Toxic epidermal necrolysis caused by viral hepatitis A: a case report and literature review.

Toxic epidermal necrolysis (TEN) is a rare but serious immune-mediated life-threatening skin and mucous membrane reaction that is mainly caused by drugs, infections, vaccines, and malignant tumors. A 74-year-old woman presented with a moderate fever of unknown cause, which was relieved after 2 days, but with weakness and decreased appetite. Red maculopapules appeared successively on the neck, trunk, and limbs, expanding gradually, forming herpes and fusion, containing a yellow turbidous liquid and rupturing to reveal a bright red erosive surface spreading around the eyes and mouth. The affected body surface area was >90%. The severity of illness score for toxic epidermal necrolysis was 2 points. The drug eruption area and severity index score was 77. She was diagnosed with TEN caused by hepatitis A virus and treated with 160 mg/day methylprednisolone, 300 mg/day cyclosporine, and 20 g/day gammaglobulin. Her skin showed improvements after 3 days of treatment and returned to nearly normal after 1 month, and liver function was completely normal after 2 months.

Double plasma molecular adsorption system for Stevens-Johnson syndrome/toxic epidermal necrolysis: A case report.

BACKGROUND: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are very serious skin allergies, with an etiology related to infections and medication. Since the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus-2 has also been considered to cause SJS/TEN. CASE SUMMARY: We report the case of a woman in her thirties who took acetaminophen after contracting COVID-19. After 3 d of fever relief, she experienced high fever and presented with SJS/TEN symptoms, accompanied by intrahepatic cholestasis. Three days of corticosteroid treatment did not alleviate the skin damage; therefore, double plasma molecular adsorption system (DPMAS) therapy was initiated, with treatment intervals of 48 h. Her skin symptoms improved gradually and were resolved after seven DPMAS treatments. CONCLUSION: DPMAS therapy is beneficial for abrogating SJS/TEN because plasma adsorption and perfusion techniques reduce the inflammatory mediators (e.g., tumor necrosis factor-alpha and interleukin-10 and-12) speculated to be involved in the pathology of the skin conditions.

Hemocholecyst caused by accidental injury associated with radiofrequency ablation for hepatocellular carcinoma: A case report.

BACKGROUND: Radiofrequency ablation (RFA) is an effective and safe treatment for hepatocellular carcinoma that features a lower incidence of serious complications than surgical resection. Hemocholecyst caused by RFA is a rare complication of secondary damage to the intrahepatic bile duct that results in hemobilia. CASE SUMMARY: Here we report on a case of a hemocholecyst caused by accidental injury during RFA that induced hematemesis and melena. Digital subtraction angiography revealed no gallbladder arterial injuries. After conservative treatment and transcatheter arterial chemoembolization, the patient's condition stabilized, and she was discharged 1 wk later. CONCLUSION: Therefore, when performing interventional procedures such as RFA, clinicians must be vigilant because even minor injuries can lead to serious complications such as hemocholecyst.

Clinicopathological features of 11 cases of chronic hepatitis B infection complicated with primary biliary cholangitis.

BACKGROUND: Only a few cases of chronic hepatitis B (CHB) with primary biliary cholangitis (PBC) have been reported based on histological evidence from liver biopsies. AIM: To observe the clinicopathological features and outcomes of 11 patients with CHB infection complicated by PBC. METHODS: Eleven patients with CHB and PBC who underwent liver biopsy at the Zhenjiang Third Hospital, affiliated with Jiangsu University, and Wuxi Fifth People's Hospital, from January 2005 to September 2020, were selected. All patients initially visited our hospital with CHB and were pathologically diagnosed with CHB and PBC. RESULTS: Only five had elevated alkaline phosphatase levels, nine were positive for anti-mitochondrial antibody (AMA)-M2, and two were negative for AMA-M2. Two had jaundice and pruritus symptoms, 10 had mildly abnormal liver function, and one had severely elevated bilirubin and liver enzyme levels. The pathological characteristics of CHB complicated by PBC overlapped with those of PBC-autoimmune hepatitis (AIH). When necroinflammation of the portal area is not obvious, the pathological features of PBC are predominant, similar to the features of PBC alone. When the interface is severe, biliangitis will occur, with a large number of ductular reactions in zone 3. Unlike the PBC-AIH overlap pathology, this pathology is characterized by a small amount of plasma cell infiltration. Unlike PBC, lobulitis is often observed. CONCLUSION: This is the first large case series to show that the rare pathological features of CHB with PBC are similar to those of PBC-AIH and small duct injury was observed.

Baseline hepatocyte ballooning is a risk factor for adverse events in patients with chronic hepatitis B complicated with nonalcoholic fatty liver disease.

BACKGROUND: Although many studies have investigated the impact of chronic hepatitis B virus (HBV) infection and nonalcoholic fatty liver disease (NAFLD) on liver disease, few have investigated the relationship between nonalcoholic steatohepatitis (NASH) defined by liver pathology and the prognosis of chronic HBV infection. Most patients were followed up for a short time. This study aimed to further explore the impact of NAFLD and the pathological changes confirmed by liver pathology in patients with chronic HBV infection. AIM: To study the effect of NAFLD confirmed using liver pathology on the outcomes of long-term serious adverse events [cirrhosis, hepatocellular carcinoma (HCC), and death] in patients with chronic hepatitis B (CHB) virus infection. METHODS: We enrolled patients with chronic hepatitis B virus (HBV) infection who underwent liver biopsy at the Third People's Hospital of Zhenjaing Affiliated Jiangsu University between January 2005 and September 2020. Baseline clinical and pathological data on liver pathology and clinical data at the end of follow-up were collected. Propensity score matching (PSM) was used to balance baseline parameters, Kaplan-Meier (K-M) survival analysis was used to evaluate the risk of clinical events, and Cox regression was used to analyze the risk factors of events. RESULTS: Overall, 456 patients with chronic HBV infection were included in the study, of whom 152 (33.3%) had histologically confirmed NAFLD. The median follow-up time of the entire cohort was 70.5 mo. Thirty-four patients developed cirrhosis, which was diagnosed using ultrasound during the follow-up period. K-M survival analysis showed that NAFLD was not significantly associated with the risk of cirrhosis (log-rank test, P > 0.05). Patients with CHB with fibrosis at baseline were more prone to cirrhosis (log-rank test, P = 0.046). After PSM, multivariate analysis showed that diabetes mellitus, ballooning deformation (BD), and platelet (PLT) were independent risk factors for cirrhosis diagnosed using ultrasound (P < 0.05). A total of 10 patients (2.2%) developed HCC, and six of these patients were in the combined NAFLD group. K-M survival analysis showed that the cumulative risk of HCC in the NAFLD group was significantly higher (log-rank test, P < 0.05). Hepatocyte ballooning, and severe liver fibrosis were also associated with an increased risk of HCC (log-rank test, all P < 0.05). Cox multivariate analysis revealed that hepatocyte ballooning, liver fibrosis, and diabetes mellitus were independent risk factors for HCC. CONCLUSION: There was no significant correlation between chronic HBV infection and the risk of cirrhosis in patients with NAFLD. Diabetes mellitus, BD, and PLT were independent risk factors for liver cirrhosis. Patients with chronic HBV infection and NASH have an increased risk of HCC. BD, liver fibrosis, and diabetes mellitus are independent risk factors for HCC.

Risk stratification of primary liver cancer.

The risk stratification of primary liver cancer (PLC) discussed in a review of viral hepatitis and PLC could lead to misunderstandings by readers. For example, a single study or a small number of studies cannot comprehensively summarize the risk factors of PLC, is not included in the family history of liver cancer, and chronic hepatitis D is listed as a medium risk factor for the development of PLC. Currently, PLC prediction models with good clinical validation values have been applied clinically, such as the Toronto hepatocellular carcinoma risk index, REACH-B model, and PAGE-B model. Therefore, the Chinese, together with several research societies, have formulated the "Guideline for stratified screening and surveillance of primary liver cancer (2020 edition)." This guideline outlines PLC screening in at-risk populations, both in hospitals and communities. It is recommended to stratify the at-risk population into four risk levels: low-, intermediate-, high-, and extremely high-risk. This is highly recommended and applied in clinical practice.

Early diagnostic value of liver stiffness measurement in hepatic sinusoidal obstruction syndrome induced by hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT)-sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease, is a clinical syndrome characterized by symptoms, such as right upper quadrant pain, jaundice, fluid retention, and hepatomegaly, and is caused by pre-treatment-related hepatotoxicity during the early stages after HSCT. Clinical diagnosis of HSCT-SOS is based on the revised Seattle or Baltimore standards. The revised standard by the European Society for Bone Marrow Transplantation in 2016 has good practicability and can be used in combination with these two standards. Eight studies have shown the value of liver stiffness measurement (LSM) in the early diagnosis of HSCT-SOS. Four studies investigated LSM specificity and sensitivity for the early diagnosis of HSCT-SOS. LSM can distinguish SOS from other post-HSCT complications, enabling a clear differential diagnosis. It has been shown that median LSM of patients with SOS is significantly higher than that of patients with other treatment-related liver complications (e.g., acute cholecystitis, cholangitis, antifungal drug-related liver injury, liver graft-versus-host disease, isolated liver biochemical changes, and fulminant Epstein Barr virus related hepatitis reactivation). Therefore, the above data confirmed the utility of LSM and strongly suggested that LSM improves the positive predictive value of the SOS diagnostic clinical score after allogeneic HSCT. Early diagnosis of SOS is beneficial in preventing severe HSCT complications.

Establishment of a risk assessment score for deep vein thrombosis after artificial liver support system treatment.

BACKGROUND: The artificial liver support system (ALSS) is an effective treatment method for liver failure, but it requires deep venous intubation and long-term indwelling catheterization. However, the coagulation mechanism disorder of basic liver failure diseases, and deep venous thrombosis (DVT) often occur. AIM: To evaluate the risk factors for DVT following use of an ALSS and establish a risk assessment score. METHODS: This study was divided into three stages. In the first stage, the risk factors for DVT were screened and the patient data were collected, including ALSS treatment information; biochemical indices; coagulation and hematology indices; complications; procoagulant use therapy status; and a total of 24 indicators. In the second stage, a risk assessment score for DVT after ALSS treatment was developed. In the third stage, the DVT risk assessment score was validated. RESULTS: A total of 232 patients with liver failure treated with ALSS were enrolled in the first stage, including 12 with lower limb DVT. Logistic regression analysis showed that age [odds ratio (OR), 1.734; P = 0.01], successful catheterization time (OR, 1.667; P = 0.005), activity status (strict bed rest) (OR, 3.049; P = 0.005), and D-dimer level (≥ 500 ng/mL) (OR, 5.532; P < 0.001) were independent risk factors for DVT. We then established a scoring system for risk factors. In the validation group, a total of 213 patients with liver failure were treated with ALSS, including 14 with lower limb DVT. When the cutoff value of risk assessment was 3, the specificity and sensitivity of the risk assessment score were 88.9% and 85.7%, respectively. CONCLUSION: A simple risk assessment scoring system was established for DVT patients with liver failure treated with ALSS and was verified to have good sensitivity and specificity.

Is simultaneous presence of IgG4-positive plasma cells and giant-cell hepatitis a coincidence in autoimmune hepatitis? A case report.

BACKGROUND: The immune-mediated invasion of IgG4-positive plasma cells in the liver is found in some autoimmune hepatitis. Giant-cell hepatitis (GCH) is a very rare pathological feature in adults, and the clinical characteristics of the simultaneous appearance of the two pathological phenomena are not clear. CASE SUMMARY: A 68-year-old woman was hospitalized with fatigue, poor appetite, and yellow urine for 20 d. Liver function tests and immunological indexes were significantly abnormal and accompanied by elevated serum IgG4 levels. Liver pathology revealed severe inflammation of the interface between the portal tract and hepatocytes, portal area inflammation, plasma cell infiltration, formation of rosette cells, IgG4-positive plasma cells > 10/high-power field, IgG4/IgG > 40%, and multinucleated liver cell swelling. IgG4-related autoimmune hepatitis (AIH) combined with GCH was diagnosed, and methylprednisolone was administered at 40 mg/day. Two weeks later, the clinical symptoms disappeared, and the liver function and immunological indicators were significantly improved. Methylprednisolone was reduced at a rate of 4-8 mg per week to 8 mg/day for maintenance. A second liver biopsy 48 wk later indicated that liver inflammation and fibrosis were significantly improved. IgG4-positive plasma cells and GCH were not detected. A literature search was conducted to analyze articles reporting similar pathological phenomena. CONCLUSION: AIH with simultaneous IgG4-positive plasma cell infiltration and GCH, liver inflammation, and fibrosis is possibly more severe than typical AIH but sensitive to corticosteroids.

Efficacy of artificial liver support system in severe immune-associated hepatitis caused by camrelizumab: A case report and review of the literature.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can lead to immune-related hepatitis (IRH) and severe liver damage, which is life-threatening in the absence of specific treatment. CASE SUMMARY: A 75-year-old man was admitted to our hospital complaining of loss of appetite, yellow urine, and abnormal liver function for the past 2 wk. Three months prior to admission, he was treated with two rounds of capecitabine in combination with camrelizumab for lymph node metastasis of esophageal cancer. Although liver function was normal before treatment, abnormal liver function appeared at week 5. Capecitabine and camrelizumab were discontinued. Ursodeoxycholic acid and methylprednisolone 40 mg daily were administered. Liver function continued to deteriorate. Prothrombin time and international normalized ratio were 19 s and 1.8, respectively. The patient was diagnosed with acute liver failure. A pathological analysis of liver biopsy indicated a strongly positive immunohistochemical staining of T8+ cells, thereby suggesting that drug-induced liver injury was related to IRH caused by camrelizumab. Subsequently, we performed sequential dual-molecule plasma adsorption system (DPMAS) treatment with plasma exchange (PE). After two rounds of treatment, the patient's appetite significantly improved, the yellow color of urine reduced, and liver function improved (total bilirubin level decreased) after five rounds of treatment. Liver function normalized 4 wk after discharge. CONCLUSION: The use of sequential DPMAS with PE can reduce liver injury and systemic toxic reactions by clearing inflammatory mediators and harmful substances from blood, and regulate immune cell activity, which may be effective in the treatment of severe ICI-induced IRH.

Argon-helium cryoablation for thoracic vertebrae with metastasis of hepatocellular carcinoma-related hepatitis B: A case report.

BACKGROUND: Spinal metastasis of hepatocellular carcinoma (HCC) is rare, with an extremely poor prognosis and results in severe pain. Argon-helium cryotherapy is a local ablation method for HCC. CASE SUMMARY: A 54-year-old man was diagnosed with HCC related to hepatitis B one year ago and underwent surgical tumor resection and tenofovir antiviral treatment. However, a new lesion developed on the right liver after 1 mo. Transarterial chemoembolization was performed four times. One month ago, the patient developed back pain, and metastasis on the 11th thoracic vertebra was detected. Argon-helium cryoablation was performed to treat the right occupancy and metastatic lesion, which immediately alleviated the pain and prolonged survival. CONCLUSION: The use of argon-helium cryoablation for thoracic vertebrae with metastasis of HCC achieved favorable results.

Rare spontaneous intrahepatic portosystemic shunt in hepatitis B-induced cirrhosis: A case report.

BACKGROUND: The portosystemic shunt is the pathway between the portal vein (PV) and systemic circulation. A spontaneous intrahepatic portosystemic shunt (SPISS) is a rare portosystemic shunt type. Here we report an extremely rare type of SPISS, a spontaneous intrahepatic PV-inferior vena cava shunt (SPIVCS). CASE SUMMARY: A 66-year-old woman was admitted to our hospital with the complaint of abdominal distention and a decreased appetite for 1 mo. The patient had a 20-year history of hepatitis B surface antigen positivity and a 5-year history of cirrhosis. She had been treated with Chinese herbal medicine for a long time. Liver function tests showed: alanine aminotransferase, 35 U/L; aspartate aminotransferase, 42 U/L; serum albumin (ALB) 32.2 g/L; and serum ascites ALB gradient, 25.2 g/L. Abdominal ultrasonography and enhanced computed tomography showed that the left branch of the PV was thin and occluded; the right branch of the PV was thick and showed a vermicular dilatation vein cluster in the upper pole of the right kidney that branched out and converged into the inferior vena cava from the bare area of the lower right posterior lobe of the liver. We diagnosed her with an extremely rare SPIVCS caused by portal hypertension and provided symptomatic treatment after admission. One week later, her symptoms disappeared and she was discharged. CONCLUSION: SPIVCS is a rare portosystemic shunt with a clear history of cirrhosis and portal hypertension. Clarifying the type PV shunt has important clinical significance.

Therapeutic plasma exchange and a double plasma molecular absorption system in the treatment of thyroid storm with severe liver injury: A case report.

BACKGROUND: Thyroid storm is resistant to conventional treatments including antithyroid drugs and 131I therapeutic means. Plasma exchange (PE) and double plasma molecular absorption system (DPMAS) can be used as an effective treatment for thyroid storm with severe liver injury. CASE SUMMARY: A 52-year-old woman presented with a 10-day history of nausea and vomiting accompanied by yellowing of the skin and mucosa. Further, her free T3 (FT3) and FT4 levels were significantly elevated, whereas her thyrotropin level was reduced. After admission, her condition continued to deteriorate, and she presented with continued high fever, vomiting, palpitation, and shortness of breath. After being diagnosed with thyroid storm, the patient was immediately treated with PE combined with DPMAS. Her symptoms improved immediately. After three PE + DPMAS treatments, and she was discharged from the hospital. She was treated with methylprednisolone and methylthimidazole. After six months, the patient spontaneously discontinued methylthimidazole treatment. Her previous clinical manifestations and liver dysfunction reoccurred. The patient was treated with PE + DPMAS two times, and her condition rapidly improved. Liver histopathology indicated immunological liver injury. CONCLUSION: Our experience suggests that PE combined with DPMAS can effectively relieve the development of thyroid storm.

Ductopenia and cirrhosis in a 32-year-old woman with progressive familial intrahepatic cholestasis type 3: A case report and review of the literature.

Progressive familial intrahepatic cholestasis type 3 is caused by a mutation in the ATP-binding cassette, subfamily B, member 4 (ABCB4) gene encoding multidrug resistance protein 3. A 32-year-old woman with a history of acute hepatitis at age 9 years was found to have jaundice during pregnancy in 2008, and was diagnosed as having intrahepatic cholestasis of pregnancy. In 2009, she underwent cholecystectomy for gallstones and chronic cholecystitis. However, itching and jaundice did not resolve postoperatively. She was admitted to our hospital with fatigue, jaundice, and a recently elevated γ-glutamyl transpeptidase level. Liver biopsy led to the diagnosis of biliary cirrhosis with ductopenia. Genetic testing revealed a pathogenic heterozygous mutation, ex13 c.1531G > A (p.A511T), in the ABCB4 gene. Her father did not carry the mutation, but her mother's brother carried the heterozygous mutation. We made a definitive diagnosis of familial intrahepatic cholestasis type 3. Her symptoms and liver function improved after 3 mo of treatment with ursodeoxycholic acid.

Epidemiological features of chronic hepatitis C infection caused by remunerated blood donors: A nearly 27-year period survey.

AIM: To understand the prevalence of hepatitis C virus (HCV) infection in blood donors over a nearly 27-year interval and to explore the factors that affect the outcome of HCV infection. METHODS: A retrospective and cross-sectional study was conducted. The participants, mostly plasma donors, were selected from three administrative villages in the Jiangsu province in Eastern China. A questionnaire was administered among the villagers who had a history of blood donation from the late 1980s to the early 1990s. All participants underwent physical examination, liver B-ultrasonography, and liver stiffness measurement. In addition, 10 mL of blood was collected from each participant to measure simple liver function parameters (albumin, alanine aminotransferase, aspirate aminotransferase), blood factors (platelet), and for hepatitis B surface antigen, antiHCV, and antihuman immunodeficiency virus detection. HCV RNA detection, HCV genotyping, and other tests were carried out in antiHCV-positive patients. RESULTS: After a median of 27 years (25-31 years) from the last blood donation to the time of survey, a total of 1694 participants were investigated, and the antiHCV-positive individuals were categorized into three groups: blood donors (n = 12, 3.3%), plasma donors (n = 534, 68.5%), and mixed donors (n = 324, 58.8%). A total of 592 (68.05%) patients had detectable HCV RNA, and 91.9% had genotype 1b. A total of 161 (27.2%, 161/592) patients with chronic HCV were considered to have cirrhosis with a liver stiffness measurement level higher than 12 kPa. Multiple logistic (binary) regression analysis results showed that platelet and IgG levels were associated with cirrhosis. CONCLUSION: The nearly 27-year interval investigation revealed that chronic hepatitis C infection is a very serious public health problem in Eastern China. Plasma donation and subsequent return of blood cells to the donor are the main causes of hepatitis C infection. The main HCV genotype is 1b. Nearly 28% of cases progressed to cirrhosis. Age, especially over 60 years, and regular drinking habits were risk factors associated with cirrhosis.

Diagnostic value of FIB-4, aspartate aminotransferase-to-platelet ratio index and liver stiffness measurement in hepatitis B virus-infected patients with persistently normal alanine aminotransferase.

AIM: To assess the diagnostic value of FIB-4, aspartate aminotransferase-to-platelet ratio index (APRI), and liver stiffness measurement (LSM) in patients with hepatitis B virus infection who have persistently normal alanine transaminase (PNALT). METHODS: We enrolled 245 patients with chronic hepatitis B: 95 in PNALT group, 86 in intermittently elevated alanine transaminase (PIALT1) group [alanine transaminase (ALT) within 1-2 × upper limit of normal value (ULN)], and 64 in PIALT2 group (ALT > 2 × ULN). All the patients received a percutaneous liver biopsy guided by ultrasonography. LSM, biochemical tests, and complete blood cell counts were performed. RESULTS: The pathological examination revealed moderate inflammatory necrosis ratios of 16.81% (16/95), 32.56% (28/86), and 45.31% (28/64), and moderate liver fibrosis of 24.2% (23/95), 33.72% (29/86), and 43.75% (28/64) in the PNALT, PIALT1, and PIALT2 groups, respectively. The degrees of inflammation and liver fibrosis were significantly higher in the PIALT groups than in the PNALT group (P < 0.05). No significant difference was found in the areas under the curve (AUCs) between APRI and FIB-4 in the PNALT group; however, significant differences were found between APRI and LSM, and between FIB-4 and LSM in the PNALT group (P < 0.05 for both). In the PIALT1 and PIALT2 groups, no significant difference (P > 0.05) was found in AUCs for all comparisons (P > 0.05 for all). In the overall patients, a significant difference in the AUCs was found only between LSM and APRI (P < 0.05). CONCLUSION: APRI and FIB-4 are not the ideal noninvasive hepatic fibrosis markers for PNALT patients. LSM is superior to APRI and FIB-4 in PNALT patients because of the influence of liver inflammation and necrosis.

Hepatitis B surface antigen levels of cessation of nucleos(t)ide analogs associated with virological relapse in hepatitis B surface antigen-negative chronic hepatitis B patients.

AIM: To investigate the virological relapse rate in hepatitis B e antigen (HBeAg)-negative patients after antiviral therapy discontinuation and analyze the factors associated with virological relapse. METHODS: Among patients diagnosed with chronic hepatitis B infection between May 2005 and July 2010, 204 were eligible for analysis. The Kaplan-Meier method and log-rank test were used to calculate the cumulative rate of relapse and compare cumulative relapse rates between groups. The Cox proportional hazards regression model was used to evaluate the predictive factor of virological relapse. RESULTS: The 2 and 1 year cumulative risks of virological relapse after antiviral therapy discontinuation were 79.41% (162/204) and 43.82% (71/162), respectively. Multivariate analysis revealed that only post treatment hepatitis B surface antigen (HBsAg) level was associated with virological relapse (P = 0.011). The cumulative risk of virological relapse was higher in the patients with HBsAg levels ≥ 1500 IU/L than in those with HBsAg levels < 1500 IU/L (P = 0.0013). The area under the curve was 0.603 (P = 0.033). The cutoff HBsAg value for predicting virological relapse was 1443 IU/L. CONCLUSION: We found that the virological relapse rate remained high after antiviral therapy discontinuation in the HBeAg-negative patients and that the post treatment HBsAg levels predicted virological relapse.

Natural YMDD-motif mutants affect clinical course of lamivudine in chronic hepatitis B.

AIM: To investigate the prevalence of nature tyrosine-methionine-aspartic acid-aspartic acid motif mutations in chronic hepatitis B (CHB) patients and to evaluate the efficacy of lamivudine. METHODS: A total of 1268 CHB patients were recruited from the outpatient and inpatient departments of six centers. Tyrosine-methionine-aspartic acid-aspartic acid (YMDD) mutations were analyzed using the hepatitis B virus (HBV) drug resistance line probe assay. Forty voluntary patients were selected from those with positive or negative natural YMDD mutations to undergo treatment with lamivudine. RESULTS: YMDD mutations were detected in 288 (22.71%) of the 1268 CHB patients. Multivariate analysis revealed that the patients' HBV DNA level (P=0.0282) and hepatitis B e antigen status (P=0.0133) were also associated with natural YMDD mutations. The rates of normalization of alanine aminotransferase levels and HBV DNA nondetection at 6, 24, 36, and 48 wk were compared between the patients with natural YMDD mutations and those without, and the differences were not significant. However, there was a significant difference in the cumulative emergence rates of virological breakthrough at 48 wk in the patients with natural YMDD mutations and those without (32.5% vs 12.5%, P=0.032). CONCLUSION: Naturally occurring YMDD mutations are detectable in a large proportion of CHB patients; breakthrough hepatitis tended to occur in patients with natural YMDD mutations.