Little information is available on acute liver failure (ALF) in the United States. We gathered demographic data retrospectively for a 2-year period from July 1994 to June 1996 on all cases of ALF from 13 hospitals (12 liver transplant centers). Data on the patients included age, hepatic coma grade on admission, presumed cause, transplantation, and outcome. Among 295 patients, 74 (25%) survived spontaneously, 121 (41%) underwent transplantation, and 99 (34%) died without undergoing transplantation. Ninety-two of 121 patients (76%) survived 1 year after transplantation. Acetaminophen overdose was the most frequent cause (60 patients; 20%), followed by cryptogenic/non A non B non C (NANBNC; 15%), idiosyncratic drug reactions (12%), hepatitis B (10%), and hepatitis A (7%). Spontaneous survival rates were highest for patients with acetaminophen overdose (57%) and hepatitis A (40%) and lowest for those with Wilson's disease (no survivors of 18 patients). The transplantation rate was highest for Wilson's disease (17 of 18 patients; 94%) and lowest for autoimmune hepatitis (29%) and acetaminophen overdose (12%). Age did not differ between survivors and nonsurvivors, perhaps reflecting a selection bias for patients transferred to liver transplant centers. Coma grade on admission was not a significant determinant of outcome, but showed a trend toward affecting both survival and transplantation rate. These findings on retrospectively studied patients from the United States differ from those previously gathered in the United Kingdom and France, highlighting the need for further study of trends in each country.

deaths due to NHL in the United States. 1 The overall incidence rate of NHL is increasing worldwide, especially in developed countries, 2-4 whereas the rate in the United States has been relatively stable during 1995 to 2003. 5 NHL disproportionately affects males and is more common in white non-Hispanics than in other racial or ethnic groups. 5 For the period of 1995 to 2002, the median age of NHL diagnosis in the United States was 67 years. 5 Immune suppression and pesticide/insecticide exposure are thought to be related to NHL development, and there is strong evidence that infections with human T-cell leukemia virus, Epstein-Barr virus, helicobacter pylori, and hepatitis C virus (HCV) are involved in the etiology of NHL. 2 Infection with hepatitis B virus (HBV) 6,7 is a major global public health problem with 50 million people infected per year 8 and more than 350 million people chronically infected worldwide. 9 In the United States, chronic HBV infection is more common in Asians than in other racial-ethnic groups. Among the common sequelae of chronic HBV infection are cirrhosis of the liver 10 and hepatocellular carcinoma (HCC). 11 Given the relationship between chronic HCV infection and NHL, [12][13][14][15][16] an association between HBV infection and NHL is quite plausible. HCV infection is thought to promote the development of NHL by inducing chronic lymphoprolifAbbreviations: HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HBsAg, hepatitis B surface antigen; HFHS, Henry Ford Health System; HIV, human immunodeficiency virus; KPMCP, Kaiser Permanente Medical Care Program; NHL, non-Hodgkins lymphoma; SEER, Surveillance Epidemiology and End Results. From

The hypothesis was tested that human donor livers with higher ATP content and energy charge achieve better results after hepatic transplantation. Biopsies were obtained from 25 donor livers immediately prior to implantation and analyzed for adenine nucleotides using high-performance liquid chromatography. The results were correlated with organ histology, transplant function and outcome. Significantly higher concentrations of ATP (4.22 +/- 2.87 vs. 0.71 +/- 0.69 nmoles per mg protein, p less than 0.01), ADP (8.75 +/- 2.96 vs. 4.49 +/- 1.95 nmoles per mg protein, p less than 0.01) and energy charge (0.43 +/- 0.15 vs. 0.21 +/- 0.04, p less than 0.02) were found in successful (n = 20) relative to failed (n = 5) livers. No significant differences were found in AMP, xanthine or hypoxanthine for the two groups, although the average values were higher in failed livers. Fifteen recipients with liver ATP concentration above 2 nmoles per mg protein and energy charge above 0.3 recovered well. Five other successful patients with lower ATP concentration (0.70 +/- 0.39 nmoles per mg protein) and energy charge (0.20 +/- 0.03) had postoperative courses complicated by infection or prolonged hyperbilirubinemia. In five patients whose livers failed, all had low ATP content and energy charge. Of these, three received a replacement liver and two died shortly after the transplantation. The study demonstrates a direct correlation between high ATP content and good posttransplant outcome.

Background: Abemaciclib is a selective oral inhibitor of CDK4 and CDK6. Dosed on a continuous schedule, abemaciclib showed evidence of antitumor clinical activity in patients (pts) with metastatic BC in monotherapy or in combination with non-steroidal aromatase inhibitor (NSAI) or fulvestrant. NeoMONARCH (NCT02441946) is a Phase 2 trial in women with stage I-IIIB, HR+/HER2- BC evaluating neoadjuvant treatment with abemaciclib + anastrozole, ANZ. As previously reported, NeoMONARCH met its primary endpoint showing abemaciclib, alone or in combination with ANZ, significantly reduced Ki67 expression compared to ANZ alone after 2 weeks (wks) of treatment. Final results are presented here. Methods: 223 pts were randomized (1:1:1) and treated for 2 wks with abemaciclib (150 mg PO Q12H) + ANZ (1 mg PO QD), abemaciclib alone, or ANZ alone. Then, all pts were treated for 14 wks with the combination. Pts were treated with loperamide (2 mg PO Q12H) for 4 wks while receiving abemaciclib. Tumor biopsy was collected at baseline, Wk 2 and Wk 16. Blood samples were collected through Cycle 5 to measure abemaciclib and ANZ concentrations. Primary objective was Ki67 change from baseline to Wk 2. Secondary objectives evaluated after Wk 16 of treatment, were radiologic, pathological and clinical responses, safety, and pharmacokinetics (PK). Exploratory objectives included the mutational analysis of PIK3CA and ESR1 at baseline. Results: Table 1 shows subgroup analyses of percent change in Ki67 from baseline to Wk 2 by disease stage, baseline lymph node (LN) involvement, tumor grade, and tumor size in Ki67 evaluable (KE) population (baseline Ki67 ≥ 5%) comparing combination to ANZ alone. Data for abemaciclib arm will be shown at the meeting. 185 pts completed treatment. At the end of treatment, response rates were radiologic 46.4% (all pts), and caliper 53.6% (all pts), and pCR 3.7% (pts who completed BC surgery assessment). Ki67 end of treatment analysis in 138 pts will be presented. The most common adverse events, all pts, were diarrhea (61.4%; G3: 4.9%), constipation (43.5%; G3: 1.8%), and nausea (41.7%; G3: 2.2%). Treatment discontinuation due to AEs was low (7.6%). Results of PIK3CA and ESR1 mutational analysis, and PK will be presented. Subgroup analyses at Wk 2 of KE population CombinationANZSubgroup treatment comparaison Pts, nGM % ChangePts, nGM % ChangeGMR (95% CI)PKE population59-92.8656-62.780.19 (0.13, 0.28)<0.001Disease Stage      I/II51-92.5646-65.840.22 (0.14, 0.34)<0.001III7-95.288-54.910.10 (0.04, 0.27)<0.001Baseline LN Involvement      No29-93.1826-62.210.18 (0.11, 0.31)<0.001Yes29-92.7528-69.020.23 (0.13, 0.42)<0.001Tumor Grade      1 or 233-92.8837-69.610.23 (0.15, 0.36)<0.001316-92.7910-59.680.18 (0.05, 0.60)0.011Tumor Size      < 2 cm9-93.258-65.460.20 (0.08, 0.35)0.004≥ 2 cm and < 5 cm39-91.2229-62.160.23 (0.14, 0.40)<0.001≥ 5 cm11-94.2419-59.730.14 (0.07, 0.28)<0.001Abbreviations: GM, geometric mean; GMR, geometric mean ratio Conclusions: Abemaciclib + ANZ is an effective treatment with manageable toxicities in pts with HR+/HER2- early BC. Abemaciclib-driven change in Ki67 was not associated with disease stage, baseline LN involvement, tumor grade, or tumor size. Citation Format: Martin M, Hurvitz SA, Chan D, Fernandez-Abad M, Petru E, Rostorfer R, Guarneri V, Huang C-S, Press MF, Costigan TM, Caldwell CW, Wijayawardana S, Turner PK, Barriga S, Slamon DJ. Final results of NeoMONARCH: A phase 2 neoadjuvant study of abemaciclib in postmenopausal women with hormone receptor positive (HR+), HER2 negative breast cancer (BC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD5-01.

No abstract

Hepatic myelopathy (HM) is a rarely reported disorder characterized by progressive spastic paraparesis due to impaired corticospinal tract function in the setting of cirrhosis or portosystemic shunting. HM has not to date been recognized as a Model for End-Stage Liver Disease (MELD) exception for transplantation. Outcomes for a small number of patients from Europe and Asia who have undergone liver transplantation (LT) for HM suggest a potential neurological benefit, especially with earlier transplantation. We report the first use of MELD exception points for the condition of HM to enable early LT resulting in the reversal of marked spastic paraparesis. Our patient, whose myelopathy had markedly progressed without further hepatic decompensation, underwent LT 14 months after the diagnosis of HM with an adjusted MELD score of 30, which was granted as a United Network for Organ Sharing exception. After LT, there was significant neurological improvement as the patient progressed from wheelchair dependency to full ambulation. We reviewed the literature of other HM patients who had undergone LT. With our patient, there were in all 15 reported cases of LT in individuals with HM. LT can lead to a marked improvement in HM, particularly in the earlier clinical stages of the disorder. Early LT can be accomplished, as in our case, by the submission of an appeal for a MELD upgrade. Liver Transpl 16:818-826, 2010. V C 2010 AASLD.Received November 22, 2009; accepted March 16, 2010. Hepatic encephalopathy or portosystemic encephalopathy (PSE) is a well-established and common complication in patients with end-stage liver disease (ESLD), whereas hepatic myelopathy (HM) is a rare and possibly underrecognized neurological complication of cirrhosis. Findings of spastic paraparesis, hyperreflexia, and extensor plantar responses characterize HM.

No abstract

Goals To determine the efficacy and safety of combination therapy in patients with hepatitis C virus (HCV) and end-stage renal disease (ESRD). Background There is little data on the treatment of ESRD patients with pegylated interferon and ribavirin. We designed a pilot study to determine the initial and 12-week posttreatment viral response. Study A nonrandomized, prospective observational study of adjusted-dose combination therapy. Twenty patients were enrolled and began pegylated interferon at 135 μg/wk SC, and 4 weeks later ribavirin was started at 200 mg PO weekly, increasing gradually to 3 times a week for a total of 48 weeks. Results Twenty patients: M:F 18:2; mean age 52.4 years; genotype 1: 18, non-genotype 1: 2. Of the 20 patients, 5 withdrew before starting treatment. Of the 11 patients who reached 3 months, 6 had early virologic response, defined as at least a 2-log drop in their HCV count (54.5%). Of the 5 patients who were treated for 1-year, only 1 patient had a response 12 weeks after treatment. Side effects included 4 cases of anemia and 1 patient with headache. Conclusions The initial response rate in individuals taking 3 months of treatment in our study is comparable with studies in non-ESRD patients with no serious adverse side effects. However, the sustained posttreatment rate was low. This demonstrates that combination therapy is a safe therapeutic option in the ESRD population with HCV infection which needs further testing to determine if increasing the length of treatment and/or the dose of ribavirin will affect posttreatment rates.