Helena Allende

High rate of infectivity and liver disease in blood donors with antibodies to hepatitis C virus.

OBJECTIVE To determine the epidemiologic, clinical, serologic, and histologic importance of antibodies to hepatitis C virus (anti-HCV) in blood donors. DESIGN Cross-sectional identification and prospective evaluation of seropositive donors; retrospective assessment of infectivity; and nested case-control study for risk factors. SETTING Liver unit of a referral-based university hospital. SUBJECTS Of 30,231 consecutive donors, 368 (1.2%) were found to be anti-HCV-reactive by enzyme-linked immunosorbent assay (ELISA). Two hundred and fifty-four of these 368 donors were evaluated for risk factors by comparison with 284 age- and sex-matched controls. Eighty-six spouses of seropositive donors were also evaluated. MEASUREMENTS AND MAIN RESULTS Twenty-four percent of the seropositive donors had a history of percutaneous exposure to blood. This rate increased to 45% when only those donors confirmed to be anti-HCV positive by a second-generation recombinant immunoblot assay (RIBA-2) were considered. A family history of liver disease (odds ratio, 2.8; 95% Cl, 1.6 to 4.8), previous blood transfusion (odds ratio, 6.1; 95% Cl, 3 to 12.5), and a history of tattooing or intravenous drug abuse (odds ratio, 8.4; 95% Cl, 2.3 to 31) were associated with anti-HCV seropositivity. An elevated alanine aminotransferase (ALT) level was found in 58% of the seropositive donors. Of the 150 donors tested, 104 (69%; Cl, 62% to 77%) were confirmed by RIBA-2 to be anti-HCV positive. Of the 105 donors who had a biopsy, 16% had normal histologic findings, 11% had minimal changes, 21% had chronic persistent hepatitis, 45% had chronic active hepatitis, and 7% had active cirrhosis. All 77 donors with RIBA-2-confirmed seropositivity had histologic abnormalities. Of 43 donors evaluated in an infectivity study, 82% were implicated in previous HCV transmission. Only 2.3% of the spouses were anti-HCV positive. The ELISA, RIBA-2, and ALT results correlated with infectivity and abnormal histologic findings. CONCLUSIONS In our geographic area, almost 70% of donors who are anti-HCV positive by ELISA are confirmed to be positive by RIBA-2; most of these donors appear to be chronic carriers of HCV and have substantial liver disease.

Liver Transplantation for Malignant Diseases: Selection andPattern of Recurrence

Liver transplantation (LT) for malignant tumors should be accepted if, with adequate case selection, long-term results are similar to those in patients transplanted for benign diseases. The aim of the present study was to reexamine selection criteria for LT in malignant diseases with particular emphasis on hepatocellular carcinoma (HCC) in cirrhosis. One hundred-three of 369 patients transplanted in our unit had HCC in cirrhosis (28%), 15 of which were incidental tumors, and 234 patients underwent LT for non-cholestatic cirrhosis. Pretransplant arterial chemoembolization(TACE) was performed in 36 cases (41%) of known HCC. Only early,well-delimited tumors in advanced cirrhosis with no extrahepatic disease were accepted for LT. Hepatocellular carcinoma characteristics included mean tumor size (3.1 cm), multiple (59%), bilobular involvement (31%), and vascular invasion (9.2%). Postoperative mortality was 4%. Median follow-up was 67.5 months. Tumor recurrence rate was 14.5%, 33% (5/15) in incidental tumors and 11.4% (10/88) in known HCC and by tumor stage (pTNM): 7.7% (1/13) in stage I, 16.7%(5/30) in stage II, 15% (3/20) in stage III, and 17% (6/35) in stage IV. Mean time for recurrence was 20.6 months. Tumoral vascular invasion, tumor differentiation, and satellite tumors were significant factors for tumor recurrence in univariate analysis, whereas tumor vascular invasion was the only significant factor for tumor recurrence in multivariate analysis. Actuarial survival rates at 1, 3, and 5 years were 81%, 66%, 58%, respectively, in patients with HCC and were similar to those of cirrhotic patients 76%, 67%, 63%, respectively. In conclusion, patients with early HCC in cirrhosis are good candidates for LT; results are similar when compared with those of cirrhotic patients without tumor. Liver transplantation for other malignancies is admitted only in fibrolamellar hepatoma, hepatoblastoma, epithelioid hemangioendothelioma without extrahepatic disease, and in metastases from carcinoid tumors.

High-Resolution Hepatitis C Virus Subtyping Using NS5B Deep Sequencing and Phylogeny, an Alternative to Current Methods

ABSTRACT Hepatitis C virus (HCV) is classified into seven major genotypes and 67 subtypes. Recent studies have shown that in HCV genotype 1-infected patients, response rates to regimens containing direct-acting antivirals (DAAs) are subtype dependent. Currently available genotyping methods have limited subtyping accuracy. We have evaluated the performance of a deep-sequencing-based HCV subtyping assay, developed for the 454/GS-Junior platform, in comparison with those of two commercial assays (Versant HCV genotype 2.0 and Abbott Real-time HCV Genotype II) and using direct NS5B sequencing as a gold standard (direct sequencing), in 114 clinical specimens previously tested by first-generation hybridization assay (82 genotype 1 and 32 with uninterpretable results). Phylogenetic analysis of deep-sequencing reads matched subtype 1 calling by population Sanger sequencing (69% 1b, 31% 1a) in 81 specimens and identified a mixed-subtype infection (1b/3a/1a) in one sample. Similarly, among the 32 previously indeterminate specimens, identical genotype and subtype results were obtained by direct and deep sequencing in all but four samples with dual infection. In contrast, both Versant HCV Genotype 2.0 and Abbott Real-time HCV Genotype II failed subtype 1 calling in 13 (16%) samples each and were unable to identify the HCV genotype and/or subtype in more than half of the non-genotype 1 samples. We concluded that deep sequencing is more efficient for HCV subtyping than currently available methods and allows qualitative identification of mixed infections and may be more helpful with respect to informing treatment strategies with new DAA-containing regimens across all HCV subtypes.

Outcome and hepatic hemodynamics in liver transplant patients with portal vein arterialization.

Few cases of successful portal vein arterialization in orthotopic and auxiliary liver transplantation have been reported.

Surgically induced weight loss by gastric bypass improves non alcoholic fatty liver disease in morbid obese patients

AIM To evaluate the effects of surgical weight loss (Roux-en-Y gastric bypass with a modified Fobi-Capella technique) on non alcoholic fatty liver disease in obese patients. METHODS A group of 26 morbidly obese patients aged 45 ± 2 years and with a body mass index > 40 kg/m(2) who underwent open surgical weight loss operations had paired liver biopsies, the first at surgery and the second after 16 ± 3 mo of weight loss. Biopsies were evaluated and compared in a blinded fashion. The presence of metabolic syndrome, anthropometric and biochemical variables were also assessed at baseline and at the time of the second biopsy. RESULTS Percentage of excess weight loss was 72.1% ± 6.6%. There was a reduction in prevalence of metabolic syndrome from 57.7% (15 patients) to 7.7% (2 patients) (P < 0.001). Any significance difference was observed in aspartate aminotransferase or alanine aminotransferase between pre and postsurgery. There were improvements in steatosis (P < 0.001), lobular (P < 0.001) and portal (P < 0.05) inflammation and fibrosis (P < 0.001) at the second biopsy. There were 25 (96.1%) patients with non alcoholic steatohepatitis (NASH) in their index biopsy and only four (15.3%) of the repeat biopsies fulfilled the criteria for NASH. The persistence of fibrosis (F > 1) was present in five patients at second biopsy. Steatosis and fibrosis at surgery were predictors of significant fibrosis postsurgery. CONCLUSION Restrictive mildly malabsorptive surgery provides significant weight loss, resolution of metabolic syndrome and associated abnormal liver histological features in most obese patients.

Hepatitis B virus genotypes and G1896A precore mutation in 486 Spanish patients with acute and chronic HBV infection.

Summary.  This study aims to determine the prevalence of hepatitis B virus (HBV) genotypes (A–F) and their association with the G1896A precore mutation in 486 patients positive for HBV surface antigen. Genotypes were determined by RFLP and precore mutation by real‐time PCR. Genotypes D (48.1%) and A (39.5%) were the most common, followed by F (4.1%) and B, C and E (<1%). The A to D ratio (A:D) was 1.4 in HBeAg+ chronic hepatitis B (CHB), 0.6 in HBeAg− CHB and 1.4 in HBeAg− inactive carriers. Distribution of these genotypes was different between HBeAg+ CHB and HBeAg− CHB (P = 0.02), and between HBeAg− CHB and HBeAg− inactive carriers (P = 0.009). Genotype A was the most prevalent in HBeAg+ CHB with elevated alanine aminotransferase (ALT) (68.6%) and genotype D in HBeAg+ CHB with fluctuating ALT (60.7%). There was a difference in genotype prevalence between chronic and acute infection (P = 0.03). The precore mutant correlated with high levels of HBV‐DNA in genotype d HBeAg− CHB. Genotype D is not as highly prevalent in Spanish patients as would be expected in a Mediterranean area. The unequal prevalence of genotypes between acute and chronic infection suggests that genotype A is associated with a higher tendency to cause chronic infection.

Early detection of nonresponse to interferon plus ribavirin combination treatment of chronic hepatitis C

We have investigated the value of early hepatitis C virus (HCV) RNA decline (ΔHCV RNA) to predict response to combination therapy in 66 chronic hepatitis C patients treated with IFN‐α2b (3 MU thrice weekly) and ribavirin (800 mg daily) for 12 months [25 sustained responders (SR) and 41 nonresponders or relapsers (NR)]. Serum HCV RNA was retrospectively measured in samples obtained at baseline and 4, 8 and 12 weeks after treatment onset, using a commercially available quantitative RT‐PCR assay. At 4 weeks, serum HCV RNA had decreased a mean of 2.6 ± 0.8 logs among SR as compared with only 0.5 ± 0.8 logs in NR (P < 0.001), and was already undetectable (< 600 IU/mL) in 12 (48%) of the SR but in none of the NR. At 8 weeks, HCV RNA was undetectable in 21 SR and in 2 NR and mean ΔHCV RNA were 4.2 ± 1.3 and 0.8 ± 1.0 logs, respectively (P < 0.001). At week 12 all SR had undetectable HCV RNA as compared with only five NR (P < 0.001). Stepwise logistic regression analysis identified ΔHCV RNA at 12 weeks as the strongest predictor of sustained response. Receiver operating characteristic (ROC) curves of ΔHCV RNA for sustained response prediction identified sensitivity peaks with 100% negative predictive value corresponding to ΔHCV RNA > 1 log at 4 weeks, > 2 logs at 8 weeks and > 3 logs at 12 weeks. Our results show that early changes in the HCV RNA level may reliably identify patients having no chance of a sustained virological response during the first 3 months of combination therapy, thus providing an excellent tool for optimizing antiviral treatment of chronic hepatitis C.

Chronic delta hepatitis : Is the prognosis worse when associated with hepatitis C virus and human immunodeficiency virus infections ?

Eighty‐six patients were followed for 6.5 years to study the epidemiological, virological, and histological course of chronic delta hepatitis and the relationship of this disease with HIV and HCV infection.

Transjugular intrahepatic portosystemic shunt for the treatment of sinusoidal obstruction syndrome in a liver transplant recipient and review of the literature

Sinusoidal obstruction syndrome (SOS) is a rare, life‐threatening clinical syndrome resulting from sinusoidal congestion, and it is characterized by hepatomegaly, ascites, weight gain, and jaundice. The frequency of this condition after liver transplantation (LT) is low, but when SOS is severe and refractory to medical therapy, the ultimate solution is retransplantation. We describe a patient with SOS after LT who was successfully treated by the placement of a transjugular intrahepatic portosystemic shunt (TIPS). Although information on this approach is scarce because of the low incidence of SOS in LT patients, we review the available literature on treating this condition with a TIPS. On the basis of the reported information and our patients outcome, we suggest that prompt TIPS placement can be considered for SOS when medical treatment fails. Nonetheless, a formal assessment and prospective studies are needed to confidently indicate TIPS placement in this situation. Liver Transpl 18:201–205, 2012.

Anti-HD IgM as a marker of chronic delta infection.

The value of anti-HD IgM as a marker of chronic delta infection was evaluated by correlating its presence in serum with that of HD-Ag in liver cells and with the degree of inflammatory activity. Thirty-six patients with HBsAg-positive chronic hepatitis and anti-HD at high titers were studied. Overall, the liver cells of 26 patients contained HD-Ag and 27 were positive for IgM anti-HD. The correlation between both markers was excellent: 25 cases were positive for both serum anti-HD IgM and intrahepatic HD-Ag and 8 were negative for both markers. There was only 1 HD-Ag-positive patient, who was anti-HD IgM-negative. Two patients were anti-HD IgM-positive and HD-Ag-negative. Histological damage was more severe in anti-HD IgM-positive cases than in those negative for this marker (Knodells index 13.5 vs 11.9, P less than 0.01). We conclude that anti-HD IgM is a good marker of chronic active delta infection.