Handgrip strength is associated with 12-month survival in male patients suffering with advanced chronic liver disease.

BACKGROUND: Advanced chronic liver disease (ACLD) patients are usually malnourished, and both conditions in combination increase the likelihood of unfavourable clinical outcomes. Handgrip strength (HGS) has been suggested as a relevant parameter for nutritional assessment and predictor of adverse clinical outcomes in ACLD. However, the HGS cut-off values for ACLD patients have not yet been reliably established. The aims of this study were to preliminarily identify HGS reference values in a sample population of ACLD male patients and to assess their association with survival over a 12-month follow-up period. METHODS: This was a prospective observational study with preliminary analysis of outpatients and inpatients. A total of 185 male patients with a medical diagnosis of ACLD met the inclusion criteria and were invited to participate in the study. The physiological variation in muscle strength related to the age of the individuals included in the study was considered to obtain cut-off values. RESULTS: After categorising HGS by age group (adults: 18-60 years; elderly: ≥60 years), the reference values obtained were 32.5 kg for the adults and 16.5 kg for the elderly. During the 12-month follow-up, 20.5% of the patients died, and 76.3% of those had been identified with reduced HGS. CONCLUSIONS: Patients with adequate HGS showed significantly higher 12-month survival than those with reduced HGS within the same period. Our findings show that HGS is an important predictive parameter for clinical and nutritional follow-up in ACLD male patients.

Specific nutrition evaluation of patients with advanced chronic liver disease: Development and validation.

BACKGROUND: Malnutrition is frequently identified in patients with advanced chronic liver disease (ACLD), and its early identification is necessary for effective nutrition treatment. The aim of this study was to develop and validate a tool for specific nutrition evaluation of patients with ACLD (SNE-ACLD). METHODS: SNE-ACLD was developed by consensus among experts using Delphi technique. The initial proposal for the SNE-ACLD had six domains (history of weight loss, changes in food intake, gastrointestinal symptoms, changes in functional capacity, presence of complications of liver disease, and a nutrition-focused physical examination) and 11 items. Fifteen experts participated in content validation. In a cross-sectional study design, the new tool was applied to 129 inpatients and outpatients from a gastrohepatology unit. Nutrition status was evaluated with SNE-ACLD and subjective global assessment by one researcher. Content validation and semantic analysis were obtained by content validity index. To verify accuracy of SNE-ACLD, the sensitivity, specificity, Youden index, and area under the receiver operating characteristic curve (AUC) were calculated. RESULTS: After five evaluative sequences conducted by experts, experts excluded the domain for history of weight loss and its respective item. The final version of SNE-ACLD consists of five domains and 10 items. The new instrument showed good accuracy in identifying any level of malnutrition (AUC = 0.83; 95% CI, 0.76-0.91) and severe malnutrition (AUC = 0.90; 95% CI, 0.79-1.00). CONCLUSION: SNE-ACLD can be used in nutrition assessment of patients with liver disease. Future works should investigate its agreement with other methods and its predictive value.

Effect of dietary carbohydrate and lipid modification on clinical and anthropometric parameters in nonalcoholic fatty liver disease: a systematic review and meta-analysis.

CONTEXT: Nonalcoholic fatty liver disease (NAFLD) is estimated to affect approximately 25% of the adult population, making it one of the most common chronic liver diseases worldwide and a major public health problem. Still, there is no consensus on the most appropriate nutritional intervention for disease treatment. OBJECTIVE: To systematize and synthesize the results of randomized controlled trials that have evaluated the effect of dietary interventions with different, quantitative, macronutrient compositions on hepatic steatosis attenuation, serum levels of alanine aminotransferase, aspartate aminotransferase, lipid profile, glucose metabolism markers, and anthropometric parameters of adults and the elderly (age ≥ 60 years) with NAFLD. DATA SOURCES: MEDLINE databases via PubMed, Embase, Science Direct, LILACS, Web of Science, ClinicalTrials.gov, and Cochrane Library were searched. Randomized controlled trials that compared interventions as diets with values ≤ 45% or 20% of the total daily energy intake from carbohydrates or lipids, respectively, compared with dietary reference intakes, were included. DATA EXTRACTION: Risk of bias was assessed through the Cochrane Collaboration tool. The meta-analysis was only performed to evaluate the effect of carbohydrate-modified diets on the outcome variables. The number of participants and mean values and respective standard deviations of the outcome variables were extracted and used to calculate weighted mean differences and their respective 95%CIs. RESULTS: The search strategy resulted in 21 146 studies, of which 10 were retained for qualitative analysis and 6 were included in the meta-analysis. From the analysis of 10 studies were identified 8 articles in which low-calorie diets were evaluated and 3 interventions that used an isocaloric diet. Only 3 studies were classified as having low risk of bias. CONCLUSION: The observed effects on hepatic steatosis, serum alanine aminotransferase and aspartate aminotransferase levels, parameters of lipid and glucose metabolism, and anthropometric variables were mostly related to a hypocaloric diet. The use of reduced macronutrient interventions had no efficacy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42018088824.

HBV carrying drug-resistance mutations in chronically infected treatment-naive patients.

BACKGROUND: Nucleoside/nucleotide analogue (NA) treatment causes selection pressure for HBV strains carrying mutations conferring NA resistance. Drug-resistance mutations occur in the reverse transcriptase (RT) region of the HBV polymerase gene and spontaneously arise during viral replication. These mutations can also alter the hepatitis B surface (HBs) protein and in some cases reduce binding to HBs antibodies. The spread of NA-resistant HBV may impact the efficacy of antiviral treatment and hepatitis B immunization programmes. In this study, we used direct sequencing to assess the occurrence of HBV carrying known mutations that confer NA resistance in the largest cohort of treatment-naive patients with chronic hepatitis B (CHB) to date. METHODS: HBV DNA samples isolated from 702 patients were sequenced and the RT region subjected to mutational analysis. RESULTS: There was high genetic variability among the HBV samples analysed: A1 (63.7%), D3 (14.5%), A2 (3.3%), A3 (0.1%), B1 (0.1%), B2 (0.1%), C2 (0.9%), D1 (0.9%), D2 (4.6%), D4 (5.1%), D unclassified subgenotype (0.7%), E (0.6%), F2a (4.6%), F4 (0.4%) and G (0.4%). HBV strains harbouring mutations conferring NA resistance alone or combined with compensatory mutations were identified in 1.6% (11/702) of the patients. CONCLUSIONS: HBV strains harbouring resistance mutations can comprise the major population of HBV quasispecies in treatment-naive patients. In Brazil, there is a very low frequency of untreated patients who are infected with these strains. These findings suggest that the spread and natural selection of drug-resistant HBV is an uncommon event and/or most of these strains remain unstable in the absence of NA selective pressure.

Serotonin-1A receptor CC genotype is associated with persistent depression related to interferon-alpha in hepatitis C patients.

OBJECTIVE: The aim of this study is to investigate the development of depression during interferon-alpha (IFN-α) therapy and the variations in the expression of the serotonin receptor (5-HTR) and transporter (5-HTT) in hepatitis C patients. METHOD: Hepatitis C patients (n=277) were given the Mini International Neuropsychiatric Interview at the end of IFN-α therapy. Three polymorphisms were genotyped: the serotonin transporter repeat length polymorphic region [5-HTT gene-linked polymorphic region (5-HTTLPR)], as well as SNPs rs25531 and rs6295, located within the 5-HTTLPR and the transcriptional control region of the 5-HTR1A gene, respectively. RESULTS: The diagnosis of current depression, which was associated with IFN-α-related depression (P<.001), demonstrated a statistically significant association with the CC genotype of the 5-HTR1A gene (odds ratio=5.57, 95% confidence interval=1.61-19.24, P=.007). CONCLUSIONS: Persistent depression may represent a more specific type of IFN-α-related psychopathology. Future studies need to investigate the genetic risk factors for vulnerability associated with persistent depression. Limitations, such as the study's cross-sectional design, small sample size and retrospective assessment of IFN-α-induced depression diagnosis, must be taken into account while interpreting the results found in this study.

Improved inflammatory activity with peginterferon alfa-2b maintenance therapy in non-cirrhotic prior non-responders: a randomized study.

BACKGROUND & AIMS: Therapeutic options for patients failing hepatitis C retreatment are limited. EPIC(3) included a prospective trial assessing long-term peginterferon alfa-2b (PegIFNα-2b) maintenance therapy in patients with METAVIR fibrosis scores (MFS) of F2 or F3 who previously failed hepatitis C retreatment. METHODS: Patients with F2/F3 MFS who failed retreatment were randomized to PegIFNα-2b (0.5 µg/kg/week, n=270) or observation (n=270) for 36 months. Blinded liver biopsies obtained before retreatment and after maintenance therapy were evaluated using MFS and activity scores, and confirmatory testing was performed using FibroTest and ActiTest. RESULTS: In total, 348 patients had paired biopsies: 192 patients had missing post-treatment biopsies and were considered as having no change in fibrosis/activity scores. In total, 16% of patients receiving PegIFNα-2b and 11% of observation patients had improvement in MFS (p=0.32). More PegIFNα-2b than observation patients had improvement in activity score (20% vs. 9%; p <0.001). Among patients treated for >2.5 years, improvement in MFS or activity score was more common with PegIFNα-2b than observation (21% vs. 14%, p=0.08 and 26% vs. 10%, p <0.001). FibroTest and ActiTest evaluations indicated significant benefit associated with PegIFNα-2b in terms of reduced fibrosis progression and improved activity score. The safety profile of PegIFNα-2b was similar to previous studies. CONCLUSIONS: PegIFNα-2b did not significantly improve MFS estimated by biopsy compared with observation; however, activity scores were significantly improved and MFS trended toward increased improvement with treatment durations >2.5 years. Both FibroTest and ActiTest were significantly improved during maintenance therapy.

Effect of soy protein supplementation in patients with chronic hepatitis C: a randomized clinical trial.

AIM: To evaluate the effects of soy supplementation on insulin resistance, fatty liver and alanine aminotransferase (ALT) levels in non-diabetic patients with chronic hepatitis C (CHC). METHODS: In a prospective, randomized and single-blinded clinical trial, we compared patients with CHC who had casein as a supplement (n = 80) (control group), with patients who consumed a soy supplement diet (n = 80) [intervention group (IG)]. Both groups received 32 g/d of protein for 12 wk. RESULTS: Patients' baseline features showed that 48.1% were overweight, 43.7% had abdominal fat accumulation, 34.7% had hepatic steatosis and 36.3% had an homeostasis model assessment index of insulin resistance (HOMA-IR) ≥ 3.0. Descriptive analysis showed that protein supplementation diet reduced hepatic steatosis in both groups; however, significant reductions in ALT levels occurred in the soy group. Multiple regression modeling indicated that in the presence of severe fibrosis (F3/F4), γ glutamyl transferase elevation and high density lipoprotein (HDL) reduction, the intervention group had 75% less chance of developing hepatic steatosis (OR= 0.25; 95% CI: 0.06-0.82) and 55% less chance of presenting with an ALT level ≥ 1.5 × the upper limit of normal (ULN) (OR = 0.45, 95% CI: 0.22-0.89). Soy treatment did not have any effect on insulin resistance (OR = 1.92; 95% CI: 0.80-4.83), which might be attributed to the fact that the HOMA-IR values at baseline in most of our patients were in the normal range. Advanced hepatic fibrosis, an ALT level > 1.5 × ULN and visceral fat were predictors of an HOMA-IR ≥ 3. The IG group had a reduced risk of an ALT level > 1.5 × ULN. An HOMA-IR ≥ 3.0 and HDL < 35 mg/dL were also risk factors for increased ALT. CONCLUSION: Soy supplementation decreased ALT levels and thus may improve liver inflammation in hepatitis C virus (HCV) patients; it also reduced hepatic steatosis in a subgroup of patients but did not change insulin resistance. It should be considered in the nutritional care of HCV patients.

IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population.

BACKGROUND: IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not. AIMS: To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry. METHODS: rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers. RESULTS: IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 × 10(-5) ). IL28B rs8099917 T/T was associated with SVR, and G/G and G/T were associated with nonresponse/relapse (NR/R) (P = 8.00 × 10(-3) ). Among HCV genotype 1 patients with C/C genotype, genomic ancestry did not interfere with therapy response. Among patients with rs12979860 T/T genotype, African genetic contribution was greater in the NR/R group (P = 1.51 × 10(-3) ), whereas Amerindian and European genetic ancestry contribution were higher in the SVR group (P = 3.77 × 10(-3) and P = 2.16 × 10(-2) respectively). Among HCV type 1 patients with rs8099917 T/T, African genetic contribution was significantly greater in the NR/R group (P = 5.0 × 10(-3) ); Amerindian and European ancestry genetic contribution were greater in the SVR group. CONCLUSION: IL28B rs12979860 and rs8099917 polymorphisms were predictors of therapy response in HCV genotypes 1, 2 and 3 subjects from an admixed population. Genomic ancestry did not interfere with response to therapy in patients with rs12979860 C/C, whereas it interfered in patients with C/T and T/T genotypes. Among HCV genotype 1 rs8099917 T/T patients, genomic ancestry interfered with response to therapy.

Lack of association of indoleamine 2,3-dioxygenase polymorphisms with interferon-alpha-related depression in hepatitis C.

BACKGROUND: Major depression is a frequent adverse effect of interferon-alpha (IFN-α) therapy. Although the indoleamine 2,3-dioxygenase (IDO) enzyme seems to be involved in the pathophysiology of IFN-α-induced depression, no pharmacogenetic study has investigated whether variation in the IDO gene modifies vulnerability to this adverse effect. METHODS: A cross-sectional study assessing 277 hepatitis C patients recruited in two specialized outpatient clinics of Brazil. They were interviewed with the Mini International Neuropsychiatric Interview (MINI) approximately 1 month after the end of IFN-α plus ribavirin therapy. Genomic DNA of individuals was extracted from venous blood. Three IDO single-nucleotide polymorphisms (SNPs) were genotyped (rs3824259; rs10089084 and rs35099072). RESULTS: MINI indicated that 21.3% of the sample met criteria for a major depressive episode during the course of IFN-α therapy. No association with the diagnosis of a major depressive episode during the course of IFN-α therapy was observed genotype or allele-wise (p>0.05). Current major depression and/or current anxiety disorder was significantly associated with IFN-α-related depression (p<0.005). However, gender, age, route of infection, result of the antiviral treatment, past history of substance use disorders, depression or any other psychiatric disorder showed no association with IFN-α-related depression (p>0.05). CONCLUSIONS: Our results suggest no influence of the variants in the IDO gene and the diagnosis of interferon-α-related depression in the Brazilian population. Interferon-α-related depression may impose persistent psychopathology on at least 15% of the depressed patients even 2 years after antiviral therapy termination. The cross-sectional design is a limitation of our study, predisposing memory bias. Prospective pharmacogenetic studies are warranted to continue investigation of the impact of IDO polymorphisms on the development of IFN-α-induced depression.

Is the interferon-α-triggered depressive episode a self-limited kind of depression? Four cases of persistent affective symptoms after antiviral treatment in HCV-infected individuals.

OBJECTIVES: To discuss relevant aspects in a series of cases in which interferon-α-triggered depressive symptoms persisted up to 4 years after therapy cessation in HCV-infected patients. METHODS: Two experienced psychiatrists (AGA and LCQ) identified these four cases in a systematic evaluation program of HCV patients in the Hepatology Unit of the Teaching Hospital at the Federal University of Bahia, Brazil. Lifetime psychiatric diagnoses were confirmed by the Mini International Neuropsychiatric Interview (MINI Plus), and a questionnaire was submitted in order to gather clinical and sociodemographic characteristics. RESULTS: In three out of the four cases identified, major depression diagnosis was reached after more than 12 months of interferon-α therapy interruption and, in one case, depression recurred 6 months after antiviral treatment cessation in a patient on antidepressants. The only case that referred a past history of psychiatric diagnosis reported no offer of mental health care despite the presence of a major depressive episode with psychotic features and suicidal behaviour during the cytokine usage. CONCLUSIONS: Interferon-α-triggered depression may remain undiagnosed even in tertiary university hospitals, may persist years after the antiviral therapy cessation, and may recur even in patients on adequate antidepressant treatment.

CD81 binding regions of hepatitis C virus remain conserved after liver transplantation.

CD81 is a surface-associated protein expressed in the membranes of mammalian cells. It has been suggested that CD81 interacts with hepatitis C virus E2 protein, and thus might facilitate the entry of HCV into hepatocytes. The envelope-binding site appears to involve amino acids (aa) 480-493 and 544-551 within the E2 glycoprotein. Little is known about the quasispecies genetic diversity of these two regions. We studied four patients who underwent transplantation for HCV-related cirrhosis and who developed recurrent hepatitis C. We evaluated HCV quasispecies diversity in serum samples obtained at the time of transplantation and at several time points thereafter. Quasispecies diversity was assessed by cloning and sequencing of viral isolates, with computer analysis of evolution models. The genetic distance in the region that spans aa 480 to 493 was 0.019 +/- 0.004 before the transplant, and 0.039 +/- 0.014 after the transplant (p=0.324). In the aa 544 to 551 region, the pre-transplant genetic distance was 0.012 +/- 0.008 and the post-transplant distance, 0.010 +/- 0.007 (p=0.890). There was also no significant difference between the number of nonsynonymous substitutions per nonsynonymous site before and after transplantation. In conclusion, the HCV genetic sequences of putative CD81 binding regions aa 480-493 and aa 544-551 did not diversify significantly after liver transplantation. This may favor HCV re-infection of the allograft after liver transplantation.

CD81 binding regions of hepatitis C virus remain conserved after liver transplantation

CD81 is a surface-associated protein expressed in the membranes of mammalian cells. It has been suggested that CD81 interacts with hepatitis C virus E2 protein, and thus might facilitate the entry of HCV into hepatocytes. The envelope-binding site appears to involve amino acids (aa) 480-493 and 544-551 within the E2 glycoprotein. Little is known about the quasispecies genetic diversity of these two regions. We studied four patients who underwent transplantation for HCV-related cirrhosis and who developed recurrent hepatitis C. We evaluated HCV quasispecies diversity in serum samples obtained at the time of transplantation and at several time points thereafter. Quasispecies diversity was assessed by cloning and sequencing of viral isolates, with computer analysis of evolution models. The genetic distance in the region that spans aa 480 to 493 was 0.019 ñ 0.004 before the transplant, and 0.039 ñ 0.014 after the transplant (p=0.324). In the aa 544 to 551 region, the pre-transplant genetic distance was 0.012 ñ 0.008 and the post-transplant distance, 0.010 ñ 0.007 (p=0.890). There was also no significant difference between the number of nonsynonymous substitutions per nonsynonymous site before and after transplantation. In conclusion, the HCV genetic sequences of putative CD81 binding regions aa 480-493 and aa 544-551 did not diversify significantly after liver transplantation. This may favor HCV re-infection of the allograft after liver transplantation.

Infection with hepatitis C virus genotype 4 in the United States.

BACKGROUND: Hepatitis C virus genotype differences seem to be of considerable clinical significance because they affect responses to antiviral therapy. HCV genotype 4 is rare in the United States and there are few published data regarding response to therapy in patients with HCV genotype 4 infection. OBJECTIVES: To assess epidemiologic factors associated with HCV genotype 4 infection in United States and to describe the response rate to therapy with the combination of alpha interferon and ribavirin. METHODS: All hepatologists in our Division were asked for information about patients they had treated with HCV genotype 4. In addition, we searched the computer database from Saint Louis University Hospital in the last 40 months (1999 to 2002). Twenty HCV genotype 4 patients were identified. A retrospective chart review was performed to collect information about their demographics, risk factors for acquisition of infection, baseline laboratory studies and response to antiviral therapy. RESULTS: A risk factor for exposure to HCV was noted in 14 cases (70%); 12 patients had a history of illicit drug use, whereas a history of blood transfusion was detected in three cases; 1 patient had both risk factors. Only 4 of 20 individuals had fibrosis stage 3 or 4 on liver biopsy. Seventeen patients were treated, 14 of whom completed therapy; 10 patients were sustained responders. CONCLUSIONS: As with other HCV genotypes, most patients with HCV genotype 4 in the United States acquire the infection through intravenous drug use, liver disease is often mild to moderate in severity and 59% of our patients had a sustained virologic response after combination therapy with interferon and ribavirin.

Seroprevalence and risk factors associated with Helicobacter pylori infection in blood donors in Salvador, Northeast-Brazil.

Helicobacter pylori plays an important role in the etiology of peptic ulcer disease. Its prevalence appears to be higher in developing countries. We evaluated the seroprevalence of H. pylori and risk factors associated with infection in voluntary blood donors who attended the main blood center of the city of Salvador, Brazil. The subjects responded to an epidemiological questionnaire, with information about sex, age, race, lifestyle, social-economic level indicators, and residence and hygiene conditions. Anti-H. pylori antibody was determined by ELISA (Cobas Core, Roche). Three hundred and seven subjects were included in the study. Anti-H. pylori antibody results were indeterminate in 33 individuals (10.8%), who were excluded from analysis. Among the remaining 274 subjects, 187 (68.2%) were anti-H. pylori positive. Based on multivariate logistic regression analysis three variables were found to be significantly associated with a higher prevalence of H. pylori infection: absence of plumbing in the residence during childhood, a history of rainwater invading the dwelling during childhood, and low ingestion of milk.

Seroprevalence and risk factors associated with Helicobacter pylori infection in blood donors in Salvador, Northeast-Brazil

Helicobacter pylori plays an important role in the etiology of peptic ulcer disease. Its prevalence appears to be higher in developing countries. We evaluated the seroprevalence of H. pylori and risk factors associated with infection in voluntary blood donors who attended the main blood center of the city of Salvador, Brazil. The subjects responded to an epidemiological questionnaire, with information about sex, age, race, lifestyle, social-economic level indicators, and residence and hygiene conditions. Anti-H. pylori antibody was determined by ELISA (Cobas Core, Roche). Three hundred and seven subjects were included in the study. Anti-H. pylori antibody results were indeterminate in 33 individuals (10.8 percent), who were excluded from analysis. Among the remaining 274 subjects, 187 (68.2 percent) were anti-H. pylori positive. Based on multivariate logistic regression analysis three variables were found to be significantly associated with a higher prevalence of H. pylori infection: absence of plumbing in the residence during childhood, a history of rainwater invading the dwelling during childhood, and low ingestion of milk.

Hepatitis C-related hepatocellular carcinoma in the United States: influence of ethnic status.

OBJECTIVES: The incidence of hepatocellular carcinoma (HCC) seems to be rising in the United States (US), and considerable variability in the incidence and etiology of HCC has been noted among different racial and ethnic groups in this country. The aim of this study was to evaluate the influence of racial and ethnic status in the viral etiology of HCC in the US. METHODS: Retrospective surveys were conducted at liver transplantation centers in the US. Respondents were asked to review the charts of all patients with HCC seen at their institution for the 2-yr period between July, 1997, and June, 1999, and provide information about the racial and ethnic distribution of cases and their serological status with regard to hepatitis B and C markers. RESULTS: Complete information was available on 691 patients who formed the basis of this study, comprising 59% whites, 14% blacks, 16% Asians, and 11% other racial groups. Of the patients, 107 patients (15.4%) were positive for hepatitis B surface antigen (HBsAg), 322 had antibodies to hepatitis C virus (anti-HCV) (46.5%), 33 (4.7%) had both HBsAg and anti-HCV), and 229 (33.1%) had neither marker present. Clear differences were seen among racial groups. Anti-HCV positivity was the most frequent risk factor in both blacks and whites, whereas HBsAg positivity was the most frequent etiological factor in Asians with HCC. CONCLUSIONS: HCV infection seems to be the major risk factor for HCC in the US, particularly among individuals of white and black ethnicity, whereas hepatitis B remains the main risk factor among patients of Asian ethnicity. These preliminary findings indicate the need for a more detailed study of ethnic variability in the pathogenesis of HCC.

Prevalence of TTV in blood donors and patients with acute viral hepatitis and genotyping by phylogenetic analysis

O objetivo desse estudo foi avaliar a prevalência da infecção pelo TTV em pacientes com hepatite aguda A e B e genotipar os isolados do TTV através de análise filogenética. Foram avaliados soros de 82 pacientes que apresentaram hepatite aguda A(N = 40) e B (N = 42)e 71 doadores de sangue. O TTV foi determinado atraváes nested-PCR, e a análise filogenetica foi realizada utilizando o metódo neighbor-Joining". O TTV foi detectado em 23por cento dos pacientes com hepatite aguda e em 31 por cento dos doadores. Os níveis médiosde aminotransferases foram semelhantes em pacientes TTV positivos e pacientes TTV negativos. Uma árvore filogenética foi construída e mostrou isolados do TTV dos genótipos1,2,3 e 4. Em conclusão, a infecção pelo TTV foi mais frequente entre doadores de sangue do que em pacientes com hepatite aguda A ou B, em Salvdor-Bahia. O TTV não aumentou a gravidade da atividade necroinflamatória dos pacientes com hepatite aguda A ou B. Através de análise filogenétiaca foram encontrados isolados do TTV dos genótipos 1,2,3 e 4 na população estudada

Liver transplantation with hepatitis C virus-infected graft: interaction between donor and recipient viral strains.

Superinfection of different viral strains within a single host provides an opportunity for studying host-virus and virus-virus interactions, including viral interference and genetic recombination, which cannot be studied in infections with single viral strains. Hepatitis C virus (HCV) is a positive single-strand RNA virus that establishes persistent infection in as many as 85% of infected individuals. However, there are few reports regarding coinfection or superinfection of HCV. Because of the lack of tissue culture systems and small animal models supporting efficient HCV replication, we explored these issues in the setting of liver transplantation where both recipient and donor were infected with different HCV strains and therefore represent a distinct model for HCV superinfection. Serial serum samples collected at multiple time points were obtained from 6 HCV-positive liver donor/recipient pairs from the National Institute of Diabetes and Digestive and Kidney Diseases liver transplantation database. At each time point, HCV genotype was determined by both restriction fragment length polymorphism analysis and phylogenetic analysis. Furthermore, we selectively sequenced 3 full-length HCV isolates at the earliest time points after liver transplantation, including both 5' and 3' ends. Detailed genetic analyses showed that only one strain of HCV could be identified at each time point in all 6 cases. Recipient HCV strains took over in 3 cases, whereas donor HCV strains dominated after liver transplantation in the remaining 3 cases. In conclusion, in all 6 cases studied, there was no genetic recombination detected among HCV quasispecies or between donor and recipient HCV strains.

Evolution of hepatitis C viral quasispecies after liver transplantation.

BACKGROUND & AIMS: To determine whether HCV quasispecies diversity correlated positively with liver disease progression after orthotopic liver transplantation (OLT). METHODS: We studied 11 patients undergoing OLT for HCV-related cirrhosis with recurrent hepatitis C in 2 groups according to the stage of hepatic fibrosis on follow-up. The mild group had stage 1 or 2 fibrosis; the severe group, stage 3 or 4 fibrosis. HCV quasispecies diversity was assessed by cloning and sequencing in pretransplantation and posttransplantation serum samples. RESULTS: In the mild fibrosis group, intrasample hypervariable region 1 (HVR1) genetic distance and nonsynonymous substitutions increased after OLT, whereas in the severe fibrosis group, these parameters decreased in follow-up. In contrast, intrasample diversity progressed similarly in both groups in the adjacent sequences flanking HVR1. There was an inverse correlation between the stage of hepatic fibrosis and amino acid complexity after OLT. Among all patients, the estimated rate of amino acid change was greater initially and became more constant after 36 months. CONCLUSIONS: After OLT, a more complex HCV HVR1 quasispecies population was associated with mild disease recurrence. Among those patients with severe recurrent hepatitis C, HCV appeared to be under greater immune pressure. The greatest change in viral amino acid sequences occurred in the first 36 months after OLT.