The natural history of acute hepatitis C: clinical presentation, laboratory findings and treatment outcomes.

BACKGROUND: Acute hepatitis C has variable modes of presentation and frequently results in chronic infection. Its optimal management has yet to be defined. AIM: To establish natural history and complications of treatment of acute hepatitis C. METHODS: Data from all patients presenting with acute hepatitis C to the National Institutes of Health between 1994 and 2007 were reviewed. RESULTS: Twenty-five patients were identified. Symptoms were reported by 80% and jaundice by 40%. Aminotransferase levels and hepatitis C virus (HCV) RNA levels fluctuated greatly; 18% of patients were intermittently negative for HCV RNA. Five patients recovered spontaneously whereas 20 developed chronicity or received interferon-based therapy during the acute phase. Among 15 patients treated during the acute phase with peginterferon with or without ribavirin for 24 weeks, all became HCV RNA negative within 4-8 weeks, and all except two (HIV-positive) achieved a sustained virological response. Side effects (particularly psychiatric) were common and limited treatment in 30%. CONCLUSIONS: Among 25 patients with acute HCV infection, fluctuating illness was common and spontaneous recovery occurred in only 20%. Anti-viral treatment with a 24-week course of peginterferon and ribavirin was highly effective, but marked by frequent and severe side effects.

Management of patients with chronic hepatitis C infection.

Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality throughout the world. Although reliable figures regarding the global prevalence of HCV infection are wanting, it is likely that HCV prevalence will continue to increase. Injection drug use is the most important source of HCV transmission in the developed world, while unsafe therapeutic injection is an important source of transmission in developing nations. The majority of exposed individuals become chronically infected, of whom 50% develop chronic liver injury. Cirrhosis and hepatocellular carcinoma can arise in those chronically infected over a mean of 20-30 years. Despite this high prevalence and morbidity, recommendations regarding who to screen by antibody testing remain disparate. Quantitative measurement of HCV RNA and HCV genotyping is useful in predicting response to antiviral therapy. Noninvasive methods of detecting liver injury, such as serologic batteries, have not been as informative or predictable as liver biopsy. The current pharmacologic standard of care for chronic HCV infection is the combination of subcutaneous peginterferon and oral ribavirin, which yields sustained virologic response in 54%-56%. Higher rates of SVR are seen in those patients who are infected with HCV genotypes 2 and 3. As intravenous drug use remains the most important source of HCV transmission in the US and Europe, education within this group is an important preventive tool.

Liver disease and diabetes mellitus.

The liver plays an important role in the pathogenesis of NIDDM. More importantly to the clinician is the myriad of situations in which the care of the patient with diabetes is affected by or causes an effect to the liver. Patients with underlying diabetes can present with abnormal liver chemistries, which can represent findings as benign as hepatic steatosis or as severe as cirrhosis of the liver. The medications used to treat diabetes can be potent hepatotoxins. Several primary liver diseases are associated with increased risk of the development of diabetes. Epidemiologically, there seems to be a correlation between diabetes mellitus, the most common endocrinologic disease, and hepatitis C, the leading cause of chronic liver disease in the United States. In the management of end-stage liver disease, both cirrhosis and orthotopic liver transplantation promote glucose intolerance and diabetes in a number of patients through various mechanisms including insulin resistance and impaired insulin secretion. These relationships highlight both the importance of the liver as an endocrine organ and the multisystem aspects of the patient with diabetes mellitus.

Pregnancy after liver transplantation.

The first known posttransplantation pregnancy was in 1958 in a renal transplant recipient who had received a kidney from her identical twin sister. The first known posttransplantation pregnancy in a liver transplant recipient was in 1978. Information available from female kidney transplant recipients helped in the decision making involved in the management of this case, as well as those that followed. Over the last 20 years, issues specific to liver transplantation and pregnancy have been identified. Similar to the kidney transplant recipient population, when prepregnancy recipient graft function is stable and adequate, pregnancy appears to be well tolerated. Also similar to kidney transplant recipients, there has been no evidence of a specific malformation pattern among the children, and although prematurity and low birth weight occur, overall newborn outcomes have been favorable. Pregnancy in the setting of recurrent liver disease, such as recurrent hepatitis C, poses a potential problem among liver transplant recipients, as well as the possible adverse effects of immunosuppression on maternal kidney function. Also of significance, peripartum graft deterioration has more severe consequences in this transplant recipient population. Therefore, pregnancy must be considered carefully in this transplant recipient group. Since 1991, the National Transplantation Pregnancy Registry (NTPR) has studied the safety of pregnancy outcomes in solid-organ transplant recipients. The purpose of this review is to catalog studies in the literature, as well as to present current data from the registry with management guidelines.

Safety and efficacy of sonographically guided random core biopsy for diffuse liver disease.

Sonographic guidance is commonly used in the biopsy of focal hepatic lesions, but biopsy for diffuse disease is often non-image-guided. We evaluated the safety and efficacy of real-time sonographically guided random core biopsy in the assessment of diffuse liver disease in 210 patients. The two most common indications for biopsy were viral hepatitis (in 113 patients) and elevated liver function test results of unknown cause (in 54 patients). Ultrasonography and pathology reports were reviewed retrospectively to determine number of needle passes and final diagnoses. Adequate tissue was obtained in all 210 patients, with 259 of 269 (96%) passes having been successful. Specimens were submitted for light microscopy and other tests as indicated. No difference in success rates was found for right and left lobe biopsies. No major complications occurred. Minor complications occurred in 10 of 210 (4.8%) patients and were self-limited. Sonographically guided core liver biopsy is a safe and effective method for the diagnosis of liver disease.

Reproductive function after liver transplantation.

Successful pregnancy outcomes are possible after liver transplantation. Although there are risks to the mother and fetus, there has not been an increased incidence of malformations noted in the newborn of liver recipients. Close, coordinated care involving the hepatologist, surgeon, and high-risk obstetrician is essential to ensure a favorable outcome. Immunosuppression peripartum should be maintained at appropriate levels. Of note, a small subset of recipients may suffer worsened graft function during pregnancy. Recurrent liver disease, especially viral hepatitis, and CMV infection appear to pose significant risks to mother and offspring, respectively, although the magnitude of the risks is unknown. It therefore would seem prudent to consider pregnancy only in female liver recipients who have passed at least 1 year with stable graft function. In addition, new immunosuppressive regimens further add to the lack of information regarding pregnancy safety. The NTPR is an ongoing database to collect information and pregnancy outcomes. That information should be helpful in counseling recipients and in pregnancy management.