed that rtG172E, rtG174C, and rtG172E/rtG174C mutants had a decreased replication competence compared with wild type (33%, 27%, and 15% of the wild type HBV, respectively). Our result suggest that genotypic monitoring of YMDD mutant is important for the management of patients treated with lamivudine.

A novel hepatitis B virus genotyping system by using restriction fragment length polymorphism patterns of S gene amplicons.

AIM: Traditional hepatitis B virus (HBV) genotyping methods using restriction fragment length polymorphism (RFLP) can reliably identify genotypes A to F. As HBV genotypes G and H have been recently identified, this study was to establish an accurate and simple genotyping method for all eight HBV genotypes (A to H). METHODS: Two hundred and forty HBV small S sequences obtained from GeneBank were analysed for restriction enzyme sites that would be genotype-specific. Restriction patterns following digestion with restriction enzymes BsrI, StyI, DpnI, HpaII, and EaeI, were determined to identify all eight HBV genotypes. Mixed genotype infections were confirmed by cloning and further RFLP analysis. RESULTS: The new genotyping method could identify HBV genotypes A to H. Genotypes B and C could be determined by a single step digestion with BsrI and StyI in parallel. This was particularly useful in the Far East where genotypes B and C are predominant. Serum samples from 187 Chinese HBV carriers were analysed with this genotyping system, and the genotype distribution was 1.1% (2), 51.9% (97), 40.6% (76) and 4.8% (9) for genotypes A, B, C, and D, respectively. Mixed genotypes were found in only 3 patients (1.6%). Sequence data analysis confirmed the validity of this new method. CONCLUSION: This HBV genotyping system can identify all eight HBV genotypes. It is accurate and simple, and can be widely used for studies on HBV genotyping.

[Hepatitis B virus genotypes and the heterogeneity of its polymerase gene].

OBJECTIVE: To study the heterogeneity of polymerase gene (P gene) within hepatitis B virus (HBV) genotypes based on a systematic analysis of 202 HBV P genes, providing some useful references for further studies on the relationship among HBV genotypes, P gene mutations, replication and nucleoside analogues drug-resistance. METHODS: 202 HBV complete sequences containing P genes were obtained from GenBank and were analysed using computer softwares. RESULTS: There were some genotype-related characteristics of HBV P genes. As reverse transcriptase domain was concerned, there were more amino acid divergences in genotype C and D compared with these in genotype A. There were also amino acid substitutions in the A-F conserved regions of the reverse transcriptase domain within and between HBV genotypes. CONCLUSIONS: There are divergences of P genes and amino acids within and between HBV genotypes, which should be considered when amino acid changes are analyzed whether they are proposed to be drug-resistance mutations or the results from quasispecies-selected. Moreover, these divergences may affect the antiviral effect of nucleoside analogues on HBV with different genotypes.