Manirath K. Srishord

Changes in the Prevalence of the Most Common Causes of Chronic Liver Diseases in the United States From 1988 to 2008

BACKGROUND & AIMS Chronic liver diseases (CLDs) are major causes of morbidity and mortality worldwide. We assessed changes in the prevalence of different types of CLD in the United States. METHODS National Health and Nutrition Examination Surveys conducted between 1988 and 2008 were used to estimate changes in the prevalence and predictors of CLDs. Serologic and clinical data were used to establish the diagnoses of CLDs in 39,500 adults. Statistical analyses were conducted with SUDAAN 10.0 (SAS Institute, Inc, Cary, NC). RESULTS The prevalence rates for CLD were 11.78% (1988-1994), 15.66% (1999-2004), and 14.78% (2005-2008). During the same period, the prevalence of hepatitis B virus infection (0.36%, 0.33%, and 0.34%), hepatitis C virus (1.95%, 1.97%, and 1.68%), and alcoholic liver disease (1.38%, 2.21%, and 2.05%) remained generally stable. In contrast, the prevalence of nonalcoholic fatty liver disease (NAFLD) increased from 5.51% to 9.84% to 11.01%. From 1988 to 1994, NAFLD accounted for 46.8% of CLD cases; from 1994 to 2004 its prevalence increased to 62.84%, and then to 75.1% from 2005 to 2008. During these time periods, steady increases were observed in obesity (21.74%, 30.02%, and 33.22%), visceral obesity (35.18%, 48.16%, and 51.43%), type II diabetes (5.55%, 7.88%, and 9.11%), insulin resistance (23.29%, 32.50%, and 35.00%), and hypertension (22.68%, 33.11%, and 34.08%). A multivariate analysis showed that during all time periods, obesity was an independent predictor of NAFLD. CONCLUSIONS National Health and Nutrition Examination Surveys data collected from 1988 to 2008 show that the prevalence of major causes of CLD remained stable, except for NAFLD, which increased steadily, along with the prevalence of metabolic conditions. Given the increasing rates of obesity, NAFLD prevalence is expected to contribute substantially to the burden of CLD in the United States.

Nonalcoholic fatty liver disease in lean individuals in the United States.

AbstractThe presence of hepatic steatosis in individuals without a known cause of chronic liver disease, including excessive alcohol consumption, is the hallmark of nonalcoholic fatty liver disease (NAFLD). Although NAFLD is usually associated with obesity, nonobese patients can also present with NAFLD (“lean NAFLD”). Our objective was to determine factors independently associated with lean NAFLD in the United States population. For this purpose, we used data from National Health and Nutrition Examination Survey III (NHANES III) conducted between 1988 and 1994 with available hepatic ultrasound, clinico-demographic, and laboratory data. NAFLD was defined as the presence of moderate-severe hepatic steatosis (by ultrasound), the absence of excessive alcohol use (>20 g/d in men and 10 g/d in women), hepatitis B surface antigen(−), and hepatitis C antibody(−). Nonalcoholic steatohepatitis (NASH) was defined as having moderate-severe steatosis and elevated aminotransferases in the presence of type 2 diabetes or insulin resistance (IR). Logistic regression was used to identify independent predictors of lean NAFLD. As a result, of the 11,613 participants included in the study, 2185 (18.77% ± 0.76%) had NAFLD; of these, 307 (11.78% ± 1.03%) had NASH. Multivariate analysis showed that lean NAFLD was independently associated with younger age, female sex, and a decreased likelihood of having IR and hypercholesterolemia (p values < 0.05). Additionally, multivariate analysis showed that NASH was independently associated with being Hispanic, having a younger age, and having components of metabolic syndrome such as hypertension (p values < 0.05). Therefore, we conclude that lean individuals with NAFLD have a different clinical profile than overweight-obese individuals with NAFLD. Furthermore, patients with NASH are commonly Hispanic and have components of metabolic syndrome.

Independent Predictors of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. We investigated factors associated with advanced fibrosis in NAFLD. METHODS The study included 432 patients with histologically proven NAFLD (26.8% with nonalcoholic steatohepatitis [NASH] and 17.4% with moderate-to severe fibrosis). NASH was defined as steatosis, lobular inflammation, and ballooning degeneration with or without Mallory-Denk bodies and/or fibrosis. Fibrosis was classified into 2 groups: those with no or minimal fibrosis and those with moderate-to-severe fibrosis. Groups were compared using Mann-Whitney and chi-square method analyses. A model was constructed using a stepwise bidirectional method; its predictive power was measured using a 10-fold cross-validation technique. RESULTS Patients with NASH were more likely to be male (P < .0001); have lower hip-to-waist ratios (P = .03); were less likely to be African American (P = .06); have higher levels of alanine aminotransferase (ALT; P < .0001), aspartate aminotransferase (AST; P < .0001), and serum triglycerides (P = .0154), but lower levels of high-density lipoprotein cholesterol (P < .0001). Patients with moderate-to-severe fibrosis were older (P = .0245); more likely to be male (P = .0189), Caucasian (P = .0382), have diabetes mellitus (P = .0238), and hypertension (P = .0375); and have a lower hip-to-waist ratio (P = .0077) but higher serum AST (P < .0001) and ALT (P < .0001) levels. The multivariate analysis model to predict moderate-to-severe fibrosis included male sex, Caucasian ethnicity, diabetes mellitus, and increased AST and ALT levels (model P value < .0001). CONCLUSIONS In patients with NAFLD, diabetes mellitus and aminotransferase levels are independent predictors of moderate-to-severe fibrosis. They can be used to identify NAFLD patients at risk for advanced fibrosis.

A phase II dose finding study of darbepoetin alpha and filgrastim for the management of anaemia and neutropenia in chronic hepatitis C treatment

Summary.  Dose reductions of pegylated interferon alpha and ribavirin may be avoided by using growth factors. This phase II clinical trial assesses the dose, efficacy and safety of darbepoetin alpha and filgrastim for treatment of anaemia and neutropenia associated with combination therapy for hepatitis C virus (HCV). Chronic hepatitis C patients (n = 101) received pegylated interferon alpha‐2b (1.5 μg/kg once weekly) and ribavirin (800–1400 mg once daily). Patients with anaemia [haemoglobin (Hb) ≤ 10.5 g/dL] received darbepoetin alpha (3 μg/kg once every 2 weeks); the dose was titrated to achieve a Hb level of 12.0 g/dL. Patients with neutropenia [absolute neutrophil count (ANC) ≤ 0.75 × 109/L] received filgrastim with the dose titrated from 150 μg QW to 300 μg thrice weekly to maintain ANC ≥ 0.75 × 109/L and <10 × 109/L. During antiviral therapy, 52% of patients required darbepoetin alpha, filgrastim or both. Hb at the time of darbepoetin alpha initiation was 10.2 ± 0.4 g/dL. After 81 days of darbepoetin alpha, Hb increased by 1.9 ± 1.0 g/dL to 12.1 ± 1.1 g/dL (P < 0.0001). Filgrastim resulted in a significant increase in ANC [0.75 ± 0.16 × 109/L to 8.28 ± 5.67 × 109/L (P < 0.0001)]. In treatment‐naïve patients, 48% achieved sustained virological response (SVR), whereas 27% of patients previously treated with a course of pegylated interferon alpha achieved SVR. Low viral load, nongenotype 1 and treatment with growth factors were independently associated with SVR. Mild and severe anaemia were associated with quality of life impairments. Darbepoetin alpha resulted in an improvement in the Vitality domain of Short Form‐36. No significant adverse events were related to growth factors. During anti‐HCV therapy, filgrastim improved neutropenia and darbepoetin alpha improved both anaemia and quality of life. Future randomized clinical trials are needed to establish the impact of growth factors in improving sustained virological response.

Association of hepatitis C with insulin resistance and type 2 diabetes in US general population: the impact of the epidemic of obesity

Summary.  Studies from tertiary care medical centres have linked hepatitis C virus (HCV) to the development of insulin resistance (IR) and type 2 diabetes. The aim of the study is to assess the relationship between HCV positivity and insulin resistance/diabetes in the US population. Three cycles of the National Health and Nutrition Examination Survey (NHANES) conducted between 1988 and 2008 were used. HCV infection was diagnosed using a positive serologic anti‐HCV test. Additionally, diabetes was diagnosed as fasting blood glucose ≥126 mg/dL and/or the use of hypoglycaemic medications. Insulin resistance was defined as a homeostasis of model assessment (HOMA) score of >3.0. Logistic regression was used to estimate the odds ratios (ORs) of each of the potential risk factors for diabetes mellitus (DM). The SUDAAN 10.0 was used to run descriptive and regression analyses. A total of 39 506 individuals from three NHANES cycles (1988–1994, 1999–2004 and 2005–2008) with complete demographic and relevant clinical data were included. Over these three NHANES cycles, prevalence of hepatitis C did not significantly change. During the first NHANES cycle (1988–1994), insulin and diabetes were independently associated with hepatitis C. However, during the later study cycles (1998–2008), these associations were no longer significant. In contrast, other important known risk factors for diabetes and IR (male gender, non‐Caucasian race, age and obesity) remained significant over all three NHANES cycles. Although HCV infection was independently associated with an increased risk of diabetes and IR in the US population over a decade ago, assessment of the later NHANES cycles shows that this relationship may have become diluted by the rapid rise of other risks for diabetes, specifically, the prevalence of obesity.

Vietnamese community screening for hepatitis B virus and hepatitis C virus

Summary.  Asian Americans represent an important cohort at high risk for viral hepatitis. To determine the prevalence of Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection and HBV vaccination in a Vietnamese community, a total of 322 Vietnamese subjects from a local doctor’s office and annual Vietnamese Health Fair were included in this study. Demographic and clinical data were collected. 2.2% of the screened cohort tested positive for anti‐HCV and 9.3% tested positive for HBsAg. Unlike HBV‐positive subjects, HCV‐positive subjects had significantly higher liver enzymes (P = 0.0045 and P = 0.0332, respectively). The HBV‐positive group was more likely to report jaundice (P = 0.0138) and a family history of HBV (P = 0.0115) compared to HBV‐negative subjects. Forty‐eight patients (15.5%) reported a family history of liver disease (HBV, HCV, HCC, cirrhosis, other). Of this 48, 68.8% reported no personal history of HBV vaccination and 77.1% reported no family history of vaccination for HBV. Among the 183 subjects without a family history of liver disease, 156 (85.2%) reported no personal history of vaccination and 168 (91.8%) reported no family history of vaccination. HBV vaccination rates in those reporting a family history of liver disease were significantly higher (P = 0.020). There was a high prevalence of HBV infection in this community screening. Nevertheless, the rate for HBV vaccination was low. The low prevalence of abnormal liver enzymes in HBV‐positive subjects emphasizes the need for screening to be triggered by risk factors and not by abnormal liver enzymes.

Inpatient economic and mortality assessment for liver transplantation: a nationwide study of the United States data from 2005 to 2009.

Background Liver transplantation is a standard of care for treatment of end-stage liver disease. The aim of this study was to evaluate resource utilization for patients admitted to the U.S. hospitals for liver transplantation from 2005 to 2009. Methods Nationwide inpatient sample was used. Results A total of 5527 hospital admissions were included to the study cohort approximating 27,350 procedures nationwide (compared with 32,228 reported by United Network for Organ Sharing). Approximately 75% of patients had major or extreme severity of illness (All Patient Refined Diagnosis-Related Groups). The most prevalent comorbidities were coagulopathy (36.0%), fluid and electrolyte disorders (39.8%), anemia (18.7%), and type 2 diabetes (23.8%). Furthermore, 5.1% patients died in the hospital, 80.0% were discharged routinely or to home healthcare, and 14.9% were transferred to other healthcare facilities. The mean number of inpatient procedures was 7.2, and 3.5 were minimal therapeutic. The mean length of hospitalization was 22.2 days, the mean hospital charges were

The impact of viral hepatitis-related hepatocellular carcinoma to post-transplant outcomes

358,200, and the mean inpatient costs of liver transplantation were

Su1034 Central Fatigue and Peripheral Fatigue in Patients With Chronic Hepatitis C and Their Relationships to Patient-Reported Outcomes

114,300. In multivariate analysis, the most significant factors associated with longer stay were younger age, major or extreme severity of illness, and more procedures performed during hospitalization. Similar factors were also associated with higher cost of inpatient treatment. Inpatient mortality, however, was associated only with more severe illness and more procedures while being inversely associated with younger age and higher income. Conclusions Liver transplantation is a life-saving procedure with significant economic burden to our society. Severity of illness is the common driver of both in hospital mortality and resource utilization.

The Association of Hepatitis C and Type 2 Diabetes in U.S. General Population: The Impact of the Epidemic of Obesity

Hepatocellular carcinoma (HCC) is the most common complication of HCV infection leading to liver transplantation. We evaluated the impact of aetiology of liver disease on patient and graft survival following liver transplantation for HCC. From the Scientific Registry of Transplant Recipients (2002–2011), all adults who underwent liver transplantation for HCC were retrospectively included. Aetiology of liver disease was grouped into HCV, HBV, HCV–HBV co‐infection and nonviral liver disease. Of 8,733 liver transplant recipients with HCC, 5507 had HCV, 631 had HBV, 163 were co‐infected, and 2432 had nonviral causes of liver disease. In follow‐up (48 ± 32 months), 8.2% had graft failure and 29.5% died. The mean rates of graft failure were 9.5%, 4.7%, 6.1% and 6.4% in HCV, HBV, HCV–HBV co‐infection and nonviral liver disease, respectively (P < 0.0001). Post‐transplant mortality rate in patients with HBV was 20.2%, HCV 31.0%, HCV–HBV 28.5% and nonviral 28.5% (P < 0.0001). This difference was significant starting one year post‐transplant and became even more prominent later in follow‐up. Five‐year post‐transplant survival was 64.7% in HCV, 77.7% in HBV, 71.0% in HCV–HBV and 69.1% in nonviral HCC (P < 0.0001). A diagnosis of HCV in patients with HCC was also independently associated with an increased risk of both graft failure (adjusted hazard ratio = 1.84 (1.46–2.33), P < 0.0001) and mortality (1.35 (1.21–1.50), P < 0.0001) in multivariate analysis. Patients with HCV‐related HCC are at higher risk of adverse post‐transplant outcomes. These patients should be considered for preemptive interferon‐free antiviral therapy prior to or immediately following liver transplantation.