Beyond obesity: Is cholesterol‐induced liver injury the cause of non‐alcoholic steatohepatitis?

See article in J. Gastroenterol. Hepatol. 2012; 27: 1520-1527.     

Can non‐invasive assessment of liver fibrosis replace liver biopsy?

Transient elastgraphy, acoustic radiation force impulse and real-time elastography are the methods with very good or excellent diagnostic accuracy for the assessment of liver fibrosis stage. They do not provide the information on inflammatory activity, steatosis, iron deposition or other findings derived from liver biopsy. Even on account of fibrosis stage, these non-invasive methods do not give us the estimation completely corresponding to that of liver biopsy. However they provide us useful clinical information that liver biopsy has been providing us, such as appropriate time to start antiviral therapy, prediction of response to antiviral therapy, evaluation of effects of antiviral therapy, assessment of natural course of hepatitis and estimation of prognosis of hepatitis. Recently non-invasive methods for assessment of inflammatory activity, steatosis and iron deposition in the liver have been developed. Thus in the near future, non-invasive methods will replace liver biopsy.     

Should cirrhosis change our attitude towards treating non‐hepatic cancer?

Cirrhosis is a major cause of morbidity and mortality and is the end stage of any chronic liver disease. Cancer, a leading cause of death worldwide, is a growing global health issue. There are limited data in the literature on the incidence, prevalence and management of non-hepatic cancers (NHC) in cirrhotic patients. The aim of this brief review was to underline the main concerns, pitfalls and warnings regarding practice for these patients. Survival of patients with compensated cirrhosis is significantly longer than that of decompensated cirrhosis and patients with NHC and in Child-Pugh class C should not be candidates for cytotoxic chemotherapy. It is important before starting cytotoxic chemotherapy to assess the aetiology and stage of liver disease and to screen these patients for portal hypertension and fluid retention. During cytotoxic chemotherapy, the effectiveness of cancer treatment, as well the appearance of early signs of hepatic decompensation, must be thoroughly monitored. Future phase 3 trial designs in oncology should include a share of patients with compensated cirrhosis to obtain specific information in this setting. Identification of tests able to measure the global degree of hepatic impairment caused by cirrhosis could help in the management of this particular clinical situation.     

Why have meta‐analyses of randomized controlled trials of the association between non‐white‐blood‐cell‐reduced allogeneic blood transfusion and postoperative infection produced discordant results?

Intention-to-treat analyses of randomized controlled trials (RCTs) of the association between non-white-blood-cell (WBC)-reduced allogeneic blood transfusion (ABT) and postoperative infection were reported as the reason why meta-analyses of RCTs of this association have produced discordant results. We examined three possible reasons for disagreements between meta-analyses: (i) sources of medical heterogeneity and integration of RCTs despite extreme heterogeneity; (ii) reliance on as-treated (vs. intention-to-treat) comparisons; and (iii) inclusion (or not) of the three most recent RCTs. When nine RCTs reported up to 2002 were combined despite extreme heterogeneity, both intention-to-treat and as-treated comparisons found an association between non-WBC-reduced ABT and postoperative infection [summary odds ratio (OR) = 1.38, 95% confidence interval (CI) 1.03-1.85, P < 0.05; and summary OR = 1.56, 95% CI 1.06-2.31, P < 0.05, respectively]. When 12 RCTs reported up to 2005 were integrated despite extreme heterogeneity, both intention-to-treat and as-treated comparisons found no association of non-WBC-reduced ABT with postoperative infection (summary OR = 1.24, 95% CI 0.98-1.56, P > 0.05; and summary OR = 1.31, 95% CI 0.98-1.75, P > 0.05, respectively). In both analyses, the separate integration of four RCTs transfusing red blood cells (RBCs) or whole blood filtered after storage showed an association between non-WBC-reduced ABT and postoperative infection, whereas the separate integration of six (or nine) RCTs, reported through 2002 or 2005, and transfusing prestorage-filtered RBCs showed no association, whether intention-to-treat or as-treated comparisons were used. Thus, the published meta-analyses have produced discordant results because they did (or did not) investigate medical sources of heterogeneity and did (or did not) include the most recent RCTs. Intention-to-treat and as-treated comparisons produced concordant results.     

Are mosquitoes diverted from repellent‐using individuals to non‐users? Results of a field study in Bolivia

Outside sub-Saharan Africa, Anopheline mosquito exophagic and/or crepuscular behaviour patterns imply that insecticide-treated nets may provide incomplete protection from malaria-infective mosquito bites. Supplementary repellent treatment has been recommended in such circumstances, especially where vectors are exophilic and so are not susceptible to residual insecticide spraying. As maintaining complete usage of repellents in a community is unrealistic, the potential negative impact on non-users of repellent usage by 'neighbours' in the same community needs to be addressed in the context of health policy promoting equity. This study quantifies diversion of host-seeking mosquitoes, from repellent wearing to unprotected individuals, 1 m apart under field conditions in Bolivia. Each of the six volunteer-pairs sat >20 m apart from other pairs. Volunteers were allocated di-ethyl toluamide (DEET) or mineral oil in ethanol control. Treatments were rotated, so that during the trial, both pair-members wore repellent on 72 occasions; both pair-members wore control on 72 occasions; and on 36 occasions, one pair-member wore repellent and the other control. Unprotected (control) pair-members received 36.4% [95% confidence interval (CI): 8.1-72.0%] more Anopheles darlingi landings (P = 0.0096) and 20.4% (95% CI: 0.6-44.0%) more mosquito landings (P = 0.044), when their 'partner' wore repellent than when their partner also wore control. A second, smaller Latin-square trial using 30% lemongrass (Cymbopogon citratus) repellent, with control, obtained 26.0% (95% CI: 5.2-51.0%) more mosquito landings when controls sat with repellent-wearers rather than other controls (P = 0.0159). With incomplete community repellent usage, non-users could be put at an increased risk of malaria. The results also have implications for repellent-efficacy assay design, as protection will appear magnified when mosquitoes are given a choice between repellent-users and non-users.     

What is the significance of non‐specific pleuritis? A trick question

Non‐specific pleuritis (NSP) is defined as fibrinous or inflammatory pleuritis which cannot be attributed to a specific benign or malignant etiology. It can be diagnosed in biopsies in up to 30% of cases of exudative pleuritis after thoracoscopy, with a mean of 19.2%. In 66 out of 469 (14.2%) patients in combined series, a malignant pleural disease (mostly mesothelioma) was found during a follow‐up of at least 21 months. Most likely, a follow‐up time of 12 months is sufficient, although the current routine is a follow‐up of 2 years. Because of a benign course in 85% of patients with NSP, a repeated invasive procedure after thoracoscopy is only indicated in a limited group of patients. The most important indications for a repeated pleural biopsy are persistent chest pain, recurrent pleural effusion, radiologic findings suggestive for malignant pleural disease.     

Chronic cough at a non‐teaching hospital: Are extrapulmonary causes overlooked?

OBJECTIVE: To estimate the prevalence, assess the diagnostic approach and to identify specific causes and treatment response of chronic persistent cough (CPC) in consecutive adult patients attending the chest clinic at a non-teaching hospital in Riyadh, Saudi Arabia. METHODOLOGY: Chronic persistent cough was defined as cough persisting for more than 3 weeks. Patients were assessed clinically and investigated according to the suspected diagnosis. The specific causes were confirmed by appropriate investigations, as well as response to specific therapy. Improvement in cough following therapy was assessed subjectively by patients on a scale from 0 to 100%. RESULTS: Of 1332 patients seen in the chest clinic, 136 (10.2%; 95% confidence interval 8.6-11.8%) presented with CPC as the main complaint. One hundred patients (55% males) were assessed, after excluding 36 patients who were lost to follow up. The common presenting diagnoses (for the 81 patients who had previously consulted a physician) were upper respiratory tract infection (17.1%), asthma (15.9%), bronchitis (9.8%) and unknown in 30.8% of patients. Final diagnoses (as a sole or contributory cause) were established in 96% of patients and included rhinosinusitis (RS; 60%), asthma (26%), gastro-oesophageal reflux (GERD; 9%), postinfectious cough (8%) and bronchiectasis (5%). The agreement between the presenting and final diagnoses was generally poor, especially for extrapulmonary causes, which was as low as 5.3%. All patients, except for one, had complete or substantial improvement in the severity of cough. CONCLUSIONS: In a non-teaching hospital setting, CPC is a common benign disorder that rarely requires specialized investigations and is easily treated once the causes are identified. The multiplicity of causes and extrapulmonary triggers of CPC, particularly RS, are often overlooked. The principal causes in our series remain the same as in studies elsewhere, namely RS, asthma and GERD.     

Coffee and non‐alcoholic fatty liver disease: Brewing evidence for hepatoprotection?

Coffee is one of the most popular beverages in the world. Several studies consistently show that coffee drinkers with chronic liver disease have a reduced risk of cirrhosis and a lower incidence of hepatocellular carcinoma regardless of primary etiology. With the increasing prevalence of non‐alcoholic fatty liver disease (NAFLD) worldwide, there is renewed interest in the effect of coffee intake on NAFLD severity and positive clinical outcomes. This review gives an overview of growing epidemiological and clinical evidence which indicate that coffee consumption reduces severity of NAFLD. These studies vary in methodology, and potential confounding factors have not always been completely excluded. However, it does appear that coffee, and particular components other than caffeine, reduce NAFLD prevalence and inflammation of non‐alcoholic steatohepatitis. Several possible mechanisms underlying coffee's hepatoprotective effects in NAFLD include antioxidative, anti‐inflammatory, and antifibrotic effects, while a chemopreventive effect against hepatocarcinogenesis seems likely. The so‐far limited data supporting such effects will be discussed, and the need for further study is highlighted.     

Hepatocellular carcinoma in non‐alcoholic steatohepatitis: Growing evidence of an epidemic?

The incidence of hepatocellular carcinoma in non‐viral‐related chronic liver disease has gradually increased in Japan. Obesity and diabetes mellitus type 2 have been established as a significant risk factor for hepatocellular carcinoma (HCC) by epidemiologic observations and experimental studies. The risks of these factors for HCC are likely conferred by two factors: the increased risk for development of non‐alcoholic steatohepatitis (NASH) and the carcinogenic potential of themselves. Hepatocellular carcinoma in NASH is difficult to evaluate because histological diagnosis is required for diagnosis of NASH, which can lead selection bias. Furthermore, end‐stage NASH is in effect “burned‐out” NASH, for which the diagnosis of NASH cannot be made any more. At all events, previous studies on the etiology of Japanese HCC showed that non‐alcoholic fatty liver disease accounts for 1–5% of all HCC (male predominant, median age 72 years). They have high prevalences of obesity and/or diabetes mellitus type 2 and 10–75% of the HCC arose from non‐cirrhotic livers. HCC in NASH may be of multicentric origin, similar to HCC based on viral hepatitis. Regular screening for HCC is extremely important especially in cirrhotic NASH patients and recurrence should be warned. In western and Asian countries, the prevalence of non‐alcoholic fatty liver disease in the general population is increasing dramatically. Therefore, there is an urgent need to elucidate pathogenesis and clinical features of HCC in NASH. In this review we summarize current concepts for HCC in NASH.