Vitamin D deficiency, parathyroid hormone levels, and bone disease among patients with end-stage liver disease and normal serum creatinine awaiting liver transplantation.

UNLABELLED: Vitamin D deficiency is common among patients with end-stage liver disease (ESLD). The primary aim of our study was to assess the prevalence of vitamin D deficiency, secondary hyperparathyroidism, and bone disease in patients with ESLD awaiting LT. METHODS: We retrospectively studied 190 patients at our center. Serum total 25-hydroxyvitamin D (25-OH D), parathyroid hormone (PTH), calcium, and bone mineral analysis (BMA) were recorded. Standard World Health Organization (WHO) criteria were used to diagnose osteopenia/osteoporosis. Only patients with normal serum creatinine were analyzed. RESULTS: Thirty-two of 190 patients were excluded from the final analysis (missing serum total 25-OH D levels in three patients and elevated serum creatinine, 29 patients). 105 of 158 (66.4%) evaluable patients had 25-OH D levels <25 ng/mL. Patients included in the analysis (n = 158) were divided according to serum total 25-OH D levels: 0-10 ng/mL (n = 23), 11-20 ng/mL (n = 64), and >20 ng/mL (n = 71). There were no significant differences in mean serum PTH and corrected calcium levels among the three subgroups. Only three patients had elevated serum PTH. Patients with total 25-OH D ≤ 10 ng/mL had higher model for end-stage liver disease (MELD) scores vs. those with 25-OH D > 20 ng/mL (13.3 ± 3, range 8-21, vs. 11.9 ± 3.4, range 6-29, p = 0.004). Irrespective of vitamin D status, bone disease was present in 64.6% of patients. CONCLUSION: Low vitamin D levels and bone disease are common among patients with ESLD awaiting LT. Despite a high prevalence of low serum total 25-OH D, our cohort maintained normal corrected calcium levels and did not develop secondary hyperparathyroidism. We propose that free serum 25-OH D and vitamin D-binding protein may be necessary to accurately establish the diagnosis of vitamin D deficiency in the setting of ESLD. Additional studies are needed to further define mechanisms of bone disease in patients with ESLD.

In a 12-year study, sustainability of quality of life benefits after liver transplantation varies with pretransplantation diagnosis.

BACKGROUND & AIMS: As life-extending benefits of liver transplantation (LTX) are realized, the focus of improving outcomes after LTX transitioned from merely extending quantity of life to improving quality of life (QOL). Numerous cross-sectional studies have shown that QOL improves within 1 year after LTX; however, the long-term prospective pattern of QOL is not known. We assessed the sustainability of early QOL benefits after LTX. METHODS: Patients who underwent LTX (n = 381) were followed for 12 years. We collected clinical information, survival data, and data on 5 QOL domains: physical distress (PHY), psychological distress (PSY), social/role function (SRF), personal function (PF), and general health perception (GHP). Mixed model analysis was used to determine whether initial gains in QOL were sustained long term. Outcomes were analyzed according to the primary liver diagnosis. RESULTS: After 12 years, liver recipients had marked declines in PHY (P < .001), SRF (P = .006), and GHP (P < .001) scores, whereas improvements in PSY (P = .09) and PF (P = .09) were sustained. Women had worse outcomes in PHY and PF than men. Patients with autoimmune disease had decreased QOL PHY, SRF, PF, and GHP domains. Patients with alcoholic liver disease and hepatitis C initially had lower QOL in all domains, with the greatest decreases in PHY (P < .001) and PF (P = .03). CONCLUSIONS: Although QOL improves within 1 year after patients receive liver transplants, not all groups of patients achieve or sustain the same level of QOL for 12 years. QOL decreases with time in most areas. Efforts should be made to improve QOL and function in the initial recovery period in liver transplant recipients.

Increased prevalence of reduced estimated glomerular filtration rate in chronic hepatitis C patients.

BACKGROUND: To investigate the prevalence and severity of reduced estimated glomerular filtration rate (eGFR) in patients with chronic hepatitis C (CHC). METHODS: Medical record review of 831 consecutive CHC patients seen in our clinic between July 2000 and August 2003; eGFR was estimated using the abbreviated Modification of Diet in Renal Disease (aMDRD) equation. The stage of kidney disease was determined based on eGFR expressed in milliliters per minute per 1.73 m(2): stage 1 (signs of kidney damage but normal or elevated (eGFR >or= 90), stage 2 (eGFR 60-89), stage 3 (30-59), stage 4 (eGFR 15-29), stage 5 (eGFR < 15 or dialysis-dependent). RESULTS: A total of 522 patients had available data with using the aMDRD equation, 51% had abnormal eGFR (stage 1, 4.6%; stage 2, 36.4%; stage 3 or 4, 6.1%; stage 5, 3.8%). Of 190 patients with stage 2 kidney disease, 189 patients (99.5%) had normal serum creatinine and only one patient (0.5%) had elevated creatinine concentrations (>1.4 mg/dl). Of the 32 patients with stage 3 or 4 disease, 20 (62.5%) had a normal serum creatinine concentration. Of 349 patients without diseases known to cause renal insufficiency, 38% had stage 2-4 renal disease. In a subset of these patients, 95/522 (18%) the measured creatinine clearance showed good correlation with their aMDRD (R = 0.47, (p < 0.0001). CONCLUSIONS: In CHC patients, a normal serum creatinine concentration does not assure normal kidney function. Estimation of eGFR with the aMDRD equation is a more accurate method of identifying patients with chronic kidney disease and reduced eGFR. Therefore, CHC patients should be screened more rigorously for chronic kidney disease because of the high prevalence of reduced eGFR. Lastly, in all CHC patients, the aMDRD eGFR should be used in each encounter with these patients when assessing their renal function irrespective of their serum creatinine.

Safety and antiviral activity of albinterferon alfa-2b in prior interferon nonresponders with chronic hepatitis C.

BACKGROUND & AIMS: Pegylated interferon alfa-2a/2b is used in combination with ribavirin to treat patients with chronic hepatitis C (CHC), although many do not achieve a sustained virologic response (SVR). Albinterferon alfa-2b, a recombinant protein consisting of interferon alfa-2b fused to human albumin, may increase drug exposure. This phase 2 study evaluated the safety/efficacy of albinterferon in CHC patients who had not responded to interferon-based regimens. METHODS: A total of 115 patients were assigned to 5 groups given 1200 microg albinterferon every 4 weeks or 900, 1200, 1500, or 1800 microg every 2 weeks, plus oral ribavirin, for 48 weeks. The primary efficacy end point was achievement of an SVR after 24 weeks. Treatment was extended to 72 weeks for 6 slow responders who were negative for hepatitis C virus RNA after 24 weeks. RESULTS: The types of adverse events were similar across groups; the overall discontinuation rate as a result of adverse events was 10.4%. Reductions in absolute neutrophil counts were less frequent in the every 4 weeks group and comparable among the every 2 weeks groups. The overall SVR rate was 17% (11% for previous nonresponders to pegylated interferon-alfa/ribavirin with genotype 1 infection). An SVR occurred in 3 of 6 slow responders by 72 weeks. The greatest reductions in hepatitis C virus RNA in nonresponders to pegylated interferon-alfa/ribavirin with genotype 1 infection were observed in the 1800-microg group. CONCLUSIONS: In patients with CHC who did not respond to interferon-based regimens, higher doses of albinterferon had significant early antiviral activity and a low incidence of adverse events, with the types of adverse events similar to those observed with interferon.

Long-term outcome of human leukocyte antigen mismatching in liver transplantation: results of the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database.

UNLABELLED: A perfect or nearly perfect human leukocyte antigen (HLA) match has been associated with better immediate and long-term survival of diseased donor kidney transplants. However, the effect of HLA matching for hepatic allografts remains poorly defined. Using data from the National Institutes of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database, we investigated the association between HLA mismatches and hepatic allograft survival, disease recurrence, and immunosuppression interactions. A, B, and DR loci were used to calculate total mismatch scores of 0 (no mismatches in any loci) to 6 (mismatches in all loci). Seven hundred ninety-nine adults (male, 55%; female, 45%) underwent 883 liver transplants. The 10-year graft survival according to total mismatch score was as follows: 0-2, 60%; 3-4, 54%; and 5-6, 57%. There was a negative effect of mismatching at the A locus on patient survival, with shorter survival for patients with 1 or 2 mismatches compared with 0 mismatches [P = 0.05, hazard ratio (HR) = 1.6]. Patients on tacrolimus with 1 or 2 mismatches at B or DR loci appeared to have increased rates of patient and graft survival compared to patients with 0 mismatches, with the appearance of a protective effect of tacrolimus (HR = 0.67). The effect of HLA mismatching was more pronounced on certain disease recurrences. DR-locus mismatch increased recurrence of autoimmune hepatitis (P = 0.01, HR = 4.2) and primary biliary cirrhosis (P = 0.04, HR = 2). Mismatch in the A locus was associated with more recurrence of hepatitis C virus (P = 0.01, HR = 1.6) and primary sclerosing cholangitis (P = 0.03, HR = 2.9). CONCLUSION: Mismatching at the A locus decreases patient survival in liver transplant recipients, and mismatching at the DR and A loci affects recurrence of autoimmune liver diseases and hepatitis C, respectively.

Modulation of interferon-specific gene expression by albumin-interferon-alpha in interferon-alpha-experienced patients with chronic hepatitis C.

Albumin-interferon-alpha (alb-IFN) is a novel recombinant protein derived from IFN-alpha2b genetically fused to human albumin. The resulting single polypeptide combines in one molecule the antiviral properties of IFN-alpha with the long serum half-life of albumin. IFN-mediated biological responses stem from the engagement of IFN-alpha with its target receptor and subsequent modulation of IFN-specific gene (ISG) expression. To evaluate the pharmacodynamics of alb-IFN during the Phase I/II study conducted in patients with chronic hepatitis C (CHC) who had previously failed IFN-alpha-containing regimens, ISG induction was evaluated in peripheral blood and compared with antiviral response. Whole blood was obtained at day 0, day 7 and day 28 from 21 patients enrolled in the higher dose (500-900 microg) alb-IFN cohort, who received two injections on day 0 and day 14. Taqman real-time PCR was used to assess candidate ISG expression. There was sustained induction on day 7 and day 28 of the ISG's OAS1, IRF-7, IFI44 and IFI27. Although all patients showed a molecular response to alb-IFN, individual variability in pretreatment gene expression levels and fold of modulation during treatment was observed. At day 28, induction of OAS1, IFI44 and IRF7 showed pairwise correlation in individual patients (P < 0.05). Moreover, the induction of expression at day 28, and pretreatment levels of OAS1 and IFI44 correlated with hepatitis C virus RNA reduction at day 28 (P < 0.05). In conclusion, alb-IFN demonstrated robust induction of ISG that was consistent with the response associated with an IFN-alpha.

A Phase I/II study evaluating escalating doses of recombinant human albumin-interferon-alpha fusion protein in chronic hepatitis C patients who have failed previous interferon-alpha-based therapy.

Albumin-interferon-alpha (IFN-alpha) is a novel 85.7-kDa recombinant protein consisting of IFN-alpha that is genetically fused to human serum albumin. In this Phase I/II, multicentre, open-label study, we evaluated the safety and tolerability, pharmacokinetics and pharmacodynamics of albumin-IFN-alpha in IFN-alpha-experienced patients with chronic hepatitis C. Albumin-IFN-alpha was administered in 22 escalating doses (7-900 microg) in a single injection or in two injections 14 days apart. In the 119 patients studied, there were no discontinuations because of adverse events, and albumin-IFN-alpha had a favourable safety profile at doses up to 900 microg. The most common adverse events were headache (56%), fatigue (52%), injection site erythema (38%), arthralgias (32%) and pyrexia (27%). Reduced clearance resulted in a mean elimination half-life of 159 h, which supports dosing at 2- to 4-week intervals. Induction of the IFN-specific gene OAS1 was maintained for > or = 28 days following a single injection of albumin-IFN-alpha at doses of > or = 40 microg. Dose-dependent antiviral activity was observed in this IFN-alpha-experienced study population. Antiviral activity of > or = 1.0-log reductions in HCV RNA was observed in 47% (37/78) of patients in the 120- to 900-microg cohorts and in 59% (16/27) in the 400- to 900-microg double-injection cohorts. These results support further clinical studies of albumin-IFN-alpha for the treatment of patients with chronic hepatitis C.

Global transcriptional effects of PEG-IFN-alpha and ribavirin on peripheral blood cells obtained from patients with chronic hepatitis C.

The global transcriptional profile during the first 4 weeks of treatment with pegylated interferon alfa (PEG-IFN-alpha) therapy for chronic hepatitis C (CHC) was evaluated. cDNA array technology was used to assess expression of 10,918 human genes in peripheral blood cells obtained from 17 CHC patients at days 0, 7, and 28 following treatment with PEG-IFN-alpha and ribavirin. Hierarchical average linkage clustering identified seven temporal profiles of differential expression comprising 148 genes. Gene expression profiles were comparable between the PEG-IFN-alpha-2a and PEG-IFN-alpha-2b therapy. Genes representing a broad range of molecular functions were differentially regulated with distinct temporal patterns of expression. The initial global response to interferon treatment appears to be a net up-regulation of genes, consistent with gene responses identified previously in vitro, though by 4 weeks an overall down-regulation of genes was observed. Novel transcription factors potentially involved in secondary gene regulation cascades, a potential dsRNA receptor and members of the ubiquitin signaling, including a novel predicted deubiquitinating peptidase were all identified as being up-regulated upon treatment with IFN. The overall findings provide new light on possible physiological effects of IFN-alpha and open new lines of investigations on the mode of action of PEG-IFN-alpha combination therapy.

Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose.

BACKGROUND: Treatment with pegylated interferon (peginterferon) and ribavirin for 48 weeks is more effective than conventional interferon and ribavirin in patients with chronic hepatitis C. OBJECTIVE: To assess the efficacy and safety of 24 or 48 weeks of treatment with peginterferon-alpha2a plus a low or standard dose of ribavirin. DESIGN: Randomized, double-blind trial. SETTING: 99 international centers. PATIENTS: 1311 patients with chronic hepatitis C. INTERVENTION: Peginterferon-alpha2a, 180 microg/wk, for 24 or 48 weeks plus a low-dose (800 mg/d) or standard weight-based dose (1000 or 1200 mg/d) of ribavirin. MEASUREMENT: Sustained virologic response: undetectable HCV RNA concentration at the end of treatment and during 12 to 24 weeks of follow-up. RESULTS: Overall and in patients infected with HCV genotype 1, 48 weeks of treatment was statistically superior to 24 weeks and standard-dose ribavirin was statistically superior to low-dose ribavirin. In patients with HCV genotype 1, absolute differences in sustained virologic response rates between 48 and 24 weeks of treatment were 11.2% (95% CI, 3.6% to 18.9%) and 11.9% (CI, 4.7% to 18.9%), respectively, between standard- and low-dose ribavirin. Sustained virologic response rates for peginterferon-alpha2a and standard-dose ribavirin for 48 weeks were 63% (CI, 59% to 68%) overall and 52% (CI, 46% to 58%) in patients with HCV genotype 1. In patients with HCV genotypes 2 or 3, the sustained virologic response rates in the 4 treatment groups were not statistically significantly different. CONCLUSION: Treatment with peginterferon-alpha2a and ribavirin may be individualized by genotype. Patients with HCV genotype 1 require treatment for 48 weeks and a standard dose of ribavirin; those with HCV genotypes 2 or 3 seem to be adequately treated with a low dose of ribavirin for 24 weeks.

Hepatitis C virus infection with hepatocellular carcinoma: not a controversial indication for liver transplantation.

BACKGROUND: The association of hepatocellular carcinoma (HCC) and chronic hepatitis C virus (HCV) infection has been identified as a potential contraindication for orthotopic liver transplantation (LT) because of lower survival rate compared with other indications. AIM: Evaluate the outcome of patients with and without HCC and cirrhosis with and without chronic HCV infection undergoing transplantation. Determine the postLT HCC recurrence rate and frequency of de novo postLT HCC. PATIENTS AND METHODS: United Network for Organ Sharing (UNOS) data was collected from January 1998 to December 2002. Cohort included 17,968 patients (11,552 M; 6,416 F) with a mean age of 51 (18-87) years. Four groups were established: HCV (n = 7,079), HCC (n = 611), HCV+HCC (n = 1,078), and no HCV/no HCC (n = 9,200). The overall survival rate was calculated at 24 and 48 months postLT. RESULTS: Patient survival at 24 months and 48 months was 84% and 75% for HCV, 84% and 68% for HCC, 78% and 72% for HCV+HCC, and 85% and 80% for no HCV/no HCC, respectively. Survival at 48 months among the two groups was not significantly different (NS). Further analysis of these groups revealed a statistically significant advantage in survival at 48 months postLT for the no HCV/no HCC group when compared with the HCV group.(P < 0.05) The reported rate of postLT HCC recurrence and de novo postLT HCC was 3.3% and 0.05%, respectively. CONCLUSION: In this large cohort of U.S. patients, HCC does not have an impact on the survival of LT patients infected with HCV.

Treatment of recurrent hepatitis C infection after liver transplantation with combination of pegylated interferon alpha2b and ribavirin: an open-label series.

BACKGROUND: Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is universal. We aimed to evaluate the efficacy and safety of pegylated interferon (PEG-IFN) and ribavirin (RIB) in the treatment of post-OLT HCV recurrence. METHODS: Thirty-seven patients with recurrent HCV after OLT were screened and began treatment. Nineteen patients have completed therapy. PEG-IFN was started at a dose of 0.5 microg/kg per week and titrated toward a maximum dose of 1.5 microg/kg per week. RIB was started at a dose of 400 mg per day and titrated toward a maximum of 1000 mg per day, as tolerated. Therapy continued for 1 year after HCV replication was undetectable by reverse transcriptase-polymerase chain reaction and was discontinued if there was no virologic clearance at 48 weeks. RESULTS: Twelve patients (63%) completed the combination regimen. Therapy was discontinued in seven (37%) patients. Seven patients (37%) had undetectable viral load at the end of treatment. Of those, five patients (26%) had sustained viral response 6 months after discontinuation of therapy. Five patients (26%) had no virologic response. Necro-inflammatory score declined from 5.22 to 2.89 (P=0.05) in nonresponders versus 6.8 to 2.6 (P<0.01) in responders. Fibrosis stage did not change in either group. Genotype 1-infected patients had a lower likelihood of attaining end of treatment or sustained viral response (P<0.05 for both). CONCLUSIONS: Post-OLT HCV recurrence can be safely treated with PEG-IFN and RIB. Bone marrow toxicity, depression, and rejection are limiting factors that require aggressive management. There was short-term histologic benefit to the use of this regimen, even in those patients without viral clearance.

Perplexing lesions of the sinonasal cavity and skull base: IgG4-related and similar inflammatory diseases.

OBJECTIVE: IgG4-related disease (IgG4RD) causing sinonasal and skull base pathology is uncommonly described. We present a series of suspected IgG4RD patients, with a pertinent review of the literature to highlight diagnostic challenges. STUDY DESIGN: Case series. SETTING: Academic tertiary care center. SUBJECTS AND METHODS: Case series of patients with IgG4RD or suspected IgG4RD involving the sinonasal cavity and skull base. RESULTS: We present 4 patients with atypical sinonasal and/or skull base disease who were noted to have IgG4-positive plasma cell infiltration on immunohistochemistry of biopsy specimens. IgG4RD, a recently described entity affecting multiple organs, is characterized by lymphoplasmacytic infiltration and often elevated serum IgG4. IgG4RD can masquerade as malignancy or infection but responds to glucocorticosteroid and immunosuppressant therapy. IgG4RD has been infrequently reported presenting as sinonasal or skull base lesions, and definitive diagnostic criteria for these regions are not established. In our series, IgG4RD was suspected in all 4 patients, but only 1 met all current criteria for definitive diagnosis. All 4 patients, however, responded to corticosteroid therapy, and 1 was placed on long-term azathioprine. CONCLUSION: IgG4RD is rarely described in the sinonasal cavity and skull base, and specific diagnostic criteria for such disease have not been defined. We present a series of patients with IgG4-positive plasma cell inflammatory pathology who were suspected to have IgG4RD. Our series highlights diagnostic challenges associated with these patients. Tumefactive and destructive sinonasal-skull base lesions with a plasma cell-rich infiltrate should incite suspicion of IgG4RD, and immunohistochemistry for IgG4-positive plasma cells should be performed.

Treatment of hepatitis C in renal transplantation candidates: a single-center experience.

BACKGROUND: There is no consensus on hepatitis C virus (HCV) treatment in patients with renal failure. Toxicity of pegylated interferon (PEG-IFN) and ribavirin limit options; hence the ideal approach for therapy in these patients deserves attention. We report the results of kidney transplantation (KTx) candidates infected with HCV treated with PEG-IFN monotherapy. METHODS: KTx candidates with HCV infection treated with PEG-IFN monotherapy between January 2001 and February 2009 were included. Liver biopsies were performed before therapy. Response was assessed using accepted virological time points. RESULTS: From 2636 patients listed for KTx, 60 patients were tested positive for anti-HCV. Twenty-two patients were eligible for treatment. All patients were HCV treatment naïve. One patient had biopsy-confirmed cirrhosis. Mean Ishak-Knodell fibrosis stage was 1.3. Ten patients (45%) achieved sustained viral response. In genotype 1 patients, there were no relapsers among early responders, despite the limited regimen. Nine patients (40%) in the cohort have had KTx. Of these, there were four responders and five nonresponders. None of the responders have had recurrence of their HCV after their KTx. CONCLUSIONS: End-stage renal disease patients with HCV can be treated successfully with PEG-IFN monotherapy. Our sustained viral response rate was 45% (10/22) in patients treated before KTx.

Changes in B-lymphocyte stimulator protein levels during treatment with albinterferon alfa-2b in patients with chronic hepatitis C who have failed previous interferon therapy.

AIM: The pharmacodynamics of albinterferon alfa-2b (alb-IFN), a novel recombinant protein consisting of interferon-α-2b genetically fused to human albumin, was evaluated in patients with chronic hepatitis C with a previous non-response to interferon-α-based therapy. B-lymphocyte stimulator (BLyS) is an essential in vivo regulator of B-lymphocyte homeostasis. This analysis examined the relationship between serum BLyS level and virologic response across a range of alb-IFN doses. METHODS: In all, 115 patients were randomized initially to three alb-IFN treatment arms (900 and 1200 µg every two weeks [q2wk], and 1200 µg every four weeks) with weight-based ribavirin, followed by sequential enrollment in two higher dose arms (1500 and 1800 µg q2wk). Serum BLyS level was assessed by enzyme-linked immunosorbent assay. RESULTS: Serum BLyS levels at baseline were lower in African-Americans (P < 0.001). Significant BLyS inductions were observed at weeks 12 and 24 versus pretreatment; in general, serum BLyS levels returned to pretreatment levels following treatment completion. Induction of BLyS was greater in the highest dose group; a significant dose-response trend was observed at weeks 12 (P = 0.002) and 24 (P < 0.001), as well as a significant time trend, with further BLyS induction increases at week 24 versus 12 (P < 0.001). Week 24 BLyS level change correlated with hepatitis C virus RNA reduction (r = -0.28; P = 0.006), driven primarily by patients with BLyS increases > 400%, but did not correlate with sustained virologic response. CONCLUSION: Higher alb-IFN doses demonstrated dose-related BLyS increases, although the correlation with virologic response was modest.

Persistence of hepatitis C virus in peripheral blood mononuclear cells of sustained viral responders to pegylated interferon and ribavirin therapy.

The aim of this paper was to assess the persistence of hepatitis C virus (HCV) among patients successfully treated with peginterferon and ribavirin. The persistence of viral RNA was evaluated in the serum and peripheral blood mononuclear cells (PBMCs) of 25 chronic hepatitis C patients with sustained viral response to peginterferon and ribavirin treatment up to 56 months after the completion of therapy. Viral RNA was detected in the peripheral blood mononuclear cell cultures of five patients (20%), but none had detectable serum HCV RNA. At present, the clinical relevance of this finding is unclear. It is possible that viral persistence and, specifically, the presence of HCV RNA in PBMCs may lead to HCV reactivation under special circumstances, such as immunosuppression.

Inpatient admissions for drug-induced liver injury: results from a single center.

Objective To review all cases of drug-induced liver injury (DILI) requiring hospitalization at a single tertiary care center. Methods Patient records were identified by ICD-9 codes for inpatient visits from November 1998 through March 2006. Results Of a total 83,265 hospital admissions during the study period, 40 were for DILI (0.048%). Thirteen patients had non-acetaminophen DILI (NA-DILI); 27 had acetaminophen-related DILI (A-DILI). In the NA-DILI group, mean age was 59 +/- 17.9 years and liver injury was classified as hepatocellular (7), cholestatic (5), or mixed (1). A variety of medications were implicated with antimicrobials being the most common class. Resolution occurred in seven, two died of complications related to hepatotoxicity, one underwent liver transplantation, and the outcome was undetermined in three who were lost to follow-up. In the A-DILI group, mean age was 35 +/- 11.0 years. Eighteen involved intentional overdose of acetaminophen; nine were associated with chronic use. The pattern of injury was hepatocellular in all. Resolution occurred in 4 patients, death in 8, and improvement in 15. Conclusions DILI is a rare cause of inpatient admission but is associated with significant mortality. Spontaneous resolution occurs in most patients but return to normal liver function may take months. Antimicrobial agents account for the largest proportion of NA-DILI.

Infections in Patients With End-stage Liver Disease.

Infections in patients with end-stage liver disease (ESLD) are an important cause of morbidity and mortality in these patients. Abnormalities in their natural defense mechanisms, alterations in the enteric flora and the growing utilization of invasive procedures increase the risk of infections in these patients. Common bacterial infections in ESLD patients include spontaneous bacterial peritonitis, urinary tract infections, community-acquired pneumonia, dermatologic infections, and bacteremia. Viral infections such as influenza can have a devastating course in ESLD patients. Hepatitis B and C are now among the most common causes of ESLD. They also present an important therapeutic challenge. As patients with human immunodeficiency virus are surviving longer, ESLD due to hepatitis C is now emerging as a leading cause of morbidity in these patients. Prompt detection of infections, use of appropriate antibiotics for treatment and prophylactic measures such as vaccinations can help improve survival in these patients.

Selective serotonin reuptake inhibitors in the context of hepatitis C infection: reexamining the risks of bleeding.

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are used to treat interferon-associated depression in patients receiving hepatitis C virus therapy. Prior studies have cautioned against the combined use of SSRIs and interferon due to increased risk of hemorrhage. Given the morbidity of depression and its impact on interferon compliance, we sought to reexamine the data. METHOD: In a retrospective analysis of our database of hepatitis C virus patients, a consecutive series of 303 patients (receiving treatment between January 2001 and January 2005) were evaluated for any evidence of bleeding. On the basis of our standard practice of care, patients were treated prophylactically with antidepressants for 3 to 4 weeks before beginning combination therapy with interferon and ribavirin. Patients were evaluated every 4 weeks during antiviral treatment with physical examinations and complete blood cell counts with differentials and platelets. RESULTS: The overall rate of bleeding in our study was 0.3%, representing a single case of hemophilia. CONCLUSIONS: The bleeding risk of SSRIs is lower than previously reported.