Workforce in hepatology: Update and a critical need for more information.

The field of hepatology has experienced dramatic changes since the last workforce study in hepatology over 15 years ago. Hepatology practice has been dominated by hepatitis C but is now being overtaken by patients with nonalcoholic fatty liver disease. Expertise once attainable only through informal training, hepatology now has an accredited fellowship pathway and is recognized as a distinct discipline from gastroenterology with its own board certification. These changes that have occurred since the last workforce study in the prevalence and therapy of liver diseases and training may impact workforce needs. The time has come to conduct an updated analysis of the state of the hepatology workforce. The purpose of this article is to discuss the current issues facing training and workforce in hepatology and propose the next steps in conducting a workforce study. (Hepatology 2017;65:336-340).

Novel educational interventions in residency increase knowledge of chronic liver disease and career interest in hepatology.

There is an increasing burden of chronic liver disease (CLD) in the United States but a significant shortage of hepatologists. Thus, it is necessary to develop new recruitment strategies to the field of hepatology as well as ensure that non-gastroenterology-trained physicians are able to capably assist in the care of CLD. We established a novel, nonelective, inpatient hepatology rotation that uses required modules in the American Association for the Study of Liver Diseases Curriculum and Training-First Hepatitis B and C curriculums as well as in LiverLearning. A paper-based anonymous assessment was distributed to the inaugural 25 postgraduate years 2 and 3 internal medicine residents before and after the 2-week rotation over the course of 1 year. Both the prerotation and postrotation assessments included validated multiple-choice questions and Likert-type questions, which evaluated self-perceived knowledge and comfort with managing CLD. The mean comfort level (1 = not at all comfortable/strongly disagree, 5 = very comfortable/strongly agree) of managing several common liver diseases increased significantly after completion of the rotation (i.e., cirrhosis 2.8 versus 3.8, P < 0.001; hepatitis B 2.4 versus 3.4, P = 0.001; hepatitis C 2.6 versus 3.7, P = 0.002; nonalcoholic steatohepatitis 3.0 versus 4.0, P < 0.001; liver transplant care 2.1 versus 3.4, P < 0.001). There was also a significantly increased interest in hepatology as a career (2.6 versus 3.0, P = 0.03). Finally, the mean percentage of multiple-choice questions answered correctly on the pretest was 62% and posttest was 77% (P = 0.02). CONCLUSION: Our novel curriculum and nonelective hepatology rotation has effectively demonstrated improvement in internal medicine residents' comfort with and knowledge of CLD, and increased career interest in hepatology was also observed after completion of the curriculum, which suggests that more exposure to CLD could positively impact recruitment to the workforce; larger, multicenter studies are needed to validate these results. (Hepatology 2016;64:2210-2218).

Multiphase Multi-Detector Row Computed Tomography Imaging Characteristics of Large (>5 cm) Focal Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to describe the multiphase multi-detector row computed tomography (MDCT) imaging findings of large (>5 cm) focal hepatocellular carcinoma (HCC). METHODS: Following review of the medical records of 321 patients with newly diagnosed HCC who underwent MDCT within the radiology database from January 2007 to November 2014, 27 patients (20 men and 7 women; mean age, 69 [SD, 10.1] years [range, 49-87 years]) with histologically confirmed HCC greater than 5 cm were included in this institutional review board-approved study. Multiphase, dedicated liver MDCT images of these cases were retrospectively reviewed by 2 radiologists in consensus to describe the enhancement characteristics of these lesions. RESULTS: Mean tumor diameter was 8.4 (SD, 2.4) cm (range, 5.2-13.5 cm). Cirrhosis was present in 16 (59%) of 27 patients. Seventeen (85%) of 20 patients with available laboratory data presented with elevated alpha-fetoprotein (median, 97 ng/mL). Twenty-three (85%) of 27 demonstrated either heterogeneous enhancement with gradual fill-in (14/27 [52%]) or peripheral enhancement with centripetal fill-in (9/27 [33%]). Twenty-two (81%) of 27 lacked washout on delayed phase images, and 21 (78%) of 27 demonstrated a pseudocapsule. Twenty-seven of 27 lesions were well defined, 8 (30%) of 27 were exophytic, 15 (56%) of 27 were unifocal, 5 (25%) of 20 cases demonstrated vascular invasion, and 7 (26%) of 27 cases presented with extrahepatic metastases. CONCLUSIONS: Large (>5 cm) focal HCC may present as a dominant mass with a pseudocapsule and initial heterogeneous or peripheral enhancement with gradual or centripetal fill-in without washout on multiphase MDCT. Awareness of this variant is important to allow distinction from other benign (eg, hemangioma) and malignant (eg, cholangiocarcinoma) focal liver lesions.

Randomized, double-blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy.

UNLABELLED: Glycerol phenylbutyrate (GPB) lowers ammonia by providing an alternate pathway to urea for waste nitrogen excretion in the form of phenylacetyl glutamine, which is excreted in urine. This randomized, double-blind, placebo-controlled phase II trial enrolled 178 patients with cirrhosis, including 59 already taking rifaximin, who had experienced two or more hepatic encephalopathy (HE) events in the previous 6 months. The primary endpoint was the proportion of patients with HE events. Other endpoints included the time to first event, total number of events, HE hospitalizations, symptomatic days, and safety. GPB, at 6 mL orally twice-daily, significantly reduced the proportion of patients who experienced an HE event (21% versus 36%; P=0.02), time to first event (hazard ratio [HR]=0.56; P<0.05), as well as total events (35 versus 57; P=0.04), and was associated with fewer HE hospitalizations (13 versus 25; P=0.06). Among patients not on rifaximin at enrollment, GPB reduced the proportion of patients with an HE event (10% versus 32%; P<0.01), time to first event (HR=0.29; P<0.01), and total events (7 versus 31; P<0.01). Plasma ammonia was significantly lower in patients on GPB and correlated with HE events when measured either at baseline or during the study. A similar proportion of patients in the GPB (79%) and placebo groups (76%) experienced adverse events. CONCLUSION: GPB reduced HE events as well as ammonia in patients with cirrhosis and HE and its safety profile was similar to placebo. The findings implicate ammonia in the pathogenesis of HE and suggest that GPB has therapeutic potential in this population. (Clinicaltrials.gov, NCT00999167).

Screening for Zinc Deficiency in Patients with Cirrhosis: When Should We Start?

BACKGROUND: Zinc deficiency has been observed in cirrhosis, but management guidelines do not address screening for zinc deficiency. We aim to determine the prevalence of zinc deficiency in different stages of cirrhosis and to correlate zinc levels with complications of cirrhosis and clinical outcomes. Patients who had a diagnosis of cirrhosis and had serum zinc levels drawn from 2007 to 2011 were identified. Demographics, laboratory data, presence of ascites, encephalopathy, and infection were obtained; Child-Pugh and MELD scores were calculated. Stata software was used for data analysis. A total of 163 patients were included in the study. RESULTS: The median serum zinc level was 0.47 mcg/ml (IQR 0.37-0.63); 83 % of patients were zinc deficient. Zinc deficiency was more prevalent in patients with Child-Pugh score B or C, and with MELD scores ≥15. Zinc levels were lower in alcoholic, hepatitis C, and cholestatic diseases than in other etiologies of liver disease. Zinc levels correlated with INR (r = -0.56, p < 0.001), bilirubin (r = -0.51, p < 0.001), and albumin (r = 0.68, p < 0.001), and were lower in patients with ascites (0.40 vs. 0.57 mcg/ml, p < 0.001), encephalopathy (0.40 vs. 0.53 mcg/ml, p < 0.001), diuretic use (0.45 vs. 0.535 mcg/ml, p = 0.005), and infection (0.32 vs. 0.51 mcg/ml, p < 0.001). Ascites (p = 0.044) and infection (p = 0.009) were independently associated with zinc levels. Zinc-deficient patients had lower transplant-free survival rates than non-deficient patients. CONCLUSION: Zinc deficiency is highly prevalent in cirrhotic patients with Child-Pugh score B or C, and with MELD score ≥15. Zinc deficiency also correlates with disease severity, infection, and a worse transplant-free survival. Screening for zinc deficiency should be considered in this subset of patients.

Co-management between hospitalist and hepatologist improves the quality of care of inpatients with chronic liver disease.

BACKGROUND AND GOALS: Our institution shifted the care of patients with chronic liver disease (CLD) from Internal Medicine faculty, house staff, and consulting hepatology service to a co-managed unit staffed by academic hospitalists and hepatologists. The effect of co-management between hospitalists and hepatologists on the care of patients hospitalized with complications of CLD such as spontaneous bacterial peritonitis (SBP) is unknown. STUDY: A retrospective chart review of 56 adult patients admitted with CLD and SBP from July 1, 2004 to June 30, 2010 was performed. Adherence rates to current management guidelines were measured along with costs and outcomes of care. RESULTS: Patients admitted under the 2 models of care were similar; however, they consistently underwent paracentesis within 24 hours (100% vs. 79%, P=0.013), had appropriate avoidance of fresh-frozen plasma use (75% vs. 43%, P=0.05), received albumin (97% vs. 65%, P=0.002), and were discharged on SBP prophylaxis (91% vs. 37%, P<0.001) under the co-managed model compared with the conventional model. Costs of care were similar between the 2 groups. We note a trend toward improved outcomes of care under the co-management model as measured by transfer rates to the intensive care unit, inpatient mortality, 30-day readmission, and mortality rates. CONCLUSIONS: These results support co-management between hospitalists and hepatologists as a superior model of care for hospitalized patients with SBP. Furthermore, this study adds to the growing literature indicating that efforts are needed to improve the quality of care delivered to CLD patients.

Risk factors for inadequate colonoscopy bowel preparations in African Americans and whites at an urban medical center.

OBJECTIVES: Poor bowel preparation leads to inadequate examinations and shorter surveillance intervals for colorectal cancer screening. Previous studies regarding risk factors for inadequate preparation have not included large numbers of African Americans. Our aim was to determine the prevalence of inadequate bowel preparation on initial and follow-up colonoscopy in a large, racially diverse patient population. METHODS: Colonoscopies performed during a 1-year period were analyzed retrospectively. Factors including age, sex, race, and start time were recorded. Patient ZIP codes were linked to census data to estimate education and income. For examinations with inadequate bowel preparations, we collected data on recommendations and the preparation quality of follow-up procedures. RESULTS: We included 3741 patients (40.2% African American). Of these, 66.9% had adequate bowel preparation and 33.1% had inadequate bowel preparation. African Americans had the highest prevalence of inadequate preparations at 43.0%. African American race was a predictor of inadequate bowel preparation, despite controlling for education and income. Age, male sex, and procedure taking place after 12 pm also were risk factors for inadequate preparation. Receipt of specific preparation instructions on the endoscopy report did not affect preparation quality on follow-up examination. Our study found a high rate (33.1%) of inadequate bowel preparations, and African American race was found to be an independent risk factor for inadequate preparation. We validated previously reported risk factors including age, male sex, and later procedure time. Finally, we noted high rates of inadequate preparation on follow-up examinations. CONCLUSIONS: Improving the quality of colonoscopy bowel preparation is important for colorectal cancer prevention, especially in high-risk populations such as African Americans.

The impending hepatology workforce shortage: Ethical considerations for closing the gap.

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Bifidobacteria metabolize lactulose to optimize gut metabolites and prevent systemic infection in patients with liver disease.

Progression of chronic liver disease is precipitated by hepatocyte loss, inflammation and fibrosis. This process results in the loss of critical hepatic functions, increasing morbidity and the risk of infection. Medical interventions that treat complications of hepatic failure, including antibiotic administration for systemic infections and lactulose treatment for hepatic encephalopathy, can impact gut microbiome composition and metabolite production. Here, using shotgun metagenomic sequencing and targeted metabolomic analyses on 847 faecal samples from 262 patients with acute or chronic liver disease, we demonstrate that patients hospitalized for liver disease have reduced microbiome diversity and a paucity of bioactive metabolites, including short-chain fatty acids and bile acid derivatives, that impact immune defences and epithelial barrier integrity. We find that patients treated with the orally administered but non-absorbable disaccharide lactulose have increased densities of intestinal bifidobacteria and reduced incidence of systemic infections and mortality. Bifidobacteria metabolize lactulose, produce high concentrations of acetate and acidify the gut lumen in humans and mice, which, in combination, can reduce the growth of antibiotic-resistant bacteria such as vancomycin-resistant Enterococcus faecium in vitro. Our studies suggest that lactulose and bifidobacteria serve as a synbiotic to reduce rates of infection in patients with severe liver disease.

Liver Transplantation of HCV-viremic Donors Into HCV-negative Recipients in the United States: Increasing Frequency With Profound Geographic Variation.

BACKGROUND: Direct-acting antiviral therapy made possible the novel practice of utilizing hepatitis C virus (HCV)-viremic (HCV RNA-positive) donors into HCV-negative recipients in the United States. Although initial reports of outcomes have been satisfactory, higher-quality longer-term outcomes remain to be elucidated. METHODS: National data were examined from the Organ Procurement and Transplantation Network on adult patients in the United States who underwent a primary, single organ, deceased donor liver transplant from January 1, 2016 to March 31, 2020. Outcomes of HCV-negative recipients (R-) who received an allograft from donors who were HCV RNA-positive (D HCV+) donors were compared with HCV RNA-negative (D HCV-) donors. RESULTS: There has been a 35-fold increase in D HCV+/R- liver transplants over the past 4 y in the United States, from 8 in 2016 to 280 in 2019. There was an almost 6-fold difference in this practice among UNOS geographic regions. Graft survival following D HCV+/R- liver transplantation was excellent, with 1-y rates being 91% and 90% and 2-y rates being 88.5% and 87% for D HCV+/R- and D HCV-/R-, respectively (P = 0.672). In multivariate analysis, adjusting for other donor and recipient attributes, D HCV+/R- was not associated with patient or graft survival. CONCLUSIONS: The practice of D HCV+/R- continues to increase without discernible impact on medium-term outcomes. Notable geographic variation exists, suggesting inconsistent perceptions about the impact of D HCV+/R- transplantation on outcomes. These results strengthen the perceived safety in utilizing HCV-viremic donor organs as a donor pool expansion strategy, not only in the United States, but also worldwide.

Impact of experience with a retrograde-viewing device on adenoma detection rates and withdrawal times during colonoscopy: the Third Eye Retroscope study group.

BACKGROUND: Colonoscopy has been adopted as the preferred method to screen for colorectal neoplasia in the United States. However, lesions can be missed because of numerous factors, including location on the proximal aspect of folds or flexures, where they may be difficult to detect with the forward-viewing colonoscope. The Third Eye Retroscope (TER) is a disposable device that is passed through the instrument channel of a standard colonoscope to provide a retrograde view that complements the forward view of the colonoscope during withdrawal. OBJECTIVE: To evaluate whether experience with the TER affects polyp detection rates and procedure times in experienced endoscopists who had not previously used the equipment. DESIGN, SETTING, PATIENTS: This was an open-label, prospective, multicenter study at 9 U.S. sites, involving 298 patients presenting for colonoscopy, evaluating the use of the TER in combination with a standard colonoscope. INTERVENTIONS: After cecal intubation, the TER was inserted through the instrument channel of the colonoscope. During withdrawal, the forward and retrograde video images were observed simultaneously on a wide-screen monitor. MAIN OUTCOME MEASUREMENTS: Primary outcome measures were the number and size of adenomas and all polyps detected with the standard colonoscope and with the colonoscope combined with the TER. Secondary outcome measures were withdrawal phase time and total procedure time. Each endoscopist examined 20 subjects, divided into quartiles according to the order of their procedures, and results were compared among quartiles. RESULTS: Overall, 182 polyps were detected with the colonoscope and 27 additional polyps with the TER, a 14.8% increase (P < .001). A total of 100 adenomas were detected with the colonoscope and 16 more with the TER, a 16.0% increase (P < .001). For procedures performed after each endoscopist had completed 15 procedures while using the TER, the mean additional detection rates with the TER were 17.0% for all polyps (P < .001) and 25.0% for adenomas (P < .001). For lesions 6 mm or larger, the overall additional detection rates with the TER for all polyps and for adenomas were 23.2% and 24.3%, respectively. For lesions 10 mm or larger, the overall additional detection rates with the TER for all polyps and for adenomas were 22.6% and 19.0%, respectively. The mean withdrawal times in the first and fourth quartiles were 10.6 and 9.2 minutes, respectively (P = .044). LIMITATIONS: There was no randomization or separate control group. The endoscopists judged whether each lesion could have been detected with the colonscope alone by using their standard technique. CONCLUSIONS: Polyp detection rates improved significantly with the TER, especially after 15 procedures, when the mean additional detection rate for adenomas was 25.0%. Additional detection rates with the TER for medium-size and large adenomas were greater than for smaller lesions. These results suggest that, compared with a colonoscope alone, a retrograde-viewing device can increase detection rates for clinically significant adenomas without detriment to procedure time or procedure complications. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00969124.).

Predictors of mortality and endoscopic intervention in patients with upper gastrointestinal bleeding in the intensive care unit.

BACKGROUND: The outcomes of patients undergoing esophagogastroduodenoscopy (EGD) in the intensive care unit (ICU) for upper gastrointestinal bleeding (UGIB) are not well described. Our aims were to determine predictors of 30-day mortality and endoscopic intervention, and assess the utility of existing clinical-prediction tools for UGIB in this population. METHODS: Patients hospitalized in an ICU between 2008 and 2015 who underwent EGD were identified using a validated, machine-learning algorithm. Logistic regression was used to determine factors associated with 30-day mortality and endoscopic intervention. Area under receiver-operating characteristics (AUROC) analysis was used to evaluate established UGIB scoring systems in predicting mortality and endoscopic intervention in patients who presented to the hospital with UGIB. RESULTS: A total of 606 patients underwent EGD for UGIB while admitted to an ICU. The median age of the cohort was 62 years and 55.9% were male. Multivariate analysis revealed that predictors associated with 30-day mortality included American Society of Anesthesiologists (ASA) class (odds ratio [OR] 4.1, 95% confidence interval [CI] 2.2-7.9), Charlson score (OR 1.2, 95% CI 1.0-1.3), and duration from hospital admission to EGD (OR 1.04, 95% CI 1.01-1.07). Rockall, Glasgow-Blatchford, and AIMS65 scores were poorly predictive of endoscopic intervention (AUROC: 0.521, 0.514, and 0.540, respectively) and in-hospital mortality (AUROC: 0.510, 0.568, and 0.506, respectively). CONCLUSIONS: Predictors associated with 30-day mortality include ASA classification, Charlson score, and duration in the hospital prior to EGD. Existing risk tools are poorly predictive of clinical outcomes, which highlights the need for a more accurate risk-stratification tool to predict the benefit of intervention within the ICU population.

Metastatic Gastric Adenocarcinoma in Cirrhosis.

We report the case of a woman with a new diagnosis of gastric adenocarcinoma that was found to have multifocal hepatic metastasis on routine diagnostic transjugular liver biopsy. The finding of metastatic disease in a background of cirrhosis is an unexpected finding that has negative treatment implications regarding use of cytotoxic chemotheraputic agents.

Multiphasic analysis of the temporal development of the distal gut microbiota in patients following ileal pouch anal anastomosis.

BACKGROUND: The indigenous gut microbiota are thought to play a crucial role in the development and maintenance of the abnormal inflammatory responses that are the hallmark of inflammatory bowel disease. Direct tests of the role of the gut microbiome in these disorders are typically limited by the fact that sampling of the microbiota generally occurs once disease has become manifest. This limitation could potentially be circumvented by studying patients who undergo total proctocolectomy with ileal pouch anal anastomosis (IPAA) for the definitive treatment of ulcerative colitis. A subset of patients who undergo IPAA develops an inflammatory condition known as pouchitis, which is thought to mirror the pathogenesis of ulcerative colitis. Following the development of the microbiome of the pouch would allow characterization of the microbial community that predates the development of overt disease. RESULTS: We monitored the development of the pouch microbiota in four patients who underwent IPAA. Mucosal and luminal samples were obtained prior to takedown of the diverting ileostomy and compared to samples obtained 2, 4 and 8 weeks after intestinal continuity had been restored. Through the combined analysis of 16S rRNA-encoding gene amplicons, targeted 16S amplification and microbial cultivation, we observed major changes in structure and function of the pouch microbiota following ileostomy. There is a relative increase in anaerobic microorganisms with the capacity for fermentation of complex carbohydrates, which corresponds to the physical stasis of intestinal contents in the ileal pouch. Compared to the microbiome structure encountered in the colonic mucosa of healthy individuals, the pouch microbial community in three of the four individuals was quite distinct. In the fourth patient, a community that was much like that seen in a healthy colon was established, and this patient also had the most benign clinical course of the four patients, without the development of pouchitis 2 years after IPAA. CONCLUSIONS: The microbiota that inhabit the ileal-anal pouch of patients who undergo IPAA for treatment of ulcerative colitis demonstrate significant structural and functional changes related to the restoration of fecal flow. Our preliminary results suggest once the pouch has assumed the physiologic role previously played by the intact colon, the precise structure and function of the pouch microbiome, relative to a normal colonic microbiota, will determine if there is establishment of a stable, healthy mucosal environment or the reinitiation of the pathogenic cascade that results in intestinal inflammation.

Persistent spontaneous bacterial peritonitis: a common complication in patients with spontaneous bacterial peritonitis and a high score in the model for end-stage liver disease.

OBJECTIVES: Spontaneous bacterial peritonitis (SBP) is associated with a high mortality rate. After antibiotic therapy, improvement in fluid polymorphonuclear (PMN) cell count is expected within 2 days. However, our institution recognized cases unresponsive to standard treatment. METHODS: To study these recalcitrant cases, we completed a retrospective chart review of patients admitted for SBP to the University of Chicago from 2002 to 2007. SBP was defined by an ascitic PMN cell count ≥250/ml. RESULTS: Of 55 patients with SBP, 15 did not show improvement in fluid PMN cell count to below 250/ml with standard treatment, leading to a prevalence of 27%. The patients with persistent SBP were younger than those with nonpersistent SBP [mean (SD) 51.80 (9.84) compared with 58.13 (8.79); p = 0.0253]. Persistent SBP had a higher serum ascites albumin gradient (SAAG) [median (Q1, Q3) 1.85 (1.50, 2.41) compared with 1.10 (0.60, 1.60)] and a higher score in the model for end-stage liver disease (MELD) [mean (SD) 27.98 (8.09) compared with 22.22 (8.10)] than nonpersistent SBP patients; p = 0.027 and p = 0.023, respectively. In addition, persistent SBP patients were more likely to have a positive ascitic fluid culture than nonpersistent SBP patients [odds ratio (OR) (95% CI) 4.33 (1.21, 15.47); p = 0.024]. Importantly, in-hospital mortality in the persistent SBP group was 40%, compared with 22.5% in the nonpersistent SBP group [OR = 2.30 (0.64, 8.19); p = 0.20]. CONCLUSIONS: The risk of persistent SBP is nearly 40% in patients with MELD score >25, SAAG >1.5 or positive ascitic fluid culture. Furthermore, patients who develop persistent SBP tend to experience a higher mortality rate. This study underscores the importance of further examination of this vulnerable population.

Lack of Efficacy of Pegylated Interferon Monotherapy for Hepatitis C in Patients With End-Stage Renal Disease on Dialysis.

Objectives To evaluate the efficacy, safety and tolerability of pegylated interferon monotherapy for chronic hepatitis C virus (HCV) in patients who are on dialysis. Methods From the University of Chicago Clinical Hepatology Database dated May 2001 to July 2005, 13 patients on dialysis with hepatitis C who have been treated with pegylated interferon were identified. Demographic and laboratory data were obtained from medical records. Patients received pegylated interferon alfa-2a at 135 µg subcutaneous (SQ) weekly (n = 8) or pegylated interferon alfa-2b at 1 µg/kg SQ weekly (n = 5). Side effects from the medication were noted. Results There were 7 men and 6 women, with a mean age of 54±11 years; 11 patients (85%) were African American and 11 patients (85%) were infected with HCV genotype 1. The median serum HCV RNA level was 3,273,000 copies/mL (range, 207,000 to >40,000,000), and the median serum alanine aminotransferase level was 29 IU/mL (range, 19-77). Four patients (30%) had bridging fibrosis or cirrhosis on liver biopsy. None of the 13 patients achieved sustained virologic response; 2 patients (15%) had an undetectable viral load at the end of therapy but relapsed within 6 months of follow-up. The most common side effects were fatigue (100%), anemia defined as 2 g/dL or greater drop in hemoglobin level (60%), and psychiatric symptoms (30%). Conclusions Pegylated interferon is ineffective for HCV infection in patients on dialysis. Furthermore, worsening anemia, which is usually prevalent at baseline in dialysis patients, is a common adverse event even in the absence of ribavirin use.