Siu-Tong Law

Nephrotoxicity, including acquired Fanconi's syndrome, caused by adefovir dipivoxil - is there a safe dose?

Summary n n nWhat is known and Objective:u2002 Adefovir dipivoxil (ADV) is an oral bioavailable prodrug of adefovir that possesses potent in vitro activity against hepadnaviruses, retroviruses and herpes viruses. ADV is excreted unchanged in the urine through glomerular filtration and tubular secretion and is known to be nephrotoxic at doses of 60xa0mg daily and above. Thus, the long-term safety of ADV, particularly nephrotoxicity, is a major concern. Our objective is to comment on the nephrotoxcicity of low-dose (10xa0mg daily) ADV through a case report. n n n nComment:u2002 The clinical features of nephrotoxicity because of ADV are described. A case report of acquired Fanconi’s syndrome in a chronic hepatitis B patient treated with ADV 10xa0mg daily is used to illustrate several key aspects. n n n nWhat is new and Conclusion:u2002 Adefovir dipivoxil can be nephrotoxic at conventional dosage and therefore, patients treated with long-term ADV should have regular monitoring of renal function, and calcium and phosphate levels.What is known and Objective:u2002 Adefovir dipivoxil (ADV) is an oral bioavailable prodrug of adefovir that possesses potent in vitro activity against hepadnaviruses, retroviruses and herpes viruses. ADV is excreted unchanged in the urine through glomerular filtration and tubular secretion and is known to be nephrotoxic at doses of 60u2003mg daily and above. Thus, the long‐term safety of ADV, particularly nephrotoxicity, is a major concern. Our objective is to comment on the nephrotoxcicity of low‐dose (10u2003mg daily) ADV through a case report.

Acquired Fanconi syndrome associated with prolonged adefovir dipivoxil therapy in a chronic hepatitis B patient.

Adefovir dipivoxil (ADV) is one of the commonly used antiviral agents in the treatment of chronic hepatitis B infection. Nephrotoxicity is dose related and occurred at a daily dosage of >30 mg. However, it is now increasingly recognized that nephrotoxicity can occur at a daily dose of 10 mg. We present a case of acquired Fanconi syndrome in a patient with chronic hepatitis B who had been treated with ADV for 4 years. She presented with progressive muscle weakness and generalized bone pain. The laboratory results showed the feature of proximal renal tubule dysfunction, particularly severe hypophosphatemia. Diagnostic approach to hypophosphatemia and proximal renal tubular dysfunction is discussed. After switching over from ADV to entecavir, her symptoms and laboratory findings returned to normal. Acquired Fanconi syndrome can be associated with ADV at a conventional dosage, and therefore, patients treated with long-term ADV should have regular monitoring of renal function and calcium and phosphate levels.

Is pyogenic liver abscess associated with recurrent pyogenic cholangitis a distinct clinical entity? A retrospective analysis over a 10-year period in a regional hospital.

Background Recurrent pyogenic cholangitis (RPC) is recognized as an important cause of pyogenic liver abscesses (PLA). Although it is endemic to Southeast Asia, it is seen increasing in the west mainly owing to immigration. The aim of this study is to compare the clinical characteristics of PLA in patients with RPC and without RPC. Methods We performed a retrospective analysis involving patients with PLA. The demographic, clinical features, laboratory and imaging findings, management strategy, and outcome of patients with and without RPC were studied. Results From January 2000 to December 2009 inclusive, 319 patients (27 with RPC and 292 without RPC) had PLA. Patients with RPC had higher mean age (71.7 vs. 64.9 years; P=0.03) and tended to have more acute onset of presentation than it did in those without RPC. The common clinical features of the two groups were fever, chill, and right upper quadrant pain. Patients without RPC tended to have more respiratory symptoms and signs. The laboratory abnormalities of both groups shared common features such as anemia, leukocytosis, high erythrocyte sedimentation rate and C-reactive protein, hypoalbuminemia, elevated total bilirubin, and alanine aminotransferase. Left lobe was predominantly involved in patients with RPC (51.9% vs. 23.6%; P<0.01) whereas those without RPC usually had PLA at right lobe (67.5 vs. 40.7%; P<0.01). Both groups also shared common radiological features such as hypoechoic in ultrasonograpphy, rim enhancement and septal lobulation in computed tomography. However, aerobila was found more in patients with RPC than those without RPC (25.9 vs. 5.5%; P<0.01) and the latter tended to have more abscess ruptures. The biliary tract disorder was the most common cause of the disease in the two groups. The microorganisms involved had distinct patterns between these two groups. Patients with RPC tended to have fewer complications than patients without RPC as there were fewer occurrences in metastatic infections, disseminated intravascular coagulation, and acute renal and respiratory failure. PLA in patients with RPC had higher recurrence rate than those without RPC (37 vs. 2.4%; P<0.01). The odds ratio of local recurrence between RPC and non-RPC group was 23.95 (95% confidence interval, 8.11–70.72). However, both were effectively managed by the combination of antibiotic and image-guided aspiration with/without drainage, and their mortality rates are comparable with each other. Conclusion PLA associated with RPC tends to have distinct clinical syndrome in regards to different extent of clinical manifestations, radiological and microbiological features, and complications. Its recurrent rate is higher than that of non-RPC type. However, both can be effectively treated with a combination of antibiotic and image-guided aspiration with/without drainage.

Older age as a poor prognostic sign in patients with pyogenic liver abscess

BACKGROUNDnPrevious studies have focused on the role of age as a prognostic factor in pyogenic liver abscess (PLA) and results have been controversial. The aim of this study was to compare the clinical characteristics of PLA in elderly (age ≥65 years) and non-elderly patients in order to identify any differences so that an early diagnosis can be made and appropriate therapeutic measures can be instituted promptly.nnnMETHODSnWe performed a retrospective analysis of patients with PLA. The demographic and clinical features, laboratory and imaging findings, management, and clinical outcomes of elderly and non-elderly patients were studied.nnnRESULTSnBetween January 2000 and December 2010 inclusive, 319 patients had PLA; 168 (52.7%) were aged ≥65 years. Elderly patients were more likely to have acute onset of symptoms (4.2 vs. 5.3 days, p < 0.04), co-morbidities, and respiratory symptoms (25.6% vs. 14.6%, p < 0.01). They also had lower serum bilirubin (28.1 vs. 37.1 μmol/l, p < 0.04), alanine aminotransferase (71.6 vs. 94.3 U/l, p < 0.02), and glycosylated hemoglobin (8.1% vs. 10%, p < 0.01), and more often had septal lobulation (64.3% vs. 54.3%, p < 0.04) and pneumobilia (10.1% vs. 4.0%, p < 0.02). Moreover, they required a longer duration of oral antibiotics (2.63 vs. 2.05 weeks, p < 0.01) and had a higher incidence of acute coronary syndrome during the illness (7.7% vs. 2.0%, p < 0.01). Gram-negative organisms were the dominant isolates in both groups, but the elderly had a lower incidence of Gram-positive infections (5.4% vs. 13.2%, p < 0.01). Lastly, old age was associated with local recurrence of PLA (odds ratio (OR) 3.1, 95% confidence interval (CI) 1.0-9.7, p < 0.04) and mortality (OR 3.17, 95% CI 1.25-8.04, p = 0.015).nnnCONCLUSIONSnElderly patients tend to have a more atypical presentation in PLA, for which clinicians should be on high alert. We found older age to be associated with a higher recurrence of PLA and a higher mortality rate.

Intestinal tuberculosis complicated with perforation during anti-tuberculous treatment in a 13-year-old girl with defective mitogen-induced IL-12 production

Interleukin-12 (IL-12) is a cytokine which is secreted by activated phagocytes and dendritic cells and promotes cell-mediated immunity to intracellular pathogens, by inducing type 1 helper T cell (TH1) responses and interferon- γ (IFN- γ) production. Defects in the IL-12 may cause selective susceptibility to intracellular pathogens, such as mycobacteria. We herein report on a 13-year-old girl with defective mitogen-induced IL-12 production, who developed intestinal tuberculosis with wide dissemination involving the lung and urinary tract. She improved gradually, but developed terminal ileal perforation approximately 6.1 months following initiation of anti-tuberculous treatment. The paradoxical response phenomenon was suspected. The girl subsequently underwent surgical resection of the affected bowel segment with a temporary double barrel stoma, and ileocolonic anastomosis was performed after the completion of the anti-tuberculous therapy. The patient remained well, with no evidence of recurrent tuberculosis in the past 5 years. This case illustrates the possibility of underlying primary immunodeficiency in a patient with disseminated tuberculosis; delayed tuberculous intestinal perforation can develop during chemotherapy for tuberculosis.

Age-related differences in the clinical course of Crohn’s disease in an asian population: A retrospective cohort review

The aim of this study was to compare the clinical characteristics and treatment outcomes of patients with young- and adult-onset Crohn’s disease. Among 79 consecutive Crohn’s disease patients (11 (13.92%) with onset ≤16 years old), young-onset Crohn’s disease was significantly associated with fever(36.36 vs. 14.71%, P 0.041), weight loss (72.7 vs. 29.4%, P 0.003), isolated abdominal pain (45.45 vs. 16.18%, P 0.013), lower body mass index ( 17.32 vs. 21.29 kg/m2, P 0.019), and extra-intestinal manifestation, particularly oral (45.5% vs. 22.1%, P 0.049) and perianal lesion (63.6% vs. 36.8%, P 0.046). In both groups, ileocolonic disease and inflammatory lesion were the most prevalent site of involvement and dominant disease behavior respectively. Their complication and bowel resection rate were similar but the former took a longer period of time to develop in the young-onset group (84 vs 24 month, P 0.018). Cox proportional hazard regression analysis revealed that active smoking and delayed use of immuno-suppressive therapy were the only independent risk factors associated with increased risk of complications.

Splenic arteriovenous fistula: unusual cause of portal hypertension complicated with gastric variceal bleeding.

Some differences have been observed between GVs and EVs. GVs are present deep in the submucosa and are principally supplied by the left gastric, short gastric and polar veins, whereas EVs are present in the lamina propria and are composed of perforator vessels linking the internal and extrinsic esophageal veins. GVs are large diameter veins and may bleed at a lower pressure than EVs. Although the incidence of gastric variceal bleeding is half that of EVs, the bleeding due to GVs is generally much more severe than the latter, with a reported mortality of up to 25–30% within 6 weeks. Here we report a case of a 49-yearold man who developed gastric variceal bleeding due to increased portal hypertension caused by arteriovenous fistula formation between splenic artery aneurysm (SAA) and the splenic vein. CASE REPORT

Comparison of efficacy and renal safety of telbivudine and entecavir in treatment-naive elderly patients with chronic hepatitis B.

Background Data comparing the clinical outcomes of telbivudine (LdT) and entecavir (ETV) in elderly patients with chronic hepatitis B are limited. Goals The aim of the present study was to compare the efficacy and renal safety of LdT and ETV in treatment-naive elderly (≥60 years) patients with chronic hepatitis B. Methods A total of 33 patients treated with LdT were consecutively enrolled in the study. Each patient was matched on the basis of age, sex, and baseline hepatitis B virus (HBV) DNA levels with three to four randomly selected controls treated with ETV. Results Clinical characteristics were comparable between the two groups. Higher cumulative HBeAg-seroconversion rates were observed in the LdT group than in the ETV group after 2 years (50 vs. 20%) and 3 years (50 vs. 26.67%) of treatment (all P<0.0001). Virological response rate at week 24 was significantly lower in the LdT group than it was in the ETV group (54.55 vs. 70.87%, P<0.0001), but no significant difference was noted in long-term cumulative rates of undetectable HBV DNA levels between the two groups (P=0.562). Virological breakthrough occurred in six (18.18%) LdT patients, with no such cases reported in the ETV group (P<0.0001). Antiviral resistance was strongly associated with LdT use and the absence of undetectable HBV DNA at weeks 12 and 24 (P<0.0001). During the study, significant improvement was observed in the estimated glomerular filtration rate and model for end-stage liver disease score in LdT versus ETV group. Conclusion LdT has a lower clinical efficacy for viral suppression and a higher risk of antiviral resistance than does ETV. However, LdT resulted in higher HBeAg-seroconversion rates and better renoprotective effects than did ETV.

Role of C-reactive protein in response-guided therapy of pyogenic liver abscess.

Background Protocols for antibiotic treatment of pyogenic liver abscess (PLA) are usually based on clinicians’ own experience without any validation. Our study was to evaluate the clinical implication of C-reactive protein (CRP) in predicting treatment outcome and adequacy of antibiotic therapy of PLA. Patients and methods Patients with PLA in whom white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and CRP were checked regularly during the clinical course were included. The prolife of CRP during the clinical course was compared with that of ESR and WBC. The usefulness of CRP in predicting the chance of recovery and adequacy of antibiotic therapy was examined. Results From 2000 to 2011, 109 patients with PLA underwent regular monitoring of WBC, ESR, and CRP. Except for ESR, both WBC and CRP showed an initial rapid reduction in first 3 weeks, followed by a relatively slow decrease. From week 3 to week 6, the CRP ratio (relative to CRP at week 1) of patients with and without adverse events (i.e. including mortality) was compared; a significant difference was found at week 3 (P=0.001), week 4 (P=0.004), week 5 (P=0.011), and week 6 (P=0.018), whereas no statistically significant difference was found in the WBC ratio over the same period. By week 3, a CRP ratio of 0.423 or less was a marker of good outcome (sensitivity 0.846; specificity 0.667) and was also a marker of adequacy of antibiotic therapy of 5 weeks or less (sensitivity 0.786; specificity 0.714) if the ratio was 0.278 or less. Conclusion Weekly CRP measurement was useful in the identification of patients with PLA with good outcome and adequacy of antibiotic therapy of 5 weeks or less.

Clinical characteristics of concurrent and sequentially presented lupus-related protein-losing enteropathy: What are their differences?

Our objective was to compare patients with concurrent and sequentially presented systemic lupus erythematosus (SLE)-related protein-losing enteropathy (PLE). Patients with history of SLE admitted for PLE were selected and their clinical, laboratory, endoscopic and imaging characteristics, treatment and outcome were analyzed. From 2001 to 2010, 21 and 27 patients had concurrent and sequentially presented SLE-related PLE, respectively, and their clinical characteristics were comparable except the following: the concurrent group had more pleural effusion (Pxa0<xa00.01), cutaneous (Pxa0<xa00.03), neurological (Pxa0=xa00.02) manifestations, higher creatine phosphokinase (127.6xa0IU/L vs. 105.7xa0IU/L, Pxa0<xa00.05) and lactate dehydrogenase (504.0xa0IU/L vs. 422.2xa0IU/L, Pxa0<xa00.05); whereas the sequential group had higher anti-double strand DNA titer (179.8 vs. 100.4, Pxa0<xa00.05), 24-h urine protein excretion (1.1xa0g/d vs. 0.6xa0g/d, Pxa0<xa00.05) and increased proteinuria after onset of PLE (0.21xa0g/d vs. 1.1xa0g/d, Pxa0<xa00.04). The endoscopic, histological and radiological features were comparable between the two groups. More patients from the sequential group required more potent immunosuppressive therapy for induction (55.6% vs. 14.3%, Pxa0=xa00.002) and maintenance (48.2% vs. 9.5%, Pxa0<xa00.01).The concurrent group associated with better treatment outcomes, with requiring shorter mean time (4.5xa0months vs. 7.9xa0months, Pxa0=xa00.03) for normalbuminemia and more individuals (90.5% vs. 63%, Pxa0<xa00.02) achieving normalbuminemia in first year. The complications were infrequent: two drug-related adverse events from each group, one patient each from the concurrent group developed shingle and SLE nephropathy. PLE associated with concurrent and sequentially presented of SLE are comparable in clinical behavior; and the immunosuppressive therapy is generally well-responded and tolerated. However, the concurrent group is associated with better disease activity control.