Background & Aims: We aimed to evaluate serum hepatitis B surface antigen (HBsAg) quantitation as a surrogate marker for covalently closed circular DNA (cccDNA) and intrahepatic hepatitis B virus ...(HBV) DNA, and as a predictor of sustained virologic response to peginterferon and lamivudine combination therapy. Methods: Twenty-six hepatitis B e antigen–positive chronic hepatitis B patients receiving combination treatment of 32-week peginterferon alfa-2b and 2-year lamivudine were studied. All patients had liver biopsy before and after treatment for cccDNA and intrahepatic HBV DNA measurement. Sustained virologic response was defined as sustained hepatitis B e antigen seroconversion and HBV DNA less than 10,000 copies/mL at the end of treatment until 1 year posttreatment. Results: Seven patients developed sustained virologic response. At baseline, HBsAg correlated well with both log (cccDNA) (r = 0.54, P = .004) and log total intrahepatic HBV DNA (r = 0.43, P = .028). The median reduction of HBsAg was 1287 IU/mL (range, 12,223–26,763 IU/mL). Reduction of HBsAg has good correlation with reduction in log cccDNA (r = 0.68, P < .0001) and reduction in log total intrahepatic HBV DNA (r = 0.65, P < .0001). Patients with lower baseline cccDNA, intrahepatic HBV DNA, and HBsAg level but not serum HBV DNA level tend to develop sustained virologic response. A baseline HBsAg level of less than 10,000 IU/mL had sensitivity, specificity, and positive and negative predictive values for sustained virologic response of 86%, 56%, 43%, and 92%, respectively. Conclusions: Serum HBsAg levels correlate well with the cccDNA and intrahepatic HBV DNA. Low pretreatment HBsAg is better than HBV DNA to predict good response to peginterferon and lamivudine treatment.
Although nonalcoholic fatty liver disease (NAFLD) is closely linked to obesity, around 10%‐20% of nonobese Americans and Asians still develop NAFLD. Data on this special group are limited. We ...therefore studied the severity and clinical outcomes of nonobese NAFLD patients. Consecutive NAFLD patients who underwent liver biopsy were prospectively recruited. We used the NASH Clinical Research Network system to score the histology. The Asian body mass index cutoff of 25 kg/m2 was used to define nonobese NAFLD. Among 307 recruited NAFLD patients, 72 (23.5%) were nonobese. Compared to obese patients, nonobese patients had lower NAFLD activity score (3.3 ± 1.3 vs. 3.8 ± 1.2; P = 0.019), mainly contributed by steatosis (1.7 ± 0.8 vs. 2.0 ± 0.8; P = 0.014) and presence of hepatocyte ballooning (60.9% vs. 73.4%; P = 0.045). Similarly, nonobese patients had lower fibrosis stage (1.3 ± 1.5 vs. 1.7 ± 1.4; P = 0.004), serum cytokeratin‐18 fragments (283 vs. 404 U/L; P < 0.001) and liver stiffness measurement by transient elastography (6.3 vs. 8.6 kilopascals; P < 0.001). By multivariate analysis in nonobese patients, only elevated serum triglyceride level was independently associated with higher NAFLD activity score (adjusted odds ratio OR, 1.644; P = 0.021), whereas elevated creatinine level was the only factor associated with advanced fibrosis (adjusted OR, 1.044; P = 0.025). After a median follow‐up of 49 months, 6 patients died, 2 developed hepatocellular carcinoma, and 1 had liver failure, all of whom were in the obese group. Conclusion: Nonobese NAFLD patients tend to have less‐severe disease and may have a better prognosis than obese patients. Hypertriglyceridemia and higher creatinine are the key factors associated with advanced liver disease in nonobese patients. (Hepatology 2017;65:54‐64)
Some studies suggest that non-obese patients with nonalcoholic fatty liver disease (NAFLD) may have more severe disease. We aim to study the epidemiology and severity of non-obese NAFLD.
A total of ...911 community subjects were randomly recruited from the census database of the Hong Kong Government. Intrahepatic triglycerides (IHTG) and liver fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography, respectively. The Asian body mass index cutoff of 25 kg/m(2) was used to define non-obese NAFLD.
The prevalence of NAFLD was 19.3% in non-obese subjects and 60.5% in obese subjects (P<0.001). Compared with obese NAFLD patients, non-obese NAFLD patients had similar IHTG content (median 9.8% vs. 9.9%; P=0.100) but lower cytokeratin-18 fragments (149 vs. 182 IU/l; P=0.019) and liver stiffness (4.6 vs. 5.6 kPa; P<0.001). The G allele at the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3 rs738409) was more common in non-obese than obese NAFLD patients (78.4% vs. 59.8%; P=0.001). Obesity, high hemoglobin A1c, insulin resistance, hyperferritinemia, and the PNPLA3 G allele were independent factors associated with NAFLD in non-obese subjects. Even among non-obese subjects with normoglycemia, those with NAFLD were more insulin resistant (mean homeostasis model assessment of insulin resistance: 2.0±1.0 vs. 1.1±1.1; P<0.001).
One-fifth of the general non-obese Chinese population has NAFLD. Non-obese patients with NAFLD do not have a higher risk of steatohepatitis or advanced fibrosis. Patients with risk factors of advanced fibrosis such as metabolic syndrome and PNPLA3 G allele carriage should be assessed for severe NAFLD.
Recently, a group of hepatologists proposed to rename non-alcoholic fatty liver disease (NAFLD) as metabolic associated fatty liver disease (MAFLD) with modified diagnostic criteria. We aimed to ...study the impact of the new definition on the epidemiology of fatty liver disease.
We randomly selected 1013 adults from the Hong Kong census database for clinical assessment, proton-magnetic resonance spectroscopy, and transient elastography. Five hundred sixty-five subjects without fatty liver at baseline underwent follow-up assessment. MAFLD was diagnosed as intrahepatic triglyceride content (IHTG) ≥5% and the presence of overweight/obesity, diabetes, or two other metabolic risk factors, with and without concomitant liver diseases. The diagnosis of NAFLD required the exclusion of concomitant liver diseases; metabolic factors were not considered.
The population prevalence of MAFLD and NAFLD was 25.9% (95% CI 23.2-28.7%) and 25.7% (95% CI 23.1-28.5%), respectively. Among 277 subjects with IHTG ≥5%, 247 (89.2%) fulfilled both the definitions of MAFLD and NAFLD. Fourteen subjects (5.1%) had IHTG ≥5% but did not meet the metabolic criteria of MAFLD. The incidence of MAFLD was 2.8 per 100 person-years at a median interval of 47 months (range 34-60 months). Among 78 subjects with incident NAFLD, 59 (75.6%) met the criteria of MAFLD; only one of the latter, a regular drinker, had liver stiffness ≥10 kPa.
The new definition of MAFLD does not significantly change the prevalence compared with NAFLD, but it may reduce the incidence by 25%. People with hepatic steatosis but not fulfilling the definition of MAFLD unlikely have significant liver disease.
Controlled attenuation parameter (CAP) evaluated with transient elastography (FibroScan) is a recent method for non-invasive assessment of steatosis. Its usefulness in non-alcoholic fatty liver ...disease (NAFLD) is unknown. We prospectively investigated the performance of CAP for the diagnosis of steatosis in NAFLD, factors associated with discordances between CAP and steatosis grades, and relationships between CAP and clinical or biological parameters.
All CAP examinations performed in NAFLD patients with a liver biopsy performed within 1 week of CAP measurement were included. Liver biopsies were assessed for activity and fibrosis stage, NAFLD activity score, and steatosis graded as follows: S0, steatosis < 5%; S1, 5-33%; S2, 34-66%; S3, >66%.
Two hundred sixty-one patients (59% male, age 56 years) from two ethnic groups were included. No patient had steatosis < 5%. The area under the receiver-operating characteristics curve of CAP for steatosis ≥S2 and S3 was 0.80 and 0.66, respectively. At a cut-off value of 310 dB/m, the sensitivity, specificity, and positive and negative predictive values for ≥S2 steatosis were 79%, 71%, 86%, and 71%, respectively. Discordance of at least one grade between CAP and steatosis was observed in 81 patients. By multivariate analysis, only steatosis S2S3 was associated with no discordance. By multivariate analysis, only BMI ≥ 30 kg/m(2) was significantly associated with CAP > 310 dB/m.
The association of CAP with steatosis, especially in patients with non-alcoholic steatohepatitis, and with elevated BMI could be useful for the diagnosis and follow-up of NAFLD patients.
Background and Aims
Type 2 diabetes is an important risk factor for nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis. Current international guidelines recommend the use of noninvasive ...tests as initial assessments for NAFLD, but the role of noninvasive tests as monitoring tools has not been established. We aimed to study the role of transient elastography as a monitoring tool in patients with type 2 diabetes.
Approach and Results
We recruited patients with type 2 diabetes without viral hepatitis or excessive alcohol intake from a complication screening facility in Hong Kong in 2013‐2014 and repeated the assessments in 2016‐2018. The primary endpoint was an increase of liver stiffness measurement (LSM) to ≥10 kPa. The secondary endpoint was the change in the controlled attenuation parameter (CAP). A total of 611 patients with type 2 diabetes and a valid LSM (mean age, 57.7 ± 10.9 years; 342 men 56.0%) were included in this study (568 also had a valid CAP). Overall, there was moderate correlation between the baseline and follow‐up LSM (r = 0.689, P < 0.001). Among 487 patients with a baseline LSM <10 kPa, 21 (4.3%) had a follow‐up LSM ≥10 kPa. Baseline body mass index, alanine aminotransferase (ALT), and ∆ALT were independent factors associated with LSM increase. Among 124 patients with a baseline LSM ≥10 kPa, 70 (56.5%) had a follow‐up LSM <10 kPa. Among 198 patients with a CAP <248 dB/m at baseline, 103 (52.0%) had a CAP increased to ≥248 dB/m.
Conclusions
The prevalence and incidence of NAFLD in patients with type 2 diabetes are high. Although advanced fibrosis is common in this population, few patients progress to advanced fibrosis in 3 years. Future studies should define the optimal surveillance interval in patients with diabetes.
Knowledge of the epidemiology of non-alcoholic fatty liver disease (NAFLD) is incomplete because liver biopsy cannot be performed on the general population to assess disease severity. New ...non-invasive tests allow accurate and safe assessment in healthy individuals. The aim of this study was to examine the prevalence of NAFLD and advanced fibrosis in the general Hong Kong Chinese population.
Subjects were recruited from the community by random selection from the government census database. Liver fat and fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography, respectively.
Overall, 264 of 922 (28.6%) subjects had intrahepatic triglyceride content ≥5%. Excluding 12 subjects with significant alcohol consumption, the population prevalence of NAFLD was 27.3% (95% CI 24.5% to 30.2%). Each component of the metabolic syndrome increased the risk of fatty liver in a dose-dependent manner (prevalence of 4.5% in subjects without any component and 80.0% in those with all five components). 8 (3.7%) patients with fatty liver had liver stiffness ≥9.6 kPa, a level suggestive of advanced fibrosis. Body mass index and alanine aminotransferase level were independent factors associated with liver stiffness. Together with other clinical prediction scores, the estimated prevalence of advanced fibrosis in patients with fatty liver in the community was <10%. Compared with non-drinkers, modest drinkers (<10 g per day) did not have higher risk of fatty liver after adjustment for demographic and metabolic factors. The liver stiffness was 4.7±1.9 kPa in modest drinkers and 4.6±1.7 kPa in non-drinkers (p=0.54).
NAFLD is found in over a quarter of the general adult Chinese population, but the proportion of patients with advanced fibrosis is low. Modest alcohol consumption does not increase the risk of fatty liver or liver fibrosis.
There is ongoing debate on whether screening for nonalcoholic fatty liver disease (NAFLD) is worthwhile in high‐risk groups. Because of shared risk factors, NAFLD is highly prevalent in patients with ...coronary artery disease. We aimed to test the hypothesis that NAFLD screening in patients requiring coronary angiogram would identify high‐risk patients and predict long‐term clinical outcomes. This was a prospective cohort study. NAFLD screening was performed by abdominal ultrasonography before coronary angiogram in 612 consecutive patients. At baseline, 356 (58.2%) patients had NAFLD. NAFLD patients, compared with those without, were more likely to have >50% stenosis in one or more coronary arteries (84.6% vs. 64.1%; P < 0.001) and therefore require percutaneous coronary intervention (68.3% vs. 43.4%; P < 0.001). During 3,679 patient‐years of follow‐up, 47 (13.2%) NAFLD patients and 59 (23.0%) patients without NAFLD died (age‐ and sex‐adjusted hazard ratio aHR: 0.36; 95% confidence interval CI: 0.18‐0.70; P = 0.003). Composite cardiovascular outcomes (cardiovascular deaths, nonfatal myocardial infarction, heart failure, or secondary interventions) were similar between groups (36.5% vs. 37.1%; aHR, 0.90; 95% CI: 0.69‐1.18). Older age and diabetes were the only independent factors associated with cardiovascular events. Only 2 patients, both in the NAFLD group, died of primary liver cancer. No other patients developed liver‐related complications. Conclusion: In patients with clinical indications for coronary angiogram, the presence of NAFLD is associated with coronary artery stenosis and need for coronary intervention, but not increased mortality or cardiovascular complications. Liver cancer and cirrhotic complications are rare. Our data do not support NAFLD screening in this patient group at present, but studies with a longer duration of follow‐up are needed. (Hepatology 2016;63:754–763)
The human gut microbiota has profound influence on host metabolism and immunity. This study characterized the fecal microbiota in patients with nonalcoholic steatohepatitis (NASH). The relationship ...between microbiota changes and changes in hepatic steatosis was also studied.
Fecal microbiota of histology-proven NASH patients and healthy controls was analyzed by 16S ribosomal RNA pyrosequencing. NASH patients were from a previously reported randomized trial on probiotic treatment. Proton-magnetic resonance spectroscopy was performed to monitor changes in intrahepatic triglyceride content (IHTG).
A total of 420,344 16S sequences with acceptable quality were obtained from 16 NASH patients and 22 controls. NASH patients had lower fecal abundance of Faecalibacterium and Anaerosporobacter but higher abundance of Parabacteroides and Allisonella. Partial least-square discriminant analysis yielded a model of 10 genera that discriminated NASH patients from controls. At month 6, 6 of 7 patients in the probiotic group and 4 of 9 patients in the usual care group had improvement in IHTG (P=0.15). Improvement in IHTG was associated with a reduction in the abundance of Firmicutes (R(2)=0.4820, P=0.0028) and increase in Bacteroidetes (R(2)=0.4366, P=0.0053). This was accompanied by corresponding changes at the class, order and genus levels. In contrast, bacterial biodiversity did not differ between NASH patients and controls, and did not change with probiotic treatment.
NASH patients have fecal dysbiosis, and changes in microbiota correlate with improvement in hepatic steatosis. Further studies are required to investigate the mechanism underlying the interaction between gut microbes and the liver.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•In this RCT, lifestyle intervention effectively led to remission of NAFLD in most non-obese and obese patients.•Weight reduction correlated with NAFLD remission in a dose-dependent ...manner.•The amount of weight reduction needed to achieve remission was less in non-obese patients.•By 6 years, non-obese patients remained more likely to maintain weight reduction and have ALT normalization.
Around 10–20% of patients with non-alcoholic fatty liver disease (NAFLD) are non-obese. The benefit of weight reduction in such patients is unclear. We aim to study the efficacy of lifestyle intervention in non-obese patients with NAFLD and to identify factors that predict treatment response.
A total of 154 community NAFLD patients were randomised to a 12-month lifestyle intervention programme involving regular exercise, or to standard care. The primary outcome was remission of NAFLD at Month 12 by proton-magnetic resonance spectroscopy. After the programme, the patients were prospectively followed until Year 6. The Asian body mass index (BMI) cut-off of 25 kg/m2 was used to define non-obese NAFLD.
Patients were assigned to the intervention (n = 77) and control (n = 77) groups (39 and 38 in each group had baseline BMI <25 and ≥25 kg/m2, respectively). More patients in the intervention group achieved the primary outcome than the control group regardless of baseline BMI (non-obese: 67% vs. 18%, p <0.001; obese: 61% vs. 21%, p <0.001). Lifestyle intervention, lower baseline intrahepatic triglyceride, and reduction in body weight and waist circumference were independent factors associated with remission of NAFLD in non-obese patients. Half of non-obese patients achieved remission of NAFLD with 3–5% weight reduction; the same could only be achieved in obese patients with 7–10% weight reduction. By Year 6, non-obese patients in the intervention group remained more likely to maintain weight reduction and alanine aminotransferase normalisation than the control group.
Lifestyle intervention is effective in treating NAFLD in both non-obese and obese patients. Weight reduction predicts remission of NAFLD in non-obese patients, but a modest weight reduction may be sufficient in this population.
Some patients with non-alcoholic fatty liver disease (NAFLD) are non-obese. The optimal management of such patients is unclear. In this long-term follow-up study of a clinical trial, we show that remission of NAFLD can be achieved in 67% of non-obese patients after lifestyle intervention. The majority of patients can achieve NAFLD remission with modest weight loss of 3–10%. Non-obese patients are also more likely than obese patients to maintain weight reduction and normal liver enzymes in the long run.
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