Global Tonga tsunami explained by a fast-moving atmospheric source.

Volcanoes can produce tsunamis by means of earthquakes, caldera and flank collapses, pyroclastic flows or underwater explosions1-4. These mechanisms rarely displace enough water to trigger transoceanic tsunamis. Violent volcanic explosions, however, can cause global tsunamis1,5 by triggering acoustic-gravity waves6-8 that excite the atmosphere-ocean interface. The colossal eruption of the Hunga Tonga-Hunga Ha'apai volcano and ensuing tsunami is the first global volcano-triggered tsunami recorded by modern, worldwide dense instrumentation, thus providing a unique opportunity to investigate the role of air-water-coupling processes in tsunami generation and propagation. Here we use sea-level, atmospheric and satellite data from across the globe, along with numerical and analytical models, to demonstrate that this tsunami was driven by a constantly moving source in which the acoustic-gravity waves radiating from the eruption excite the ocean and transfer energy into it by means of resonance. A direct correlation between the tsunami and the acoustic-gravity waves' arrival times confirms that these phenomena are closely linked. Our models also show that the unusually fast travel times and long duration of the tsunami, as well as its global reach, are consistent with an air-water-coupled source. This coupling mechanism has clear hazard implications, as it leads to higher waves along land masses that rise abruptly from long stretches of deep ocean waters.

Serological and molecular markers of hepatitis E virus infection in HIV-infected patients in Brazil.

In Brazil, the circulation of hepatitis E virus (HEV) has been demonstrated in distinct groups of individuals and some animals, but its prevalence among individuals with human immunodeficiency virus (HIV) infection is unknown. This study aimed to assess the frequency of serological and molecular HEV markers in individuals infected with HIV from São Paulo, Brazil. Serum and plasma samples of 354 HIV-infected patients collected between 2007 and 2013 were included. All samples were tested for anti-HEV IgG and IgM antibodies and HEV RNA. Anti-HEV IgG and IgM antibodies were detected in 10.7% (38/354) and 1.4% (5/354) of the samples, respectively. Both antibodies were detected simultaneously in only two samples. HEV RNA was not detected in any sample. There was no significant correlation of anti-HEV serological status (positivity to anti-HEV IgG and/or IgM) with sex, age, CD4+ T cell count, HIV viral load, antiretroviral therapy, liver enzyme levels, or coinfection with hepatitis B virus and/or hepatitis C virus. Our study provides serological evidence of past and recent HEV infections in HIV-infected patients from São Paulo, Brazil. However, the occurrence of ongoing HEV infection appears be a rare event in this population.

Gut microbiome composition in lean patients with NASH is associated with liver damage independent of caloric intake: A prospective pilot study.

BACKGROUND AND AIM: The aim of the study was to compare the gut microbiomes from obese and lean patients with or without NASH to outline phenotypic differences. METHODS AND RESULTS: We performed a cross-sectional pilot study comprising biopsy-proven NASH patients grouped according to BMI. Microbiome DNA was extracted from stool samples, and PCR amplification was performed using primers for the V4 region of the 16S rRNA gene. The amplicons were sequenced using the Ion PGM Torrent platform, and data were analyzed using QIIME software. Macronutrient consumption was analyzed by a 7-day food record. Liver fibrosis ≥ F2 was associated with increased abundance of Lactobacilli (p = 0.0007). NASH patients showed differences in Faecalibacterium, Ruminococcus, Lactobacillus and Bifidobacterium abundance compared with the control group. Lean NASH patients had a 3-fold lower abundance of Faecalibacterium and Ruminococcus (p = 0.004), obese NASH patients were enriched in Lactobacilli (p = 0.002), and overweight NASH patients had reduced Bifidobacterium (p = 0.018). Moreover, lean NASH patients showed a deficiency in Lactobacillus compared with overweight and obese NASH patients. This group also appeared similar to the control group with regard to gut microbiome alpha diversity. Although there were qualitative differences between lean NASH and overweight/obese NASH, they were not statistically significant (p = 0.618). The study limitations included a small sample size, a food questionnaire that collected only qualitative and semi-quantitative data, and variations in group gender composition that may influence differences in FXR signaling, bile acids metabolism and the composition of gut microbiota. CONCLUSION: Our preliminary finding of a different pathogenetic process in lean NASH patients needs to be confirmed by larger studies, including those with patient populations stratified by sex and dietary habits.

Pegylated interferon alfa for chronic hepatitis B: systematic review and meta-analysis.

Conventional interferon alfa and nucleos(t)ide analogues, such as lamivudine, are frequently used for chronic hepatitis B (CHB) treatment, but are associated with adverse effects and viral resistance. Here we performed a systematic review and meta-analysis evaluating all studies of pegylated interferon alfa (PEG-IFNα) treatment in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with CHB. We searched electronic databases--PubMed, EMBASE, Cochrane Library and LILACS--for randomized controlled trials evaluating PEG-IFNα therapy between 1999 and September 2014. Virological response was the primary outcome. We identified 14 studies involving 2829 patients. Our analysis revealed that PEG-IFNα + lamivudine combination therapy produced better virological and biochemical responses than PEG-IFNα monotherapy in HBeAg-positive and HBeAg-negative patients at the end of treatment. PEG-IFNα + adefovir dipivoxil achieved better seroconversion rate than PEG-IFNα in HBeAg-positive patients at the end of treatment. The present findings demonstrated a beneficial response rate following PEG-IFNα combination therapy with nucelos(t)ides among HBeAg-positive and HBeAg-negative patients with CHB. Further trials are needed to investigate simultaneous and sequential therapy strategies.

A1c, glucose variability and hypoglycemia risk in patients with type 1 diabetes.

AIM: The aim of this paper was to compare the predictive value of glycated hemoglobin (A1c) and glucose variability (GV) in the risk of hypoglycemia in patients with type 1 diabetes (T1D). METHODS: Analysis of continuous glucose monitoring performed in 130 T1D patients with a diabetes background of 17.1±8.6 years, in intensive insulin therapy (49.8±17.9 UI per day). Mean interstitial glucose (in mg/dL), GV (standard deviation of mean glucose, in mg/dL), time per day spent in hypoglycemia (interstitial glucose ≤70 mg/dL, in %), and episodes of asymptomatic or nocturnal hypoglycemia, (hypoglycemia between midnight and 8 a.m., in %), were assessed. Patients were divided into two groups: group I (N.=84) with A1C≤7.5% and group II (N.=46) with A1C>7.5%. A statistical analysis was performed using SPSS, version 21.0®. RESULTS: Group I presented a significantly lower mean glucose (139.2±25.9 vs. 173.1±33.2 mg/dL, P<0.05) and GV (58.4±18.8 vs. 70.3±18.6 mg/dL, P<0.05) and more hypoglycemia time (7.65±7.04 vs. 5.35±5.64%, P<0.05). The number of patients with nocturnal hypoglycemia was not significantly different in both groups (8.7 vs. 5.8%, P>0.05). Hypoglycemia time was positively correlated with GV (r=0.23, P=0.01) and negatively with A1C and mean glucose (r=-0.23 and r=-0.36; P=0.01). In multivariate analysis, GV and mean glucose were associated with hypoglycemia time (ß=0.22 and ß=-0.15, P<0.01, respectively), independent of A1c, diabetes duration and insulin dose; nocturnal hypoglycemia was only associated with mean glucose (OR=0.9, P<0.05) and was associated with a 16-fold increased risk of asymptomatic hypoglycemia (OR: 16.9, P<0.01). CONCLUSION: Patients with high HbA1c still remain at risk of hypoglycemia. Glucose variability independently predicts daily time spent in hypoglycemia. At night, hypoglycemia only correlates with mean glucose, suggesting that daily fluctuations are probably due to inadequate meals insulin coverage. The potential of GV for predicting hypoglycemia time supports the inclusion of measures of GV into a global diabetes strategy.

The presence of resistance mutations to protease and polymerase inhibitors in Hepatitis C virus sequences from the Los Alamos databank.

Several new direct-acting antiviral (DAA) drugs are in development for chronic hepatitis C viral (HCV) infection, and NS3-NS4A serine protease and the NS5B RNA-dependent RNA polymerase have been the major targets. HCV variants displaying drug-resistant phenotypes have been observed both in vitro and during clinical trials. Our aim was to characterize amino acid changes at positions previously associated with resistance in protease (NS3) and polymerase (NS5B) regions from treatment-naïve HCV patients infected with genotypes 1a, 1b and 3a. All 1383 NS3 protease sequences (genotype 1a = 680, 1b = 498 and 3a = 205) and 806 NS5B polymerase sequences (genotypes 1a = 471, 1b = 329, 3a = 6) were collected from Los Alamos databank. Genotype 3a protease sequences showed the typical low-level resistance mutation V36L. NS3 sequences from other genotypes presented mutations on positions 36, 39, 41, 43, 54, 80, 109, 155 and 168 in a frequency lower than 2%, except for the mutation Q80R found in 35% of genotype 1a isolates. Polymerase sequences from genotype 3a patients showed five typical mutations: L419I, I424V, I482L, V499A and S556G. Two positions presented high polymorphism in the NS5B region from genotype 1a (V499A) and genotype 1b (C316N) subjects. Our results demonstrated a natural profile of genotype 3a that can be associated with the pre-existence of HCV variants resistant to first-generation protease inhibitors and to non-nucleoside polymerase inhibitors. Likewise, genotype 1b isolates and genotype 1a sequences exhibited pre-existing mutations associated with resistance to Palm II and Thumb I polymerase inhibitors, respectively.

HCV viremia drives an increment of CD86 expression by myeloid dendritic cells.

The host immune response, including innate and adaptive immunity, plays a critical role in determining the outcome of viral infection. Nevertheless, little is known about the exact reasons for the failure of the host immune system in controlling hepatitis C virus (HCV) infection. Impairment of dendritic cells (DCs) function is probably one of the mechanisms responsible for immune evasion of HCV. In this study, the frequency and phenotype of DCs subsets were analyzed in three groups: HCV-infected individuals who developed viral persistence (1), HCV-infected individuals who spontaneously cleared the virus (2) and HCV-seronegative uninfected subjects (3). The results showed that the frequency of DCs subsets was not statistically significant between groups. Plasmacytoid DCs circulating exhibited an immature phenotype characterized by low expression of CD86. On the other hand, CD86 expression in myeloid DCs was significantly higher in chronic infected individuals compared to healthy controls (P=0.037). A positive correlation was observed between CD86(+) myeloid DC (mDC) and HCV viral load (r=0.4121, P=0.0263). These results suggest that HCV did not have an inhibitory effect on mDC maturation and the HCV viremia drives the increase of CD86 expression in mDC. The regulation of DCs maturation and migration lies at the level of intracellular signaling. HCV can activate or block intracellular signaling pathways and alter DC function. In conclusion, the present study suggests that imbalance of DC maturation by the virus represents a mechanism of evasion of the immune system despite the fact that HCV viremia appears to exert a "stimulatory" effect on cell-surface immune phenotype.

S-Nitroso-N-acetylcysteine induces de-differentiation of activated hepatic stellate cells and promotes antifibrotic effects in vitro.

Nitric oxide (NO) has been shown to act as a potent antifibrogenic agent by decreasing myofibroblast differentiation. S-Nitroso-N-acetylcysteine (SNAC), a NO donor, attenuates liver fibrosis in rats, but the cellular and molecular mechanisms on liver myofibroblast-like phenotype still remain unknown. Here, we investigate the antifibrotic effects of SNAC on hepatic stellate cells, the major fibrogenic cell type in the liver. A murine GRX cell line was incubated with SNAC (100µM) or vehicle (control group) for 72h. Cell viability was measured by MTT colorimetric assay and the conversion of myofibroblast into quiescent fat-storing cell phenotype was evaluated by Oil-Red-O staining. TGFß-1, TIMP-1, and MMP-13 levels were measure in the supernatant by ELISA. Profibrogenic- and fibrolytic-related gene expression was quantified using real-time qPCR. SNAC induced phenotype conversion of myofibroblast-like phenotype into quiescent cells. SNAC decreased gene and protein expression of TGFß-1 and MMP-2 compared to control groups. Besides, SNAC down-regulated profibrogenic molecules and up-regulated MMP-13 gene expression, which plays a key role in the degradation of interstitial collagen in liver fibrosis. In conclusion, these findings demonstrate that SNAC efficiently can modulate the activation and functionality of murine hepatic stellate cells and could be considered as an antifibrotic treatment to human liver fibrosis.

Hepatitis B virus and hepatitis delta virus genotypes in outbreaks of fulminant hepatitis (Labrea black fever) in the western Brazilian Amazon region.

The genotypes of hepatitis B (HBV) and delta (HDV) viruses circulating among fulminant hepatitis cases from the western Amazon Basin of Brazil were characterized in this study. HBV and HDV isolates were obtained from liver samples from 14 patients who developed fulminant hepatitis and died during 1978-1989. HBV DNA and HDV RNA were detected in all samples. Phylogenetic analyses of HDV sequences showed that they all clustered with previously characterized sequences of HDV genotype 3 (HDV-3). HBV genotypes F, A and D were found in 50.0, 28.6 and 21.4 % of cases, respectively. These results confirm the predominance of HDV-3 in South America and its association with the severe form of hepatitis, and the finding of the co-infection of HDV-3 with different genotypes of HBV suggests that the association between HDV-3 and HBV-F is not necessarily causally related to a more severe clinical course of infection.

Oral cavity is not a reservoir for Helicobacter pylori in infected patients with functional dyspepsia.

INTRODUCTION: Helicobacter pylori infection is very prevalent in Brazil, infecting almost 65% of the population. The aim of this study was to evaluate the presence of this bacterium in the oral cavity of patients with functional dyspepsia (epigastric pain syndrome), establish the main sites of infection in the mouth, and assess the frequency of cagA and vacA genotypes of oral H. pylori. METHODS: All 43 outpatients with epigastric pain syndrome, who entered the study, were submitted to upper gastrointestinal endoscopy to rule out organic diseases. Helicobacter pylori infection in the stomach was confirmed by a rapid urease test and urea breath tests. Samples of saliva, the tongue dorsum and supragingival dental plaque were collected from the oral cavity of each subject and subgingival dental plaque samples were collected from the patients with periodontitis; H. pylori infection was verified by polymerase chain reaction using primers that amplify the DNA sequence of a species-specific antigen present in all H. pylori strains; primers that amplify a region of urease gene, and primers for cagA and vacA (m1, m2, s1a, s1b, s2) genotyping. RESULTS: Thirty patients harbored H. pylori in the stomach, but it was not possible to detect H. pylori in any oral samples using P1/P2 and Urease A/B. The genotype cagA was also negative in all samples and vacA genotype could not be characterized (s-m-). CONCLUSION: The oral cavity may not be a reservoir for H. pylori in patients with epigastric pain syndrome, the bacterium being detected exclusively in the stomach.

The CTLA4 +49 A/G polymorphism is not associated with susceptibility to type 1 diabetes mellitus in the Portuguese population.

CTLA4 genetic polymorphisms have been associated with type 1 diabetes. We genotyped 207 patients and 249 controls for the most frequently investigated polymorphism of the CTLA4 gene (+49A/G (rs231775)). No significant differences were observed, suggesting that this polymorphism is not strongly associated with type 1 diabetes in the Portuguese population.

Combined GSTM1 and GSTT1 null genotypes are associated with a lower risk of papillary thyroid cancer.

Individual susceptibility to cancer is influenced by polymorphisms of genes encoding drug-metabolizing enzymes such as the glutathione S-transferases (GST). The null polymorphisms of the GSTM1 and GSTT1 genes have been associated to a modified risk of several cancers but studies of thyroid cancer have produced conflicting results. The aim of this study was to investigate the relationship between these polymorphisms and the risk of papillary thyroid cancer (PTC). A total of 188 patients with PTC and 247 controls were genotyped using a PCR-based assay. Odds ratios (OR) and 95% confidence intervals (CI) for each homozygous null genotype were determined. The frequency of each of the GSTM1 and GSTT1 null genotypes did not differ significantly between patients and controls (OR=0.83, 95%CI: 0.56-1.21; p=0.328; and OR=0.66, 95%CI: 0.39-1.12; p=0.123, respectively), but the frequency of individuals that had the combined GSTM1 null/GSTT1 null genotypes was significantly lower in the patient group (OR=0.50, 95%CI: 0.26-0.97; p=0.040). The GSTM1 null genotype was associated with a lower risk of advanced cancer stages (III/IV) (OR=0.50, 95%CI: 0.26-0.96; p=0.036) and the GSTT1 null genotype was associated with a lower risk of the follicular variant of PTC (OR=0.31, 95%CI: 0.10-0.97; p=0.044). These results suggest that GSTM1 and GSTT1 null genotypes are weak, yet possible, modifiers of the risk of PTC. This protective effect may be due to a role of the GSTM1 and GSTT1 encoded enzymes in the metabolic activation of putative thyroid carcinogens or in other pathways involved in thyroid carcinogenesis.

Transient Elastography in Acute Cellular Rejection Following Liver Transplantation: Systematic Review.

BACKGROUND: Transient elastography (TE) is a noninvasive technique that measures liver stiffness. When an inflammatory process is present, this is shown by elevated levels of stiffness. Acute cellular rejection (ACR) is a consequence of an inflammatory response directed at endothelial and bile epithelial cells, and it is diagnosed through liver biopsy. This is a systematic review of the viability of TE in ACR following liver transplantation. METHODS: The Cochrane Library, Embase, and Medline PubMed databases were searched and updated to November 2016. The MESH terms used were "Liver Transplantation," "Graft Rejection," "Elasticity Imaging Techniques" (PubMed), and "Elastography" (Cochrane and Embase). RESULTS: Seventy studies were retrieved and selected using the PICO (patient, intervention, comparison or control, outcome) criteria. Three prospective studies were selected to meta-analysis and evaluation. A total of 33 patients with ACR were assessed with TE. One study showed a cutoff point of >7.9 kPa to define graft damage and <5.3 kPa to exclude graft damage (receiver operating characteristic 0.93; P < .001). Another study showed elevated levels of liver stiffness in ACR patients. However, in this study, no cutoff point for ACR was suggested. The final prospective study included 27 patients with ACR at liver biopsy. Cutoff points were defined as TE > 8.5 kPa, moderate to severe ACR, with a specificity of 100% and receiver operating characteristic curve of 0.924. The measurement of TE < 4.2 kPa excludes the possibility of any ACR (P = .02). CONCLUSIONS: TE may be an important tool for the severity of ACR in patients following liver transplantation. Further studies should be performed to better define the cutoff points and applicability of the exam.

Evolution of Biomarkers of Atherogenic Risk in Liver Transplantation Recipients.

BACKGROUND: Cardiovascular disease is a major contributing factor to long-term mortality after liver transplantation (LT). METHODS: This study evaluated the evolution of atherogenic risk in liver transplant recipients (LTRs). Thirty-six subjects were prospectively enrolled at 12 months and followed for 48 months after liver transplantation. Serum biomarkers of endothelial dysfunction (sICAM-1 and sVCAM-1), chronic inflammation (serum amyloid A), and oxidative stress (myeloperoxidase) were measured at 12 and 48 months after LT. Additionally, at 12 months all patients underwent a cardiac computed tomography (CT) scan and a coronary artery calcium score (CACS). RESULTS: The prevalence of risk factors of metabolic syndrome (MS) increased over the course of the study. The patients' sVCAM-1 and sICAM-1 increased from 1.82 ± 0.44 ng/mL to 9.10 ± 5.82 ng/mL (P < .001) and 0.23 ± 0.09 ng/mL to 2.7 ± 3.3 ng/mL, respectively from month 12 to 48. Serum myeloperoxidase increased from 0.09 ± 0.07 ng/mL to 3.46 ± 3.92 ng/mL (P < .001) over the course of the study. Serum amyloid A also increased from 21.4 ± 40.7 ng/mL at entry to 91.5 ± 143.6 ng/mL at end of study (P < .001). CONCLUSION: No association between these biomarkers and MS was noted. The cardiac CT revealed mild and moderate disease in 19% and 25% of the cohort, respectively. No association between serum biomarkers and CACS was noted. Serum biomarkers of atherogenic risk increase rapidly in LTRs and precede coronary plaques.

Susceptibility of lamivudine-resistant hepatitis B virus to other reverse transcriptase inhibitors.

The emergence of resistant hepatitis B virus (HBV), with mutations in the YMDD motif of the polymerase gene after treatment with lamivudine, is becoming an important clinical problem. In this study, susceptibility of wild-type and lamivudine-resistant HBV M552I, M552V, and L528M/M552V mutants to other reverse transcriptase inhibitors was investigated by transient transfection of full-length HBV DNA into human hepatoma cells. HBV DNA replication was monitored by Southern blot hybridization, which showed the presence of a single-stranded band (representative of the HBV replicative intermediates) in the drug-free, wild-type HBV-transfected cells. This band was diminished in the samples of wild-type HBV DNA treated with either lamivudine, adefovir, or lobucavir. The band intensities from the lamivudine-resistant mutants were not decreased by treatment with lamivudine, but were decreased by the treatments with adefovir or lobucavir. In contrast, penciclovir and nevirapine did not diminish the intensity of the single-stranded band of wild-type HBV or the lamivudine-resistant mutants. These results demonstrate that lamivudine-resistant HBV is susceptible to adefovir and lobucavir. Lamivudine-resistant HBV should be treated with adefovir or lobucavir, and combination therapy with lamivudine and adefovir/lobucavir may prevent the emergence of lamivudine-resistant HBV.

The polymerase L528M mutation cooperates with nucleotide binding-site mutations, increasing hepatitis B virus replication and drug resistance.

After receiving lamivudine for 3 years to treat chronic hepatitis B, 67-75% of patients develop B-domain L528M, C-domain M552I, or M552V mutations in the HBV polymerase that render hepatitis B virus (HBV) drug-resistant. The aim of this study was to evaluate the influence of these mutations on viral replication and resistance to antiviral agents. We investigated the replication fitness and susceptibility of the wild-type and five mutant HBVs (L528M, M552I, M552V, L528M/M552I, and L528M/M552V) to 11 compounds [lamivudine, adefovir, entecavir (BMS-200475) (+)-BCH-189 (+/-)-FTC (racivir) (-)-FTC (emtricitabine) (+)-FTC, L-D4FC, L-FMAU (clevudine), D-DAPD, and (-)-carbovir] by transfecting HBV DNA into hepatoma cells and monitoring viral products by Southern blotting. The replication competency of the single C-domain mutants M552I and M552V was markedly decreased compared with that of wild-type HBV. However, addition of the B-domain mutation L528M restored replication competence. Only adefovir and entecavir were effective against all five HBV mutants, and higher doses of these compounds were necessary to inhibit the double mutants compared with the single mutants. The B-domain mutation (L528M) of HBV polymerase not only restores the replication competence of C-domain mutants, but also increases resistance to nucleoside analogues.

Prevalence of serological markers of hepatitis B virus in pregnant women from Paraná State, Brazil.

The prevalence of hepatitis B virus (HBV) in Brazil increases from South to North but moderate to elevated prevalence has been detected in the Southwest of Paraná State. The prevalence of serological markers of HBV was evaluated in 3188 pregnant women from different counties in Paraná State and relevant epidemiological features were described. The prevalence of HBV markers in pregnant women for the state as a whole was 18.5% (95% CI = 17.2-19.9), ranging from 7.2% in Curitiba to 38.5% in Francisco Beltrão. The endemicity of HBV marker prevalence in pregnant women was intermediate in Cascavel, Foz do Iguaçu, and Francisco Beltrão, and low in Curitiba, Londrina, Maringá, and Paranaguá. Multiple logistic regression showed that HBV marker prevalence increased with age, was higher among black women, among women of Italian and German descent, and among women who had family members in neighboring Rio Grande do Sul State. Univariate analysis showed that HBV marker prevalence was also higher among women with no education or only primary education, with a lower family income and whose families originated from the South Region of Brazil. Pregnant women not having positive HBV markers (anti-HBc, HBsAg or anti-HBs detected by ELISA) corresponded to 73.7% of the population studied, implying that HBV vaccination needs to be reinforced in Paraná State. The highest prevalence was found in three counties that received the largest number of families from Santa Catarina and Rio Grande do Sul, where most immigrants were of German or Italian ascendance. This finding probably indicates that immigrants that came to this area brought HBV infection to Southwestern Paraná State.

Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease.

Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7) or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7) for 4 weeks. The control group (N = 7) was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4) and a decrease in respiratory control rate (RCR) in the CD group (S4: 32.70 +/- 3.35; RCR: 2.55 +/- 0.15 ng atoms of O2 min-1 mg protein-1) when compared to the H and control groups (S4: 23.09 +/- 1.53, 17.04 +/- 2.03, RCR: 3.15 +/- 0.15, 3.68 +/- 0.15 ng atoms of O2 min-1 mg protein-1, respectively), P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

A prospective study of hepatitis B virus markers in patients with chronic HBV infection from Brazilian families of Western and Asian origin.

The purpose of the present study was to determine the frequency of hepatitis B virus (HBV) markers in families of HBsAg-positive patients with chronic liver disease. Serum anti-HBc, HBsAg and anti-HBs were determined by enzyme immunoassay and four subpopulations were considered: genetically related (consanguineous) and non-genetically related (non-consanguineous) Asian subjects and genetically related and non-genetically related Western subjects. A total of 165 and 186 relatives of Asian and Western origin were enrolled, respectively. The occurrence of HBsAg and anti-HBs antibodies was significantly higher (P < 0.0001) in family members of Asian origin (81.8%) than in family members of Western origin (36.5%). HBsAg was also more frequent among brothers (79.6 vs 8.5%; P < 0.0001), children (37.9 vs 3.3%; P < 0.0001) and other family members (33.9 vs 16.7%; P < 0.0007) of Asian than Western origin, respectively. No difference between groups was found for anti-HBs, which was more frequently observed in fathers, spouses and other non-genetic relatives. HBV infection was significantly higher in children of Asian than Western mothers (P < 0.0004). In both ethnic groups, the mothers contributed more to their children's infection than the fathers (P < 0.0001). Furthermore, HBsAg was more frequent among consanguineous members and anti-HBs among non-consanguineous members. These results suggest the occurrence of vertical transmission of HBV among consanguineous members and probably horizontal sexual transmission among non-consanguineous members of a family cluster. Thus, the high occurrence of dissemination of HBV infection characterizes family members as a high-risk group that calls for immunoprophylaxis. Finally, the study showed a high familial aggregation rate for both ethnic groups, 18/19 (94.7%) and 23/26 (88.5%) of the Asian and Western origin, respectively.

HEV, TTV and GBV-C/HGV markers in patients with acute viral hepatitis.

The aim of the present study was to evaluate the prevalence of HEV, TTV and GBV-C/GBV-C/HGV in patients with acute viral hepatitis A, B and non-A-C. We evaluated sera of 94 patients from a sentinel program who had acute hepatitis A (N = 40), B (N = 42) and non-A-C (N = 12); 71 blood donors served as controls. IgM and anti-HEV IgG antibodies were detected by enzyme immunoassay using commercial kits. TTV and GBV-C/HGV were detected by nested PCR; genotyping was done by sequencing and phylogenetic analysis. Anti-HEV IgG was present in 38, 10 and 17% of patients with hepatitis A, B and non-A-C. Four patients with hepatitis A and 1 with non-A-C hepatitis also had anti-HEV IgM detected in serum. TTV was detected in 21% of patients with acute hepatitis and in 31% of donors. GBV-C/HGV was detected in 9% of patients with hepatitis, and in 10% of donors. We found TTV isolates of genotypes 1, 2, 3, and 4 and GBV-C/HGV isolates of genotypes 1 and 2. Mean aminotransferase levels were lower in patients who were TTV or GBV-C/HGV positive. In conclusion, the detection of anti-HEV IgM in some acute hepatitis A cases suggests co-infection with HEV and hepatitis E could be the etiology of a few cases of sporadic non-A-C hepatitis in Salvador, Brazil. TTV genotype 1, 2, 3 and 4 isolates and GBV-C/HGV genotype 1 and 2 strains are frequent in the studied population. TTV and GBV-C/HGV infection does not appear to have a role in the etiology of acute hepatitis.