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Supplemental Digital Content is available in the text., Background and aims Liver chemistry abnormalities (LCA) are common in patients with coronavirus disease 2019 (COVID-19), but their causes and clinical impact have not been adequately studied. We assessed the associations between LCA and clinical characteristics, inflammatory serum markers, in-hospital mortality. Methods Ten thousand eight hundred fifty-six adult patients with COVID-19 hospitalized in 13 hospitals in New York (1 March to 27 April 2020) were analyzed retrospectively. Abnormalities of liver chemistries [aspartate aminotransferase (AST), alanine aminotransferase, alkaline phosphatase, or total bilirubin] were defined as absent, mild-moderate (at least one value up to four times elevated), or severe. Results LCA were mild-moderate in 63.9% and severe in 7.6% at admission. Risk factors for severe LCA were male sex and chronic liver disease. Conversely, hypertension and diabetes mellitus were less likely associated with severe LCA. AST elevation correlated weakly to modestly with inflammatory markers. On adjusted analysis, in-hospital mortality was 1.56 times and 1.87 times increased in patients with mild-to-moderate and severe LCA, respectively. Diabetes, hypertension, male sex, and age greater than 60 years was associated with incremental risk of mortality with increase severity of LCA, especially in the first week of hospitalization. HTN was not associated with increased in-hospital mortality unless LCA was present. Conclusion Increasing severity of LCA on hospital admission predicts early in-hospital mortality in COVID-19 patients. Mortality associated with the known risk factors, hypertension, diabetes, male sex, and old age was accentuated in the presence of LCA. AST correlated modestly with inflammatory markers.

Treatment of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is focused on patients with NASH because they are at highest risk for progressive liver disease. Current first-line treatment consists of lifestyle modifications. Patients should lose at least 7% to 10% of body weight via a combination of physical exercise and calorie restriction dieting. Surgical or endoscopic surgery for weight loss can be considered in obese patients, depending on degree of excess body weight and comorbidities. There is no currently approved pharmacotherapy for NASH. Vitamin E and pioglitazone have the most evidence of therapeutic efficacy but have limitations. The treatment modality chosen should be individualized.

INTRODUCTION: Abnormal liver chemistries and elevated CPK (creatinine phosphokinase) levels are known to be associated with COVID-19 infection CPK is a biomarker associated with disease progression with COVID-19 Outcomes related elevated CPK levels in relationship to ALT levels elevation has not been explored Our study assessed the predictive value of the ratio of alanine aminotransferase levels and CPK in a large cohort of COVID-19 patients without known chronic liver disease (CLD) METHODS: We reviewed the charts of 11,265 patients with confirmed COVID-19 infection via nasopharyngeal swabs admitted to our health system from March 1 to April 30, 2020 Baseline ALT and CPK were drawn within 24 hours of presentation After exclusion of patients who did not have an initial RESULTS: CPK to ALT ratio ≥ 1 (CPK/ALT / 5 1) was noted in 91 5% of the patients;8 5% with CPK/ALT≤1, 32% with CPK/ALT >1 and ≤4, 29 5% with CPK/ALT >4 and ≤10, and 29 9% with CPK/ ALT >10 In Kaplan-Meier survival analyses, patients with CPK/ALT ≥1 had an increased in-hospital mortality as compared to patients with CPK/ALT1 and ≤410 compared to patients with CPK/ALT ≤1 CONCLUSION: Our study found that a CPK/ALT >1 on presentation in COVID-19 patients without known chronic liver disease was predictive of increased in-hospital mortality in this large cohort Higher CPK/ ALT (≥1) correlates with increased in-hospital mortality even when adjusted for baseline demographics and the presence of comorbidities Based upon this large study, CPK/ALT ratio should be used to predict inhospital mortality in COVID-19 infection and included in the initial assessment of these patients

INTRODUCTION: Liver injury has been noted during the disease course of the novel coronavirus infection (COVID-19) We evaluated for ethnic and racial disparities in COVID-19 patients presenting with liver injury METHODS: We reviewed 11,265 individual patient charts with confirmed COVID-19 infection admitted to our 12 hospitals in our health system between March 1 to April 30, 2020 Race and ethnicity data were collected by self-report in pre-specified categories Race categories included white, black, asian, other/multiracial and unknown, while ethnicity included non-Hispanic, Hispanic and unknown Baseline liver chemistries were collected within 24 hours of presentation Exclusion criteria included age less than 18 years and missing baseline data Patients were categorized as having liver injury if they had any elevation above the upper limit of normal set by American Association for the Study of Liver Diseases in alanine aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) or bilirubin Multivariate analysis was performed after adjusting for covariates RESULTS: After exclusion,10,856 patients were included in our study Overall, there was a significant difference of the prevalence of liver injury amongst the various races and ethnicities (Table 1) On adjusted analysis, Asian (OR: 1 65 [95% CI: [1 37-2 02]) and multi-racial patients (OR: 1 65 [95% CI: 1 37-2 02]) were more likely to develop liver injury compared to white patients A non-Hispanic ethnicity had a lower association with sustaining liver injury (OR: 0 77 [95% CI: [0 75-1 03]) (Table 2) CONCLUSION: There are racial and ethnic disparities seen in patients with liver injury during COVID-19 infection Our data suggest that Asian patients are more likely compared to white patients to sustain liver injury Non-Hispanic ethnicity conferred protective effect against liver injury These results may implicate a component underlying genetic predisposition for liver injury during COVID- 19 infection (Table Presented)

INTRODUCTION: There are several reports suggesting abnormal liver enzymes occur in as many as 50% of patients infected by the novel coronavirus-19 (COVID-19) The purpose of our study was to examine the gender disparities in the prevalence of abnormal liver enzymes at initial presentation in COVID-19 patients METHODS: We reviewed the charts of 11,265 adult patients with confirmed COVID-19 infection admitted to any of the 12 hospitals in our health system from March 1 to April 30, 2020 COVID-19 status was confirmed by polymerase chain reaction of a nasopharyngeal swab specimen Labs drawn within 24 hours of presentation were considered baseline Patients that had an age less than 18 or missing baseline data were excluded Abnormalities in liver chemistries for AST (Aspartate Amino Transferase) and ALT (Alanine Amino Transferase) were grouped as follows: (1) within normal limits;(2) mild: greater than the upper limit of normal (ULN) to less than or equal to 4 times the ULN;(3) moderate: greater than 4 times the ULN to less than or equal to 10 times the ULN;and (4) severe: greater than 10 times the ULN RESULTS: After exclusions, 10,856 patients were included in our study There was a significant difference of the prevalence of liver injury between men and women (Table 1) Liver injury was present in 61% male and 40% female (P < 0 001) On univariate analysis, men (OR: 1 77 [95% CI: 1 64-1 92] and OR: 2 56 [95% CI: 2 06-3 17]) were more likely to have mild or moderate increases in AST but the difference was not apparent with ALT levels These results were confirmed using the adjusted analysis after adjusting for baseline demographics and comorbidities (Table 2) CONCLUSION: Males presenting with COVID-19 infection are more likely to have elevated AST levels than females There were no significant differences in ALT levels based upon gender Elevated AST levels have been associated with a poor prognosis in hospitalized COVID-19 patients Further research is needed to understand the mechanism of these gender-based differences in liver enzyme elevations, and their relationship to outcomes in COVID-19 infected patients (Table Presented)

Liver biopsy is important for diagnosing primary biliary cirrhosis (PBC). Prior investigations suggest that immunostaining for biliary keratin 19 (K19) may show the earliest changes suspicious for PBC, namely, loss of the canals of Hering (CoH). We aimed to study the clinical outcomes of patients whose biopsy specimens appeared histologically near normal or with minimal inflammatory changes, but in which K19 staining revealed widespread periportal CoH loss, a finding we termed “minimal change PBC.” Ten patients were identified prospectively as having nearly normal or mildly inflamed biopsy specimens without diagnostic or suggestive histologic features of PBC, but with near complete CoH loss; six had available follow-up clinical data, one had follow-up biopsy. Controls for clinical and/or K19 analysis included six normal livers and biopsy specimens from 10 patients with confirmed early PBC, 10 with early stage chronic hepatitis C (CHC), and nine with resolving, self-limited hepatitis (RSLH). Staining for K19 in normal controls, livers with “minimal change” PBC, CHC, and RSLH showed 9.2 ± 6.0, 0.44 ± 0.37 (P < 0.0001), 5.7 ± 4.6 (n.s.), 4.1 ± 2.1 (P < 0.02) CoH per portal tract, respectively. Patients with available clinical follow up, compared to patients with diagnostic early-stage PBC biopsies, showed identical treatment responses to ursodeoxycholic acid, similar rates and types of nonhepatic autoimmune diseases, and/or subsequent development of autoimmune hepatitis overlap syndrome. Conclusion: We suggest that CoH loss demonstrated by K19 immunostaining is an early feature in PBC. Clinical findings in the years following biopsy, including response to ursodeoxycholic acid, show identical changes to patients with biopsy confirmed PBC. We suggest that this “minimal change” feature may support a clinical diagnosis of PBC even in the absence of characteristic, granulomatous, duct destructive lesions. (HEPATOLOGY 2013)

Toll-like receptors (TLRs) may play a role in the inflammatory patterns observed in primary biliary cirrhosis (PBC) and chronic hepatitis C (CHC). We investigated TLR 3, 4 and 9 expression in PBC and CHC using immunohistochemical staining.Patient biopsies of PBC (N=11) and CHC (N=15) were compared to disease free livers (n=7). The extent of TLR staining was assessed separately according to a semi-quantitative scale for hepatocytes, cholangiocytes and portal mononuclear cells (PMC).In hepatocytes, TLR4 expression was increased (PBC; P=0.019), as was TLR9 (PBC; P=0.006, CHC; P=0.001). Cholangiocyte expression of TLRs 4 and 3 was reduced in both PBC (TLR4; P0.0001, TLR3; P=0.006) and CHC (TLR4; P0.0001, TLR3; P=0.014). Cholangiocyte expression of TLR9 was elevated for both groups and was significant in CHC (P=0.0115). PMCs showed up-regulation of TLR9 in PBC (P=0.022) and CHC (P=0.0001), with almost no expression of TLR 3 or 4.In PBC and CHC, hepatocytes showed increased TLR 4 and 9 expression without change in TLR3. Cholangiocytes showed increased TLR9 expression as opposed to down-regulation of TLRs 3 and 4. PMCs in both diseases had significantly increased TLR 9 expression perhaps implicating TLR9 expression in chronic liver inflammation.

Background. Current treatment of chronic hepatitis C with pegylated interferon and ribavirin has the ability to eliminate viral infection in about half of the patients treated. Therapeutic options, for those with remaining chronic hepatitis, will remain limited until novel antivirals become available in the future. Consensus interferon is currently available and has demonstrated clinical efficacy with superior invitro antiviral activity, but the maximum tolerated dose is not defined. Methods. We assessed the efficacy of daily high-dose (24 ug) consensus interferon with weight-based (1000–1200 mg daily) ribavirin in HCV genotype 1-infected non-responder patients. Results. Six adverse events were documented in five patients, and the trial was terminated with no subject achieving viral clearance. Conclusions. The occurrence of serious adverse events effectively defined the upper limit of acceptable dose, while also revealing that this dose did not offer enhanced sustained viral clearance.

Liver biopsy plays a crucial role in assessing inflammation and fibrosis in chronic hepatitis. The aim of this study was to compare the indications and methods for performing a liver biopsy over a 15-year period when there were evolving strategies and increasing therapeutic options for the treatment for chronic hepatitis B (HBV) and C (HCV). We reviewed all percutaneous liver biopsies performed at our center from 1992 to 2007 using a pathology database. Variables collected included indication for biopsy, use of real-time ultrasound (US) guidance, and complications associated with the biopsy. A total of 3,572 total liver biopsies were performed between 1992 and 2007 with a gradual increase in annual liver biopsies from 1992 to 2001. After a peak in 2003, there was a gradual decline in liver biopsies performed. The number of liver biopsies done for HCV peaked in 2003, followed by an annual decrease until 2006, while the number of annual biopsies done for HBV increased during the same period. In addition, the proportion of liver biopsies performed with real-time US-guidance increased steadily since 1997. Changes in liver biopsy trends at our center may be related to several factors, including the evolving treatment strategies for HCV and HBV. Percutaneous liver biopsies were increasingly performed using real-time US-guidance over the past decade, a change that may reflect practice patterns around the country.

— More than 25% of undirected percutaneous liver needle biopsies that are performed in search of metastatic neoplasms yield false negative specimens. Often, however, histologic changes are observed in the liver adjacent to space-occupying lesions due to focal obstruction of bile and blood flow. These alterations were defined by semi-quantitative evaluation of 20 liver biopsy specimens with metastatic neoplasms, and revealed a characteristic histologic triad consisting of proliferated and abnormal bile ductules, polymorphonuclear leukocytes in edematous portal tracts and focal sinusoidal dilatation. When 15 patients with this combination of histologic alterations, but without malignant cells in liver biopsy specimens, were investigated prospectively, 13 patients (87%) were found to have hepatic metastases. Therefore, the observation of the histologic triad described here should lead to a continued search for space-occupying lesions in the liver.

Adherence to chronic hepatitis C (CHC) treatment may be particularly challenging in methadone maintenance patients. We assessed the safety, tolerability, and efficacy of peginterferon alfa-2a/ribavirin treatment in methadone maintenance patients previously untreated for CHC.Patients were randomized 1:1 to direct observed therapy (DOT) or self-administration (SA) of peginterferon alfa-2a. DOT patients were seen weekly at methadone clinics; SA patients were seen less frequently, only at investigative sites. Genotype 1-infected patients were treated for 48 wk with peginterferon alfa-2a (180 microg/wk)/ribavirin (1,000/1,200 mg/day); genotypes 2- and 3-infected patients were treated for 24 wk with peginterferon alfa-2a (180 microg/wk)/ribavirin (800 mg/day).Based on defined efficacy stopping rules, 77% (37/48) completed their targeted length of treatment, and 44% (21/48) achieved sustained virologic response (SVR). Two DOT and 3 SA patients were withdrawn for safety reasons and 6 and 9, respectively, for nonsafety reasons. Over 60% and 50% of each group were80% compliant with the planned cumulative doses of peginterferon alfa-2a and ribavirin, respectively, and over 60% with overall treatment duration. SVR rates were 54% (13/24) for DOT and 33% (8/24) for SA; 23% (3/13) and 38% (6/16), respectively, for genotype 1 and 91% (10/11) and 25% (2/8), respectively, for genotypes 2 and 3. Stepwise logistic regression analysis, showed that DOT (vs SA; OR 3.27, 95% CI 0.90-11.91, P = 0.073) and Caucasian race (vs Other; OR 13.31, 95% CI 1.42-124.71, P = 0.023) were predictors of SVR.Peginterferon alfa-2a/ribavirin can be used safely and successfully in CHC patients receiving methadone maintenance.

Statin treatment reduces hypercholesterolemia and may be anti-inflammatory. Case reports noted decreased alkaline phosphatase and histological improvement following statin treatment in primary biliary cirrhosis. The objective of this study was to assess the long-term effects of statin treatment in primary biliary cirrhosis. A retrospective analysis compared clinical and biochemical data from 15 hypercholesterolemic individuals with primary biliary cirrhosis who were treated long-term with atorvastatin with an age and gender matched, primary biliary cirrhosis control group. A significant decrease in total cholesterol and low-density lipoprotein (LDL)-cholesterol (por = 0.002) was observed throughout atorvastatin treatment (median time 2.5 years). LDL-cholesterol levels in the control group were not significantly changed after 2 years (p0.050). No significant changes were noted in alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin and Mayo Risk Score in either group (p0.05). Long-term atorvastatin treatment reduced LDL-cholesterol in primary biliary cirrhosis, but there was no evidence of any anti-inflammatory effect.

There are multiple possible causes of ascites in patients with end-stage renal disease on hemodialysis therapy. In this report, we describe a patient with chronic hepatitis C infection who presented with refractory inflammatory ascites, along with cachexia, hypoalbuminemia, and erythropoietin resistance associated with the chronic inflammatory state induced by a failed kidney transplant. Evaluation showed only mild hepatic fibrosis, absence of portal hypertension, and no other identifiable cause of the ascites. Furthermore, the inflammatory ascites did not respond to antibiotic therapy, but promptly resolved, along with the other manifestations of the chronic inflammatory state, after transplant nephrectomy. This report describes a novel cause for refractory inflammatory ascites in a patient with a failed kidney transplant and emphasizes the importance of transplant nephrectomy.

Primary sclerosing cholangitis (PSC) is a syndrome of unknown etiology characterized by an association with inflammatory bowel disease in 50% or more cases. Since altered immunity, including circulating immune complexes, has been implicated in the pathogenesis of inflammatory bowel disease, we postulated that humoral immune mechanisms might also be important in the development of PSC. Therefore, as an initial step in testing this hypothesis, we examined sera of patients with PSC for the presence of circulating immune complexes by two independent methods: C1q binding and Raji cell assays. Twenty-four patients with PSC, 16 of whom had coexisting chronic ulcerative colitis, were prospectively selected by predefined biochemical, histologic, and radiographic criteria. Sixteen patients with inflammatory bowel disease and normal liver tests as well as six patients with extrahepatic biliary obstruction served as disease controls. Sera were positive for circulating immune complexes by at least one method in 80% (16/20) of patients with PSC; 70% (14/20 were positive by the Raji cell assay, 58% (14/24) by the C1q binding assay, and 45% (9/20) by both methods. Levels of circulating immune complexes by each assay were higher in sera from patients with PSC than in sera from healthy controls or patients with inflammatory bowel disease alone (p less than 0.01). There were no differences in the levels of circulating immune complexes or in the frequency of positive tests in PSC patients with or without associated inflammatory bowel disease. In addition, there was no difference between the Raji cell binding of sera from six patients with extrahepatic biliary obstruction and six healthy controls tested concurrently. These data are consistent with the hypothesis that immunologic mechanisms may be important in the pathogenesis of PSC.

Summary. Hepatitis C virus (HCV) infection is a major health problem in the United States. Only about 30% of patients infected with HCV are being treated despite the development of increasingly effective therapies. The aims of this study were to determine the rate of treatment for patients with HCV after undergoing liver biopsy, to assess any change in their treatment rates over recent years and to delineate the reasons for nontreatment. We retrospectively reviewed the charts of all HCV patients who had liver biopsies at Beth Israel Medical Center, New York between 1998 and 2002. The data gathered included patient demographics, stage of liver fibrosis, insurance information, treatment history and reasons for nontreatment. There were 433 liver biopsies done for chronic hepatitis C between 1998 and 2002. Of those, 267 (61%) were men. The mean age was 47 years (range, 18–72). Only 159 (37%) patients were treated after liver biopsy. Overall there were no significant differences in the treatment rates from 1999 to 2002. The common reasons for nontreatment included minimal/mild disease (stage 0–1 fibrosis, 38%), lost to follow-up or noncompliance (31%) and patient refusal (22%). Older patients more frequently had co-morbid conditions (P = 0.009). Younger age and female gender correlated with minimal disease on biopsy (P = 0.004 and 0.01, respectively). Men were lost to follow-up more frequently than women (37%vs 22%, P = 0.01). Multivariate analysis showed that age and gender were both independent predictors of minimal disease. Patients having Medicaid with or without Medicare were significantly more likely to be treated than patients with private or commercial insurance or patients with Medicare alone. A minority of HCV infected patients were treated even after having undergone liver biopsy. The proportion of HCV patients being treated after liver biopsy has been relatively stable despite advances in therapeutic success. Liver histology frequently identified patients with mild disease in whom antiviral therapy was deemed not urgent.

Hepatitis B virus (HBV)infection is a major cause of chronic hepatitis and cirrhosis,with an estimated 350 million people worldwide infected with the virus.Despite continuing advances in antiviral therapy,a cure for chronic HBV infection is considered an elusive goal.Thus,primary prevention by immunization with HBV vaccines remains the most effective means to control the transmission of HBV infection.

The low-density lipoprotein receptor (LDLR) has been proposed as a candidate receptor for the hepatitis C virus (HCV). Competitive inhibition of HCV binding to the LDLR by low-density lipoprotein (LDL) has been shown in vitro. If similar inhibition occurs in vivo, an elevated serum concentration of beta- lipoproteins may reduce the efficiency of infecting hepatocytes with HCV by competitively inhibiting HCV viral receptor binding. We investigated the role of baseline lipid values in influencing the outcome of HCV treatment. We conducted a retrospective chart review of patients treated with an interferon-based regimen at our liver and gastroenterology clinics between 1998 and 2004. Of 99 patients enrolled in the study, 49 (49.5%) had HCV genotype 1 (LDL 100.2 ± 30.2 mg/dL [mean ± SD]), and 50 patients (50.5%) had genotype 2 or 3 (LDL 110.1 ± 40 mg/dL) infection. Early viral response (EVR), end-of-treatment response (ETR), and sustained viral response (SVR) were documented in 99, 88, and 77 patients, respectively. LDL and cholesterol levels prior to treatment were found to be higher in patients with positive EVR, ETR, and SVR. This difference remained significant independent of age. Multivariate analysis controlling for genotype and age showed that the higher the cholesterol and LDL levels prior to treatment, the greater the odds of responding to treatment. In conclusion, having higher serum LDL and cholesterol levels before treatment may be significant prognostic indicators for treatment outcome of those with chronic hepatitis C infection, particularly in genotypes 1 and 2. (HEPATOLOGY 2006;44:335–340.)

The efficacy of combination therapy with pegylated interferon (PEG IFN) alpha plus ribavirin (RBV) in the retreatment of chronic hepatitis C (CHC) in patients who previously failed combination standard IFN plus RBV or IFN monotherapy has not been well established.Three hundred and twenty-one CHC patients including virologic nonresponders to combination IFN plus RBV (n = 219) or IFN monotherapy (n = 47), and relapsers to combination therapy (n = 55) were randomized to receive PEG IFN alpha-2b 1.5 microg/kg per wk plus RBV 800 mg per day (Regimen A, n = 160) or PEG IFN alpha-2b 1.0 microg/kg per wk plus RBV 1,000-1,200 mg per day (Regimen B, n = 161) for 48 wks.Sustained virologic response (SVR) occurred in 16% of the overall study population (Regimen A vs B, 18%vs 13%, p= 0.21), in 8% of the combination therapy nonresponders (10%vs 6%, p= 0.35), in 21% of the IFN monotherapy nonresponders (16%vs 27%, p= 0.35), and in 42% of the combination therapy relapsers (50%vs 32%, p= 0.18). In nonresponders to prior combination therapy, HCV ribonucleic acid levels100,000 copies/mL at the end of the prior treatment course were associated with an increased SVR compared with levelsor=100,000 copies/mL (21%vs 5%, p= 0.002). In the overall study population, genotype 1 patients had lower SVR rates than others (14%vs 33%, p= 0.01), and African Americans had lower SVR than Caucasians (4%vs 18%, p= 0.01).Combination therapy with PEG IFN alpha-2b plus RBV is more effective in patients who relapsed after combination standard IFN plus RBV than in nonresponders to either combination therapy or IFN monotherapy. There was no significant effect of dosing regimen.

OBJECTIVES: Fatigue, which may have a significant impact on quality of life, is the most common reported symptom in primary biliary cirrhosis (PBC). Multiple instruments to quantify fatigue and quality of life in liver disease have been validated, but have not been broadly applied to U.S. PBC patients. This study examines the extent of fatigue and its effect on quality of life in U.S. PBC patients. METHODS: Seventy patients with PBC were administered two validated questionnaires about quality of life (the Mayo version of the NIDDK-QA) and fatigue (the Fisk Fatigue Impact Score) and a proposed physical measure of fatigue in PBC (the grip strength test) on the day of routine physician visit. Nonparametric methods were employed. RESULTS: The fatigue and quality of life domain scores (physical functioning, liver symptoms, health satisfaction, Karnofsky index) discriminated between patients with and without self-reported fatigue (p < 0.05), as opposed to the grip strength results. Fatigue and quality of life domains correlated strongly with each other (r between 0.33 and 0.74, p

Objectives: Patients with cirrhosis can acquire pulmonary conditions that may or may not be related to their illness. Although posing a greater risk for complications, chest tubes are sometimes placed as treatment for hepatic hydrothorax and other pulmonary conditions. The aim of this study was to analyze the outcomes of chest tube placement in cirrhotic patients. Methods: A retrospective analysis was performed of 59 adults with cirrhosis undergoing chest tube placement. Variables that were investigated included reason for chest tube placement, complications developing while having the tube in place, and outcome. Results: The 59 subjects were classified as having Child-Turcotte-Pugh (CTP) class A cirrhosis (n = 3), CTP class B cirrhosis (n = 31), and CTP class C cirrhosis (n = 25). Indications for having a chest tube placed were hepatic hydrothorax (n = 24), pneumothorax (n = 9), empyema (n = 8), video-assisted thoracoscopy (VAT) [n = 7], non-VAT (n = 5), and hemothorax (n = 3). The CTP class A subjects had their chest tubes removed without further complications early in the course, and were excluded from further statistical analysis. Twenty-five subjects (42%) had significant pleural effusions requiring chest tube placement. Among the CTP class B and class C subjects, the median duration with chest tube in place was 5.0 days (range, 1 to 53 days). Serum total bilirubin levels, presence of portosystemic encephalopathy, and CTP C classification were predictors of mortality. Mortalities were seen in 5 of 31 CTP class B subjects (16%), and 10 of 25 CTP class C subjects (40%). The tubes were successfully removed in a total of 39 subjects (66%) with no further procedure. Forty-seven subjects (80%) acquired one or more of the following complications: renal dysfunction, electrolyte imbalances, and infection. Conclusions: When placed for all indications, chest tubes may be successfully removed in the majority of cirrhotic patients. However, a third of all patients still die with the chest tube still in place. Failure to remove the chest tube increases mortality in patients with increasing severity of liver disease.

Cirrhosis resulting from hepatitis C virus is presently the most common indication for liver transplantation (OLT) in the United States. A number of U.S. transplant centers require cirrhotics who are using methadone to discontinue it before proceeding with OLT. We sought to examine the outcomes of those patients who had undergone OLT at the Mount Sinai Medical Center. A retrospective chart review of 36 subjects on methadone maintenance treatment (MMT), and off heroin, at the time of OLT was performed. The median daily methadone dose pre-OLT was 50 mg. Post-OLT, there was an increase in methadone dose in 15 subjects, a decrease in four subjects, and no dose change in 17 subjects. Four subjects had documented single episodes of intravenous drug use post-OLT; only one subject had a dose change after the event. Patient and graft survival rates were comparable to the national average. There was no significant difference in post-OLT outcome in patients on MMT when compared with the general population. The few episodes of drug relapse were not related to changes in the methadone dose. Efforts should be made to allow methadone-using cirrhotics better access to OLT without regard to methadone dosage.

Objective Preliminary data suggested possible benefits of methotrexate in primary biliary cirrhosis. We assessed the effectiveness of methotrexate use in primary biliary cirrhosis and its tolerance in patients with this disease. Methods A total of 110 primary biliary cirrhosis patients began methotrexate 15 mg/wk; for most, ursodeoxycholic acid was added during the study. We analyzed data from patients completing 5 yr of treatment with methotrexate to assess its effect on biochemical and histologic parameters after 5 yr of therapy. Based on an intent to treat analysis, we also compared survival of our patients (n = 110) with that of patients in a previously published, placebo-controlled trial of ursodeoxycholic acid (n = 180). Results Only half of the study group completed 5 yr of methotrexate therapy. Therapy did not prevent progression of disease, as indicated by a rising Mayo risk score. Portal fibrosis tended to remain the same. Methotrexate did not diminish the risk of death or liver transplantation when compared with ursodeoxycholic acid or placebo; however, ursodeoxycholic acid use decreased the risk of death or transplant (p = 0.006). Conclusions Methotrexate is not well tolerated in primary biliary cirrhosis. The toxicity of methotrexate and its inability to prevent complications of progressive liver disease or improve survival and the need for liver transplantation limits its utility. The benefits of ursodeoxycholic acid were again confirmed.

The three reported cases demonstrate that troglitazone is an idiosyncratic hepatotoxin that can lead to irreversible liver injury. Thus, troglitazone should be prescribed with caution and should not be used as a first-line agent in the treatment of type II DM when potentially less toxic alternatives are available. It remains to be seen whether the hepatotoxicity associated with troglitazone is a drug-class effect or specific to troglitazone. Other thiazolidinediones currently in clinical trials may be able to provide the therapeutic benefits of troglitazone without significant hepatotoxicity. If troglitazone is used, frequent monitoring of serum aminotransferases and symptoms is mandatory. However, as illustrated by these and other cases reported to date, the onset of troglitazone-induced liver injury is insidious and temporally variable. Thus, the value of close monitoring and when, if ever, it is safe to stop such monitoring are currently unclear.

Bromfenac, a nonnarcotic analgesic nonsteroidal anti-inflammatory drug, was associated with reversible, minor elevations in serum aminotransferase levels during clinical trials. The aim of this study is to describe the clinical, laboratory, and histological features of 4 patients with severe bromfenac hepatotoxicity identified at 3 tertiary care centers participating in the US Acute Liver Failure Study Group. Bromfenac was administered for chronic musculoskeletal disorders to 4 women in therapeutic doses of 25 to 100 mg/d for a minimum of 90 days. All patients reported a prodrome of malaise and fatigue and presented with severe, symptomatic hepatocellular injury with associated hypoprothrombinemia. None of the subjects had underlying liver or kidney disease, and there was no evidence of a hypersensitivity reaction. Other identifiable causes of acute liver failure were uniformly excluded. Despite supportive measures, all the subjects developed progressive liver failure over 5 to 37 days, leading to emergency liver transplantation in 3 patients and death in 1 patient while awaiting transplantation. Extensive confluent parenchymal necrosis that appeared to begin in the central zones and was accompanied by a predominantly lymphocytic infiltrate was noted in all the livers examined. Nodular regeneration was seen in the 2 patients with a more protracted clinical course. Administration of therapeutic doses of bromfenac for greater than 90 days was associated with the development of acute liver failure leading to liver transplantation or death in 4 adult women. The poor outcomes observed in this series, coupled with the inability to identify individuals at risk for severe, idiosyncratic bromfenac hepatotoxicity, preclude further use of bromfenac in the medical community.

Background. Epidemiological studies have detected up to a 9% incidence of hepatitis G (HGV)-RNA in patients with acute and chronic liver disease of unknown etiology. We sought to clarify the role of HGV as a causative agent in cryptogenic cirrhosis by analyzing archival liver tissue for HGV-RNA in patients undergoing orthotopic liver transplantation. Methods. Using a computer database, we identified 54 patients who underwent orthotopic liver transplantation for cryptogenic cirrhosis. After using rigorous serologic and histopathologic screening guidelines, 20 patients were studied, 7 of whom had concurrent hepatocellular carcinoma (HCC). RNA was extracted from archival paraffin-embedded liver tissue; HGV sequences were amplified by nested reverse transcription-polymerase chain reaction using primers designed from the 5' noncoding region. Results. HGV-RNA was absent from all 20 liver specimens, including those 7 with HCC. β-actin RNA, used as a positive control for cellular RNA, was isolated from all 20 liver specimens, including the 7 with HCC. Conclusions. Utilizing a highly sensitive reverse transcription-polymerase chain reaction assay for HGV-RNA, we were unable to detect HGV-RNA within the livers of patients with cryptogenic cirrhosis or in the HCC arising within them. This lends further evidence to HGV infection not being a cause of cryptogenic cirrhosis and not being associated with the development of HCC in cryptogenic cirrhosis.

Several drugs which react with DNA decrease hepatitis B viral (HBV) DNA polymerase activity in vitro. Because such an alteration of viral replication, if produced in patients with hepatitis B surface antigen (HBsAg)-positive chronic hepatitis, may lead to elimination of viral infection, we conducted a controlled trial of the use of the intercalating agent, quinacrine hydrochloride, in treatment of HBsAg-positive chronic hepatitis. No patient converted from HBsAg positive to negative during the trial and no consistent effect on HBV DNA polymerase activity was noted. Following treatment, elevated transaminase values and alterations of HBV markers were observed in several patients. Fluctuations of transaminase values and HBV markers may reflect alterations in host immunity and viral replication. Quinacrine alone is ineffective in therapy of chronic HBV infection. Additional study with intercalating agents, perhaps in conjunction with other drugs, is suggested.

Hepatitis C virus (HCV) infection is associated with development of hepatocellular carcinoma (HCC). The aim of this study was to examine clinical characteristics and outcome of patients with HCV with or without HCC undergoing liver transplant.We reviewed the charts of all 55 patients transplanted between November 1990 and December 1996 for HCV cirrhosis with HCC and compared them with a control group of HCV patients without HCC. Patients with a history of alcohol abuse or HBsAg positivity were excluded. There were 37 men and 18 women, with a mean age of 57.6 yr (range, 19-70 yr) in the HCC group.There was no significant difference between the HCC and nonHCC groups regarding Child's class or United Network for Organ Sharing (UNOS) status at the time of transplant. Twenty-six (45%) patients were diagnosed or suspected of having HCC before transplant. Twenty-five patients (45.5%) had a single focus of HCC. Fourteen percent (seven of 50) of the patients with HCC had been treated with interferon, whereas 12% (six of 52) of patients in the nonHCC group had received interferon. Duration of interferon therapy ranged from 1 to 9 months. All interferon treatment occurred within 5 yr of transplant. A history of intravenous drug use or transfusion was identified in 37 (67%) of HCC patients. Thirty-two patients (58%) without HCC had a parenteral exposure. There was no significant difference in patient or graft survival rates between the patients with and without HCC.Approximately one-half of HCC was not detected before liver transplant. There was no significant difference in the mode of transmission, clinical status at the time of transplant, or outcome between the HCV patients with and without HCC.

Hepatitis C is a common cause of chronic liver disease that may progress to cirrhosis. We conducted a multicenter double-blind placebo-controlled trial of ribavirin 600 mg given orally twice daily for 36 weeks with follow-up off therapy for an additional 16 weeks. Fifty-nine patients with compensated chronic hepatitis C were entered. Efficacy was measured at the end of therapy and after follow-up by normalization of alanine aminotransferase (ALT), improvement in liver histology, reduction in hepatitis C virus (HCV) RNA level and improvement of symptoms. Among the ribavirin recipients, 12 of 29 (41.4%) had normal ALT values at 36 weeks compared with only 1 of 30 (3.3%) placebo recipients (P < .001). No patient maintained a normal ALT when therapy was stopped. No significant decrease in level of HCV RNA was observed during the study. Histological improvement among subjects who normalized ALT (-1.67 Knodell index) was significantly greater than that in other treated patients (+0.33 Knodell index; P < .05). Fatigue improved in 19.2% of ribavirin-treated subjects and in 8.3% of placebo recipients whereas no worsening of fatigue was reported by ribavirin recipients compared with 16.7% of controls. This difference in fatigue was significant at weeks 36 and 52 (P < .05; .02, respectively). Adverse events were generally comparable between treatment groups except for a reversible hemolytic anemia experienced by ribavirin recipients. Chest pain was noted in four patients on ribavirin. Ribavirin was well tolerated and improved aminotransferase values and reduced fatigue in patients with hepatitis C viral infection while treatment was being administered. Because this action was produced without change in viral level, the mechanism of action of this agent requires further investigation.

Hepatic venous outflow obstruction caused by hepatic vein thrombosis (HVT) is a manifestation of a hypercoagulable state, most commonly a myeloproliferative disorder (MPD). In the past, HVT was thought to have a poor prognosis unless treated surgically with portosystemic shunt or orthotopic liver transplantation (OLT). The aim of this study was to assess whether early diagnosis of the underlying hematologic disorder and institution of appropriate medical therapy have altered outcome. We reviewed the charts of 22 patients with HVT evaluated at our center from January 1986 to January 1995. The median age was 32 years (range, 14 to 59 years). Underlying etiologies were MPD, 13 (polycythemia vera, 8; essential thrombocythemia, 4; undefined, 1); dysfibrinogenemia, 1; anticardiolipin antibody, 1; oral contraceptive use, 3; and idiopathic, 4. All patients had ascites, hepatomegaly, and/or abdominal pain. Two underwent mesocaval shunting, and 1 had a peritoneal-venous shunt. Seven patients, including 1 with a mesocaval shunt, underwent OLT. The median duration of symptoms before transplantation was 6 months (range, 1.5 to 11 months). Six transplant patients are alive on long-term anticoagulation therapy at a mean post-OLT follow-up of 42 months (range, 2 to 77 months), without recurrence. Of 13 patients treated medically, 10 (77%) are alive at a median follow-up of 40 months (range, 17 months to 14 years 8 months), 1 has died, and 2 have been lost to follow-up. In a majority of patients, symptoms improve with prompt treatment of the underlying hematologic disorder, with a favorable long-term prognosis. Patients with decompensated liver disease can successfully undergo OLT with a low risk of recurrence on long-term oral anticoagulation.

Objectives. We evaluated the efficacy of a hepatitis care coordination intervention to improve linkage to hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccination and clinical evaluation of hepatitis C virus (HCV) infection among methadone maintenance patients. Methods. We conducted a randomized controlled trial of 489 participants from methadone maintenance treatment programs in San Francisco, California, and New York City from February 2008 through June 2011. We randomized participants to a control arm (n = 245) and an intervention arm (n = 244), which included on-site screening, motivational-enhanced education and counseling, on-site vaccination, and case management services. Results. Compared with the control group, intervention group participants were significantly more likely (odds ratio [OR] = 41.8; 95% confidence interval [CI] = 19.4, 90.0) to receive their first vaccine dose within 30 days and to receive an HCV evaluation within 6 months (OR = 4.10; 95% CI = 2.35, 7.17). A combined intervention adherence outcome that measured adherence to HAV–HBV vaccination, HCV evaluation, or both strongly favored the intervention group (OR = 8.70; 95% CI = 5.56, 13.61). Conclusions. Hepatitis care coordination was efficacious in increasing adherence to HAV–HBV vaccination and HCV clinical evaluation among methadone patients.

To evaluate response rates to 3, 5, or 10 million units (MU) of interferon alfa-2b, given thrice weekly, and to determine whether higher doses of interferon increase the likelihood or durability of the response, a multicenter, randomized trial was performed at nine academic medical centers in the United States. Two hundred forty eight patients with chronic hepatitis C were randomized to receive 3, 5, or 10 MU of interferon alfa-2b thrice weekly for 12 weeks. Based on the alanine aminotransferase (ALT) response at treatment-week 12, the patients were rerandomized to additional therapy at the same or at increased doses for an additional 12 to 36 weeks; in the case of no response to the highest dose, the patients were discontinued from the study. Serum ALT concentrations and liver histology were measured. The overall complete response rates to 3, 5, or 10 MU were not different at treatment-week 12 (31% vs. 42% vs. 40%, not significant). The majority of week-12 responders continued to respond during additional treatment. When the treatment was discontinued, 15.4% to 19.0% of patients maintained their response. Of the nonresponders to 3 MU at week 12, who were continued on 3 MU for an additional 12 weeks, none responded. However, response to additional therapy occurred in 12% of week-12 nonresponders, whose dose was escalated from 3 or 5 MU to 10 MU. The only baseline features associated with the treatment response were the absence of fibrosis or cirrhosis on the pretreatment liver biopsy and viral genotype. We conclude that the initial response to interferon in patients with chronic hepatitis C is not increased by treatment with higher doses of the drug. Patients who do not respond to 3 MU by treatment-week 12 will not respond with continued therapy at that dose; however, a proportion of patients who do not respond to 12 weeks of treatment with 3 or 5 MU may respond to higher doses. Although the long-term sustained response rates are marginally increased with interferon doses above 3 MU three times per week, the side effects are difficult to tolerate. The analysis of baseline factors in relation to response identified no single baseline factor associated with a low-enough response rate to warrant withholding interferon therapy from patients with chronic hepatitis C.

In a significant number of patients, the etiology of fulminant hepatic failure (FHF) is unknown. To determine whether hepatitis B virus (HBV) and hepatitis C virus (HCV) play a role in patients without serologic markers of HBV and HCV infection, the authors examined tissue samples from 15 liver explants with massive hepatic necrosis for the presence of viral sequences by the polymerase chain reaction (PCR). The specimens were derived from nine patients with FHF of unknown etiology; two with serum hepatitis B surface antigen (HBsAg); two with antibodies to HCV; one with antibodies to hepatitis A virus (HAV) and anti-HBc of the IgM class; and one with isoniazid toxicity. Nucleic acids were extracted from frozen liver samples. RNA was used as a template for reverse transcription, followed by double PCR with nested primers for the 5'-untranslated region of HCV. DNA was tested by single PCR for S gene sequences of HBV. Hepatitis B virus sequences were detected in the specimens of the two HBsAg positive patients, the anti-HAV/anti-HBc positive patient, and three of nine patients with FHF of unknown etiology. Hepatitis C virus sequences were present in the explant of one patient with FHF of unknown etiology, but not in the two patients with antibodies to HCV. In two specimens with molecular findings of HBV infection (1 from a patient with serum HBsAg and 1 without), there was immunohistochemical evidence of coinfection or superinfection with hepatitis delta virus (HDV). In conclusion, in this patient population, HBV, alone or with HDV or HAV, causes fulminant hepatic failure more often than HCV infection. However, in the majority of patients, the etiology of fulminant hepatic failure remains unknown.

Recurrent hepatitis C causes significant morbidity after liver transplantation. Because immunosuppression is associated with enhanced viral replication, we postulated that clinical recurrence of the disease may be associated with augmented immunosuppression for rejection. In 96 patients with hepatitis C who received liver transplants, we recorded the interval from transplantation to recurrence, the episodes of steroid-resistant rejection (SRR) requiring OKT3, the number of rejection episodes, and the use of OKT3 induction. Recurrence was diagnosed based on elevated transaminases and characteristic histology. Hepatitis C recurred in 43 of 96 patients. Fifteen of 21 patients (71.4%) who previously had SRR had recurrence, versus 28 of 75 patients (37.3%) who either had no SRR (72 patients) or had it after recurrence was diagnosed (3 patients) (P

We fine mapped two primary biliary cirrhosis (PBC) risk loci, CLEC16A (C-type lectin domain family 16 member A)–suppressor of cytokine signaling 1 (SOCS1) and Spi-B protein (SPIB) and sequenced a locus, sialic acid acetylesterase (SIAE), proposed to harbor autoimmunity-associated mutations. In all, 1450 PBC cases and 2957 healthy controls were genotyped for 84 single-nucleotide polymorphisms (SNPs) across the CLEC16A-SOCS1 and SPIB loci. All 10 exons of the SIAE gene were resequenced in 381 cases and point substitutions of unknown significance assayed for activity and secretion. Fine mapping identified 26 SNPs across the CLEC16A-SOCS1 and 11 SNPs across the SPIB locus with significant association to PBC, the strongest signals at the CLEC16A-SOCS1 locus emanating from a SOCS1 intergenic SNP (rs243325; P = 9.91 × 10−9) and at the SPIB locus from a SPIB intronic SNP (rs34944112; P = 3.65 × 10−9). Among the associated SNPs at the CLEC16A-SOCS1 locus, two within the CLEC16A gene as well as one SOCS1 SNP (rs243325) remained significant after conditional logistic regression and contributed independently to risk. Sequencing of the SIAE gene and functional assays of newly identified variants revealed six patients with functional non-synonymous SIAE mutations (Fisher’s P = 9 × 10−4 vs controls) We demonstrate independent effects on risk of PBC for CLEC16A, SOCS1 and SPIB variants, while identifying functionally defective SIAE variants as potential factors in risk for PBC.

Background : Hepatic histological responses described in hepatitis C virus (HCV) infection include bile duct damage, lymphoid follicles and/or aggregates in portal tracts, large- and small-droplet fat, Mallory body-like material in hepatocytes, liver cell dysplasia and multinucleation, and activation of sinusoidal inflammatory cells. The specificity of these lesions for HCV infection is uncertain. Methods : In two multicenter trials of recombinant interferon alfa therapy for chronic hepatitis C and B, the frequency of these eight lesions in pretherapy and posttherapy liver biopsy specimens was examined to determine the set of features, if any, that distinguishes HCV from hepatitis B virus (HBV) infection. The lesions were scored in 317 HCV biopsy specimens and 299 HBV specimens. Results : Stepwise logistic regression determined a set of three features more likely to be seen in HCV than in HBV infection: bile duct damage [odds ratio (OR), 4.7; 95% confidence interval (CI), 1.8–12.3], lymphoid follicles and/or aggregates (OR, 2.4; 95% CI, 1.2–4.7), and large-droplet fat (OR, 2.4; 95% CI, 1.4–4.1). A fourth lesion, Mallory body-like material, was seen only in HCV biopsy specimens (OR, 71.6; 95% CI, 4.4–996.1). Conclusions : These four histological lesions are useful pathological parameters in the diagnosis of liver disease caused by HCV.

AIM: To study the significance and clinical implication of hepatic lipogranuloma in chronic liver diseases, including fatty liver disease and hepatitis C. METHODS: A total of 376 sequential, archival liver biopsy specimens were reviewed. Lipogranuloma, steatosis and steato-fibrosis were evaluated with combined hematoxylin and eosin and Masson’s trichrome staining. RESULTS: Fifty-eight (15.4%) patients had lipogranuloma, including 46 patients with hepatitis C, 14 patients with fatty liver disease, and 5 patients with other diseases. Hepatic lipogranuloma was more frequently seen in patients with hepatitis C (21%) and fatty liver disease (18%), and its incidence was significantly higher than that in control group (P < 0.0002 and P < 0.007, respectively). In addition, 39 out of the 58 patients with lipogranuloma were associated with steatosis and/or steato-fibrosis. Of the 18 lipogranuloma patients with clinical information available for review, 15 (83%) had risk factors associated with fatty liver disease, such as alcohol use, obesity, hyperlipidemia, and diabetes mellitus. Although the incidence of these risk factors was greater in patients with lipogranuloma than in control group (60%), it did not reach statistical significance. CONCLUSION: Hepatic lipogranuloma is not limited to mineral oil use and commonly associated with hepatic steatosis, hepatitis C and fatty liver disease. With additional histological features of steato-fibrosis, lipogranuloma can also be used as a marker of prior hepatic steatosis.

The prevalence of type 2 diabetes, in the United States, has increased in association with the increase in the mean weight of Americans indicative of the epidemic of obesity in this country. Complications of type 2 diabetes can be expected to rise in the near future. These complications include vascular, renal, ophthalmologic, and importantly liver disease. Hepatic complications include nonalcoholic fatty liver disease (NAFLD), cirrhosis, hepatocellular carcinoma (HCC), acute liver failure, and post-liver transplantation diabetes. There is, additionally, a relationship between type 2 diabetes and chronic hepatitis C infection with type 2 diabetes being considered an extrahepatic manifestation of chronic hepatitis C infection. The association of diabetes and liver disease is being increasingly recognized. The morbidity and mortality of acute and chronic liver disease in patients with diabetes, particularly type 2 diabetes, will continue to rise in Americans in the immediate and near future.

• Extrahepatic manifestations (EHM) of chronic hepatitis C (HCV) affect a variety of organ systems and may present with significant mortality and morbidity. • These EHM are not the direct result of viral infection but are secondary to the host immune response. • Vascular manifestations are due to the presence of cryoglobulinemia, which causes deposition of immune complexes in the small vessels of the skin, presenting with palpable purpura. • An association is noted between HCV and lymphoproliferative disorders, most commonly B-cell non-Hodgkin lymphoma. • Renal disorders, most commonly membranoproliferative glomerulonephritis (MPGN) has the strongest association with HCV associated cryoglobulinemia.

We examined 180 noninstitutionalized persons with Down syndrome for the presence of both hepatitis B surface antigens and antibodies to hepatitis B surface antigen. Two of the 180 subjects with Down syndrome had a positive test. One patient was hepatitis B surface antigen positive and the other was found to have antibodies to hepatitis B surface antigen. Also, 2 of the 155 individuals in the comparison group tested positive for hepatitis B surface antigen. Thus, we did not observe an increased prevalence of hepatitis B surface antigen or antibody in the study group and there was no significant difference between the Down syndrome and comparison groups. This is in contrast to many studies that originated in residential facilities where an increased number of persons with Down syndrome were found to have hepatitis B surface antigenemia. The related public health concerns are discussed.

Chronic hepatitis C virus HCV infection progresses through liver fibrosis and cirrhosis to hepatocellular carcinoma HCC. It appears to be causally related to B-cell non-Hodgkin's lymphoma since regression after antiviral therapy has been described. Two cases are described of non-Hodgkin's lymphoma and HCC arising simultaneously in two patients. The first patient did not have cirrhosis on liver biopsy. HCV had been undetectable in plasma following successful therapy with interferon and ribavirin treatment 7 years earlier. The second patient developed an aggressive form of hepatocellular carcinoma HCC within weeks of stopping treatment with interferon and ribavirin. Therapy had induced complete viral suppression for over 40 weeks. The two cases suggest that non-Hodgkin's lymphoma and HCC can develop in the absence of detectable hepatitis C viremia and argues for continued surveillance even after sustained virological response to treatment.

This document presents the official position of the American Association for the Study of Liver Diseases (AASLD) on the application of serum alanine aminotransferase (AL T) activity, based upon an analysis of the currently available scientific data. Its authorship was selected by the Public Policy Committee. The document is fully endorsed by the AASLD Governing Board.

Background and Methods. Chronic hepatitis B is a common and often progressive liver disorder for which there is no accepted therapy. To assess the efficacy of treatment with interferon, we randomly assigned patients with chronic hepatitis B to one of the following regimens: prednisone for 6 weeks followed by 5 million units of recombinant interferon alfa-2b daily for 16 weeks; placebo followed by 5 million units of interferon daily for 16 weeks; placebo followed by 1 million units of interferon daily for 16 weeks; or observation with no treatment. Results. Hepatitis B e antigen and hepatitis B viral DNA disappeared from serum significantly more often in the patients given prednisone plus interferon (16 of 44 patients, or 36 percent) or 5 million units of interferon alone (15 of 41; 37 percent) than in the untreated controls (3 of 43; 7 percent; P

To assess the efficacy of therapy with the antiviral agent interferon in chronic hepatitis C (non-A, non-B hepatitis), we randomly assigned 166 chronic hepatitis C patients to treatment with either 3 million or 1 million units of recombinant interferon alfa-2b three times weekly for 24 weeks, or to no treatment. The probability of normalization or near normalization of the serum alanine aminotransferase levels after 6 months of interferon therapy was 46% in patients treated with 3 million units of interferon (p less than 0.001) and 28% in those treated with 1 million units (p less than 0.02), but only 8% in untreated patients. Serum alanine aminotransferase levels became completely normal in 22 of the 26 patients (85%) who responded to treatment with 3 million units of interferon and 9 of the 16 patients (56%) who responded to treatment with 1 million units. The patients who received 3 million units of interferon had histological improvement because of the regression of lobular and periportal inflammation. Relapse within 6 months after the completion of treatment occurred in 51% of the patients treated with 3 million units of interferon and 44% of those treated with 1 million units. We conclude that a 24-week course of interferon therapy is effective in controlling disease activity in many patients with hepatitis C, although relapse after the cessation of treatment is common.