Clinical outcome and virological characteristics of hepatitis B-related acute liver failure in the United States.

The role of hepatitis B virus (HBV) genotypes in the outcome of acute HBV infection is unclear. In this study, we aimed to evaluate the clinical and virological features of patients with hepatitis B-related acute liver failure (HBV-ALF) in the US. Clinical and laboratory features of consecutive patients with HBV-ALF from the US ALF Study Group were analysed. Prevalence of HBV genotypes, precore stop (G1896A) and core promoter dual (T1762A, A1764T) variants among patients with HBV-ALF were compared with a cohort of 530 patients with chronic HBV infection. Thirty-four HBV-ALF patients were studied: mean age 41 years, 56% men, 25 had detectable HBV-DNA. HBV genotypes A, B, C and D were found in 36, 24, 8 and 32% patients, respectively. Precore stop and core promoter dual variants were detected in 32 and 44% of patients, respectively. Twenty-three (68%) patients survived: 14 after liver transplant, nine without transplant. Older age was the only independent factor associated with poor outcome. Compared with patients with chronic HBV infection, patients with ALF were more likely to be non-Asians (88% vs 44%, P = 0.005) and to have genotype D (32% vs 10%, P < 0.01). A higher prevalence of HBV genotype D persisted even after matching for race and HBeAg status (32% vs 16%, P = 0.007). We concluded that HBV genotype D was more frequently found in patients with HBV-ALF than those with chronic HBV infection in the US. Further studies are needed to determine if HBV genotypes play a role in the outcome of acute HBV infection.

Reasons for non-treatment of hepatitis C in veterans in care.

We prospectively studied 354 patients with hepatitis C virus (HCV) infection who were referred to a hepatology specialty clinic to find the reasons for non-treatment of HCV. The median age was 48 years (range 27-77 years), 98.5% were male and 71% were white. Seventy per cent of the patients were not treated. The most common reasons for non-treatment were non-adherence to follow-up visit (24%), normal liver enzymes (14%), concurrent medical problems (11%), alcohol and drug use (9%), psychiatric problems (7%), advanced liver disease (7%), referral for transplant evaluation (6.4%) and patient refusal, transfer of care to another facility and non-detectable HCV RNA levels (5% each). The reason was not recorded for 5% of the patients and was treatment deferred in 2.4% while waiting for pegylated interferon approval. Non-treatment was more likely in patients with less than 12 years of education and a history of incarceration. Patients who were lost to follow-up and refused treatment were more likely to have current alcohol and drug use and a history of incarceration.

Recurrent hepatitis C in liver allografts: prospective assessment of diagnostic accuracy, identification of pitfalls, and observations about pathogenesis.

RATIONALE AND DESIGN: The accuracy of a prospective histopathologic diagnosis of rejection and recurrent hepatitis C (HCV) was determined in 48 HCV RNA-positive liver allograft recipients enrolled in an "immunosuppression minimization protocol" between July 29, 2001 and January 24, 2003. Prospective entry of all pertinent treatment, laboratory, and histopathology results into an electronic database enabled a retrospective analysis of the accuracy of histopathologic diagnoses and the pathophysiologic relationship between recurrent HCV and rejection. RESULTS: Time to first onset of acute rejection (AR) (mean, 107 days; median, 83 days; range, 7-329 days) overlapped with the time to first onset of recurrent HCV (mean, 115 days; median, 123 days; range, 22-315 days), making distinction between the two difficult. AR and chronic rejection (CR) with and without co-existent HCV showed overlapping but significantly different liver injury test profiles. One major and two minor errors occurred (positive predictive values for AR = 91%; recurrent HCV = 100%); all involved an overdiagnosis of AR in the context of recurrent HCV. Retrospective analysis of the mistakes showed that major errors can be avoided altogether and the impact of unavoidable minor errors can be minimized by strict adherence to specific histopathologic criteria, close clinicopathologic correlation including examination of HCV RNA levels, and a conservative approach to the use of additional immunosuppression. In addition, histopathologic diagnoses of moderate and severe AR and CR were associated with relatively low HCV RNA levels, whereas relatively high HCV RNA levels were associated with a histopathologic diagnosis of hepatitis alone, particularly the cholestatic variant of HCV. CONCLUSIONS: Liver allograft biopsy interpretation can rapidly and accurately distinguish between recurrent HCV and AR/CR. In addition, the histopathologic observations suggest that the immune mechanism responsible for HCV clearance overlap with those leading to significant rejection.

Recurrent hepatitis C after liver transplantation: a nonrandomized trial of interferon alfa alone versus interferon alfa and ribavirin.

Liver transplant recipients with recurrent hepatitis C virus (HCV) infection often have histological hepatitis, and in some patients, graft failure develops. The aim of this nonrandomized study is to determine the efficacy and tolerability of interferon alfa (IFN alfa) alone and IFN alfa and ribavirin combination therapy in such patients. Forty transplant recipients with recurrent hepatitis were initiated on therapy with IFN alfa-2b at 3 million units (MU) three times weekly for 1 month followed by 5 MU three times weekly for 5 months. Twenty patients were administered IFN alfa-2b, 3 MU three times weekly for 1 month followed by 5 MU three times weekly for 11 months, and ribavirin, 600 mg, twice daily orally for 12 months concurrently. The primary end point was sustained clearance of serum HCV RNA, and secondary end points were serum alanine aminotransferase (ALT) level normalization and histological improvement. Thirty patients completed 6 months of IFN-alfa monotherapy and 15 patients completed 12 months of IFN alfa and ribavirin combination therapy. End-of-treatment biochemical responses were similar in the two groups (IFN alfa, 20% v combination therapy, 25%); however, viral clearance was greater in the combination-therapy group (40% v 15%; P = .04). Six months after the completion of therapy, only 1 patient (2.5%) in the IFN-alfa group and 4 patients (20%) in the combination-therapy group were HCV RNA negative (P = .03). Serum ALT and HCV RNA levels declined significantly in both groups during therapy. There was no improvement in inflammatory grade, and fibrosis score was worse in both groups. Ten patients (25%) in the IFN-alfa group and 5 patients (20%) in the combination-therapy group withdrew because of adverse effects. We conclude that in liver allograft recipients with recurrent hepatitis C, combination therapy with IFN alfa and ribavirin is more efficacious than treatment with IFN alfa alone. However, the efficacy is limited by tolerability.

Safety observations in phase I clinical evaluation of the Excorp Medical Bioartificial Liver Support System after the first four patients.

A Phase I clinical safety evaluation of the Excorp Medical, Inc, Bioartificial Liver Support System (BLSS) is in progress. Inclusion criteria are patients with acute liver failure of any etiology, presenting with encephalopathy deteriorating beyond Parson's Grade 2. The BLSS consists of a blood pump, heat exchanger to control blood temperature, oxygenator to control oxygenation and pH, bioreactor, and associated pressure and flow alarm systems. Patient liver support is provided by 70-100 g of porcine liver cells housed in the hollow fiber bioreactor. A single support period evaluation consists of 12 hour extracorporeal perfusion with the BLSS sandwiched between 12 hours of pre (baseline) and 12 hours of post support monitoring. Blood chemistries and hematologies are obtained every 6 hours during monitoring periods and every 4 hours during perfusion. Physiologic parameters are monitored continuously. The patient may receive a second treatment at the discretion of the clinical physician. Preliminary evaluation of safety considerations after enrollment of the first four patients (F, 41, acetaminophen induced, two support periods; M, 50, Wilson's disease, one support period; F, 53, acute alcoholic hepatitis, two support periods; F, 24, chemotherapy induced, one support period) is presented. All patients tolerated the extracorporeal perfusion well. All patients presented with hypoglycemia at the start of perfusion, treatable by IV dextrose. Transient hypotension at the start of perfusion responded to an IV fluid bolus. Only the second patient required heparin anticoagulation. No serious or unexpected adverse events were noted. Moderate biochemical response to support was noted in all patients. Completion of the Phase I safety evaluation is required to fully characterize the safety of the BLSS.

Troglitazone-induced fulminant hepatic failure. Acute Liver Failure Study Group.

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.

Prognostic value of abdominal CT scanning and hepatic histopathology in patients with acute liver failure.

Acute liver failure has extremely high mortality without liver transplantation. We attempted to determine the value of abdominal CT scanning and liver biopsy in its management. A retrospective analysis of patients with acute liver failure was performed; demographic, clinical, radiologic and histopathologic features were noted. Over a period of 13 years, 177 patients were evaluated. The mean age was 39 years and 63% were females. The patients were divided into three groups. Fourteen percent survived with medical management (group I), 37% died (group II), and 49% had liver transplantation (group III). Most patients showed diffuse low density of the liver on CT scanning and the proportions were similar in the three groups. Moderate to large ascites was not present in group I but occurred in 31% of patients in group II and in 15% in group III. Mean hepatic volumes were similar in the three groups; however, 97% of the patients with a liver volume of less than 1000 ml either died or required liver transplantation. Liver biopsies among patients with spontaneous recovery (group I) were distinguished by the presence of regenerative changes and a hepatic parenchymal necrosis of less than 50%. These results suggest that in patients with acute liver failure a liver volume of less than 1000 ml and/or hepatic parenchymal necrosis of greater than 50% is indicative of a poor prognosis. This information may assist decision making in such patients, in particular, regarding the need for liver transplantation.

Acute liver failure: clinical features, outcome analysis, and applicability of prognostic criteria.

Acute liver failure (ALF) is an uncommon condition associated with high morbidity and mortality. We performed a retrospective analysis of patients evaluated for ALF. The aim of our study is to determine the clinical features and outcome of such patients and to assess the validity of King's College Hospital (KCH) prognostic criteria. One hundred seventy-seven patients were evaluated for ALF during a period of 13 years. Mean age was 39 years, and 63% were women. The causes included viral hepatitis (31%), acetaminophen toxicity (19%), idiosyncratic drug reactions (12%), miscellaneous causes (11%), and an indeterminate group (28%). Twenty-five patients (14%) recovered with medical therapy (group I), 65 patients (37%) died without orthotopic liver transplantation (OLT; group II), and 87 patients (49%) underwent OLT (group III). Patients in group II were older and often had advanced encephalopathy, whereas those in group I had less hyperbilirubinemia and often had hyperacute failure. KCH criteria had high specificity and positive predictive value but low negative predictive value for a poor outcome. We conclude that early prognostication is needed in patients with ALF to assist decision making regarding OLT. The fulfillment of KCH criteria usually predicts a poor outcome, but a lack of fulfillment does not predict survival.

Clinical and virologic outcomes of hepatitis B and C viral coinfection after liver transplantation: effect of viral hepatitis D.

Hepatitis B (HBV) and C viral (HCV) dual-infection-associated liver disease is an uncommon indication for liver transplantation. The clinical and virologic outcomes in such patients have not been well studied. We retrospectively studied 13 patients with hepatitis B surface antigen (HBsAg) and antibody to HCV positivity who underwent orthotopic liver transplantation (OLT) and survived at least 30 days post-OLT. Antibody to hepatitis delta virus (HDV) was negative in 8 patients (group I) and positive in 5 patients (group II). Eleven of the 13 patients received standard hepatitis B immune prophylaxis, and they all remained HBsAg negative. All group I patients were HCV RNA positive after transplantation; in contrast, all group II patients were HCV RNA negative. Serum alanine aminotransferase levels were elevated in 88% (7 of 8) of the patients in group I compared with 20% (1 of 5 patients) in group II. None of the patients had graft loss from chronic rejection or recurrent hepatitis. Three patients had unsuspected hepatocellular carcinoma in the explant. We conclude that among liver transplant recipients with HBV and HCV coinfection, HDV infection is associated with the suppression of HCV replication and mild inflammatory activity after OLT.

Fulminant hepatic failure.

Fulminant hepatic failure is a disease of varied causes and a high mortality rate. A sudden onset, jaundice, hepatic encephalopathy, and multiorgan failure are the hallmarks of this syndrome. The management of patients with FHF requires a multidisciplinary approach and intense monitoring. The availability of liver transplantation has provided the means to rescue such patients from near-certain death. Early prognostication and timely availability of donor livers are requirements for a successful outcome. The development of effective artificial liver support devices may greatly prolong the window of opportunity to provide a donor liver, or alternatively, to allow the native liver to regenerate.

Etiology and outcome for 295 patients with acute liver failure in the United States.

Little information is available on acute liver failure (ALF) in the United States. We gathered demographic data retrospectively for a 2-year period from July 1994 to June 1996 on all cases of ALF from 13 hospitals (12 liver transplant centers). Data on the patients included age, hepatic coma grade on admission, presumed cause, transplantation, and outcome. Among 295 patients, 74 (25%) survived spontaneously, 121 (41%) underwent transplantation, and 99 (34%) died without undergoing transplantation. Ninety-two of 121 patients (76%) survived 1 year after transplantation. Acetaminophen overdose was the most frequent cause (60 patients; 20%), followed by cryptogenic/non A non B non C (NANBNC; 15%), idiosyncratic drug reactions (12%), hepatitis B (10%), and hepatitis A (7%). Spontaneous survival rates were highest for patients with acetaminophen overdose (57%) and hepatitis A (40%) and lowest for those with Wilson's disease (no survivors of 18 patients). The transplantation rate was highest for Wilson's disease (17 of 18 patients; 94%) and lowest for autoimmune hepatitis (29%) and acetaminophen overdose (12%). Age did not differ between survivors and nonsurvivors, perhaps reflecting a selection bias for patients transferred to liver transplant centers. Coma grade on admission was not a significant determinant of outcome, but showed a trend toward affecting both survival and transplantation rate. These findings on retrospectively studied patients from the United States differ from those previously gathered in the United Kingdom and France, highlighting the need for further study of trends in each country.

Interferon-alpha for prophylaxis of recurrent viral hepatitis C in liver transplant recipients: a prospective, randomized, controlled trial.

BACKGROUND: In a randomized, controlled trial, we sought to determine whether prophylaxis with interferon-alpha for 6 months had an impact on rate, severity, and timing of onset of recurrent hepatitis C virus (HCV) hepatitis in liver transplant recipients and to assess whether interferon use was associated with rejection in liver transplant recipients. METHODS: Twenty-four consecutive liver transplant recipients with HCV were randomized after transplantation to receive either interferon-alpha (3 million U three times weekly) for 6 months or no prophylaxis; median follow-up was 874 days. RESULTS: Recurrent HCV hepatitis (histopathologically proven) developed in 50% (6 of 12) of the interferon-alpha patients versus 42% (5 of 12) of the control patients (P=NS). Severity of recurrence (as assessed by Knodell score on liver biopsies) also did not differ between the two groups (mean 4.0 for interferon-alpha patients versus 3.5 for control patients, P=NS). Interferon-alpha, however, significantly delayed the timing of occurrence of HCV hepatitis; recurrent HCV hepatitis developed a median of 408 days after transplant in the interferon-alpha group versus 193 days in the control group (P=0.05). No difference in graft or patient survival was demonstrated in the two groups. Rejection episodes, treated with corticosteroids, occurred in 50% (6 of 12) of patients in the interferon-alpha group versus 42% (5 of 12) in the control group (P=NS). Corticosteroid resistant rejection (requiring OKT3) occurred in only one study patient (in the control group). CONCLUSIONS: Interferon-alpha in liver transplant recipients for 6 months delayed the occurrence of HCV hepatitis, but did not decrease the incidence nor the severity of HCV hepatitis after transplantation. Interferon-alpha use was not associated with a higher incidence of rejection compared with the control patients.

Geographic distribution and genetic variability of hepatitis delta virus genotype I.

Three genotypes of hepatitis delta virus (HDV) have been identified, each with different geographic distributions and disease associations. To better define the geographic distribution and genetic variability of HDV genotype I, and to evaluate the extent of genome variability in populations with different patterns of HDV infection, we have analyzed the sequence of HDV RNA in the sera of 72 patients from different areas. Patients were primarily residents of the United States and areas in and around Greece, including Archangelos, Rhodes. All sequences obtained belonged to HDV genotype I, confirming the wide geographic distribution of this genotype and its predominance in Europe and the United States. In contrast to previous studies, phylogenetic analysis of this large and diverse group of sequences, along with all available previously published HDV sequences, showed no well-defined subtypes within genotype I. Low sequence diversity was found for isolates from the United States, Archangelos, Turkey, and Albania, suggesting that HDV was introduced more recently and/or from fewer sources into these areas as compared to mainland Greece, Italy, and north Africa, where sequence diversity is much greater. The low sequence diversity among isolates from Archangelos is particularly interesting in light of the unusually mild pattern of HDV disease found in this community. Comparison of nucleic acid and amino acid sequences within and among genotypes indicated both highly conserved regions as well as genotype-specific sequences that could be related to functional differences. The most distinctive of the latter was that corresponding to the C-terminal 19-20 amino acids of the long form of hepatitis delta antigen, which is highly conserved within each genotype but considerably diverged among them.

Survival and quality of life after liver transplantation for acute alcoholic hepatitis.

The applicability of liver transplantation for ALD remains limited because of ethical arguments and also because of the perception of poor outcome after transplantation. Patients with alcoholic cirrhosis are known to do as well as patients with nonalcoholic liver disease after receiving liver allografts; however, the outcome in patients with severe acute alcoholic hepatitis in this setting is unclear. We studied 9 liver transplant recipients in whom severe acute alcoholic hepatitis was retrospectively diagnosed; 8 had underlying cirrhosis, and 1 had advanced fibrosis. All had Maddrey's discriminant function > 32, and most had hepatic encephalopathy and hepatorenal syndrome. History regarding abstinence was unreliable in some patients. Episodes of acute cellular rejection responded quickly to therapy, and despite recidivism in some patients, long-term survival was comparable to that of patients receiving transplants with alcoholic cirrhosis alone and those with a milder degree of alcoholic hepatitis and cirrhosis. This study suggests that severe acute alcoholic hepatitis may not be an appropriate contraindication for liver transplantation.

Liver transplantation for acute liver failure: outcome analysis.

Acute liver failure (ALF) remains a major cause of morbidity and mortality. Before the availability of liver transplantation only 20% of patients with ALF survived. The clinical dilemma relates to the prognostication of these patients, as early liver transplantation has been associated with better outcomes. The eligibility for liver transplantation must therefore be quickly established. The patient's age, aetiology of disease, interval between the onset of jaundice and encephalopathy, blood pH, prothrombin time, serum bilirubin and serum creatinine levels has been identified as useful prognostic markers. The degree of hepatocyte necrosis on liver biopsy and estimated hepatic volume by computed tomography may also be valuable predictors of survival; however, further studies are needed.

Routes of infection, viremia, and liver disease in blood donors found to have hepatitis C virus infection.

BACKGROUND: For many people infected with the hepatitis C virus (HCV), the route of exposure, risk of transmission, and severity of associated liver disease are unknown. We studied these variables in people who donated blood voluntarily. METHODS: Blood donors who tested positive for HCV antibodies on enzyme immunoassay were classified according to whether the results of a confirmatory second-generation recombinant immunoblot assay (RIBA) for HCV were positive, negative, or indeterminate. The evaluations also included an assessment of risk factors, a physical examination, serial determinations of alanine aminotransferase levels and HCV serologic assays, a polymerase-chain-reaction assay for HCV RNA, testing of sexual contacts and family members, and liver biopsies in some participants who were HCV-positive by RIBA. RESULTS: A total of 481 donors were studied, among whom 248 were positive for HCV by RIBA, 102 had indeterminate results, and 131 were HCV-negative. In a logistic-regression analysis, significant risk factors for HCV infection among the HCV-positive participants were a history of blood transfusion in 66 (27 percent; P < 0.001 for the comparison with RIBA-negative donors), intranasal cocaine use in 169 (68 percent, P < 0.001), intravenous drug use in 103 (42 percent, P = 0.001), sexual promiscuity in 132 (53 percent, P = 0.002), and ear piercing among men (P < 0.05). Nine of 85 sexual partners of HCV-positive donors were anti-HCV-positive; 8 had used intravenous drugs or received transfusions. HCV RNA was found in 213 HCV-positive donors (86 percent), 3 who had indeterminate results by RIBA (2 of these 3 tested positive with a more specific, third-generation RIBA), and none who were HCV-negative. Of the HCV-positive donors, 69 percent had biochemical evidence of chronic liver disease; among 77 donors positive for HCV by RIBA who underwent liver biopsy, 5 had severe chronic hepatitis or cirrhosis, 66 had mild-to-moderate chronic hepatitis, and 6 had no evidence of hepatitis. CONCLUSIONS: Among volunteer blood donors, prior blood transfusion, intranasal cocaine use, intravenous drug use, sexual promiscuity, and ear piercing in men are risk factors for HCV infection. The high frequency of intravenous drug use was unexpected, because these donors had denied such use when questioned directly at the time of their blood donations.

Diagnostic features of tuberculous peritonitis in the absence and presence of chronic liver disease: a case control study.

PURPOSE: To determine diagnostic features of tuberculous peritonitis (TBP) in the absence and presence of chronic liver disease. PATIENTS AND METHODS: Thirty-four patients with TBP (13 without [Group I] and 21 with chronic liver disease [Group II] and 26 controls with cirrhosis and uninfected ascites (Group III) were studied. RESULTS: The clinical features in Groups I and II were similar and all patients had elevated ascitic fluid total mononuclear cell count. In Groups I, II, and III, respectively, ascitic fluid protein was > 25 g/L in 100% (13/13), 70% (14/20), and 0% (0/26); serum-ascites albumin gradient (SAAG) was > 11 g/L in 0% (0/13), 52% (11/21), and 96% (25/26), (0% [0/13], 71% [15/21], and 96% [25/26] after correction for serum globulin); and ascitic fluid lactate dehydrogenase (LDH) level was > 90 U/L in 100% (12/12), 84% (16/19), and 0% (0/20), respectively. In Groups I and II combined, ascitic fluid acid-fast stain was negative in all but Mycobacterium tuberculosis culture was positive in 45% (10/22); peritoneal nodules occurred in 94% (31/33), granulomas in 93% (28/30), and positive peritoneal M tuberculosis culture in 63% (10/16). CONCLUSIONS: In patients with suspected TBP, ascitic fluid protein of > 25 g/L, SAAG of < 11 g/L and LDH of > 90 U/L have high sensitivity for the disease. With coexistent chronic liver disease, a lower protein level and higher SAAG are usually not helpful but LDH > 90 U/L is a useful parameter for screening. Diagnosis is best confirmed by laparoscopy with peritoneal biopsy and M tuberculosis culture.

Seizures during alpha interferon therapy.

BACKGROUND/AIMS: Alpha interferon is now used widely in the therapy of chronic viral hepatitis. The common side effects of interferon are well known; the uncommon side effects are less well defined. We have evaluated the incidence and characteristics of seizures that occurred during alpha interferon therapy. METHODS: A retrospective chart review was done on 311 patients with chronic hepatitis treated with alpha interferon between 1983 and 1994 at the National Institutes of Health. RESULTS: Four of 311 patients (1.3%) developed grand mal seizures while on therapy with alpha interferon. Three patients had chronic hepatitis B (two had an accompanying glomerulonephritis) and one chronic delta hepatitis. Interferon had been given in doses of 5-10 million units each day or three times weekly for 2-14 months before the onset of seizures. No other obvious cause for seizures was identified. Seizures resolved once interferon was stopped, and did not recur even without chronic anticonvulsant therapy. CONCLUSIONS: Alpha interferon in the doses used to treat chronic viral hepatitis caused seizures in approximately 1% of patients.

Volunteer blood donors with antibody to hepatitis C virus: clinical, biochemical, virologic, and histologic features. The Hepatitis C Study Group.

OBJECTIVE: To assess the clinical significance of antibody to hepatitis C virus (anti-HCV) in volunteer blood donors. DESIGN: Prospective cohort study. SETTING: National Institutes of Health Clinical Center, a tertiary referral research hospital. PATIENTS: 60 anti-HCV-positive blood donors, divided into three groups of 20 persons each: Group I had normal alanine aminotransferase levels, group II had levels elevated to values less than twice the normal range, and group III had levels elevated to values greater than twice the normal range. MEASUREMENTS: Medical history, results of laboratory and virologic testing, and percutaneous liver biopsy findings. RESULTS: Participants with normal alanine aminotransferase levels were older and more often female than those with abnormal levels. The source of infection, duration of disease, symptom score, and amount of alcohol consumed were similar in the three groups. Hepatitis C virus RNA was detectable in 85% of participants, more commonly in the groups with elevated alanine aminotransferase levels (95%) than in the group with normal levels (65%); however, titers were similar in all groups. Examination of liver biopsy specimens showed chronic hepatitis in 54 participants (90%) and cirrhosis in 1 participant. The only normal liver biopsy specimens (n = 3) were those from participants who were HCV RNA negative and had normal alanine aminotransferase levels. CONCLUSIONS: Most blood donors with anti-HCV have chronic hepatitis C regardless of their serum alanine aminotransferase levels. Donors with normal alanine aminotransferase levels and no HCV RNA in their serum generally have normal liver histologic findings or minimal changes and have probably recovered from HCV infection.