Important note: Information in this article was accurate in December 2003. The state of the art may have changed since the publication date.
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Approximately one-third of hepatitis C- (HCV) infected persons in the United States passed through jail or prison facilities in 1997.1
in some states, the prevalence of chronic HCV infection among incoming prisoners is as high as 49% (see Table 1). Correctional healthcare providers are on the front line in the diagnosis and management of HCV in this country.Among those with chronic HCV, the natural history of progression from infection to cirrhosis in an individual patient is uncertain. Ten to 15 percent of those with HCV will develop cirrhosis within 20 years of initial infection.6 7 ,Studies evaluating serial liver biopsies in HCV-infected prisoners have demonstrated distinct cohorts of fast, moderate, and non-progressors.8 Numerous studies have demonstrated that coinfection with HIV increases the rate of progression to cirrhosis.
Chronic liver disease and cirrhosis kills more than 25,000 people in the US annually9 and is among the 10 leading causes of death for White males, Hispanics, and Native Americans.10 In patients with HCV and cirrhosis, the five-year death rate is approximately 15%.11 In some correctional facilities, end-stage liver disease (ESLD) is now the leading cause of death among inmates.12 This article focuses on the treatment of ESLD in the correctional setting, primarily among patients with chronic HCV.
TABLE 1: Proportion of
persons entering state prisons
found to have HCV infection
| Women | Men | |
| California:2 | 39% | 32% |
| Maryland:3 | 39% | 25% |
| Massachusetts:4 | 44% | 27% |
| Texas:5 | 49% | 27% |
Advances in combination therapy have improved clinical options for some patients with chronic HCV. However, correctional health providers are still confronted with many patients with cirrhosis and ESLD. Reasons for this include:
(1) Even under ideal treatment conditions, sustained viral response (SVR) rates for the current anti-HCV combination therapy (pegylated interferon plus ribavirin) are less than 50% for genotype 1, and less than 80% for other less common genotypes.13
(2) Many people cannot tolerate anti-HCV combination therapy because of side effects, co-morbidities (including psychiatric issues), or other factors.
(3) Prisoners are eight to 10 times more likely than the general population to be HIV-infected.14 Coinfection with HIV is estimated to reduce SVR rates for anti-HCV combination therapy by 20 to 30%, though some of this difference may be due to adherence issues.15 As highly active antiretroviral therapy (HAART) has reduced HIV-related morbidity and mortality among HIV-infected persons, ESLD has risen in importance as a cause of death among people with HIV/AIDS16 (see Table 2).
TABLE 2: Before and after HAART: ESLD as a cause of death in HIV-infected persons17
| Setting | Pre-HAART Era | HAART Era |
| # / % YEAR | # / % YEAR | |
| Brescia, Italy | 305 / 13% 1987 | 46 / 35% 1996 |
| Madrid, Spain | 312 / 5% 1991-5 | 20 / 45% 2000 |
| Boston, MA (USA) | 36 / 12% 1991 | 22 / 50% 1998-9 |
| Paris, France | 1327 / 2% 1995 | 543 / 8% 1997 |
(4) Prisoners in the US are disproportionately African American, and HCV treatment response rates are lower among African Americans than among other racial groups. This treatment disparity has not been adequately explained, and is now the subject of a major federal study.18
(5) Some correctional healthcare systems do not routinely offer HCV testing or treatment for inmates. The number of such systems is expected to decline now that the Centers for Disease Control and Prevention (CDC) has published guidelines for managing viral hepatitis in correctional settings.19
The first step in the diagnosis of liver disease due to viral hepatitis is to offer antibody screening for hepatitis B and C (HBV, HCV). Some clinicians recommend targeted screening based upon risk factor histories. In many correctional systems, the prevalence of chronic hepatitis among inmates is sufficiently high and the reliability of risk factor history information is sufficiently low that all inmates should be offered testing for both viruses.
TABLE 3: Signs and Symptoms of Cirrhosis
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Many patients with cirrhosis have no symptoms, and are only determined to be cirrhotic by physical examination and liver biopsy. When signs or symptoms are present, they can include:
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Most of those infected with HBV will spontaneously clear the virus and be left with antibodies to the viral surface and core antigens. Approximately 5% will develop chronic HBV. Unlike HBV infection, 60-85% of those with HCV infection will develop chronic disease.20 Chronic infection with HCV can be confirmed by detection of HCV RNA in the plasma.
Among those with chronic viral hepatitis, no single test or panel is sufficient to accurately portray disease severity. A basic lab assessment for patients with liver disease should include complete blood counts (CBC), serum aminotransferase levels (ALT and AST), bilirubin, albumin, prothrombin time/INR, and platelet count. Serial measurements over time offer a more complete portrait of the severity progression of the disease than individual assays. Elevated AST/ALT values reflect inflammation, while prolonged INR and decreased albumin can reflect decreased hepatic function. Elevated direct bilirubin may be indicative of cirrhosis or bile duct obstruction; total bilirubin levels over approximately 2.5 mg/dl are associated with jaundice. Anemia can be due to variceal bleeding, while thrombocytopenia can result from bleeding or sequestration in an enlarged spleen.
Physical examination of patients with advanced liver disease may detect a firm and enlarged liver, though in very advanced cirrhosis, the liver may decrease in size. External physical examination may also detect excess fluid in the abdomen by palpating the flanks and feeling for a shifting wave of fluid. Imaging techniques such as ultrasound, CT scan, and MRI can reveal ascites, an enlarged spleen, reversed portal vein flow, and hepatocellular carcinoma (HCC).
Liver biopsy is the single best technique for determining disease progression, and is the definitive means of confirming cirrhosis and assessing its severity.21 Liver biopsy has become a contentious issue in corrections because of cost and the high number of patients with chronic viral hepatitis. Despite advances in noninvasive monitoring techniques, biopsy remains the gold standard for the assessment of severity of cirrhosis.22,23,24
Most of those with serially "normal" ALTs will have minimal inflammation, are likely to be to be slow progressors, and may not need to undergo biopsy. Just as HCV treatment costs may be reduced by price negotiation25, it may be possible to reduce biopsy costs by proactively contracting for biopsies based on HCV prevalence in the facility or system in question. Correctional health providers in Pennsylvania have reportedly reduced biopsy costs to as low as $400 per patient.26 At the California Medical Facility in the California DOC, on site biopsy costs are less than $300 per patient.27
Damage to the liver due to chronic alcohol or other toxins, infection, obstruction, or heart failure can lead pathologic changes including fibrosis and the formation of regenerative nodules. These pathologic changes are termed cirrhosis, and can result in a variety of clinical manifestations. When the liver is cirrhotic but still able to perform most basic functions, cirrhosis is referred to as "compensated". Further loss of functioning hepatocytes can result in "decompensated" cirrhosis, manifest by coagulopathy, jaundice, and edema. Extensive fibrosis can cause portal hypertension, splenomegaly, and gastroesophageal varices. In more severe cases, patients may develop excess fluid within the peritoneal cavity (ascites), spontaneous bacterial peritonitis, and/or encephalopathy. Up to 5% of those with cirrhosis will develop HCC. Deaths associated with HCV are more likely to be due to complications of decompensated cirrhosis such as variceal bleeding, encephalopathy, and peritonitis, than to HCC.28
Portal hypertension: When scar tissue obstructs the normal flow of blood through the liver, pressure within the liver's main blood vessel, the portal vein, is increased. Portal hypertension is responsible for common complications of ESLD, including variceal bleeding and ascites.
Variceal bleeding: When blood cannot flow normally through the portal vein, it must return to the heart using other blood vessels. These other blood vessels, called varices, enlarge to provide an alternative pathway for blood diverted from the liver. Varices often form in the stomach and esophagus. They pose a high risk for rupture and bleeding because they are thin-walled, often abnormally twisted and swollen, and subject to high pressure. Internal variceal bleeding occurs in 20 to 30% of cirrhotic patients and is dangerous, with mortality rates reported between 15 and 50%.29 Vomiting blood or passing black stools can be signs of variceal bleeding.
Ascites: Lowered albumin production from the cirrhotic liver and other physiological processes can result in fluid retention in the peritoneal cavity. Ascites itself is not life-threatening, but it is a marker of severe disease progression. The probability of death within two years in cirrhotic patients hospitalized with ascites is approximately 40%, and is worse for those who develop spontaneous bacterial peritonitis (SBP), a common and potentially fatal complication of ascites.30
Encephalopathy: The exact pathogenesis of hepatic encephalopathy is not clear. A build-up of toxins such as ammonia can affect the brain, causing confusion, memory loss, fatigue, agitation, and possibly coma and death. Early symptoms of encephalopathy can include confusion, drowsiness, lethargy, and difficulty concentrating. The physical examination in those with encephalopathy may demonstrate tremor, asterixis, and slowed coordination.
Hepatorenal syndrome: Hepatorenal syndrome is a potentially life-threatening complication of liver disease in which patients develop oliguria, hyponatremia, hypotension, and renal failure manifest by increases in BUN and creatinine. The exact etiology of this syndrome is not clear, but it can be precipitated by sepsis, severe variceal bleeding, aggressive diuresis or paracentesis.
Patients with advanced cirrhosis also commonly develop malnutrition, gallstones, and coagulopathy due to impaired hepatic synthesis of clotting factors and thrombocytopenia.
The prevention and treatment of complications associated with ESLD can be challenging for even experienced generalist physicians. In general, the management of those with ESLD should be done in consultation with a gastroenterologist or hepatologist. In one recent study, hospitalized patients with decompensated cirrhosis managed by a generalist in consultation with a gastroenterologist fared better than patients managed by generalists alone. Better outcomes included shorter length of hospitalization, lower cost of hospitalization, lower rates of hospital readmission, and improved survival.31
Patients with chronic hepatitis should be protected from further hepatic insult. Those who are not immune to hepatitis A and hepatitis B should be vaccinated.32 Those with liver disease should receive annual influenza vaccinations and a pneumococcal vaccine. Patients should avoid hepatotoxic medications whenever possible. Large doses of acetominophen should be avoided, however, low doses (less than 2,000 milligrams per day) are generally well-tolerated. Non-steroidal anti-inflammatory drugs such as ibuprofen (Advil®), naproxen (Aleve® or Naprosyn®), or aspirin should be used with caution both because of hepatotoxic potential and the risk for bleeding. The dosage of medications that are hepatically metabolized may need to be adjusted. Because of the increased prevalence of HIV infection among those with viral hepatitis, patients should also be encouraged to test for HIV.
Because alcohol is commonly covertly manufactured and ingested in prison, all patients should be educated about the extreme importance of avoiding alcohol. Even moderate ingestion of alcohol hastens the progression of liver disease in those with cirrhosis. Correctional physicians should link their patients to drug and alcohol abuse treatment programs both within the correctional system and at the time of release.
Maintaining adequate nutrition for patients with advanced liver disease can be difficult in the community, and poses particular challenges in the prison setting. Adequate dietary protein is important for patients with ascites and for repairing lost muscle mass. However, excess protein may pose a risk for encephalopathy. In those prone to encephalopathy, vegetable proteins may pose fewer risks than animal proteins. Iron supplementation and excessive sodium intake should be avoided in those with cirrhosis. Patients with ascites may require fluid and salt restriction.
Beta-blockers can reduce heart rate, lower portal vein pressure, and reduce the threat of variceal bleeding. Patients with diabetes, asthma, emphysema and chronic bronchitis may be unable to tolerate beta-blockers. Options for treatment of variceal bleeding and prevention of recurrence also include endoscopic scleropathy, vasoactive drugs, and band ligation. Surgical shunts and Transjugular Intrahepatic Portosystemic Shunt (TIPS) are other options to eliminate variceal bleeding. TIPS is a less invasive procedure in which the shunt is inserted through a catheter.
Patients with ascites may require a reduced salt diet, reduced fluid intake, and diuretics. Spironolactone in doses of 100-400 milligrams per day can be used to achieve diuresis. In those who fail to respond to diuretics, fluid may be drained with a catheter or plastic drainage tube inserted into the abdominal wall (paracentesis). Paracentesis should be accompanied by albumin infusion to prevent circulatory dysfunction and other complications.33 TIPS is also an option in ascites patients for whom paracentesis is ineffective, intolerable, or contraindicated.34
Patients with SBP may present with fever, hypotension, abdominal discomfort, and/or encephalopathy. Often the clinical findings are very subtle, and the clinician must act presumptively to prevent death of the patient. Gram stain and culture of ascitic fluid often fails to demonstrate the presence of an organism. To diagnose SBP, ascitic fluid should be examined by microscope and inoculated directly into blood culture bottles. An ascitic fluid neutrophil count of 250 polymorphonuclear cells/mm3 is diagnostic of SBP.30 In suspected cases, treatment should be initiated with cefotaxime, ceftriaxone, or a fluoroquinolone. Patients who have already had a previous episode of SBP are at high risk for recurrence, and should be provided prophylaxis with trimethoprim -sulfamethoxazole, ciprofloxacin, or norfloxacin.
Precipitating factors for encephalopathy in advanced liver disease can include gastrointestinal bleeding, excess dietary protein, constipation, or infection. The goal of treatment for encephalopathy is to lower the level of toxic substances affecting the brain by reducing or eliminating dietary protein and removing nitrogenous material from the gut, often by using lactulose.35
Fulminant hepatic failure is manifest as encephalopathy, worsening jaundice, gastrointestinal bleeding, sepsis, coagulopathy, hypoglycemia, renal failure, and electrolyte abnormalities. Patients with fulminant hepatic failure should be managed in the ICU setting, and should urgently be evaluated for candidacy for liver transplant.36
More than 3,000 liver transplants are performed annually in the US. For patients with cirrhosis, the two commonly used indices of liver disease severity are Child-Turcotte-Pugh (CTP) and Model for End Stage Liver Disease (MELD). CTP and MELD are designed to direct organ allocation to liver transplantation candidates based on the severity of disease. CTP score is determined using albumin, bilirubin, prothrombin time (INR), ascites, and hepatic encephalopathy. MELD score is determined using bilirubin, creatinine, and INR. MELD uses a wider range of assay values and a more complicated formula than CTP. A MELD calculator is available online at the website of the United Network for Organ Sharing: www.unos.org. Every correctional system should have policies in place that address the appropriate evaluation and referral of selected patients for consideration for transplant.
There is little clinical basis for recommendations about continued anti-HCV therapy in patients with advanced cirrhosis. Nevertheless, some studies have shown that patients with compensated cirrhosis can achieve high rates (43%) of SVR on combination therapy,37 and that anti-HCV therapy may cause histological improvement even in patients who are virological non-responders.38 Whether or not treatment of compensated cirrhotics will translate into decreased morbidity, improved quality of life, or prolonged survival remains to be seen.
Anti-HCV treatment of patients with decompensated cirrhosis may raise significant safety issues and should not generally be recommended except in the setting of clinical trials.
Chronic HCV infection is a major risk factor for HCC. The risk for HCC is greatest among patients with at least 20 years of HCV infection, cirrhosis or advanced fibrosis, male sex, older age, HBV coinfection, and heavy alcohol use.39 One to 6% of cirrhotic patients develop HCC annually.40 Screening techniques for HCC in cirrhotic patients are serum alpha-fetoprotein (AFP) testing (twice yearly) and hepatic ultrasound or CT.
Surgical liver resection and liver transplant are the main treatment strategies for HCC. Alternative approaches include percutaneous alcohol injection, arterial chemoembolization, or radiofrequency ablation.41
Patients with ESLD, especially those who are not candidates for liver transplantation, should be considered for hospice care and compassionate parole or release. Patients dying with ESLD report a high pain burden, comparable to that of patients dying with lung and colon cancer.42 Physicians working with such patients should be aware of available palliative care options, and should initiate compassionate release or medical parole proceedings where appropriate.
Over the past 20 years, correctional healthcare providers have become increasingly important in our nation's response to tuberculosis and HIV. With one-third of HCV-infected individuals in the US passing through our jails and prisons, correctional clinicians are now faced with a new challenge. As we become experts in the antiviral treatment of those with chronic hepatitis, we must also be cognizant of the management of those with ESLD. By doing so, we can decrease ESLD associated morbidity and prolong the lives of our patients suffering with this serious illness.
* Nothing to disclose
** Nothing to disclose
1. Hammett TM et al. The Burden of Infectious Disease among Inmates of and Releasees from US Correctional Facilities, 1997. Am J Public Health. 2002 Nov;92(11):1789-94. .
2. Fox et al. Prevalence of Hepatitis C in a Sample of California Prison Inmates. Society of General Internal Medicine 25th Anniversary Meeting, Atlanta, GA, May 2-4, 2002.
3. AIDS Administration and Division of Correction, State of Maryland. Final Report: Examination of HIV, Syphilis, Hepatitis B and Hepatitis C in Maryland Correctional Facilities. March 2003.
4. Massachusetts Public Health Association "Correctional Health: The Missing Key to Improving the Public's Health and Safety" Boston: MPHA. October 2003.
5. Baillargeon J, et al. Hepatitis C Seroprevalence among Newly Incarcerated Inmates in the Texas Correctional System. Public Health. 2003 Jan;117(1):43-8.
6. National Institutes of Health Consensus Development Conference Statement "Management of Hepatitis C: 2002" Final Statement. August 2002. See also Ghany et al "Progression of Fibrosis in Chronic Hepatitis C" Gastroenterology. 2003 Jan;124(1):97-104.
7. Some practitioners use a fibrosis index (fibrosis stage divided by number of years infected) to divide patients into rapid, intermediate, and slow progressors (see Cassidy W "Hepatitis C Infections in Prison" HCV Advocate Medical Writers' Circle: June 2003).
8. Cassidy WM. Treating Hepatitis C in Prisons. Proceedings of the Management of Hepatitis C in Prisons Conference; 2003 Jan 25-26; San Antonio, Texas.
9. Anderson RN. Deaths: Leading causes for 1999. National vital statistics reports 49(11):8. Hyattsville,Maryland: National Center for Health.
10. National Center for Health Statistics. Health, United States, 2003. Hyattsville, Maryland: NCHS. 2003. Table 32.
11. Degos et al . Hepatitis C Virus Related Cirrhosis: Time to Occurrence of Hepatocellular Carcinoma and Death. Gut 47(1):131-6. July 2000.
12. Personal communication, Joseph Bick, MD: Chief Medical Officer, California Medical Facility, California Department of Corrections.
13. National Institutes of Health Consensus Development Conference Statement "Management of Hepatitis C: 2002" Final Statement. August 2002.
14. National Commission on Correctional Health Care. Report to Congress: The Health Status of Soon-to-be-Released Inmates. Chicago: NCCHC. 2002.
15. Personal communication, Jules Levin: Director, National AIDS Treatment Advocacy Project.
16. Bica I et al. "Increasing Mortality Due to End-stage Liver Disease in Patients with Human Immunodeficiency Virus" Clin Infect Dis. 2001 Feb 1;32(3):492-7.
17. Soriano V. Liver Disease in HIV: an Update. The PRN Notebook June 2002.
18. National Institute of Diabetes and Digestive and Kidney Disorders. VIRAHEP-C: Hepatitis C Antiviral Resistance in African Americans. Phase III Clinical Trial. Start date: August 2002. www.virahepc.org.
19. CDC. Prevention and Control of Infections with Hepatitis Viruses in Correctional Settings. MMWR 2003 52(RR-1).
20. National Institutes of Health Consensus Development Conference Statement "Management of Hepatitis C: 2002" Final Statement. August 2002.
21. National Institutes of Health Consensus Development Conference Statement "Management of Hepatitis C: 2002" Final Statement. August 2003.
22. Afdhal NH "Diagnosing Fibrosis in Hepatitis C: Is the Pendulum Swinging from Biopsy to Blood Tests?" Editorial. Hepatology 37(5):972-974. May 2003.
23. Gebo KA et al. "Role of Liver Biopsy in Management of Chronic Hepatitis C: A Systematic Review" Hepatology 36(5) Supp.1:S161-S172. November 2002.
24. Marcellin P et al. "Fibrosis and Disease Progression in Hepatitis C" Hepatology 36(5)Supp.1:S47-S56. November 2002.
25. Spaulding A (2003) "NIH Consensus Statement: Implications" Management of Hepatitis C in Corrections. San Antonio, TX. January 25-26.
26. Pennsylvania's DOC Plans to Revamp Hepatitis C Protocol. Positive Populations 5(1) August 2002.
27. Persona communication, Joseph Bick, MD: Chief Medical Officer, California Medical Facility, California DOC.
28. National Institutes of Health Consensus Development Conference Statement "Management of Hepatitis C: 2002" Final Statement. August 2002.
29. Worobetz LJ et al. "The Liver" in First Principles of Gastroenterology: The Basis of Disease and an Approach to Management. 3rd ed. Canadian Association of Gastroenterology.
30. Moore KP et al. "The Management of Ascites in Cirrhosis: Report on the Consensus Conference of the International Ascites Club" Hepatology 38(1): 258-266. July 2003.
31. Bini EJ et al. "Impact of Gastroenterology Consultation on the Outcomes of Patients Admitted to the Hospital with Decompensated Cirrhosis" Hepatology 34(6): 1089-1095. December 2001.
32. National Institutes of Health Consensus Development Conference Statement "Management of Hepatitis C: 2002" Final Statement. August 2002.
33. Garcia-Tsao G "Portal Hypertension" Current Opinion in Gastroenterology 19(3):250-258. 2003.
34. Moore KP et al. "The Management of Ascites in Cirrhosis: Report on the Consensus Conference of the International Ascites Club" Hepatology 38(1): 258-266. July 2003.
35. Worobetz LJ et al. "The Liver" in First Principles of Gastroenterology: The Basis of Disease and an Approach to Management. 3rd ed. Canadian Association of Gastroenterology.
36. Ahya SN et al. The Washington Manual of Therapeutics. 30th ed. St. Louis, MO: Washington U. School of Medicine. 2001.
37. Heathcote EJ et al. "Treatment Considerations in Patients with Hepatitis C and Cirrhosis" Journal of Clinical Gastroenterology 37(5):395-398. November-December 2003.
38. Wright TL "Treatment of Patients with Hepatitis C and Cirrhosis" Hepatology 26(5)Supp.1:S185-S194. November 2002.
39. El-Sarag HB "Hepatocellular Carcinoma and Hepatitis C in the United States" Hepatology 36(5) Supp.1:S74-S83. November 2002.
40. Gebo KA et al. "Screening Tests for Hepatocellular Carcinoma in Patients with Chronic Hepatitis C: A Systematic Review" Hepatology 36(5) Supp.1: S84-S92. November 2002.
41. Ahya SN et al. The Washington Manual of Therapeutics. 30th ed. St. Louis, Missouri: Washington U. School of Medicine. 2001.
42. Roth K et al. "Dying with End-stage Liver Disease with Cirrhosis: Insights from SUPPORT. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment" Journal of the American Geriatrics Society 48(5) Supp.: S122-30. May 2000.
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©1997,1998,1999,2000,2001,2002, 2003. The recently formed HIV Education Prison Project (HEPP) is a medical education program that targets a growing population, inmates in correctional facilities, that has been underserved in HIV care. It is part of the Brown University AIDS Program. Permission to use and reproduce portions of this newsletter is hereby granted provided that author and publication are fully credited and both copyright and permission notice appear with reprinted material. Inquiries may be directed to heppnews@brown.edu. Website: HIV Education Prison Project.
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