E. Maltezos

The role of serial measurement of serum HBV DNA levels in patients with chronic HBeAg(−) hepatitis B infection: Association with liver disease progression. A prospective cohort study

BACKGROUND/AIMS To evaluate the fluctuating course of serum HBV-DNA levels during the natural history of chronic HBV infection in the general population of North-Eastern Greece, in association with liver disease progression. METHODS Two hundred and sixty-three adults with chronic HBV, median 34 years of age, were randomly selected and prospectively followed-up for a maximum period of 12 years. Viral markers, liver biochemistry and physical examination were performed every 6 months, and liver biopsy/abdominal ultrasound every 2-4 years. RESULTS At entry, 195/263 (76%) were HBeAg (-)/anti-HBe (+) inactive carriers: (a) almost all 195 individuals with undetectable or HBV-DNA levels <2000IU/ml had no liver disease at entry and at follow-up period by imaging or liver histology evaluation (b) only 4/195 (2%) showed HBV reactivation with HBV-DNA >2000IU/ml. At entry, 48/263 (18%) patients were chronic HBeAg(-); (a) 1/3 patients had intermittently HBV-DNA <2000IU/ml for at least one occasion and were misclassified as inactive carriers (b) 22/48 (46%) had moderate/severe histology at entry and 5/48 (10%) showed liver disease progression during follow-up. Logistic regression analysis was used to derive OR (95%CI) for factors associated with liver disease progression. CONCLUSIONS Close monitoring of serum HBV-DNA levels is useful in the management of chronic HBeAg(-) patients, as associated with liver disease progression.

Natural history of chronic hepatitis B virus infection in children of different ethnic origins : A cohort study with up to 12 years' follow-up in northern Greece

Aim: To investigate the mode of transmission and the natural history of chronic hepatitis B virus (HBV) infection in children of different ethnicities in Greece. This study was part of the Interreg I-II EC project. Patients and Methods: One hundred seventy-three hepatitis B surface antigen (HBsAg)(+) carriers, median age 6.9 (5–12) y, were prospectively followed-up for a mean period of 5.3 (1–12) y for serological markers of HBV infection, serum alanine aminotransferase (ALT), HBV-DNA, α-fetoprotein levels and ultrasonography. Results: Vertical transmission predominates (61.8%) in Moslem children and horizontal (44%) in those born in Russia. At entry, 73 of 173 (42%) HBsAg(+) genotype D children were hepatitis B e antigen (HBeAg)(+), ranging from 27% to 67% among ethnic groups; 55 of 173 (32%) had ALT > 2 × upper normal limit (UNL), ranging from 21% to 39%. Of 100 anti-HBe(+) children, 85 (85%) were inactive carriers. During the follow-up period, seroconversion to anti-HBe was observed in 40 of 73 (55%) children with an annual rate of 11%; 35 of 40 (87.5%) had biochemical remission, and 28 of 35 (80%) lost HBV-DNA. In the anti-HBe(+) group, 27 of 100 (27%) lost HBV-DNA and 9 of 100 (9%) lost HBsAg. The annual seroconversion rate for HBeAg was significantly lower: in children with vertical transmission compared with horizontal (7.7% vs 14.8%, respectively, P < 0.001) and in Muslim children compared with both Christian children and those born in Russia (8.6% vs 12%, respectively, P < 0.001). No differences were found among the ethnic groups after adjusting for the mode of infection. Two of 173 children had progression of liver disease. Conclusions: The differences in HBeAg(+) status and seroconversion rate among the ethnic groups are related to the time/mode of HBV infection. The majority of children who developed anti-HBe immunity had biochemical remission, and a substantial number of the inactive carriers lost viremia during the observation period of up to 12 y.

Maximal voluntary ventilation in myasthenia gravis

Assessment of respiratory muscle weakness is important at all stages of myasthenia gravis. The maximal voluntary ventilation (MVV) is an objective dynamic method for measuring the working capacity of respiratory muscles. The clinical value of this method was studied in 24 newly diagnosed patients with myasthenia gravis, classified according to Osserman criteria (grades I, IIa, and IIb). The MVV values were normal in group I, whereas a characteristic “myasthenic pattern” of decremental respiratory volumes was demonstrated during MVV in group IIa and IIb patients, with or without dyspnea. Despite some limitations and lack of specificity, MVV may be a valuable tool in the assessment of respiratory dysfunction in patients with myasthenia gravis. Muscle Nerve, 27: 715–719, 2003

The potential of SGLT2 inhibitors in phase II clinical development for treating type 2 diabetes

ABSTRACT Introduction: There is now an abundance of anti-diabetic agents. However, only few patients achieve glycemic targets. Moreover, current glucose-lowering agents mainly depend upon insulin secretion or function. Sodium glucose co-transporter type 2 (SGLT2) inhibitors present a novel glucose-lowering therapy, inducing glycosuria in an insulin-independent fashion. Areas covered: In this review, the authors discuss the key efficacy and safety data from phase II clinical trials in type 2 diabetes mellitus (T2DM) of the main SGLT2 inhibitors approved or currently in development, and provide a rationale for their use in T2DM. Expert opinion: Despite the very promising characteristics of this new therapeutic class, a number of issues await consideration. One important question is what to expect from head-to-head comparison data. We also need to know if dual inhibition of SGLT1/SGLT2 is more efficacious in reducing HbA1c and how this therapy affects metabolic and cardiovascular parameters. Additionally, several SGLT2 agents that have not yet come to market have hitherto been evaluated in Asian populations, whereas approved SGLT2 inhibitors have been frequently studied in other populations, including Caucasian subjects. Thus, we need more information on the potential role of ethnicity on their efficacy and safety.

Simultaneous, painless, homolateral oculomotor and trochlear nerve palsies in a patient with type 2 diabetes mellitus. Neuropathy or brainstem infarction?

Combined palsies of cranial nerves, especially of the oculomotor nerves, are distinctly uncommon, even in patients with diabetes mellitus. We present a patient with type 2 diabetes mellitus, arterial hypertension and hyperlipidaemia, who had simultaneous oculomotor and trochlear nerve palsies. An MRI scan showed multiple brainstem ischaemic infarcts. The patient was treated with intensified insulin regimen and clopidogrel. Symptoms gradually improved, and at 9 months there was no further improvement.

Charcot osteoarthropathy and coronary artery disease in diabetes: the twilight of innocence?

Sir, Traditionally, Charcot osteoarthropathy (COA) in diabetes was thought to occur in relatively younger patients, often free from macrovascular disease [1]. Indeed, the presence of peripheral arterial disease was considered to protect from the development of COA [1]. However, van Baal et al. [2] showed that patients presenting with acute COA had a marked and significant reduction in life expectancy. Importantly, patients with neuropathic foot ulceration had a comparable reduction in life expectancy [2]. However, the causes of premature death in this work could not be ascertained [2]. Interestingly, two studies recently published in this journal [3, 4] have demonstrated an association between COA and coronary artery disease (CAD), providing some insight into the possibility of increased mortality in patients with COA. Pitocco et al. [3] have reported that patients with COA exhibit a higher prevalence of severe coronary plaques, as compared with those having diabetic neuropathy but no COA. Bergis et al. [4] have identified CAD as an independent and the most important predictor of survival in patients with COA. Taken together, the data suggest that COA should no longer be deemed a relatively innocent local condition without increased cardiovascular morbidity. Conversely, it is linkedwith highermortality rates, possibly due toCAD [2–4]. Certainly, the mechanisms underlying the relationship between COA and CAD are far from clear. For instance, cytokines play a crucial role in the pathogenesis of COA [1], and so it is attractive to implicate them in the development of CAD [3], but this is merely a speculation. We also need to ascertain whether this excess mortality is observed in the acute versus chronic phase of COA [1], as well as to investigate the potential role of confounding factors. Meanwhile, the everyday clinician needs to become aware that patients with COA may be at increased risk of cardiovascular morbidity and need appropriate screening. In this context, they deserve to be taken as seriously as those with neuropathic foot ulceration, given the growing appreciation of increased atherosclerotic disease in the latter [5].

Cardiovascular autonomic neuropathy and distal symmetric sensorimotor polyneuropathy: these two diabetic microvascular complications do not invariably co-exist.

BACKGROUND Cardiovascular autonomic neuropathy (CAN) and distal symmetrical sensorimotor polyneuropathy (DSPN) are serious microvascular complications of diabetes mellitus (DM). Their simultaneous development remains disputable. The aim of the present study was to examine the correlation between CAN and the presence/severity of DSPN in DM. PATIENTS AND METHODS Subjects with type 1 (group A: n=51; mean age 40.4 years) and type 2 DM (group B: n=153; mean age 64.6 years) were studied. Evaluation of DSPN was based on neuropathy disability score. Assessment of CAN was based on the battery of 4 standardized cardiovascular autonomic function tests. RESULTS In group A, patients with moderate/severe DSPN exhibited a 12-fold higher likelihood of CAN in univariate analysis (p=0.035). However, significance was lost after adjustment for gender, age, DM duration, and haemoglobin A1c. In group A, likelihood for CAN did not correlate with the presence of mild DSPN in univariate and multivariate analysis. In group B, likelihood of CAN was similar in patients with mild and in those with moderate/severe DSPN compared with patients without DSPN in univariate and multivariate analysis. In between group comparison CAN was similarly distributed in the 2 groups (p for interaction=0.367), in patients with no, mild and moderate/severe DSPN. CONCLUSIONS CAN does not always co-exist with degrees of DSPN, ranging from mild to moderate/severe and is similarly distributed in T1DM and T2DM patients with mild and moderate/severe DSPN and in patients without DSPN.