This study aimed to investigate the ratios of precore stop mutant (codon 28; TGG to TAG) to total viremia in 53 HBeAg-positive patients with chronic hepatitis B by amplification-created restriction site assays along the course of HBeAg-to-anti-HBe seroconversion. At baseline, 11% had exclusive wild-type hepatitis B virus (HBV), 15% had exclusively precore mutant, and 74% had mixed viral strains. Precore mutant ratios correlated little with age, sex, or HBV DNA levels (all P > 0.1), but correlated modestly with alanine aminotransferase (ALT) levels (P ‫؍‬ 0.05). The intervals from presentation to anti-HBe seroconversion correlated significantly with ALT and precore mutant ratios in univariate analysis but with only precore mutant ratios in multivariate analysis (P ‫؍‬ 0.003). Precore mutant ratios at baseline were significantly higher (P < 0.001) in six patients with persistent high viremia and ALT elevation after anti-HBe seroconversion (group 1) than in 47 with remission (group 2). All group 1 patients had exclusive precore mutant after anti-HBe seroconversion, as did only 14 (30%) of the group 2 patients (P ‫؍‬ 0.003). Among group 2 patients, precore mutant ratios at baseline or after anti-HBe seroconversion showed no significant difference between 34 patients with sustained remission and 13 with relapse. Cirrhosis developed in 50% (5 of 10) of patients with precore mutant ratios >50% at baseline but only in 12% (5 of 43) of those with precore mutant ratios of <50% at baseline (P < 0.05). In conclusion, precore mutant of variable ratios was frequently detected in HBeAg-positive patients with chronic hepatitis B. Precore mutant ratios tended to correlate with ALT levels and anti-HBe seroconversion, but high precore mutant ratios were associated with persistent hepatitis after anti-HBe seroconversion and increased risk of cirrhosis.In the natural history of chronic hepatitis B virus (HBV) infection, seroconversion from HBVe antigen (HBeAg) to its antibody (anti-HBe) is usually accompanied by a decrease in HBV replication and remission of liver disease (18,19,31). However, in areas with high or intermediate HBV endemicity, viral replication and liver damage persist in about 10% of anti-HBe-positive carriers (2,10,15,23). HBV mutants unable to secrete HBeAg because of translational defects in the precore region have been isolated in these patients (1,4,7,14,36). In the great majority of them (Ͼ 90%), an unusual HBV strain was characterized with a G-to-A mutation at nucleotide 1896, which generates a stop codon in the precore sequence (28,32,36). Notably, many recent studies have shown that precore mutant also can be detected in HBeAg-positive patients with chronic HBV infection (5,17,25,27,29). The prevalence of precore mutant and its relative ratio to total HBV in HBeAgpositive patients with chronic HBV infection has varied considerably in the published reports: precore mutant is detected in 0 to 80% of HBeAg-positive patients, and the majority have had coexisting predominant wild-type HBV, but a few even have ha...

Although most of the recipients with split liver transplantation had high MELD scores, the results were comparable with those of living donor liver transplantation. Split liver transplantation for 2 adults is still feasible in the MELD era.

Virus-specific cytotoxic T lymphocytes (CTLs) have been suggested to be responsible for the liver injuries in patients with hepatitis C virus (HCV) infection. However, there has been no report of direct evidence to substantiate this hypothesis. In this study, we performed in vitro autologous hepatocytotoxicity assay in 45 patients to examine a possible role of CTLs to HCV-infected live cells. The data were correlated with histology activity index of liver biopsy specimens. Lymphocyte subsets and hepatocyte expression of human major histocompatibility complex antigens class I and class II (HLA-I and HLA-II) were also evaluated. The immunohistochemical study showed more prominent HLA-I expression than HLA-II on hepatocytes (mean score +/- SEM:2.34 +/- 0.11 vs. 0.42 +/- 0.08; P < .01). The lymphocyte subset analysis showed that CD8+ T cells were dominant in the lobular areas showing spotty necrosis, whereas CD4+ T cells were prominent in the portal and periportal areas (P < .01). Most patients had a significant T cell-mediated cytotoxicity to hepatocytes as compared with non-T cells (percentage cytotoxicity +/- SEM:46.4 +/- 2.3 vs. 13.8 +/- 2.7; P < .001). T cell-mediated hepatocytotoxicity had a linear correlation with HAI (P < .05). The T cell-mediated cytotoxicity could be blocked by anti-CD8 (43.7% vs. 18.5%, P < .05) but not by anti-CD4 or anti-HLA-II monoclonal antibodies. These findings strongly suggest that HLA-I-restricted, CD8+ T cell-mediated hepatocytotoxicity is an important pathogenetic mechanism in patients with chronic HCV infection.

BackgroundAlthough the outcomes of caustic ingestion differ between children and adults, it is unclear whether such outcomes differ among adults as a function of their age. This retrospective study was performed to ascertain whether the clinical outcomes of caustic ingestion differ significantly between elderly and non-elderly adults.MethodsMedical records of patients hospitalized for caustic ingestion between June 1999 and July 2009 were reviewed retrospectively. Three hundred eighty nine patients between the ages of 17 and 107 years were divided into two groups: non-elderly (< 65 years) and elderly (≥ 65 years). Mucosal damage was graded using esophagogastroduodenoscopy (EGD). Parameters examined in this study included gender, intent of ingestion, substance ingested, systemic and gastrointestinal complications, psychological and systemic comorbidities, severity of mucosal injury, and time to expiration.ResultsThe incidence of psychological comorbidities was higher for the non-elderly group. By contrast, the incidence of systemic comorbidities, the grade of severity of mucosal damage, and the incidence of systemic complications were higher for the elderly group. The percentages of ICU admissions and deaths in the ICU were higher and the cumulative survival rate was lower for the elderly group. Elderly subjects, those with systemic complications had the greatest mortality risk due to caustic ingestion.ConclusionsCaustic ingestion by subjects ≥65 years of age is associated with poorer clinical outcomes as compared to subjects < 65 years of age; elderly subjects with systemic complications have the poorest clinical outcomes. The severity of gastrointestinal tract injury appears to have no impact on the survival of elderly subjects.

The objective of this study was to evaluate the results of adult ABO-incompatible living donor liver transplantation (LDLT).ABO-incompatible LDLT is an aggressive treatment that crosses the blood-typing barrier for saving lives from liver diseases. Although graft and patient survival have been improved recently by various treatments, the results of adult ABO-incompatible LDLT require further evaluation.Two regimens were designed based on isoagglutinin IgG and IgM titers and the time course of immunological reactions at this institute. When isoagglutinin IgG and IgM titers were ≤64, liver transplantation was directly performed and rituximab (375 mg/m2) was administrated on postoperative day 1 (regimen I). When isoagglutinin titers were >64, rituximab (375 mg/m2) was administered preoperatively with or without plasmapheresis and boosted on postoperative day 1 (regimen II). Immunosuppression was achieved by administration of mycophenolate mofetil, tacrolimus, and steroids.Forty-six adult ABO-incompatible and 340 ABO-compatible LDLTs were performed from 2006 to 2013. The Model for End-Stage Liver Disease scores for ABO-incompatible recipients ranged from 7 to 40, with a median of 14. The graft-to-recipient weight ratio ranged from 0.61% to 1.61% with a median of 0.91%. The 1-, 3-, and 5-year survival rates were 81.7%, 75.7%, and 71.0%, respectively, for ABO-incompatible LDLT recipients, compared to 81.0%, 75.2%, and 71.5% for ABO-C recipients (P = 0.912). The biliary complication rate was higher in ABO-incompatible LDLT recipients than in the ABO-compatible recipients (50.0% vs 29.7%, P = 0.009).In the rituximab era, the blood type barrier can be crossed to achieve adult ABO-incompatible LDLT with survival rates comparable to those of ABO-compatible LDLT, but with more biliary complications.

No abstract

TO THE EDITORS:The application of split liver transplantation in adults effectively increases the pool of donor organs available for liver transplantation. 1 The accurate estimation of the sizes of full right and left lobe grafts facilitates optimal matches with graft recipients and is a necessary requirement for successful split liver transplantation. We report an easy method for precisely estimating the sizes of full right and left lobe liver grafts to enable the selection of size-matched recipients.The basis of this method is that the relative sizes of the right and left hemilivers in the whole liver should correspond to the relative blood flow in the right and left portal veins. The blood flow in the right and left portal veins is proportional to the cross-sectional area of the respective vessels. The whole liver volume is calculated 2 with the following equation:where SLV is the standard liver volume (mL). The liver weight has been found to be almost equivalent to its volume. The right and left hemilivers as proportions of the whole liver are determined from the relative cross-sectional areas of the right and left portal veins. A potential donor, whose liver might be split to enable liver transplantation in 2 adults, undergoes bedside ultrasonography. The maximal diameter of the right portal vein (R; mm) and the maximal diameter of the left portal vein (L; mm) are measured. The size of each hemiliver graft is calculated by the determination of the ratio of the maximal cross-sectional area of the relevant portal vein branch to the total cross-sectional area of both portal vein branches and by the multiplication of this ratio by the SLV. Thus, the size of the right hemiliver is represented by, and the size of the left hemiliver is repre-]. In these calculations, the cross-sectional area of a branch of the portal vein is determined as p(D/2) 2 , where D is the maximal diameter (mm). For the application of this method, the livers of 4 donors, whose ages ranged from 19 to 36 years, were split into full right and left lobes. Their body mass indices ranged from 20 to 23 kg/m 2 . The liver grafts did not exhibit fatty changes. Each donor had sustained a head injury as a result of either a traffic accident or fighting. After brain death was declared, bedside abdominal ultrasonography was undertaken, and the diameters of the right and left portal veins were measured (Table 1). According to the cross-sectional areas of the 2 main branches of the portal vein, the right hemiliver constituted 56.6% to 61.0% of the whole liver, and the left hemiliver constituted 39.0% to 43.4% of the whole liver. The weights of the right and left hemilivers were estimated with the SLV (Table 1).All the livers were split and perfused with histidinetryptophan-ketoglutarate preservation solution in situ. After the right and left hemilivers were separated surgically, they were weighed. The weights of the whole livers and the right and left hemilivers are listed in Table 2. The whole liver weights, measured directly, corresponded very closely ...

Re-bleeding occurs in approximately one-fifth of patients after initial successful endoscopic hemostasis for delayed post-ES bleeding. Severity of initial bleeding and serum bilirubin level of greater than 10 mg/dL are predictors of re-bleeding.