Jordan J. Feld

Autoimmune hepatitis: Effect of symptoms and cirrhosis on natural history and outcome

Although the natural history of autoimmune hepatitis (AIH) has been characterized, little is known about patients who present asymptomatically. Consequently, whether they require immunosuppressive therapy with its associated complications is unclear. To compare the natural history of asymptomatic AIH with symptomatic AIH, a large cohort of patients from a single center was examined. All patients with a clinical diagnosis of AIH were reassessed using the revised criteria of the International Autoimmune Hepatitis Group. Liver histology, response to therapy, and survival were assessed. Patients asymptomatic at presentation (n = 31) had lower serum aminotransferase, bilirubin, and immunoglobulin G (IgG) values at baseline. Half of the asymptomatic patients received no therapy, and their survival was no different from that of the total cohort. Ten‐year survival was 80.0% (62.5%‐97.5%) in the asymptomatic group and 83.8% (75.1%‐92.6%) in the symptomatic patients (P = NS). Survival to liver‐related endpoints at 10 years was similar in both groups: 89.5% (75.7%‐100%) asymptomatic and 83.8% (75.1%‐92.6%) symptomatic patients (P = NS). Patients with cirrhosis at baseline had poorer 10‐year survival (61.9% [CI 44.9%‐78.9%]) than those without cirrhosis at presentation (94.0% [CI 87.4%‐100%]) (P = .003) regardless of whether they presented with symptoms or whether they received immunosuppressive therapy. In conclusion, patients with AIH who are asymptomatic at presentation have a good prognosis and may not require immunosuppressive therapy. Cirrhosis on initial liver biopsy portends a poor prognosis in all patients with AIH. (HEPATOLOGY 2005.)

Effectiveness of Simeprevir Plus Sofosbuvir, with or Without Ribavirin, in Real-World Patients with HCV Genotype 1 Infection

BACKGROUND & AIMSnThe interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guidelines for certain patients with hepatitis C virus (HCV) genotype 1 infection based on the findings of a phase 2 trial. We aimed to evaluate the safety and efficacy of this regimen in clinical practice settings in North America.nnnMETHODSnWe collected demographic, clinical, and virologic data, as well as reports of adverse outcomes, from sequential participants in HCV-TARGET--a prospective observational cohort study of patients undergoing HCV treatment in routine clinical care settings. From January through October 2014, there were 836 patients with HCV genotype 1 infection who began 12 weeks of treatment with simeprevir plus sofosbuvir (treatment duration of up to 16 weeks); 169 of these patients received ribavirin. Most patients were male (61%), Caucasian (76%), or black (13%); 59% had cirrhosis. Most patients had failed prior treatment with peginterferon and ribavirin without (46%) or with telaprevir or boceprevir (12%). The primary outcome was sustained virologic response (SVR), defined as the level of HCV RNA below quantification at least 64 days after the end of treatment (beginning of week 12 after treatment--a 2-week window). Logistic regression models with inverse probability weights were constructed to adjust for baseline covariates and potential selection bias.nnnRESULTSnThe overall SVR rate was 84% (675 of 802 patients, 95% confidence interval, 81%-87%). Model-adjusted estimates indicate patients with cirrhosis, prior decompensation, and previous protease inhibitor treatments were less likely to achieve an SVR. The addition of ribavirin had no detectable effects on SVR. The most common adverse events were fatigue, headache, nausea, rash, and insomnia. Serious adverse events and treatment discontinuation occurred in only 5% and 3% of participants, respectively.nnnCONCLUSIONSnIn a large prospective observational cohort study, a 12-week regimen of simeprevir plus sofosbuvir was associated with high rates of SVR and infrequent treatment discontinuation. ClinicalTrials.gov: NCT01474811.

Epidemiology of autoimmune liver disease.

Primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) are chronic liver diseases that likely have an autoimmune basis to their pathogenesis. Although significant strides have been made in the clinical management of these conditions, their pathogenesis remains obscure. Understanding of various epidemiological factors may shed light on predisposing or causative factors for these diseases. Most is known about the epidemiology of PBC, with only minimal information on that of PSC and AIH. In this review, the current data on the epidemiology of PBC, AIH and PSC are summarized and suggestions are made for future work in this important area.

Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication.

BACKGROUND & AIMSnThe risk of hepatocellular carcinoma (HCC) is reduced but not eradicated among patients with hepatitis C virus (HCV)-induced advanced hepatic fibrosis who attained sustained viral response (SVR). We aimed to assess the risk of cirrhosis-related complications in this specific group of patients.nnnMETHODSnData from previously reported Western cohort studies including patients with chronic HCV infection and bridging fibrosis or cirrhosis who attained SVR were pooled for survival analyses on the individual patient level. The primary endpoint was HCC and the secondary endpoint was clinical disease progression, defined as liver failure, HCC or death.nnnRESULTSnIncluded were 1000 patients with SVR. Median age was 52.7 (IQR 45.1-59.7) years, 676 (68%) were male and 842 (85%) had cirrhosis. Median follow-up was 5.7 (IQR 2.9-8.0) years. Fifty-one patients developed HCC and 101 had clinical disease progression. The cumulative 8-year HCC incidence was 1.8 (95% CI 0.0-4.3) among patients with bridging fibrosis and 8.7% (95% CI 6.0-11.4) among those with cirrhosis (p=0.058). Within the cirrhosis group, the 8-year HCC incidence was 2.6% (95% CI 0.0-5.5) among patients <45years, 9.7% (95% CI 5.8-13.6) among patients from 45-60years, and 12.2% (95% CI 5.3-19.1) among patients >60years of age at start of therapy (p=0.006). Multivariable Cox analyses indicated that higher age, lower platelet count and diabetes mellitus were independently associated with development of HCC. After 8years 4.2% (95% CI 0.1-8.3) of patients with bridging fibrosis and 15.8% (95% CI 12.3-19.3) of patients with cirrhosis experienced clinical disease progression (p=0.007).nnnCONCLUSIONSnPatients with HCV-induced cirrhosis and SVR showed an annual risk of approximately 1% for HCC and 2% for clinical disease progression. Therefore, to prevent HCC surveillance, chronic HCV infection should preferably be treated before cirrhosis has developed.nnnLAY SUMMARYnPatients with cirrhosis who were able to eradicate their chronic HCV infection remain at substantial risk of primary liver cancer. The risk of liver cancer increases with higher age, laboratory makers suggesting more severe liver disease, and presence of diabetes mellitus. Also after successful antiviral therapy patients with HCV-induced cirrhosis should thus remain included in follow-up for early detection of liver cancer.

Prevalence, Correlates, and Viral Dynamics of Hepatitis Delta among Injection Drug Users

BACKGROUNDnMost hepatitis delta virus (HDV) prevalence estimates from the United States are >10 years old, and HDV has shown significant temporal variation in other populations. HDV-hepatitis B virus (HBV) dual infection progresses rapidly, has more complications, and has a different treatment regimen than HBV infection alone. Accurate estimates of prevalence and risk factors are important to help clinicians decide who to screen.nnnMETHODSnInjection drug users in Baltimore, Maryland, who were positive for HBV serologic markers were tested for hepatitis delta antibody (HDAb) at 2 time periods: 1988-1989 (194 participants) and 2005-2006 (258 participants). Those who were HDAb positive in 2005-2006, plus a random sample of HDAb negative, HBV-positive participants were tested for HDV RNA, HBV DNA, and HCV RNA. Characteristics associated with HDV exposure and viremia were identified.nnnRESULTSnHDV prevalence declined from 15% in 1988-1989 to 11% in 2005-2006. Among those with chronic HBV infection, prevalence increased from 29% (14 of 48 participants) to 50% (19 of 38 participants) (P=.05). Visiting a shooting gallery (a location where people gather to inject illegal drugs) was a strong correlate of HDAb positivity (relative risk, 3.08; P=.01). Eight (32%) of those who were HDAb positive had HDV viremia. Viremic participants had elevated liver enzyme levels and more emergency room visits.nnnCONCLUSIONSnThe temporal increase in HDV prevalence among those with chronic HBV infection is troubling; understanding this change should be a priority to prevent the burden from increasing.

Immigration and viral hepatitis

WHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231 million individuals) migrated into a new host nation. Migrants predominantly originate from the developing countries of the south, into the developed economies of North America and Western Europe. This mass migration of individuals from areas of high-prevalence of viral hepatitis poses a unique challenge to the healthcare systems of the host nations. Due to a lack of universal standards for screening, vaccination and treatment of viral hepatitis, the burden of chronic liver disease and hepatocellular carcinoma continues to increase among migrant populations globally. Efforts to increase case identification and treatment among migrants have largely been limited to small outreach programs in urban centers, such that the majority of migrants with viral hepatitis continue to remain unaware of their infection. This review summarizes the data on prevalence of viral hepatitis and burden of chronic liver disease among migrants, current standards for screening and treatment of immigrants and refugees, and efforts to improve the identification and treatment of viral hepatitis among migrants.

Health care costs associated with hepatocellular carcinoma: a population-based study.

Although the burden of hepatocellular carcinoma (HCC) is an escalating public health problem, it has not been rigorously estimated within a Canadian context. We conducted a population‐based study using Ontario Cancer Registry linked administrative data. The mean net costs of care due to HCC were estimated using a phase of care approach and generalized estimating equations. Using an incidence approach, the mean net costs of care were applied to survival probabilities of HCC patients to estimate 5‐year net costs of care and extrapolated to the Canadian population of newly diagnosed HCC patients in 2009. During 2002‐2008, 2,341 HCC cases were identified in Ontario. The mean (95% confidence interval [CI]) net costs of HCC care per 30 patient‐days (2010 US dollars) were

Is there sufficient evidence to recommend antiviral therapy in hepatitis C

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Reliable prediction of clinical outcome in patients with chronic HCV infection and compensated advanced hepatic fibrosis: a validated model using objective and readily available clinical parameters

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A Canadian screening program for hepatitis C: Is now the time?

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