Patient profiled data for treatment decision-making: valuable as an add-on to hepatitis C clinical guidelines?

BACKGROUND AND AIMS: Systematic reviews and medical guidelines are widely used in clinical practice. However, these are often not up-to-date and focussed on the average patient. We therefore aimed to evaluate a guideline add-on, TherapySelector (TS), which is based on monthly updated data of all available high-quality studies, classified in specific patient profiles. METHODS: We evaluated the TS for the treatment of hepatitis C (HCV) in an international cohort of patients treated with direct-acting antivirals between 2015 and 2020. The primary outcome was the number of patients receiving one of the two preferred treatment options of the HCV TS, based on the highest level of evidence, cure rate, absence of ribavirin-associated adverse effects, and treatment duration. RESULTS: We enrolled 567 patients. The number of patients treated with one of the two preferred treatment options according to the HCV TS ranged between 27% (2015) and 60% (2020; p < 0.001). Most of the patients received a regimen with a longer treatment-duration (up to 34%) and/or addition of ribavirin (up to 14%). The effect on the expected cure-rate was minimal (1-6% higher) when the first preferred TherapySelector option was given compared to the actual treatment. CONCLUSIONS: Medical decision-making can be optimised by a guideline add-on; in HCV its use appears to minimise adverse effects and cost. The use of such an add-on might have a greater impact in diseases with suboptimal cure-rates, high costs or adverse effects, for which treatment options rely on specific patient characteristics.

Comparison of lumen-apposing metal stents versus double-pigtail plastic stents for infected necrotising pancreatitis.

OBJECTIVE: Lumen-apposing metal stents (LAMS) are believed to clinically improve endoscopic transluminal drainage of infected necrosis when compared with double-pigtail plastic stents. However, comparative data from prospective studies are very limited. DESIGN: Patients with infected necrotising pancreatitis, who underwent an endoscopic step-up approach with LAMS within a multicentre prospective cohort study were compared with the data of 51 patients in the randomised TENSION trial who had been assigned to the endoscopic step-up approach with double-pigtail plastic stents. The clinical study protocol was otherwise identical for both groups. Primary end point was the need for endoscopic transluminal necrosectomy. Secondary end points included mortality, major complications, hospital stay and healthcare costs. RESULTS: A total of 53 patients were treated with LAMS in 16 hospitals during 27 months. The need for endoscopic transluminal necrosectomy was 64% (n=34) and was not different from the previous trial using plastic stents (53%, n=27)), also after correction for baseline characteristics (OR 1.21 (95% CI 0.45 to 3.23)). Secondary end points did not differ between groups either, which also included bleeding requiring intervention-5 patients (9%) after LAMS placement vs 11 patients (22%) after placement of plastic stents (relative risk 0.44; 95% CI 0.16 to 1.17). Total healthcare costs were also comparable (mean difference -€6348, bias-corrected and accelerated 95% CI -€26 386 to €10 121). CONCLUSION: Our comparison of two patient groups from two multicentre prospective studies with a similar design suggests that LAMS do not reduce the need for endoscopic transluminal necrosectomy when compared with double-pigtail plastic stents in patients with infected necrotising pancreatitis. Also, the rate of bleeding complications was comparable.

Diagnostic accuracy of endoscopic ultrasonography-guided tissue acquisition prior to resection of pancreatic carcinoma: a nationwide analysis.

INTRODUCTION: Endoscopic ultrasonography guided tissue acquisition (EUS + TA) is used to provide a tissue diagnosis in patients with suspected pancreatic cancer. Key performance indicators (KPI) for these procedures are rate of adequate sample (RAS) and sensitivity for malignancy (SFM). AIM: assess practice variation regarding KPI of EUS + TA prior to resection of pancreatic carcinoma in the Netherlands. PATIENTS AND METHODS: Results of all EUS + TA prior to resection of pancreatic carcinoma from 2014-2018, were extracted from the national Dutch Pathology Registry (PALGA). Pathology reports were classified as: insufficient for analysis (b1), benign (b2), atypia (b3), neoplastic other (b4), suspected malignant (b5), and malignant (b6). RAS was defined as the proportion of EUS procedures yielding specimen sufficient for analysis. SFM was calculated using a strict definition (malignant only, SFM-b6), and a broader definition (SFM-b5+6). RESULTS: 691 out of 1638 resected patients (42%) underwent preoperative EUS + TA. RAS was 95% (range 89-100%), SFM-b6 was 44% (20-77%), and SFM-b5+6 was 65% (53-90%). All centers met the performance target RAS>85%. Only 9 out of 17 met the performance target SFM-b5+6 > 85%. CONCLUSION: This nationwide study detected significant practice variation regarding KPI of EUS + TA procedures prior to surgical resection of pancreatic carcinoma. Therefore, quality improvement of EUS + TA is indicated.

Low value of second-look endoscopy for detecting residual colorectal cancer after endoscopic removal.

BACKGROUND AND AIMS: Endoscopic resection is often feasible for submucosal invasive colorectal cancers (T1 CRCs) and usually judged as complete. If histology casts doubt on the radicality of resection margins, adjuvant surgical resection is advised, although residual intramural cancer is found in only 5% to 15% of patients. We assessed the sensitivity of biopsy specimens from the resection area for residual intramural cancer as a potential tool to estimate the preoperative risk of residual intramural cancer in patients without risk factors for lymph node metastasis (LNM). METHODS: In this multicenter prospective cohort study, patients with complete endoscopic resection of T1 CRC, scheduled for adjuvant resection due to pathologically unclear resection margins, but absent risk factors for LNM, were asked to consent to second-look endoscopy with biopsies. The results were compared with the pathology results of the surgical resection specimen (criterion standard). RESULTS: One hundred three patients were included. In total, 85% of resected lesions were unexpectedly malignant, and 45% were removed using a piecemeal resection technique. Sixty-four adjuvant surgical resections and 39 local full-thickness resections were performed. Residual intramural cancer was found in 7 patients (6.8%). Two of these patients had cancer in second-look biopsy specimens, resulting in a sensitivity of 28% (95% confidence interval, <58%). The preoperative risk of residual intramural cancer in the case of negative biopsy specimens was not significantly reduced (P = .61). CONCLUSIONS: The sensitivity of second-look endoscopy with biopsies for residual intramural cancer after endoscopic resection of CRC is low. Therefore, it should not be used in the decision whether or not to perform adjuvant resection. (Clinical trial registration number: NCT02328664.).

Pancreatic cyst surveillance imposes low psychological burden.

BACKGROUND/OBJECTIVES: For the currently recommended pancreatic cyst surveillance to be feasible, participant adherence is a prerequisite. Our objective was to evaluate the psychological burden of pancreatic cyst surveillance from a participant's perspective. METHODS: The present participant survey is part of an international cohort study (PACYFIC study, www.pacyfic.net), which prospectively records the outcome of surveillance of asymptomatic pancreatic cysts. Participants are invited to complete questionnaires before and during cyst surveillance. RESULTS: 109 participants, 31 enrolled before and 78 during surveillance (median time since cyst diagnosis 16.5 (IQR 36) months), returned a total of 179 questionnaires. The majority indicated that surveillance reduces concerns of developing pancreatic cancer (82%), gives a sense of certainty (81%) and is a good method to detect cancer (91%). Participants already undergoing surveillance reported more negative aspects than those still to commence, like sleeping worse (30% vs 13%, P = 0.035), postponing plans (32% vs 13%, P = 0.031), and finding the follow-up burdensome (33% vs 13%, P = 0.044). Overall, the vast majority (94%) deemed advantages to outweigh disadvantages. Anxiety and depression scores were low (median Hospital Anxiety and Depression Scale 4 for anxiety (IQR 6), 2 for depression (IQR 5)). CONCLUSION: The psychological burden of pancreatic cyst surveillance is low. Therefore, participant adherence is expected to be high and annual surveillance seems feasible.

Sustained response and HBsAg loss after nucleo(s)tide analogue discontinuation in chronic hepatitis B patients: the prospective SNAP study.

BACKGROUND & AIM(S): Current guidelines suggest that nucleos(t)ide analogues (NA) can be discontinued before HBsAg loss in a selected group of chronic hepatitis B (CHB) patients. We aimed to study the safety and off-treatment response after NA cessation. METHODS: This is a prospective, multicentre, cohort study in which eligible patients discontinued NA therapy. Adult patients, with a CHB mono-infection, HBeAg-negative, without a (history of) liver cirrhosis, who had achieved long-term viral suppression were eligible. Follow-up visits were planned at week 2-4-8-12-24-36-48-72-96. Re-treatment criteria included severe hepatitis (ALT >10x ULN), signs of imminent liver failure (bilirubin >1.5x ULN or INR >1.5), or at the physician's own discretion. RESULTS: In total, 33 patients were enrolled. Patients were predominantly Caucasian (45.5%) and had genotype A/B/C/D/unknown in 3/4/6/10/10 (9.1/12.1/18.2/30.3/30.3%). At week 48, 15 patients (45.5%) achieved a sustained response (HBV DNA <2,000 IU/mL). At week 96, 13 patients (39.4%) achieved a sustained response, 4 (12.1%) achieved HBsAg loss, and 12 (36.4%) were re-treated. Severe hepatitis was the main reason for re-treatment (n=7, 21.2%). One patient with severe hepatitis developed jaundice, without signs of hepatic decompensation. Re-treatment was successful in all patients. CONCLUSION: NA therapy can be ceased in a highly selected group of CHB patients if close follow-up can be guaranteed. Treatment cessation may increase the chance of HBsAg loss in selected patients, which is counterbalanced by a significant risk of severe hepatitis.

Patients treated with rituximab are poorly screened for hepatitis B infection: Data from a low-incidence country.

BACKGROUND & AIMS: Patients with chronic or resolved hepatitis B are at risk of hepatitis B reactivation (HBVr) when treated with high-risk immunosuppressive therapy such as rituximab. Therefore, international guidelines recommend HBV screening prior to rituximab treatment and subsequent antiviral prophylaxis among patients with a (resolved) infection. In this study, we evaluated the adherence to those recommendations. METHODS: This is a retrospective multicentre study including patients treated with rituximab between 2000-2021. Performance of correct screening was assessed, defined as the measurement of hepatitis B surface antigen (HBsAg) and hepatitis B core antibodies (anti-HBc). Next, initiation of antiviral prophylaxis and HBVr rate among patients with a chronic or resolved HBV infection was studied. RESULTS: We enrolled 3,176 patients of whom 1,448 (46%) were screened correctly. Screening rates differed significantly between academic and non-academic hospitals; respectively 65% vs 32% (p<0.001). In addition, screening rates differed across specialties and improved throughout the years; from 32% before 2012 to 75% after 2020 among academic prescribers, versus 1% to 60% among non-academic prescribers (both p<0.001). Antiviral prophylaxis was initiated in 58% vs 36% of the patients with a chronic or resolved HBV infection. Seven patients experienced HBVr, including one fatal liver decompensation. CONCLUSIONS: Many patients treated with rituximab were not correctly screened for HBV infection and antiviral prophylaxis was often not initiated. Although screening rates improved over time, rates remain suboptimal. With the increasing number of indications for rituximab and other immunosuppressive agents these findings could raise awareness among all medical specialties prescribing these agents.

The additive value of CA19.9 monitoring in a pancreatic cyst surveillance program.

BACKGROUND: Surveillance of pancreatic cysts focuses on the detection of (mostly morphologic) features warranting surgery. European guidelines consider elevated CA19.9 as a relative indication for surgery. We aimed to evaluate the role of CA19.9 monitoring for early detection and management in a cyst surveillance population. METHODS: The PACYFIC-registry is a prospective collaboration that investigates the yield of pancreatic cyst surveillance performed at the discretion of the treating physician. We included participants for whom at least one serum CA19.9 value was determined by a minimum follow-up of 12 months. RESULTS: Of 1865 PACYFIC participants, 685 met the inclusion criteria for this study (mean age 67 years, SD 10; 61% female). During a median follow-up of 25 months (IQR 24, 1966 visits), 29 participants developed high-grade dysplasia (HGD) or pancreatic cancer. At baseline, CA19.9 ranged from 1 to 591 kU/L (median 10 kU/L [IQR 14]), and was elevated (≥37 kU/L) in 64 participants (9%). During 191 of 1966 visits (10%), an elevated CA19.9 was detected, and these visits more often led to an intensified follow-up (42%) than those without an elevated CA19.9 (27%; p < 0.001). An elevated CA19.9 was the sole reason for surgery in five participants with benign disease (10%). The baseline CA19.9 value was (as continuous or dichotomous variable at the 37 kU/L threshold) not independently associated with HGD or pancreatic cancer development, whilst a CA19.9 of ≥ 133 kU/L was (HR 3.8, 95% CI 1.1-13, p = 0.03). CONCLUSIONS: In this pancreatic cyst surveillance cohort, CA19.9 monitoring caused substantial harm by shortening surveillance intervals (and performance of unnecessary surgery). The current CA19.9 cutoff was not predictive of HGD and pancreatic cancer, whereas a higher cutoff may decrease false-positive values. The role of CA19.9 monitoring should be critically appraised prior to implementation in surveillance programs and guidelines.

Cumulative sum learning curves guiding multicenter multidisciplinary quality improvement of EUS-guided tissue acquisition of solid pancreatic lesions.

Background and study aims In this study, we evaluated the performance of community hospitals involved in the Dutch quality in endosonography team regarding yield of endoscopic ultrasound (EUS)-guided tissue acquisition (TA) of solid pancreatic lesions using cumulative sum (CUSUM) learning curves. The aims were to assess trends in quality over time and explore potential benefits of CUSUM as a feedback-tool. Patients and methods All consecutive EUS-guided TA procedures for solid pancreatic lesions were registered in five community hospitals between 2015 and  2018. CUSUM learning curves were plotted for overall performance and for performance per center. The American Society of Gastrointestinal Endoscopy-defined key performance indicators, rate of adequate sample (RAS), and diagnostic yield of malignancy (DYM) were used for this purpose. Feedback regarding performance was provided on multiple occasions at regional interest group meetings during the study period. Results A total of 431 EUS-guided TA procedures in 403 patients were included in this study. The overall and per center CUSUM curves for RAS improved over time. CUSUM curves for DYM revealed gradual improvement, reaching the predefined performance target (70 %) overall, and in three of five contributing centers in 2018. Analysis of a sudden downslope development in the CUSUM curve of DYM in one center revealed temporary absence of a senior cytopathologist to have had a temporary negative impact on performance. Conclusions CUSUM-derived learning curves allow for assessment of best practices by comparison among peers in a multidisciplinary multicenter quality improvement initiative and proved to be a valuable and easy-to-interpret means to evaluate EUS performance over time.

Optimizing cytological specimens of EUS-FNA of solid pancreatic lesions: A pilot study to the effect of a smear preparation training for endoscopy personnel on sample quality and accuracy.

BACKGROUND: In the absence of rapid on-side pathological evaluation, endoscopy staff generally "smears" endoscopic ultrasound guided fine needle aspiration (EUS-FNA) specimens on a glass slide. As this technique is vulnerable to preparation artifacts, we assessed if its quality could be improved through a smear-preparation-training for endoscopy staff. METHODS: In this prospective pilot study, 10 endosonographers and 12 endoscopy nurses from seven regional EUS-centers in the Netherlands were invited to participate in a EUS-FNA smear-preparation-training. Subsequently, post training slides derived from solid pancreatic lesions were compared to pre-training "control" slides. Primary outcome was to assess if the training positively affects smear quality and, consequently, diagnostic accuracy of EUS-FNA of solid pancreatic lesions. RESULTS: Participants collected and prepared 71 cases, mostly pancreatic head lesions (48%). Sixty-eight controls were selected from the pretraining period. The presence of artifacts was comparable for smears performed before and after training (76% vs 82%, P = .36). Likewise, smear cellularity (≥50% target cells) before and after training did not differ (44% (30/68) vs 49% (35/71), P = .48). Similar, no difference in diagnostic accuracy for malignancy was detected (P = .10). CONCLUSION: In this pilot EUS-FNA smear-preparation-training for endoscopy personnel, smear quality and diagnostic accuracy were not improved after the training. Based on these results, we plan to further study other training programs and possibilities.

Diagnostic yield and agreement on fine-needle specimens from solid pancreatic lesions : comparing the smear technique to liquid-based cytology.

Background and study aims The traditional "smear technique" for processing and assessing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is sensitive to artifacts. Processing and evaluation of specimens collected in a liquid medium, liquid-based cytology (LBC) may be a solution. We compared the diagnostic value of EUS-FNA smears to LBC in pancreatic solid lesions in the absence of rapid on-site evaluation (ROSE). Patients and methods Consecutive patients who required EUS-FNA of a solid pancreatic lesion were included in seven hospitals in the Netherlands and followed for at least 12 months. Specimens from the first pass were split into two smears and a vial for LBC (using ThinPrep and/or Cell block). Smear and LBC were compared in terms of diagnostic accuracy for malignancy, sample quality, and diagnostic agreement between three cytopathologists. Results Diagnostic accuracy for malignancy was higher for LBC (82 % (58/71)) than for smear (66 % (47/71), P  = 0.04), but did not differ when smears were compared to ThinPrep (71 % (30/42), P  = 0.56) or Cell block (62 % (39/63), P  = 0.61) individually. Artifacts were less often present in ThinPrep (57 % (24/42), P  = 0.02) or Cell block samples (40 % (25/63), P  < 0.001) than smears (76 % (54/71)). Agreement on malignancy was equally good for smears and LBC (ĸ = 0.71 versus ĸ = 0.70, P  = 0.98), but lower for ThinPrep (ĸ = 0.26, P  = 0.01) than smears. Conclusion After a single pass, LBC provides higher diagnostic accuracy than the conventional smear technique for EUS-FNA of solid pancreatic lesions in the absence of ROSE. Therefore, LBC, may be an alternative to the conventional smear technique, especially in centers lacking ROSE.

Collaboration of community hospital endosonographers improves diagnostic yield of endoscopic ultrasonography guided tissue acquisition of solid pancreatic lesions.

Background and study aims Endoscopic ultrasound (EUS)-guided tissue acquisition (TA) is the method of choice for establishing a pathological diagnosis of solid pancreatic lesions. Data on quality and yield of EUS-guided TA performed in community hospitals are lacking. A study was performed to determine and improve the diagnostic yield of EUS-guided TA in a group of community hospitals. Methods Following analysis of the last 20 EUS-guided TA procedures of solid pancreatic lesions performed in each of four community hospitals, a collaborative EUS interest group was formed and a prospective registry was started. During meetings of the interest group, feedback on results per center were provided and strategies for improvement were discussed. Results In the BEFORE team formation cohort, 80 procedures were performed in 66 patients. In the AFTER team formation cohort, 133 procedures were performed in 125 patients. After team formation, the rate of adequate sample increased from 80 % (95 %CI [0.7 - 0.9]) to 95 % (95 %CI [0.9 - 1.0]) , diagnostic yield of malignancy improved from 28 % (95 %CI [0.2 - 0.4]) to 64 % (95 % CI [0.6 - 0.7]), and sensitivity of malignancy improved from 63 % (95 %CI [0.4 - 0.8]) to 84 % (95 %CI [0.8 - 0.9]). Multivariate regression analysis revealed team formation to be the only variable significantly associated with an increased rate of adequate sample. Conclusions Formation of a regional EUS interest group with regular feedback on results per center, and discussions on methods and techniques used, significantly improved the outcome of EUS-guided TA procedures in patients with solid pancreatic lesions in community hospitals.

[Nephrotic syndrome in Crohn's disease]. / Nefrotisch syndroom bij de ziekte van Crohn.

BACKGROUND: The differential diagnosis of nephrotic syndrome is diverse. Systemic conditions and medication such as NSAIDs can cause this syndrome. CASE DESCRIPTION: A 33-year-old male with Crohn's disease for which he was receiving adalimumab noticed he was gaining weight and had swollen ankles. Examination revealed nephrotic syndrome without renal insufficiency. Renal biopsy showed a membranous glomerulopathy. We excluded secondary causes of membranous glomerulopathy such as diabetes mellitus, systemic lupus erythematosus, viral infection or malignancy. We treated the patient with high-dose glucocorticoids on a weaning schedule and adalimumab was discontinued. This regimen resulted in complete remission. It is likely that the nephrotic syndrome with membranous glomerulopathy was associated with adalimumab. CONCLUSION: In patients with nephrotic syndrome based on membranous glomerulopathy both primary and secondary causes, such as use of medication, need to be excluded.

[Revision of the practical guideline 'Treatment of chronic viral hepatitis B infection']. / Revisie van de richtlijn 'Behandeling van chronische hepatitis B-virusinfectie'.

This article contains our comments on the practical guideline for treating chronic hepatitis B in the Netherlands, which was published in 2008. Revision of this guideline had already become necessary in 2011 due to rapidly changing therapeutic strategies. New second-generation drugs show minimal antiviral resistance and their use should be considered more frequently. In addition, certified multidisciplinary centres of expertise should contribute to the improvement of care for patients with chronic hepatitis B. Our opinion is that the revisions make the guideline for treating chronic hepatitis B more complete and up to date.

A solitary Peutz-Jeghers type polyp in the jejunum of a 19 year-old male.

A 19-year old male presented with melena and anemia. A duodenoscopy revealed no abnormalities, but a small bowel X-ray series demonstrated a large jejunal polyp. This 4 cm large polyp was visualised during peroperative small bowel endoscopy and was subsequently surgically removed. The polyp had the characteristic histologic appearance of a Peutz-Jeghers type polyp, but the patient had no other signs of Peutz-Jeghers syndrome, such as the characteristic mucocutaneous pigmentation, the presence of multiple polyps or a positive family history. After removal of the polyp, melena did not recur and his hemoglobin concentration normalized. Altogether, the patient does not fulfill the diagnostic criteria for Peutz-Jeghers syndrome and appears to have a solitary jejunal Peutz-Jeghers type polyp. All previously reported patients with such polyps were older than this patient.

Environmental monitoring of hydrophobic organic contaminants: the case of mussels versus semipermeable membrane devices.

Concentrations of hydrophobic chemicals in mussels and semipermeable membrane devices (SPMDs) from nine studies published over the past decade, amended with new data obtained in the Scheldt-North Sea area, were assessed to understand the similarities and differences between these sampling matrixes. A model was developed to describe the concentration ratios, using literature values of elimination rate constants and steady-state accumulation factors of both samplers as key parameters. The model could successfully describe the results of seven studies. Differences in concentration ratios among these studies were related to the variability of mussel bioaccumulation factors (BAFs) and water sampling rates of SPMDs. For two studies, the model could only describe the data by adopting unrealistically high water sampling rates, and for one study there were not enough data to test the model. We argue that SPMDs will generally yield more reliable estimates of exposure concentrations than mussels, because in situ BAF values are difficult to estimate, whereas the in situ exchange kinetics of SPMDs can be quantified by measuring the dissipation rates of performance reference compounds. The implications of the results for future and existing monitoring programs are discussed.

Risk factors for the development of esophageal adenocarcinoma in Barrett's esophagus.

OBJECTIVE: To identify risk factors for esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). METHODS: A hospital-based case-control study was performed in which 91 cases with EAC and 244 controls with histologically confirmed BE (>2 cm) with no dysplasia or low-grade dysplasia were included. Information on demographic, anthropometric, and lifestyle characteristics, physical activity levels, working posture, family history, gastroesophageal reflux disease (GERD) symptoms, and medication use was collected by questionnaire. RESULTS: Cases more often were current smokers (odds ratio 3.7, 95% confidence interval 1.4-9.9), more often had a body mass index >25 assessed at age 20 (2.6, 1.2-5.5), and more frequently had been working in a stooped posture at age 20 (2.0, 1.1-3.9), compared to controls. In addition, cases less often experienced symptoms of heartburn (0.3, 0.2-0.5) and less frequently used proton pump inhibitors (0.1, 0.05-0.2), compared to controls, whereas use of nonsteroidal anti-inflammatory drugs/aspirin was more common among cases (1.8, 1.1-3.2). Cases more often were men, compared to controls (91%vs 67%, p < 0.001). CONCLUSION: In patients with BE, the risk of EAC is related to risk factors for GERD, which is, however, asymptomatic. As these risk factors are common in Western countries, they are probably not helpful in individualization of surveillance intervals.

Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B.

Data on the long-term effects of interferon alfa (IFN) treatment on disease progression and mortality in patients with chronic hepatitis B (CHB) are limited. To evaluate factors that influence clinical outcome and survival, we performed a follow-up study on 165 hepatitis B e antigen (HBeAg) positive CHB patients treated with IFN between 1978 and 2002. The median IFN dose was 30 megaunits (MU)/week (range, 2-70 MU/week), and the median duration of therapy was 16 weeks (range, 1-92 weeks). Response to treatment was defined as HBeAg loss within 12 months after the end of IFN therapy. Median follow-up was 8.8 years (range, 0.3-24 years). Fifty-four patients (33%) responded to IFN treatment. Relapse (HBeAg reactivation) occurred in 7 of the 54 (13%) responders. Fifty-two percent of the responders lost hepatitis B surface antigen (HBsAg) as compared with 9% of the nonresponders (P <.001). Liver histology showed a decreased necroinflammatory activity and less progression of fibrosis in responders. Twenty-six patients died during follow-up. Hepatocellular carcinoma (HCC) was found in 8 patients, 6 of whom were nonresponders. Of the two responders who developed HCC, one patient had relapsed after discontinuation of therapy. Multivariate analysis showed significantly improved survival (relative risk (RR) of death 0.28, 95% CI 0.10-0.78) and reduced risk of developing HCC (RR 0.084, 95% CI 0.09-0.75) in responders. In conclusion, response to IFN therapy results in a prolonged clinical remission with an increased rate of HBsAg seroconversion and improved liver histology. Our results indicate that after correction for baseline factors, response to IFN therapy increases survival and reduces the risk of developing HCC.