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Changing patterns of hepatocellular carcinoma
AJG – September, 1999
Letters to the Editor
to IFN-␣, impressively demonstrate the causal relationship between IFN-␣ and liver failure in previously well compensated hepatitis C-induced chronic liver disease. Histology of the pretherapeutic liver tissue described some disturbances in lobular architecture, but a diagnosis of complete and advanced micronodular cirrhosis was made only after explantation. The possible existence of an underlying autoimmune disease may explain the very rapid increase in aminotransferase levels and liver failure after IFN-␣ treatment initiation. Even though the dose was reduced, the second (and potentially fatal) attempt at IFN-␣ treatment should not have been started in this situation. In conclusion, physicians involved in the treatment of hepatitis C should be very well aware of rising aminotransferase levels (especially in a patient with suspected liver cirrhosis), which may indicate impending liver failure. G. Lock, M.D. C. M. Reng, M.D. J. Scho¨lmerich, Professor of Medicine Department of Internal Medicine I University of Regensburg Regensburg, Germany C. Graeb, M.D. M. Anthuber, M.D. Department of Surgery University of Regensburg Regensburg, Germany K. H. Wiedmann, Professor of Medicine Krankenhaus der Barmherzigen Bru¨der Regensburg, Germany
REFERENCES 1. Dusheiko G. Side effects of alpha interferon in chronic hepatitis C. Hepatology 1997;26(suppl 1):112S–21S. 2. Janssen HLA, Brower JT, Nevens F, et al. European concerted action on viral hepatitis. Fatal hepatic decompensation associated with interferon alpha. Br Med J 1993;306:107– 8. 3. Sheen IS, Liaw YF, Tai DI, et al. Hepatic decompensation associated with hepatitis e antigen clearance in chronic type B hepatitis. Gastroenterology 1985;89:732–5. Reprint requests and correspondence: G. Lock, M.D., Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg, Germany. Received Apr. 28, 1999; accepted May 4, 1999.
2571
sible for this increased incidence (1, 2). In context of these findings, we would like to report the results of a small retrospective study recently conducted at our institution. The purpose of this retrospective study was to analyze the trends in the characteristics of hepatocellular carcinoma (HCC) over time, especially with regard to hepatitis B and C, and to investigate the predictive value of ␣-fetoprotein (AFP) in determining the prognosis in patients with HCC. We retrospectively reviewed the charts of 50 patients with histologically proven HCC on biopsy or autopsy at a community and a Veterans Affairs (VA) hospital between 1983 and 1997. Patients were divided into two groups: 1980s (1983–90) and 1990s (1991–97). Clinical characteristics including age, alcohol use, presence or absence of hepatitis B and C, cirrhosis on biopsy, AFP, and survival were analyzed in these two groups. Survival was also compared according to AFP levels. Mean values between the two groups were compared by using t test, and median survival was analyzed by using Mann-Whitney test. Clinical characteristics are shown in Table 1. There were 19 patients in the 1980s group and 31 patients in the 1990s group. Hepatitis B surface antigen (HBsAg) was positive in 50% of the patients tested in 1980s group, whereas only 6% of the 1990s patients were HBsAg positive. Hepatitis C virus antibody was positive in 29% of the patients in the 90s group. Patients with hepatitis C were significantly younger than those without hepatitis C (49.2 ⫾ 3.6 vs 69.9 ⫾ 1.9 yr, p ⬍ 0.0001) and had significantly higher AFP levels (17,307 ⫾ 8,294 vs 2,674 ⫾ 1,502, p ⬍ 0.02). AFP was elevated in 73% of the patients. There was no significant difference in median survival in groups based on AFP levels. In conclusion, patients with hepatitis C are at risk for developing HCC at a younger age. Association of hepatitis B with HCC seems to be decreasing in the 1990s. Median survival in patients with HCC has not changed with time and remains very poor. AFP levels do not correlate with survival. Although this is a very small study from which to draw any firm conclusions, the increasing incidence of HCC in a younger hepatitis C patient population is particularly intriguing. Patients with chronic hepatitis B and C infection and cirrhosis should be monitored very closely with serum Table 1. Clinical Characteristics of Patients With Hepatocellular Carcinoma During the 1980s and 1990s
Changing Patterns of Hepatocellular Carcinoma TO THE EDITOR: Primary hepatocellular carcinoma is occurring with increasing frequency in the United States, as recently shown in a study (1). Chronic hepatitis B and C infection leading to cirrhosis are believed to be respon-
Group (n)
Age, Mean (yr)
Alco- Cir- Hepa- Hepahol rhosis titis B titis C
All (50) 65.1 ⫾ 1.3 84% 97% 18% 1980s (19) 65.8 ⫾ 1.7 79% 100% 50% 1990s (31) 64.6 ⫾ 1.7 86% 96% 6% NA ⫽ not available.
Survival, Mean (Range) (mo)
29% 5.0 (0.1–120) NA 4.0 (0.3–120) 29% 5.0 (0.1–50)
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Letters to the Editor
AFP levels and ultrasonography of the liver, to detect HCC at an early stage. Adil M. Choudhary, M.D. Ingram Roberts, M.D. Tarun Gupta, M.D. Section of Gastroenterology Department of Medicine Bridgeport Hospital/Yale University School of Medicine Bridgeport, Connecticut
REFERENCES 1. El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 1999;340:745– 50. 2. Ince N, Wands JR. The increasing incidence of heptocellular carcinoma. N Engl J Med 1999;340:798 –9.
AJG – Vol. 94, No. 9, 1999
syndromes (1) are Peutz-Jegher syndrome (mucocutaneous pigmentation and intestinal polyposis) and Cronkhite-Cananda syndrome (ectodermal defects such as alopecia, excessive skin pigmentation, and generalized gastrointestinal popyposis) and Gardener’s syndrome (soft tissue tumors such as sebaceous cysts and fibromas, bony tumors such as osteoma, adenomatous polyps of the colon and rectum associated with development of periampullary tumors). The case reported here had a somewhat different configuration: pancreatic cancer, multiple benign gastric polyps, multiple intradermal and junctional nevus, and no colonic or rectal polyposis. The purpose of this letter is to find out whether any similar cases have been noticed by readers. Is this reported combination just a coincidence, or could here be any relationship that should be explored further?
Reprint requests and correspondence: Adil M. Choudhary, M.D., 116 Mark Twain Drive, No. 17, River Ridge, LA 70123. Received May 3, 1999; accepted May 4, 1999.
T. C. Chauhan, M.D. Uniontown Hospital Uniontown, Pennsylvania
Variant of Gardener’s Syndrome
REFERENCE
TO THE EDITOR: Recently, I came across a 54-yr-old white woman with a history of abdominal pain and weight loss. Evaluation included EGD (Fig. 1), colonoscopy, and CT scan of the abdomen. She was found to have multiple benign gastric polyps. Her records revealed a past history of multiple intradermal and junctional nevus. Later, she developed obstructive jaundice, and ERCP detected pancreatic cancer. There are many well-known syndromes reported with an association between gastrointestinal polyps, ectodermal neoplasia and pancreatic cancer. Examples of such
1. Sabiston D, Jr. Textbook of surgery, 1986.
Figure 1. EGD report shows polyps.
Reprint requests and correspondence: T. C. Chauhan, M.D., Unidade de Figado, Uniontown Hospital, Uniontown, PA 15401. Received Apr. 3, 1998; accepted Mar. 20, 1999.
Spontaneous Bacterial Peritonitis Due to Brucella Melitensis in a Cirrhotic Patient TO THE EDITOR: We read with interest two separate articles, one by Beales (1), and the other by Jajaraj et al. (2), describing two unusual infective causes of spontaneous bacterial peritonitis (SBP). The authors indicate that unusual organisms can be causative. One of these unusual agents is brucella, and SBP due to brucella is extremely rare. To best of our knowledge there are only four reported peritonitis cases in cirrhotic patients caused by brucella (3– 6). We present herein a case of blood and ascitic culture-proven SBP caused by Brucella melitensis. A 51-yr-old man was admitted to Osmangazi University Hospital with complaints of fever with rigor, abdominal swelling, abdominal pain, and peripheral edema. He was experiencing increased abdominal distention during the past 3 wk. His fluid intake was about 1 L/day; he was not using any medication that would cause fluid retention; and his diuresis was not reduced. He was receiving spiranolactone, lactulose, and multivitamins at the time of admission. He had been admitted elsewhere several times, and was diagnosed as having alcoholically decompensated liver cirrhosis. He has been free of alcohol for 2 yr. His physical examination revealed a temperature of 38.4°C, and was compatible with chronic liver disease. The
Letters to the Editor
to IFN-␣, impressively demonstrate the causal relationship between IFN-␣ and liver failure in previously well compensated hepatitis C-induced chronic liver disease. Histology of the pretherapeutic liver tissue described some disturbances in lobular architecture, but a diagnosis of complete and advanced micronodular cirrhosis was made only after explantation. The possible existence of an underlying autoimmune disease may explain the very rapid increase in aminotransferase levels and liver failure after IFN-␣ treatment initiation. Even though the dose was reduced, the second (and potentially fatal) attempt at IFN-␣ treatment should not have been started in this situation. In conclusion, physicians involved in the treatment of hepatitis C should be very well aware of rising aminotransferase levels (especially in a patient with suspected liver cirrhosis), which may indicate impending liver failure. G. Lock, M.D. C. M. Reng, M.D. J. Scho¨lmerich, Professor of Medicine Department of Internal Medicine I University of Regensburg Regensburg, Germany C. Graeb, M.D. M. Anthuber, M.D. Department of Surgery University of Regensburg Regensburg, Germany K. H. Wiedmann, Professor of Medicine Krankenhaus der Barmherzigen Bru¨der Regensburg, Germany
REFERENCES 1. Dusheiko G. Side effects of alpha interferon in chronic hepatitis C. Hepatology 1997;26(suppl 1):112S–21S. 2. Janssen HLA, Brower JT, Nevens F, et al. European concerted action on viral hepatitis. Fatal hepatic decompensation associated with interferon alpha. Br Med J 1993;306:107– 8. 3. Sheen IS, Liaw YF, Tai DI, et al. Hepatic decompensation associated with hepatitis e antigen clearance in chronic type B hepatitis. Gastroenterology 1985;89:732–5. Reprint requests and correspondence: G. Lock, M.D., Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg, Germany. Received Apr. 28, 1999; accepted May 4, 1999.
2571
sible for this increased incidence (1, 2). In context of these findings, we would like to report the results of a small retrospective study recently conducted at our institution. The purpose of this retrospective study was to analyze the trends in the characteristics of hepatocellular carcinoma (HCC) over time, especially with regard to hepatitis B and C, and to investigate the predictive value of ␣-fetoprotein (AFP) in determining the prognosis in patients with HCC. We retrospectively reviewed the charts of 50 patients with histologically proven HCC on biopsy or autopsy at a community and a Veterans Affairs (VA) hospital between 1983 and 1997. Patients were divided into two groups: 1980s (1983–90) and 1990s (1991–97). Clinical characteristics including age, alcohol use, presence or absence of hepatitis B and C, cirrhosis on biopsy, AFP, and survival were analyzed in these two groups. Survival was also compared according to AFP levels. Mean values between the two groups were compared by using t test, and median survival was analyzed by using Mann-Whitney test. Clinical characteristics are shown in Table 1. There were 19 patients in the 1980s group and 31 patients in the 1990s group. Hepatitis B surface antigen (HBsAg) was positive in 50% of the patients tested in 1980s group, whereas only 6% of the 1990s patients were HBsAg positive. Hepatitis C virus antibody was positive in 29% of the patients in the 90s group. Patients with hepatitis C were significantly younger than those without hepatitis C (49.2 ⫾ 3.6 vs 69.9 ⫾ 1.9 yr, p ⬍ 0.0001) and had significantly higher AFP levels (17,307 ⫾ 8,294 vs 2,674 ⫾ 1,502, p ⬍ 0.02). AFP was elevated in 73% of the patients. There was no significant difference in median survival in groups based on AFP levels. In conclusion, patients with hepatitis C are at risk for developing HCC at a younger age. Association of hepatitis B with HCC seems to be decreasing in the 1990s. Median survival in patients with HCC has not changed with time and remains very poor. AFP levels do not correlate with survival. Although this is a very small study from which to draw any firm conclusions, the increasing incidence of HCC in a younger hepatitis C patient population is particularly intriguing. Patients with chronic hepatitis B and C infection and cirrhosis should be monitored very closely with serum Table 1. Clinical Characteristics of Patients With Hepatocellular Carcinoma During the 1980s and 1990s
Changing Patterns of Hepatocellular Carcinoma TO THE EDITOR: Primary hepatocellular carcinoma is occurring with increasing frequency in the United States, as recently shown in a study (1). Chronic hepatitis B and C infection leading to cirrhosis are believed to be respon-
Group (n)
Age, Mean (yr)
Alco- Cir- Hepa- Hepahol rhosis titis B titis C
All (50) 65.1 ⫾ 1.3 84% 97% 18% 1980s (19) 65.8 ⫾ 1.7 79% 100% 50% 1990s (31) 64.6 ⫾ 1.7 86% 96% 6% NA ⫽ not available.
Survival, Mean (Range) (mo)
29% 5.0 (0.1–120) NA 4.0 (0.3–120) 29% 5.0 (0.1–50)
2572
Letters to the Editor
AFP levels and ultrasonography of the liver, to detect HCC at an early stage. Adil M. Choudhary, M.D. Ingram Roberts, M.D. Tarun Gupta, M.D. Section of Gastroenterology Department of Medicine Bridgeport Hospital/Yale University School of Medicine Bridgeport, Connecticut
REFERENCES 1. El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 1999;340:745– 50. 2. Ince N, Wands JR. The increasing incidence of heptocellular carcinoma. N Engl J Med 1999;340:798 –9.
AJG – Vol. 94, No. 9, 1999
syndromes (1) are Peutz-Jegher syndrome (mucocutaneous pigmentation and intestinal polyposis) and Cronkhite-Cananda syndrome (ectodermal defects such as alopecia, excessive skin pigmentation, and generalized gastrointestinal popyposis) and Gardener’s syndrome (soft tissue tumors such as sebaceous cysts and fibromas, bony tumors such as osteoma, adenomatous polyps of the colon and rectum associated with development of periampullary tumors). The case reported here had a somewhat different configuration: pancreatic cancer, multiple benign gastric polyps, multiple intradermal and junctional nevus, and no colonic or rectal polyposis. The purpose of this letter is to find out whether any similar cases have been noticed by readers. Is this reported combination just a coincidence, or could here be any relationship that should be explored further?
Reprint requests and correspondence: Adil M. Choudhary, M.D., 116 Mark Twain Drive, No. 17, River Ridge, LA 70123. Received May 3, 1999; accepted May 4, 1999.
T. C. Chauhan, M.D. Uniontown Hospital Uniontown, Pennsylvania
Variant of Gardener’s Syndrome
REFERENCE
TO THE EDITOR: Recently, I came across a 54-yr-old white woman with a history of abdominal pain and weight loss. Evaluation included EGD (Fig. 1), colonoscopy, and CT scan of the abdomen. She was found to have multiple benign gastric polyps. Her records revealed a past history of multiple intradermal and junctional nevus. Later, she developed obstructive jaundice, and ERCP detected pancreatic cancer. There are many well-known syndromes reported with an association between gastrointestinal polyps, ectodermal neoplasia and pancreatic cancer. Examples of such
1. Sabiston D, Jr. Textbook of surgery, 1986.
Figure 1. EGD report shows polyps.
Reprint requests and correspondence: T. C. Chauhan, M.D., Unidade de Figado, Uniontown Hospital, Uniontown, PA 15401. Received Apr. 3, 1998; accepted Mar. 20, 1999.
Spontaneous Bacterial Peritonitis Due to Brucella Melitensis in a Cirrhotic Patient TO THE EDITOR: We read with interest two separate articles, one by Beales (1), and the other by Jajaraj et al. (2), describing two unusual infective causes of spontaneous bacterial peritonitis (SBP). The authors indicate that unusual organisms can be causative. One of these unusual agents is brucella, and SBP due to brucella is extremely rare. To best of our knowledge there are only four reported peritonitis cases in cirrhotic patients caused by brucella (3– 6). We present herein a case of blood and ascitic culture-proven SBP caused by Brucella melitensis. A 51-yr-old man was admitted to Osmangazi University Hospital with complaints of fever with rigor, abdominal swelling, abdominal pain, and peripheral edema. He was experiencing increased abdominal distention during the past 3 wk. His fluid intake was about 1 L/day; he was not using any medication that would cause fluid retention; and his diuresis was not reduced. He was receiving spiranolactone, lactulose, and multivitamins at the time of admission. He had been admitted elsewhere several times, and was diagnosed as having alcoholically decompensated liver cirrhosis. He has been free of alcohol for 2 yr. His physical examination revealed a temperature of 38.4°C, and was compatible with chronic liver disease. The