Therapeutic Advances in Viral Hepatitis A-E.

Viral hepatitis remains a significant global health problem. All forms of viral hepatitis A through E (A-E) can lead to acute symptomatic infection, while hepatitis B and C can lead to chronic infection associated with significant morbidity and mortality related to progression to cirrhosis, end-stage-liver disease, and liver cancer. Viral hepatitis occurs worldwide, though certain regions are disproportionately affected. We now, remarkably, have highly effective curative regimens for hepatitis C, and safe and tolerable medications to suppress hepatitis B activity, and to prevent liver damage and slow disease progression. We have effective vaccines for hepatitis A and B which provide long-lasting immunity, while improved sanitation and awareness can curb outbreaks of hepatitis A and E. However, more effective and available preventive and curative strategies are needed to achieve global eradication of viral hepatitis. This review provides an overview of the epidemiology, transmission, diagnosis, and clinical features of each viral hepatitis with a primary focus on current and future therapeutic and curative options.

An Update on the Treatment and Follow-up of Patients with Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by chronic granulomatous lymphocytic cholangitis of the small bile ducts. PBC was a leading indication for liver transplant in the United States; with early diagnosis and treatment, the majority of patients with PBC have a normal life expectancy. Pathogenesis involves inflammatory damage of bile duct epithelium secondary to innate and adaptive immune responses, and toxicity from accumulated bile acids. Cholestasis and disease progression can lead to cirrhosis. Extrahepatic complications include dyslipidemia, metabolic bone disease, and fat-soluble vitamin deficiency. Ursodeoxycholic acid is a well-established therapy. Novel targeted therapeutics are being developed.

Moderate Alcohol Use and Insulin Action in Chronic Hepatitis C Infection.

BACKGROUND AND AIM: Chronic hepatitis C (HCV) is associated with metabolic abnormalities including insulin resistance (IR) and diabetes. While moderate alcohol consumption is known to have beneficial metabolic effects in the general population, such potential effects in HCV are unknown. We aimed to assess the association between graded alcohol intake and IR, insulin secretion, and metabolic syndrome in HCV. METHODS: Ninety-five non-diabetic HCV-infected patients underwent detailed metabolic testing. IR was directly measured via steady-state plasma glucose (SSPG) during a 240-min insulin suppression test. Total insulin secretion and insulinogenic index were determined by 75-g oral glucose tolerance test. Genotyping of CYP2E1 was performed to detect genetic polymorphisms influencing alcohol metabolism. RESULTS: In this cohort, 61 % were abstinent from alcohol for the past 12 months, while 22 % were moderate, and 17 % heavy drinkers. Obesity and nonwhite ethnicity were the strongest predictors of IR. Moderate alcohol intake (vs none) was significantly associated with lower SSPG only among those with normal BMI (coef -72.9, 95 % CI -128.1 to -17.6, p = 0.01). Alcohol use was not associated with insulin secretion parameters when controlling for IR and other factors. Heavy alcohol intake (OR 3.2, 95 % CI 0.86-12.3) and nonwhite ethnicity (OR 7.1, 95 % CI 1.5-33.3) were associated with metabolic syndrome. Among nonwhites, the odds of metabolic syndrome were fivefold higher for heavy drinkers. CONCLUSIONS: Moderate alcohol intake is associated with improved insulin sensitivity in HCV, although this benefit was limited to normal-weight individuals. The potential benefit of moderate alcohol on IR and its metabolic consequences in HCV warrants further longitudinal investigation.

Assessment of HBV preventive services in a medically underserved Asian and Pacific Islander population using provider and patient data.

BACKGROUND: Hepatitis B (HBV) represents a significant health disparity among medically underserved Asian and Hawaiian/Pacific Islander (API) populations. Studies evaluating adherence to HBV screening and vaccination guidelines in this population are limited. OBJECTIVE: The purpose of this study was to evaluate HBV screening and vaccination practices using both provider self-report and patient records. DESIGN: Medical records for 20,574 API adults were reviewed retrospectively and primary care providers were surveyed to evaluate rates and adherence to HBV screening and vaccination guidelines. PARTICIPANTS: The study included primary care providers and their adult API patients in the San Francisco safety-net healthcare system. MAIN MEASURES: Patient, practice, and provider factors, as well as HBV screening and vaccination practices, were assessed using provider survey constructs and patient laboratory and clinical data. Generalized linear mixed models and multivariate logistic regression analyses were used to identify factors associated with recommended HBV screening and vaccination. KEY RESULTS: The mean age of patients was 52 years, and 63.4 % of patients were female. Only 61.5 % underwent HBV testing, and 47.4 % of HBV-susceptible patients were vaccinated. Of 148 (44.8 %) responding providers, most were knowledgeable and had a favorable attitude towards screening, but 43.2 % were unfamiliar with HBV guidelines. HBV screening was positively associated with favorable provider attitude score (OR per unit 1.80, 95 % CI 1.18-2.74) and negatively associated with female patient sex (OR 0.82, 95 % CI 0.73-0.92), a higher number of clinic patients per week (OR per 20 patients 0.46, 95 % CI 0.28-0.76), and provider barrier score (OR per unit 0.45, 95 % CI 0.24-0.87). HBV vaccination was negatively associated with provider barrier score (OR per unit 0.48, 95 % CI 0.25-0.91). CONCLUSIONS: Rates of HBV screening and vaccination of API patients in this safety-net system are suboptimal, and provider factors play a significant role. Efforts to cultivate positive attitudes among providers and expand healthcare system resources to reduce provider barriers to HBV care are warranted.

Liver inflammation is a risk factor for prediabetes in at-risk latinos with and without hepatitis C infection.

BACKGROUND & AIMS: Early recognition of prediabetes can lead to timely clinical interventions to prevent type 2 diabetes. Both Latino ethnicity and chronic hepatitis C (HCV) have been identified as diabetic risk factors. We aimed to investigate predictors of impaired fasting glucose (IFG), a common prediabetic state, among Latinos with and without HCV. METHODS: One hundred Latino adults with no history of diabetes or cirrhosis underwent clinical, laboratory, and metabolic evaluation, including oral glucose tolerance testing (OGTT) and insulin suppression testing to quantify directly measured insulin resistance (IR). Isolated IFG was defined as fasting glucose ≥100 mg/dl and <140 mg/dl at 2 h during normal glucose tolerance during OGTT. RESULTS: Overall subject characteristics included median age 44 years, 64% male, 40% HCV-positive and 32% with isolated IFG. Factors associated with isolated IFG included subject age (OR 2.42 per decade, 95%CI 1.40-3.90, P = 0.001), HCV infection (OR 4.0, 95%CI 1.71-9.72, P = 0.002) and alanine aminotransferase (ALT) (OR 2.35 per doubling, 95%CI 1.46-3.77, P < 0.0001). Multipredictor logistic regression analysis identified ALT (OR 2.05 per doubling, P = 0.005, 95% CI 1.24-3.40) and age (OR 2.20 per 10 years, P = 0.005, 95%CI 1.27-3.80) as factors independently associated with IFG. While HCV was associated with 4-fold higher odds of IFG, this entire effect was mediated by ALT. CONCLUSIONS: We found strong evidence that liver inflammation is a risk factor for prediabetes among Latinos with and without HCV. Among HCV-infected individuals, early antiviral therapy could mitigate the effect of inflammation and represent an important intervention to prevent diabetes in this at-risk population.

Postpartum care for mothers diagnosed with hepatitis B during pregnancy.

OBJECTIVE: We sought to determine rates of maternal postpartum hepatitis B virus (HBV) follow-up with a HBV specialist and identify factors associated with poor follow-up, as prior research has focused on infant outcomes and not maternal care. STUDY DESIGN: We conducted a retrospective review of data from Partners HealthCare system, the largest health care system in Massachusetts, and identified women with chronic HBV who delivered from 2002 through 2012. RESULTS: We identified 291 women (mean age 31.5 years, 51% Asian) with incident HBV during pregnancy. In all, 47% had postpartum follow-up with a HBV specialist, but only 19% also had appropriate laboratory tests (hepatitis B e antigen [HBeAg], hepatitis B e antibody, HBV DNA, and ALT) within 1 year of their HBV diagnosis. Mothers with HBV follow-up were more likely to have a primary care physician (PCP) within the Partners HealthCare system (66% vs 38%, P < .0001), a positive HBeAg (20% vs 8%, P = .004), and elevated AST values (17% vs 8%, P = .02). On multivariable logistic regression analysis, a mother who had a PCP (odds ratio, 2.50; 95% confidence interval, 1.37-4.59) or positive HBeAg (odds ratio, 4.45; 95% confidence interval, 1.64-12.06) had a greater likelihood of having HBV follow-up. CONCLUSION: Only 19% of HBV-infected mothers met care guidelines 1 year after being diagnosed with HBV. Inadequate postpartum HBV care affects women of all races/ethnicities. Women who had a PCP as well as those who were HBeAg positive were more likely to be referred for postpartum follow-up with a HBV specialist, suggesting that providers might be referring patients when they perceive HBV to be more serious or complex.

Hepatitis B management in vulnerable populations: gaps in disease monitoring and opportunities for improved care.

BACKGROUND: Hepatitis B (HBV) is prevalent in certain US populations and regular HBV disease monitoring is critical to reducing associated morbidity and mortality. Adherence to established HBV monitoring guidelines among primary care providers is unknown. AIMS: The purpose of this study was to evaluate HBV disease monitoring patterns and factors associated with adherence to HBV management guidelines in the primary care setting. METHODS: Primary providers within the San Francisco safety net healthcare system were surveyed for HBV management practices, knowledge, attitudes, and barriers to HBV care. Medical records from 1,727 HBV-infected patients were also reviewed retrospectively. RESULTS: Of 148 (45 %) responding providers, 79 % reported ALT and 44 % reported HBV viral load testing every 6-12 months. Most providers were knowledgeable about HBV but 43 % were unfamiliar with HBV management guidelines. Patient characteristics included: mean age 51 years, 54 % male and 67 % Asian. Within the past year, 75 % had ALT, 24 % viral load, 21 % HBeAg tested, and 40 % of at-risk patients had abdominal imaging for HCC. Provider familiarity with guidelines (OR 1.02, 95 % CI 1.00-1.03), Asian patient race (OR 4.18, 95 % CI 2.40-7.27), and patient age were associated with recommended HBV monitoring. Provider HBV knowledge and attitudes were positively associated, while provider age and perceived barriers were negatively associated with HCC surveillance. CONCLUSIONS: Comprehensive HBV disease monitoring including HCC screening with imaging were suboptimal. While familiarity with AASLD guidelines and patient factors were associated with HBV monitoring, only provider and practice factors were associated with HCC surveillance. These findings highlight the importance of targeted provider education to improve HBV care.

Increased detection of HIV-1 drug resistance at time of diagnosis by testing viral DNA with a sensitive assay.

OBJECTIVE: HIV-1 drug resistance has been detected in 8%-24% of recently infected North Americans when assessed by consensus sequencing of plasma. We hypothesized that rates were likely higher but not detected because drug-resistant mutants are transmitted or regressed to levels below the limit of detection by consensus sequencing of HIV-1 RNA. METHODS: Specimens from antiretroviral-naive individuals recently diagnosed with HIV-1 infection were compared at 15 codons to determine if testing of DNA using a sensitive oligonucleotide ligation assay (OLA) would detect drug resistance mutants not evident by consensus sequencing of serum. RESULTS: HIV-1 drug resistance at 15 major resistance codons was greater by OLA compared with consensus sequencing: 18 of 104 vs. 12 of 104 individuals (P < or = 0.008) and 33 vs. 18 total mutations (P < or = 0.001); increasing the rate of detection at these 15 codons by 83%. Additional mutations were detected by consensus sequencing at L33, M46, D67, V108, and K219 that were not assessed by OLA. CONCLUSIONS: The increased detection of drug-resistant HIV-1 by testing peripheral blood cells with a sensitive assay implies that both low and high levels of drug-resistant mutants are transmitted or persist in antiretroviral-naive individuals, suggesting that the clinical relevance of mutants persisting at both levels should be evaluated.