Are Non-cardiac Surgeries Safe for Dialysis Patients? – A Population-Based Retrospective Cohort Study

Background

End-stage renal disease represents a risk complex that complicates surgical results. The surgical outcomes of dialysis patients have been studied in specific fields, but the global features of postoperative adverse outcomes in dialysis patients receiving non-cardiac surgeries have not been examined.

Methods

Taiwan’s National Health Insurance Research Database was used to study 8,937 patients under regular dialysis with 8,937 propensity-score matched-pair controls receiving non-cardiac surgery between 2004 and 2007. We investigated the influence of hemodialysis and peritoneal dialysis, effects of hypertension and diabetes, and impact of additional comorbidities on postoperative adverse outcomes.

Results

Postoperative mortality in dialysis patients was higher than in controls (odds ratio [OR] 3.33, 95% confidence interval [CI] 2.56 to 4.33) when receiving non-cardiac surgeries. Complications such as acute myocardial infarction, pneumonia, bleeding, and septicemia were significantly increased. Postoperative mortality was significantly increased among peritoneal dialysis patients (OR 2.71, 95% CI 1.70 to 4.31) and hemodialysis patients (OR 3.42, 95% CI 2.62 to 4.47) than in controls. Dialysis patients with both hypertension and diabetes had the highest risk of postoperative complications; these risks increased with number of preoperative medical conditions. Patients under dialysis also showed significantly increased length of hospitalization, more ICU stays and higher medical expenditures.

Conclusion

Surgical patients under dialysis encountered significantly higher postoperative complications and mortality than controls when receiving non-cardiac surgeries. Different dialysis techniques, pre-existing hypertension/diabetes, and various comorbidities had complication-specific impacts on surgical adverse outcomes. These findings can help surgical teams provide better risk assessment and postoperative care for dialysis patients.     

Tonsillectomy and the Risk for Deep Neck Infection—A Nationwide Cohort Study

Background

Although the tonsils contribute to first line immunity against foreign pathogens in the upper aero-digestive tract, the association of tonsillectomy with the risk of deep neck infection remains unclear. The aim of this study was to assess the incidence rate and risk of deep neck infection among patients who had undergone a tonsillectomy.

Methods

This retrospective cohort study evaluated all patients who had undergone tonsillectomy between 2001 and 2009 as identified from the Taiwan National Health Insurance Research Database. For each post-tonsillectomy patient, 10 age-, sex-, and index date-matched controls without a history of tonsillectomy were randomly selected. Cox Proportional hazard model and propensity score model were performed to evaluate the association between tonsillectomy and deep neck infection after adjusting for demographic and clinical data.

Results

There were 34 (71.6 cases per 100,000 person-years) and 174 (36.6 cases per 100,000 person-years) patients that developed deep neck infection in the tonsillectomized and comparison cohorts, respectively. After adjusting for covariates, patients who had undergone a tonsillectomy had a 1.71-fold greater risk of deep neck infection by both Cox proportional hazard model (95% confidence interval, 1.13-2.59) and propensity score model (95% confidence interval, 1.10-2.66). This association was not altered regardless of the indication for tonsillectomy (i.e. chronic/recurrent tonsillitis or sleep apnea/hypertrophy of tonsil) (p = 0.9797).

Conclusions

Based on our review of a nationwide cohort study we identified that the risk of deep neck infection is significantly increased among patients who have undergone a tonsillectomy. Additional research is needed to explore the possible mechanisms behind these findings.     

Rhabdomyolysis in Community Acquired Bacterial Sepsis – A Retrospective Cohort Study

Background and Objectives

Rhabdomyolysis is often associated with sepsis and gram positive bacterial pathogens are reported to be the most frequent cause of sepsis induced rhabdomyolysis. We report the pattern of infecting bacterial pathogens and associated causal factors in a South-Indian cohort.

Design, Setting, Participants & Measurements

Retrospective cohort study of adult patients with community acquired bacterial sepsis complicated by rhabdomyolysis from March 2003 - August 2008. Rhabdomyolysis was defined as serum creatine kinase >2000 IU/L. The study population was divided into group-I (sepsis with gram positive pathogens), group–II (sepsis with gram negative pathogens) and group-III (culture negative sepsis).

Results

103 patients (group I -15, group II- 34 and group III- 54) formed the study cohort. Mean age was 55 years and two-third had diabetes. Mean creatine kinase was 7114 IU/L and mean serum creatinine on admission was 2.4 mg/dl. Causative pathogen of sepsis was identified in 47.5%. Gram negative pathogens were more frequently (33%) associated with rhabdomyolysis than gram positive pathogens (14.5%). Lung was the commonest foci of sepsis (38.8%). 78.6% of the study population had one or more additional causal factor for rhabdomyolysis like statin intake, chronic alcoholism, hypokalemia, hypernatremia and hypophosphatemia. Mortality was 59%.

Conclusions

Gram negative bacterial pathogens were more frequently associated with rhabdomyolysis than gram positive pathogens. Rhabdomyolysis in patients with sepsis is multifactorial and is associated with high mortality.     

PLASMANATE?—A New Plasma Substitute for Pediatric Therapy

Plasmanate®, a human-serum protein solution, appears to have all the attributes of an ideal plasma expander. Freedom from infection, immediate availability in a clear, stable solution and the apparent absence of antigenic properties are particularly valuable qualities. The efficacy and safety of Plasmanate was clinically demonstrated in the treatment of 125 infants and children. This solution seems especially effective in the treatment of acute shock states and for the physiologic correction of hypoproteinemia. Comparison with other plasma expanders makes Plasmanate the agent of choice in the initial treatment of shock states in pediatrics.     

Serum Autotaxin Is a Parameter for the Severity of Liver Cirrhosis and Overall Survival in Patients with Liver Cirrhosis – A Prospective Cohort Study

Background

Autotaxin (ATX) and its product lysophosphatidic acid (LPA) are considered to be involved in the development of liver fibrosis and elevated levels of serum ATX have been found in patients with hepatitis C virus associated liver fibrosis. However, the clinical role of systemic ATX in the stages of liver cirrhosis was unknown. Here we investigated the relation of ATX serum levels and severity of cirrhosis as well as prognosis of cirrhotic patients.

Methods

Patients with liver cirrhosis were prospectively enrolled and followed until death, liver transplantation or last contact. Blood samples drawn at the day of inclusion in the study were assessed for ATX content by an enzyme-linked immunosorbent assay. ATX levels were correlated with the stage as well as complications of cirrhosis. The prognostic value of ATX was investigated by uni- and multivariate Cox regression analyses. LPA concentration was determined by liquid chromatography-tandem mass spectrometry.

Results

270 patients were enrolled. Subjects with liver cirrhosis showed elevated serum levels of ATX as compared to healthy subjects (0.814±0.42 mg/l vs. 0.258±0.40 mg/l, P<0.001). Serum ATX levels correlated with the Child-Pugh stage and the MELD (model of end stage liver disease) score and LPA levels (r = 0.493, P = 0.027). Patients with hepatic encephalopathy (P = 0.006), esophageal varices (P = 0.002) and portal hypertensive gastropathy (P = 0.008) had higher ATX levels than patients without these complications. Low ATX levels were a parameter independently associated with longer overall survival (hazard ratio 0.575, 95% confidence interval 0.365–0.905, P = 0.017).

Conclusion

Serum ATX is an indicator for the severity of liver disease and the prognosis of cirrhotic patients.     

Laparoscopic Hepatectomy for Hepatic Colorectal Metastases – A Retrospective Comparative Cohort Analysis and Literature Review

Background

Laparoscopic hepatectomy (LH) for management of hepatic colorectal metastases (HCRM) is commonly being performed; however, there are limited reports comparing LH outcomes with those of open hepatectomy (OH) procedure. The aim of the present study was to compare perioperative outcomes between the LH and OH procedures performed at a single medical center.

Methods

From Jan 2008 to May 2012, 30 patients with pathologically confirmed HCRM underwent LH, and 140 patients underwent OH at our hospital. Patients'' demographics, perioperative outcomes were retrospectively analyzed.

Results

2 patients (6.7%) in the LH group underwent laparotomies for intraoperative hemorrhage. The LH group had an increased surgical duration (235 min vs. 365 min, (P<0.001), shorter hospital stay (7.5 days vs. 11.5 days, P<0.001), and fewer complications (26.2% vs. 55%, P<0.001) than the OH group. However, in a matched cohort comparison of 30 LH cases and 30 OH cases, no significant variations were observed in the following parameters: surgical duration (235 min vs. 255 min, P = 0.23), positive margin rates (6.7% vs. 0.0%, P = 0.27), or postoperative hematological changes. LH patients had less estimated blood loss (215 ml vs. 385 ml, P<0.001), less morbidity (26.2% vs. 50%, P = 0.02), shorter hospital stay (7.5 days vs. 11.5 days, P<0.001), and lower analgesic requests than with those in the OH group.

Conclusions

LH for metastatic colorectal cancer is a safe and feasible treatment, even in patients who underwent prior laparotomy surgeries and provides significantly less morbidity and shorter hospital stay than OH, without compromising curability or increasing morbidity.     

Predicting Neuropathy and Reactions in Leprosy at Diagnosis and Before Incident Events—Results from the INFIR Cohort Study

Background

Leprosy is a disease of skin and peripheral nerves. The process of nerve injury occurs gradually through the course of the disease as well as acutely in association with reactions. The INFIR (ILEP Nerve Function Impairment and Reactions) Cohort was established to identify clinically relevant neurological and immunological predictors for nerve injury and reactions.

Methodology/Principal Findings

The study, in two centres in India, recruited 188 new, previously untreated patients with multi-bacillary leprosy who had no recent nerve damage. These patients underwent a series of novel blood tests and nerve function testing including motor and sensory nerve conduction, warm and cold detection thresholds, vibrometry, dynamometry, monofilament sensory testing and voluntary muscle testing at diagnosis and at monthly follow up for the first year and every second month for the second year. During the 2 year follow up a total of 74 incident events were detected. Sub-clinical changes to nerve function at diagnosis and during follow-up predicted these new nerve events. Serological assays at baseline and immediately before an event were not predictive; however, change in TNF alpha before an event was a statistically significant predictor of that event.

Conclusions/Significance

These findings increase our understanding of the processes of nerve damage in leprosy showing that nerve function impairment is more widespread than previously appreciated. Any nerve involvement, including sub-clinical changes, is predictive of further nerve function impairment. These new factors could be used to identify patients at high risk of developing impairment and disability.     

Survival after Acute Hemodialysis in Pennsylvania, 2005–2007: A Retrospective Cohort Study

Background

Little is known about acute hemodialysis in the US. Here we describe predictors of receipt of acute hemodialysis in one state and estimate the marginal impact of acute hemodialysis on survival after accounting for confounding due to illness severity.

Materials and Methods

This is a retrospective cohort study of acute-care hospitalizations in Pennsylvania from October 2005 to December 2007 using data from the Pennsylvania Health Care Cost Containment Council. Exposure variable is acute hemodialysis; dependent variable is survival following acute hemodialysis. We used multivariable logistic regression to determine propensity to receive acute hemodialysis and then, for a Cox proportional hazards model, matched acute hemodialysis and non-acute hemodialysis patients 1∶5 on this propensity.

Results

In 2,131,248 admissions of adults without end-stage renal disease, there were 6,657 instances of acute hemodialysis. In analyses adjusted for predicted probability of death upon admission plus other covariates and stratified on age, being male, black, and insured were independent predictors of receipt of acute hemodialysis. One-year post-admission mortality was 43% for those receiving acute hemodialysis, compared to 13% among those not receiving acute hemodialysis. After matching on propensity to receive acute hemodialysis and adjusting for predicted probability of death upon admission, patients who received acute hemodialysis had a higher risk of death than patients who did not over at least 1 year of follow-up (hazard ratio 1·82, 95% confidence interval 1·68–1·97).

Conclusions

In a populous US state, receipt of acute hemodialysis varied by age, sex, race, and insurance status even after adjustment for illness severity. In a comparison of patients with similar propensity to receive acute hemodialysis, those who did receive it were less likely to survive than those who did not. These findings raise questions about reasons for lack of benefit.     

Scrub Typhus Meningitis in South India — A Retrospective Study

Background

Scrub typhus is prevalent in India although definite statistics are not available. There has been only one study on scrub typhus meningitis 20 years ago. Most reports of meningitis/meningoencephalitis in scrub typhus are case reports

Methods

A retrospective study done in Pondicherry to extract cases of scrub typhus admitted to hospital between February 2011 and January 2012. Diagnosis was by a combination of any one of the following in a patient with an acute febrile illness- a positive scrub IgM ELISA, Weil-Felix test, and an eschar. Lumbar puncture was performed in patients with headache, nuchal rigidity, altered sensorium or cranial nerve deficits.

Results

Sixty five cases of scrub typhus were found, and 17 (17/65) had meningitis. There were 33 males and 32 females. Thirteen had an eschar. Median cerebrospinal fluid (CSF) cell count, lymphocyte percentage, CSF protein, CSF glucose/blood glucose, CSF ADA were 54 cells/µL, 98%, 88 mg/dL, 0.622 and 3.5 U/mL respectively. Computed tomography was normal in patients with altered sensorium and cranial nerve deficits. Patients with meningitis had lesser respiratory symptoms and signs and higher urea levels. All patients had received doxycycline except one who additionally received chloramphenicol.

Conclusion

Meningitis in scrub typhus is mild with quick and complete recovery. Clinical features and CSF findings can mimic tuberculous meningitis, except for ADA levels. In the Indian context where both scrub typhus and tuberculosis are endemic, ADA and scrub IgM may be helpful in identifying patients with scrub meningitis and in avoiding prolonged empirical antituberculous therapy in cases of lymphocytic meningitis.     

The Frequency and Determinants of Liver Stiffness Measurement Failure: A Retrospective Study of “Real-Life” 38,464 Examinations

Objective

To investigate the frequency and determinants of liver stiffness measurement (LSM) failure by means of FibroScan in “real-life” Chinese patients.

Methods

A total of 38,464 “real-life” Chinese patients in 302 military hospital of China through the whole year of 2013, including asymptomatic carrier, chronic hepatitis B, chronic hepatitis C, liver cirrhosis (LC), alcoholic liver disease, autoimmune liver disease, hepatocellular carcinoma (HCC) and other, were enrolled, their clinical and biological parameters were retrospectively investigated. Liver fibrosis was evaluated by FibroScan detection. S probe (for children with height less than 1.20 m) and M probe (for adults) were used. LSM failure defined as zero valid shots (unsuccessful LSM), or the ratio of the interquartile range to the median of 10 measurements (IQR/M) greater than 0.30 plus median LSM greater or equal to 7.1 kPa (unreliable LSM).

Results

LSM failure occurred in 3.34% of all examinations (1286 patients out of 38,464), among them, there were 958 cases (2.49%) with unsuccessful LSM, and 328 patients (0.85%) with unreliable LSM. Statistical analyses showed that LSM failure was independently associated with body mass index (BMI) greater than 30 kg/m², female sex, age greater than 50 years, intercostal spaces (IS) less than 9 mm, decompensated liver cirrhosis and HCC patients. There were no significant differences among other diseases. By changing another skilled operator, success was achieved on 301 cases out of 1286, which reduced the failure rate to 2.56%, the decrease was significant (P<0.0001).

Conclusions

The principal reasons of LSM failure are ascites, obesity and narrow of IS. The failure rates of HCC, decompensated LC, elder or female patients are higher. These results emphasize the need for adequate operator training, technological improvements and optimal criteria for specific patient subpopulations.     

Effect of Beta-Blocker Therapy on the Risk of Infections and Death after Acute Stroke – A Historical Cohort Study

BackgroundInfections are a frequent cause for prolonged hospitalization and increased mortality after stroke. Recent studies revealed a stroke-induced depression of the peripheral immune system associated with an increased susceptibility for infections. In a mice model for stroke, this immunosuppressive effect was reversible after beta-blocker administration. The aim of our study was to investigate the effect of beta-blocker therapy on the risk of infections and death after stroke in humans.Methods625 consecutive patients with ischemic or hemorrhagic stroke, admitted to a university hospital stroke unit, were included in this historical cohort study. The effect of beta-blocker therapy on post-stroke pneumonia, urinary tract infections and death was investigated using multivariable Poisson and Cox regression models.Results553 (88.3%) patients were admitted with ischemic stroke, the remaining 72 (11.7%) had a hemorrhagic stroke. Median baseline NIHSS was 8 (IQR 5–16) points. 301 (48.2%) patients received beta-blocker therapy. There was no difference in the risk of post-stroke pneumonia between patients with and without beta-blocker therapy (Rate Ratio = 1.00, 95%CI 0.77–1.30, p = 0.995). Patients with beta-blocker therapy showed a decreased risk for urinary tract infections (RR = 0.65, 95%CI 0.43–0.98, p = 0.040). 7-days mortality did not differ between groups (Hazard Ratio = 1.36, 95%CI 0.65–2.77, p = 0.425), while patients with beta-blocker therapy showed a higher 30-days mortality (HR = 1.93, 95%CI 1.20–3.10, p = 0.006).ConclusionsBeta-blocker therapy did not reduce the risk for post-stroke pneumonia, but significantly reduced the risk for urinary tract infections. Different immune mechanisms underlying both diseases might explain these findings that need to be confirmed in future studies.     

Cardioversion and Risk of Adverse Events with Dabigatran versus Warfarin—A Nationwide Cohort Study

Aim

Cardioversion can rapidly and effectively restore sinus rhythm in patients with persistent atrial fibrillation. Since 2011 dabigatran has been available as an alternative to warfarin to prevent thromboembolic events in patients with non-valvular atrial fibrillation undergoing cardioversion. We studied time to cardioversion, risk of adverse events, and risk of readmission with atrial fibrillation after cardioversion according to anticoagulation therapy.

Methods and Results

Through the nationwide Danish registries we included 1,230 oral anticoagulation naïve patients with first time non-valvular atrial fibrillation and first time cardioversion from 2011 to 2012; 37% in the dabigatran group (n = 456), and 63% in the warfarin group (n = 774). Median time to cardioversion was 4.0 (interquartile range [IQR] 2.9 to 6.5) and 6.9 (IQR 3.9 to 12.1) weeks in the dabigatran and warfarin groups respectively, and the adjusted odds ratio of cardioversion within the first 4 weeks was 2.3 (95% confidence interval [CI] 1.7 to 3.1) in favor of dabigatran. The cumulative incidence of composite endpoint of stroke, bleeding or death were 2.0% and 1.0% at 30 weeks in the warfarin and dabigatran groups respectively, with an adjusted hazard ratio of 1.33 (95% CI 0.33 to 5.42). Cumulative incidence of readmission with atrial fibrillation after 30 weeks were 9% and 11% in the warfarin and dabigatran groups, respectively, and an adjusted hazard ratio of 0.66 (95% CI 0.41 to 1.08).

Conclusion

Anticoagulation treatment with dabigatran allows shorter time to cardioversion for atrial fibrillation than warfarin, and appears to be an effective and safe alternative treatment strategy to warfarin.     

Organisational Factors Induce Prolonged Emergency Department Length of Stay in Elderly Patients – A Retrospective Cohort Study

Study objective

To assess the association of patient and organisational factors with emergency department length of stay (ED-LOS) in elderly ED patients (226565 years old) and in younger patients (<65 years old).

Methods

A retrospective cohort study of internal medicine patients visiting the emergency department between September 1^st 2010 and August 31^st 2011 was performed. All emergency department visits by internal medicine patients 226565 years old and a random sample of internal medicine patients <65 years old were included. Organisational factors were defined as non-medical factors. ED-LOS is defined as the time between ED arrival and ED discharge or admission. Prolonged ED-LOS is defined as ≥75^th percentile of ED-LOS in the study population, which was 208 minutes.

Results

Data on 1782 emergency department visits by elderly patients and 597 emergency department visits by younger patients were analysed. Prolonged ED-LOS in elderly patients was associated with three organisational factors: >1 consultation during the emergency department visit (odds ratio (OR) 3.2, 95% confidence interval (CI) 2.3–4.3), a higher number of diagnostic tests (OR 1.2, 95% CI 1.16–1.33) and evaluation by a medical student or non-trainee resident compared with a medical specialist (OR 4.2, 95% CI 2.0–8.8 and OR 2.3, 95% CI 1.4–3.9). In younger patients, prolonged ED-LOS was associated with >1 consultation (OR 2.6, 95% CI 1.4–4.6). Factors associated with shorter ED-LOS were arrival during nights or weekends as well as a high urgency level in elderly patients and self-referral in younger patients.

Conclusion

Organisational factors, such as a higher number of consultations and tests in the emergency department and a lower seniority of the physician, were the main aspects associated with prolonged ED-LOS in elderly patients. Optimisation of the organisation and coordination of emergency care is important to accommodate the needs of the continuously growing number of elderly patients in a better way.     

Maternal Use of Selective Serotonin Reuptake Inhibitors and Lengthening of the Umbilical Cord: Indirect Evidence of Increased Foetal Activity—A Retrospective Cohort Study

BackgroundAntenatal depression affects up to 19% of pregnant women. Some of these women are also in need of antidepressant treatment. Nevertheless, the impact of maternal antidepressant treatment and prenatal depression on the course of pregnancy, foetal development and delivery outcomes is not fully understood.MethodsWe analysed data from 24 818 women who gave birth at Kuopio University Hospital between 2002–2012. Logistic regression analysis was used to estimate associations between the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and the progression of pregnancy, development of the foetus and delivery outcomes.ResultsAltogether, 369 (1.5%) women used SSRIs. A regression model adjusted for age, overweight, nulliparity, prior termination, miscarriages, smoking, maternal alcohol consumption, chronic illness and polyhydramnion showed that pregnant women exposed to SSRI medication had significantly lower Apgar scores at 1 minute (p < 0.0001) and 5 minutes (p < 0.0001) and more admissions to the neonatal intensive care unit (p < 0.0001) than unexposed pregnant women. In addition, exposed newborns had longer umbilical cords (p < 0.0001) than non-exposed newborns.ConclusionIn addition to the previously known associates with maternal SSRI exposure, such as lowered Apgar scores, SSRI exposure appeared to be associated with increased umbilical cord length. The observation related to increased umbilical cord length may be explained by an SSRI-induced increase in the movements of the developing foetus.     

Pneumocystis Carinii Pneumonia—Problems in Diagnosis and Therapy in 24 Cases

Twenty-four instances of Pneumocystis carinii pneumonia were recognized in 23 patients at the Stanford University Hospitals between 1962 and 1970. The affected persons could be broadly characterized as “compromised” hosts. All but one were receiving immunosuppressive drug therapy for such underlying disease as hematopoietic malignant disease, collagen vascular disorder, and organ transplant rejection. The one patient not receiving immunosuppressant medication had congenital dysgammaglobulinemia and suffered two discrete bouts of pneumocystis pneumonia. Most of the patients were concomitantly infected with other “opportunistic” pathogens.Open lung biopsy remained the most reliable method of antemortem diagnosis of pneumocystis infection during this eight-year period. It resulted in little morbidity. Unfortunately, direct examination of appropriately stained sputum specimens for cysts was almost uniformly nonproductive.The majority of patients received specific antipneumocystis drug treatment (pentamidine isethionate or pyrimethamine and sulfadiazine). “Cure” was achieved when institution of therapy was prompt and duration of therapy approached the empirically recommended two-week course.The fact that pneumocystis pneumonia can be controlled if recognized early is compelling reason to pursue diagnosis of pneumocystosis in an appropriate clinical setting, namely, in patients with impaired host defenses who have pulmonary infection unresponsive to conventional therapy. There is hope that a noninvasive (serological) technique will be developed shortly to simplify identification of this not uncommon cause of diffuse interstitial pneumonitis.     

Longitudinal Study of a Human Drug-Induced Model of Autoantibody to Cytoplasmic Rods/Rings following HCV Therapy with Ribavirin and Interferon-α

Background

A novel pattern in the indirect immunofluorescence antinuclear antibody assay on HEp-2 cells (IIF-HEp-2) characterized by cytoplasmic rods and rings (RR) was reported in HCV patients, but stringent disease specificity studies and longitudinal analysis are lacking. We investigated the clinical significance of anti-RR in an HCV cohort with up to a 12-month treatment follow up.

Methodology/Results

597 patients (342 HCV, 55 HCV/HIV, 200 non-HCV) were screened and titered for anti-RR. Serial samples were available from 78 of 176 treated and 27 of 166 untreated patients. Anti-RR was detected in 14.1% of 342 HCV patients, 9.1% of 55 HCV/HIV, 3.4% of 29 Hepatitis B, and none of 171 non-HCV (p<0.0001; HCV versus non-HCV). Anti-RR was present in 38% of 108 patients receiving interferon-α/ribavirin, but none in 26 receiving either interferon-α or ribavirin, or 166 untreated patients (p<0.0001). Other IIF-HEp-2 patterns were more frequently associated with interferon-α treatment alone (52.2%) as compared to interferon-α/ribavirin (25%), ribavirin alone (33.3%), and no therapy (26.5%). Anti-RR frequency was not associated with sex, age, ethnicity, HCV genotype or viral load. Anti-RR occurred only after initiation of treatment, beginning as early as 1 month (6%), but by the sixth month >47% tested positive for anti-RR. The anti-RR titer generally increased with sustained treatment and remained high in 53% of patients. After treatment, anti-RR titer was negative in 41%. Non-responders to HCV therapy were 77% in anti-RR-positive versus 64% in anti-RR-negative patients. Response to treatment was not associated with anti-RR titer or the dynamics of anti-RR reactivity during and after treatment.

Conclusions

The exquisite association of anti-RR reactivity with combined interferon-α/ribavirin therapy in HCV patients represents a unique model for drug-induced autoantibody generation in humans as demonstrated by the fact that a significant fraction of patients who have anti-RR during therapy becomes anti-RR-negative after completion of therapy.